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Barth</submitter><technology_type>Mass Spectrometry</technology_type><technology_type>Data-independent acquisition</technology_type><technology_type>Bottom-up proteomics</technology_type><software></software><submitter_keywords>Plasma proteomics</submitter_keywords><submitter_keywords>Neat plasma</submitter_keywords><full_dataset_link>https://www.ebi.ac.uk/pride/archive/projects/PXD073409</full_dataset_link><tissue>Blood Plasma</tissue><sample_protocol>Plasma samples were randomized on a plate and prepared for LC-MS analysis with the autoSP3 protocol on an Agilent Bravo liquid handling platform (Agilent Technologies, Santa Clara, CA, USA). Briefly, plasma samples were diluted in 100mM ammonium bicarbonate and 1µL plasma per sample was used. Reduction and alkylation were performed at 1% SDS, 10mM TCEP, 40mM CAA at 95°C for 10 minutes. 5µL of magnetic beads were added (Cytiva, Marlborough, MA, USA; #45152105050250 and #65152105050250 1:1) and proteins bound to beads upon addition of 50% (v/v) acetonitrile (ACN). Beads were washed twice with 80% ethanol (v/v) and once with acetonitrile. Beads were resuspended in 100mM ammonium bicarbonate and 1.2µg trypsin are added for overnight digestion at 37°C. Peptides were acidified to 1% TFA and 0.25µL of that solution were loaded on Evotip Pure tips (Evosep, Odense, Denmark) with a semi-automated protocol on the Agilent Bravo according to manufacturer’s instruction: tips were washed with ACN/0.1% formic acid (FA), conditioned with 2-propanol, conditioned with 0.1% FA before sample loading. Tips were washed twice with 0.1% FA and stored in 0.1% FA to prevent drying out. Evotip Pure tips were placed in the Evosep One (Evosep, Odense, Denmark) autosampler and peptides injected from there using the 30 samples per day method with 44 minutes gradient. A EV1137 column with C18 material was used (15cm x 150µm, 1.5µm). Eluted peptides were electrosprayed (2kV, 275°C) into an Exploris 480 mass spectrometer (MS) (Thermo Fisher Scientific, Bremen, Germany). The MS was operated in data-independent acquisition (DIA) mode with an MS1-scan at a resolution of 120.000 (at m/z 200), scan range 380–980 m/z, 300% AGC target and 100ms maximum injection time; followed by 30 MS/MS scans in windows of 20 m/z with 1 m/z overlap and normalized collision energy 30%. MS2 resolution was 30.000 (at m/z 200), ACG target 3000%, auto maximum injection time, and data were recorded in centroid mode.</sample_protocol><repository>Pride</repository><quantification_method>Not available</quantification_method><modification></modification><data_protocol>Proteins were identified and quantified using the software Spectronaut (version 20.1.250624.92449; Biognosys, Schlieren, Switzerland). For identification, directDIA mode and the fasta file “uniprot_sprot_2024-01-01_HUMAN” featuring 20428 entries downloaded in the software Spectronaut were used. Carbamidomethylation was set as fixed modification, protein N-terminal acetylation and methionine oxidation as variable modifications, and two miscleavages were allowed. Cross-run normalization was activated.</data_protocol><omics_type>Proteomics</omics_type><labhead>Martin Bernhard Mueller</labhead><instrument_platform></instrument_platform><labhead_affiliation>1 Department of Anaesthesiology, LMU University Hospital, Ludwig-Maximilian-University (LMU), Munich, Germany 2 Walter Brendel Center of Experimental Medicine, Research Unit Immune Function and Immune Metabolism, Ludwig-Maximilian-University (LMU), Munich, Germany</labhead_affiliation><submission_type>PARTIAL</submission_type><species>Homo Sapiens (human)</species><publication>42286659 Müller MB, Kammerer T, Khan H, Schmid A, Hirschberger S, Hübner M, Barth TK, Mitsigiorgi R, Stihl C, Holzer M, Jira D, Patscheider M, Weiss BG, Reichel CA, Uhl B. Endothelial glycocalyx perturbation in obstructive sleep apnea is associated with repetitive hypoxemia and immunothrombotic endothelial dysfunction. J Transl Med. 2026 24(1):777 10.1186/s12967-026-08409-2</publication><submitter_mail>teresa.barth@bmc.med.lmu.de</submitter_mail><submitter_affiliation>Biomedical Center Munich, Ludwig-Maximilians-Universitaet Munich</submitter_affiliation><submitter_country>Germany</submitter_country><pubmed_abstract>&lt;h4>Background&lt;/h4>Obstructive sleep apnea (OSA) is associated with cardiovascular disease. The endothelial glycocalyx (eGCX) is a shear-sensitive intravascular barrier. The relevance of OSA and intermittent hypoxia (IH) for eGCX perturbation and cardiovascular disease in humans remains unclear.&lt;h4>Methods&lt;/h4>In a prospectively recruited observational cohort with cross-sectional biomarker analysis in men (n = 60), polysomnography quantified apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and hypoxic burden (HB). Using single-time-point plasma sampling, eGCX glycosaminoglycans hyaluronan (HA) and heparan sulfate (HS) and the proteoglycan syndecan-1 (SDC-1) were related to OSA severity and repetitive hypoxemia, including multivariable adjustment for cardiometabolic, inflammatory, and renal determinants. Plasma proteomics defined pathways associated with OSA and HA/HS. Shear-matured primary human endothelial cells were exposed to OSA-characteristic IH cycles under arterial flow to assess eGCX structure, oxidative stress, nitric oxide (NO) signaling, thromboinflammatory status, and antioxidant treatment with N-acetylcysteine.&lt;h4>Results&lt;/h4>Plasma HA and HS were higher in OSA than in non-OSA individuals and increased stepwise with disease severity, tracking AHI, ODI, and HB. These associations persisted in multivariable analyses adjusting for age, BMI, hypertension, hs-CRP, fasting glucose, and eGFR. Plasma SDC-1 did not differ between groups and remained non-associated in adjusted analyses. Proteomics revealed enrichment of inflammatory, coagulation, and oxidative stress-related pathways that strengthened with increasing OSA burden and higher HA/HS levels. Experimentally, IH caused loss of endothelial surface HA/HS with increased shedding, increased reactive oxygen species, reduced redox capacity, impaired NOS3/eNOS signaling and reduced NO bioavailability. IH or enzymatic eGCX digestion each enhanced monocyte and platelet adhesion, tissue factor expression, and fibrin deposition under shear, while N-acetylcysteine attenuated oxidative stress and partially restored surface HA expression.&lt;h4>Conclusions&lt;/h4>Integrated patient and IH-model data show that OSA severity and repetitive hypoxemia are associated with circulating markers consistent with eGCX perturbation, while the endothelial IH model supports induction of oxidative-inflammatory stress and a proadhesive, prothrombotic phenotype by intermittent hypoxia. Together, circulating HA and HS emerge as candidate biomarkers associated with OSA-related eGCX perturbation, warranting further evaluation in longitudinal and interventional studies of eGCX-stabilizing adjunct therapies. These findings derive from an all-male cohort and require validation in women and more diverse populations.</pubmed_abstract><pubmed_title>Endothelial glycocalyx perturbation in obstructive sleep apnea is associated with repetitive hypoxemia and immunothrombotic endothelial dysfunction.</pubmed_title><pubmed_authors>Müller Martin Bernhard MB, Kammerer Tobias T, Khan Humayun H, Schmid Annika A, Hirschberger Simon S, Hübner Max M, Barth Teresa K TK, Mitsigiorgi Rea R, Stihl Clemens C, Holzer Martin M, Jira Daniel D, Patscheider Martin M, Weiss Bernhard G BG, Reichel Christoph Andreas CA, Uhl Bernd B</pubmed_authors></additional><is_claimable>false</is_claimable><name>Endothelial Glycocalyx Injury in Obstructive Sleep Apnea Links Repetitive Hypoxemia to Immunothrombotic Endothelial Dysfunction</name><description>BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular disease. The endothelial glycocalyx (eGCX) is a shear-sensitive, interfacial barrier towards the intravascular compartment. The relevance of OSA and intermittent hypoxia (IH) for eGCX injury and, subsequently, cardiovascular pathologies in humans remains unclear. METHODS: In a prospective, single-center observational study in men, polysomnography quantified apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and hypoxic burden (HB). Plasma levels of the key eGCX glycosaminoglycans hyaluronan (HA) and heparan sulfate (HS) and the proteoglycan syndecan-1 (SDC-1) were related to OSA severity and repetitive hypoxemia. Plasma proteomics defined pathways associated with OSA and an HA/HS-derived eGCX score. In parallel, shear-matured primary human endothelial cells were exposed to OSA-characteristic IH cycles under arterial flow to assess eGCX structure, oxidative stress, nitric-oxide (NO) signaling, thromboinflammatory status, and to test N-acetylcysteine as an antioxidant. RESULTS: Plasma levels of HA and HS were higher in OSA than in non-OSA individuals and increased stepwise with disease severity, tracking AHI, ODI and HB. Plasma SDC-1 did not differ between the groups. Proteomics revealed enrichment of inflammation, coagulation, and oxidative stress-related pathways that strengthened with increasing OSA burden and higher eGCX scores. Experimentally, IH caused loss of endothelial surface HA/HS with increased shedding, increased reactive oxygen species, reduced redox capacity, and decreased endothelial NO synthase expression and NO bioavailability. IH or enzymatic eGCX digestion each enhanced monocyte adhesion and fibrin deposition on the endothelium under physiological shear, while N-acetylcysteine attenuated oxidative stress and partially restored surface HA expression. CONCLUSIONS: Integrated patient and IH-model data indicate that OSA is associated with eGCX degradation linked to oxidative-inflammatory stress and a pro-adhesive, pro-thrombotic endothelial phenotype. These data highlight circulating HA and HS as translational biomarkers of OSA-related eGCX injury with potential utility for risk stratification and as pharmacodynamic readouts for eGCX-stabilizing adjunct therapies.</description><dates><publication>2026-06-29</publication><submission>2026-01-22</submission></dates><accession>PXD073409</accession><cross_references><TAXONOMY>NEWT:6945</TAXONOMY><TAXONOMY>NEWT:3555</TAXONOMY><TAXONOMY>NEWT:2</TAXONOMY><TAXONOMY>NEWT:157546</TAXONOMY><TAXONOMY>NEWT:35554</TAXONOMY><TAXONOMY>NEWT:38942</TAXONOMY><TAXONOMY>NEWT:307972</TAXONOMY><TAXONOMY>NEWT:32046</TAXONOMY><TAXONOMY>NEWT:544496</TAXONOMY><TAXONOMY>NEWT:2042546</TAXONOMY><TAXONOMY>NEWT:45351</TAXONOMY><TAXONOMY>NEWT:43179</TAXONOMY><TAXONOMY>NEWT:4513</TAXONOMY><TAXONOMY>NEWT:5722</TAXONOMY><TAXONOMY>NEWT:376741</TAXONOMY><TAXONOMY>NEWT:55153</TAXONOMY><TAXONOMY>NCBITaxon:10407</TAXONOMY><TAXONOMY>NEWT:1736309</TAXONOMY><TAXONOMY>NEWT:309800</TAXONOMY><TAXONOMY>NEWT:1211601</TAXONOMY><TAXONOMY>NEWT:876138</TAXONOMY><TAXONOMY>NEWT:237561</TAXONOMY><TAXONOMY>NEWT:5833</TAXONOMY><TAXONOMY>NEWT:6928</TAXONOMY><TAXONOMY>NEWT:10036</TAXONOMY><TAXONOMY>NEWT:36745</TAXONOMY><TAXONOMY>NEWT:1351</TAXONOMY><TAXONOMY>NEWT:1438992</TAXONOMY><TAXONOMY>NEWT:2649997</TAXONOMY><TAXONOMY>NEWT:272563</TAXONOMY><TAXONOMY>NEWT:224326</TAXONOMY><TAXONOMY>NCBITaxon:79857</TAXONOMY><TAXONOMY>NEWT:1096976</TAXONOMY><TAXONOMY>NEWT:95648</TAXONOMY><TAXONOMY>NEWT:3885</TAXONOMY><TAXONOMY>NEWT:3888</TAXONOMY><TAXONOMY>NEWT:1589</TAXONOMY><TAXONOMY>NEWT:135622</TAXONOMY><TAXONOMY>NCBITaxon:4896</TAXONOMY><TAXONOMY>NEWT:6915</TAXONOMY><TAXONOMY>NEWT:3649</TAXONOMY><TAXONOMY>NEWT:101510</TAXONOMY><TAXONOMY>NEWT:3880</TAXONOMY><TAXONOMY>NEWT:272559</TAXONOMY><TAXONOMY>NEWT:3641</TAXONOMY><TAXONOMY>NEWT:383379</TAXONOMY><TAXONOMY>NEWT:466585</TAXONOMY><TAXONOMY>NEWT:10029</TAXONOMY><TAXONOMY>NEWT:1000589</TAXONOMY><TAXONOMY>NEWT:85963</TAXONOMY><TAXONOMY>NEWT:85962</TAXONOMY><TAXONOMY>NEWT:317447</TAXONOMY><TAXONOMY>NEWT:7955</TAXONOMY><TAXONOMY>NEWT:7959</TAXONOMY><TAXONOMY>NEWT:2261</TAXONOMY><TAXONOMY>NEWT:31156</TAXONOMY><TAXONOMY>NEWT:398580</TAXONOMY><TAXONOMY>NEWT:4565</TAXONOMY><TAXONOMY>NEWT:1264690</TAXONOMY><TAXONOMY>NEWT:515619</TAXONOMY><TAXONOMY>NEWT:192875</TAXONOMY><TAXONOMY>NEWT:34305</TAXONOMY><TAXONOMY>NEWT:59729</TAXONOMY><TAXONOMY>NCBITaxon:183674</TAXONOMY><TAXONOMY>NEWT:224308</TAXONOMY><TAXONOMY>NEWT:84645</TAXONOMY><TAXONOMY>NEWT:626528</TAXONOMY><TAXONOMY>NEWT:139927</TAXONOMY><TAXONOMY>NEWT:4558</TAXONOMY><TAXONOMY>NEWT:209285</TAXONOMY><TAXONOMY>NEWT:5888</TAXONOMY><TAXONOMY>NEWT:1283</TAXONOMY><TAXONOMY>NEWT:931281</TAXONOMY><TAXONOMY>NEWT:4550</TAXONOMY><TAXONOMY>NEWT:1000561</TAXONOMY><TAXONOMY>NEWT:197</TAXONOMY><TAXONOMY>NCBITaxon:79824</TAXONOMY><TAXONOMY>NEWT:4787</TAXONOMY><TAXONOMY>NCBITaxon:4563</TAXONOMY><TAXONOMY>NEWT:5755</TAXONOMY><TAXONOMY>NEWT:44689</TAXONOMY><TAXONOMY>NEWT:3218</TAXONOMY><TAXONOMY>NEWT:5759</TAXONOMY><TAXONOMY>NEWT:1736231</TAXONOMY><TAXONOMY>NEWT:1270</TAXONOMY><TAXONOMY>NEWT:2242</TAXONOMY><TAXONOMY>NEWT:4784</TAXONOMY><TAXONOMY>NEWT:11320</TAXONOMY><TAXONOMY>NEWT:360106</TAXONOMY><TAXONOMY>NEWT:286</TAXONOMY><TAXONOMY>NEWT:287</TAXONOMY><TAXONOMY>NEWT:10117</TAXONOMY><TAXONOMY>NEWT:10239</TAXONOMY><TAXONOMY>NEWT:10116</TAXONOMY><TAXONOMY>NEWT:1280</TAXONOMY><TAXONOMY>NEWT:1735272</TAXONOMY><TAXONOMY>NEWT:83334</TAXONOMY><TAXONOMY>NEWT:83332</TAXONOMY><TAXONOMY>NEWT:44685</TAXONOMY><TAXONOMY>NEWT:317513</TAXONOMY><TAXONOMY>NEWT:1148</TAXONOMY><TAXONOMY>NEWT:580240</TAXONOMY><TAXONOMY>NEWT:294128</TAXONOMY><TAXONOMY>NEWT:11676</TAXONOMY><TAXONOMY>NEWT:55571</TAXONOMY><TAXONOMY>NEWT:100226</TAXONOMY><TAXONOMY>NEWT:4530</TAXONOMY><TAXONOMY>NEWT:4896</TAXONOMY><TAXONOMY>NEWT:75058</TAXONOMY><TAXONOMY>NEWT:13616</TAXONOMY><TAXONOMY>NEWT:1094343</TAXONOMY><TAXONOMY>NEWT:296543</TAXONOMY><TAXONOMY>NEWT:1773</TAXONOMY><TAXONOMY>NEWT:1895</TAXONOMY><TAXONOMY>NEWT:1182590</TAXONOMY><TAXONOMY>NEWT:3712</TAXONOMY><TAXONOMY>NEWT:935293</TAXONOMY><TAXONOMY>NEWT:64152</TAXONOMY><TAXONOMY>NEWT:4924</TAXONOMY><TAXONOMY>NEWT:749200</TAXONOMY><TAXONOMY>NEWT:990346</TAXONOMY><TAXONOMY>NEWT:145953</TAXONOMY><TAXONOMY>NEWT:257309</TAXONOMY><TAXONOMY>NEWT:100816</TAXONOMY><TAXONOMY>NEWT:263</TAXONOMY><TAXONOMY>NEWT:230741</TAXONOMY><TAXONOMY>NEWT:52283</TAXONOMY><TAXONOMY>NEWT:284812</TAXONOMY><TAXONOMY>NCBITaxon:1313</TAXONOMY><TAXONOMY>NEWT:43330</TAXONOMY><TAXONOMY>NEWT:1603293</TAXONOMY><TAXONOMY>NEWT:408169</TAXONOMY><TAXONOMY>NEWT:44544</TAXONOMY><TAXONOMY>NEWT:4911</TAXONOMY><TAXONOMY>NEWT:645463</TAXONOMY><TAXONOMY>NEWT:3702</TAXONOMY><TAXONOMY>NEWT:129249</TAXONOMY><TAXONOMY>NEWT:243277</TAXONOMY><TAXONOMY>NEWT:990119</TAXONOMY><TAXONOMY>NEWT:408172</TAXONOMY><TAXONOMY>NEWT:408170</TAXONOMY><TAXONOMY>NEWT:493760</TAXONOMY><TAXONOMY>NEWT:260710</TAXONOMY><TAXONOMY>NEWT:257313</TAXONOMY><TAXONOMY>NEWT:400772</TAXONOMY><TAXONOMY>NEWT:3708</TAXONOMY><TAXONOMY>NEWT:128161</TAXONOMY><TAXONOMY>NEWT:332648</TAXONOMY><TAXONOMY>NEWT:106592</TAXONOMY><TAXONOMY>NEWT:536231</TAXONOMY><TAXONOMY>NEWT:460519</TAXONOMY><TAXONOMY>NEWT:1187947</TAXONOMY><TAXONOMY>NEWT:1432138</TAXONOMY><TAXONOMY>NEWT:10312</TAXONOMY><TAXONOMY>NEWT:1424507</TAXONOMY><TAXONOMY>NCBITaxon:1773</TAXONOMY><TAXONOMY>NEWT:9598</TAXONOMY><TAXONOMY>NEWT:8030</TAXONOMY><TAXONOMY>NEWT:1639</TAXONOMY><TAXONOMY>NEWT:188229</TAXONOMY><TAXONOMY>NEWT:3818</TAXONOMY><TAXONOMY>NEWT:480</TAXONOMY><TAXONOMY>NEWT:4909</TAXONOMY><TAXONOMY>NEWT:67767</TAXONOMY><TAXONOMY>NEWT:432359</TAXONOMY><TAXONOMY>NEWT:46835</TAXONOMY><TAXONOMY>NEWT:1182263</TAXONOMY><TAXONOMY>NEWT:2711</TAXONOMY><TAXONOMY>NEWT:376686</TAXONOMY><TAXONOMY>NEWT:95486</TAXONOMY><TAXONOMY>NEWT:9103</TAXONOMY><TAXONOMY>NEWT:29159</TAXONOMY><TAXONOMY>NEWT:253</TAXONOMY><TAXONOMY>NEWT:10306</TAXONOMY><TAXONOMY>NCBITaxon:2759</TAXONOMY><TAXONOMY>NEWT:1233435</TAXONOMY><TAXONOMY>NEWT:8022</TAXONOMY><TAXONOMY>NEWT:145943</TAXONOMY><TAXONOMY>NCBITaxon:4932</TAXONOMY><TAXONOMY>NEWT:595536</TAXONOMY><TAXONOMY>NEWT:240906</TAXONOMY><TAXONOMY>NEWT:593117</TAXONOMY><TAXONOMY>NEWT:3635</TAXONOMY><TAXONOMY>NEWT:5811</TAXONOMY><TAXONOMY>NEWT:235443</TAXONOMY><TAXONOMY>NEWT:272624</TAXONOMY><TAXONOMY>NEWT:411483</TAXONOMY><TAXONOMY>NEWT:884019</TAXONOMY><TAXONOMY>NEWT:198215</TAXONOMY><TAXONOMY>NEWT:411490</TAXONOMY><TAXONOMY>NEWT:983964</TAXONOMY><TAXONOMY>NEWT:169963</TAXONOMY><TAXONOMY>NEWT:32644</TAXONOMY><TAXONOMY>NEWT:499175</TAXONOMY><TAXONOMY>NEWT:109779</TAXONOMY><TAXONOMY>NEWT:476272</TAXONOMY><TAXONOMY>NEWT:3747</TAXONOMY><TAXONOMY>NEWT:195051</TAXONOMY><TAXONOMY>NEWT:367830</TAXONOMY><TAXONOMY>NEWT:1255228</TAXONOMY><TAXONOMY>NEWT:178616</TAXONOMY><TAXONOMY>NEWT:410289</TAXONOMY><TAXONOMY>NEWT:373153</TAXONOMY><TAXONOMY>NEWT:352472</TAXONOMY><TAXONOMY>NEWT:357</TAXONOMY><TAXONOMY>NEWT:360094</TAXONOMY><TAXONOMY>NEWT:470</TAXONOMY><TAXONOMY>NEWT:1313</TAXONOMY><TAXONOMY>NEWT:411469</TAXONOMY><TAXONOMY>NEWT:84023</TAXONOMY><TAXONOMY>NEWT:559292</TAXONOMY><TAXONOMY>NEWT:39491</TAXONOMY><TAXONOMY>NCBITaxon:5811</TAXONOMY><TAXONOMY>NEWT:411464</TAXONOMY><TAXONOMY>NEWT:411460</TAXONOMY><TAXONOMY>NEWT:2014887</TAXONOMY><TAXONOMY>NEWT:2762</TAXONOMY><TAXONOMY>NEWT:1174673</TAXONOMY><TAXONOMY>NEWT:562</TAXONOMY><TAXONOMY>NEWT:411470</TAXONOMY><TAXONOMY>NEWT:33952</TAXONOMY><TAXONOMY>NEWT:2094720</TAXONOMY><TAXONOMY>NCBITaxon:2697049</TAXONOMY><TAXONOMY>NEWT:571256</TAXONOMY><TAXONOMY>NEWT:28038</TAXONOMY><TAXONOMY>NEWT:1663</TAXONOMY><TAXONOMY>NEWT:1423</TAXONOMY><TAXONOMY>NEWT:4932</TAXONOMY><TAXONOMY>NEWT:3603</TAXONOMY><TAXONOMY>NEWT:2759</TAXONOMY><TAXONOMY>NEWT:3847</TAXONOMY><TAXONOMY>NEWT:327159</TAXONOMY><TAXONOMY>NEWT:178876</TAXONOMY><TAXONOMY>NEWT:327160</TAXONOMY><TAXONOMY>NEWT:573</TAXONOMY><TAXONOMY>NEWT:9031</TAXONOMY><TAXONOMY>NEWT:7091</TAXONOMY><TAXONOMY>NEWT:241368</TAXONOMY><TAXONOMY>NEWT:42528</TAXONOMY><TAXONOMY>NEWT:190802</TAXONOMY><TAXONOMY>NEWT:9778</TAXONOMY><TAXONOMY>NEWT:150475</TAXONOMY><TAXONOMY>NEWT:303</TAXONOMY><TAXONOMY>NEWT:9417</TAXONOMY><TAXONOMY>NEWT:7111</TAXONOMY><TAXONOMY>NEWT:347515</TAXONOMY><TAXONOMY>NEWT:1216979</TAXONOMY><TAXONOMY>NEWT:5180</TAXONOMY><TAXONOMY>NEWT:256737</TAXONOMY><TAXONOMY>NEWT:115104</TAXONOMY><TAXONOMY>NEWT:1121114</TAXONOMY><TAXONOMY>NEWT:663</TAXONOMY><TAXONOMY>NEWT:1081927</TAXONOMY><TAXONOMY>NEWT:1238993</TAXONOMY><TAXONOMY>NEWT:67825</TAXONOMY><TAXONOMY>NEWT:185579</TAXONOMY><TAXONOMY>NEWT:941442</TAXONOMY><TAXONOMY>NEWT:220668</TAXONOMY><TAXONOMY>NEWT:13076</TAXONOMY><TAXONOMY>NEWT:1249668</TAXONOMY><TAXONOMY>NEWT:7108</TAXONOMY><TAXONOMY>NEWT:317</TAXONOMY><TAXONOMY>NEWT:7227</TAXONOMY><TAXONOMY>NEWT:7469</TAXONOMY><TAXONOMY>NEWT:885318</TAXONOMY><TAXONOMY>NEWT:9402</TAXONOMY><TAXONOMY>NEWT:415540</TAXONOMY><TAXONOMY>NEWT:550</TAXONOMY><TAXONOMY>NEWT:675060</TAXONOMY><TAXONOMY>NEWT:4081</TAXONOMY><TAXONOMY>NEWT:334542</TAXONOMY><TAXONOMY>NEWT:554</TAXONOMY><TAXONOMY>NEWT:98334</TAXONOMY><TAXONOMY>NEWT:426428</TAXONOMY><TAXONOMY>NEWT:7574</TAXONOMY><TAXONOMY>NEWT:1715256</TAXONOMY><TAXONOMY>NEWT:7215</TAXONOMY><TAXONOMY>NEWT:575412</TAXONOMY><TAXONOMY>NEWT:29204</TAXONOMY><TAXONOMY>NEWT:2172103</TAXONOMY><TAXONOMY>NEWT:507601</TAXONOMY><TAXONOMY>NEWT:643680</TAXONOMY><TAXONOMY>NCBITaxon:6157</TAXONOMY><TAXONOMY>NEWT:746360</TAXONOMY><TAXONOMY>NEWT:6239</TAXONOMY><TAXONOMY>NEWT:470150</TAXONOMY><TAXONOMY>NEWT:216257</TAXONOMY><TAXONOMY>NEWT:102169</TAXONOMY><TAXONOMY>NEWT:9986</TAXONOMY><TAXONOMY>NEWT:4054</TAXONOMY><TAXONOMY>NEWT:73239</TAXONOMY><TAXONOMY>NEWT:226186</TAXONOMY><TAXONOMY>NEWT:1268063</TAXONOMY><TAXONOMY>NEWT:8782</TAXONOMY><TAXONOMY>NEWT:1263854</TAXONOMY><TAXONOMY>NEWT:435590</TAXONOMY><TAXONOMY>NEWT:1902</TAXONOMY><TAXONOMY>NEWT:160488</TAXONOMY><TAXONOMY>NEWT:28104</TAXONOMY><TAXONOMY>NEWT:1908</TAXONOMY><TAXONOMY>NCBITaxon:2</TAXONOMY><TAXONOMY>NEWT:985076</TAXONOMY><TAXONOMY>NEWT:1215323</TAXONOMY><TAXONOMY>NEWT:52641</TAXONOMY><TAXONOMY>NEWT:7038</TAXONOMY><TAXONOMY>NEWT:6192</TAXONOMY><TAXONOMY>NEWT:28532</TAXONOMY><TAXONOMY>NCBITaxon:38727</TAXONOMY><TAXONOMY>NEWT:353152</TAXONOMY><TAXONOMY>NEWT:2829</TAXONOMY><TAXONOMY>NEWT:366581</TAXONOMY><TAXONOMY>NEWT:216599</TAXONOMY><TAXONOMY>NEWT:216595</TAXONOMY><TAXONOMY>NEWT:51329</TAXONOMY><TAXONOMY>NEWT:243230</TAXONOMY><TAXONOMY>NEWT:8355</TAXONOMY><TAXONOMY>NEWT:9685</TAXONOMY><TAXONOMY>NEWT:7029</TAXONOMY><TAXONOMY>NEWT:1080772</TAXONOMY><TAXONOMY>NEWT:8479</TAXONOMY><TAXONOMY>NEWT:1283300</TAXONOMY><TAXONOMY>NEWT:6183</TAXONOMY><TAXONOMY>NEWT:6063</TAXONOMY><TAXONOMY>NEWT:334747</TAXONOMY><TAXONOMY>NEWT:61235</TAXONOMY><TAXONOMY>NEWT:6289</TAXONOMY><TAXONOMY>NEWT:436486</TAXONOMY><TAXONOMY>NEWT:6287</TAXONOMY><TAXONOMY>NEWT:300641</TAXONOMY><TAXONOMY>NEWT:727</TAXONOMY><TAXONOMY>NEWT:9796</TAXONOMY><TAXONOMY>NEWT:725</TAXONOMY><TAXONOMY>NEWT:170187</TAXONOMY><TAXONOMY>NEWT:260707</TAXONOMY><TAXONOMY>NCBITaxon:6191</TAXONOMY><TAXONOMY>NEWT:1836</TAXONOMY><TAXONOMY>NEWT:185431</TAXONOMY><TAXONOMY>NEWT:29760</TAXONOMY><TAXONOMY>NEWT:260704</TAXONOMY><TAXONOMY>NEWT:703612</TAXONOMY><TAXONOMY>NEWT:260705</TAXONOMY><TAXONOMY>NEWT:80863</TAXONOMY><TAXONOMY>NEWT:2697049</TAXONOMY><TAXONOMY>NEWT:105231</TAXONOMY><TAXONOMY>NEWT:1216981</TAXONOMY><TAXONOMY>NCBITaxon:6073</TAXONOMY><TAXONOMY>NEWT:884204</TAXONOMY><TAXONOMY>NEWT:6279</TAXONOMY><TAXONOMY>NEWT:1123869</TAXONOMY><TAXONOMY>NEWT:9544</TAXONOMY><TAXONOMY>NEWT:7370</TAXONOMY><TAXONOMY>NEWT:83906</TAXONOMY><TAXONOMY>NEWT:607699</TAXONOMY><TAXONOMY>NEWT:6282</TAXONOMY><TAXONOMY>NEWT:208964</TAXONOMY><TAXONOMY>NEWT:1134506</TAXONOMY><TAXONOMY>NEWT:575584</TAXONOMY><TAXONOMY>NEWT:38783</TAXONOMY><TAXONOMY>NEWT:8727</TAXONOMY><TAXONOMY>NEWT:4006</TAXONOMY><TAXONOMY>NEWT:8726</TAXONOMY><TAXONOMY>NEWT:6426</TAXONOMY><TAXONOMY>NEWT:6669</TAXONOMY><TAXONOMY>NEWT:10090</TAXONOMY><TAXONOMY>NEWT:4120</TAXONOMY><TAXONOMY>NEWT:51515</TAXONOMY><TAXONOMY>NEWT:5693</TAXONOMY><TAXONOMY>NEWT:8724</TAXONOMY><TAXONOMY>NEWT:51511</TAXONOMY><TAXONOMY>NEWT:92867</TAXONOMY><TAXONOMY>NEWT:8723</TAXONOMY><TAXONOMY>NEWT:5334</TAXONOMY><TAXONOMY>NEWT:37334</TAXONOMY><TAXONOMY>NEWT:382352</TAXONOMY><TAXONOMY>NCBITaxon:10359</TAXONOMY><TAXONOMY>NEWT:242619</TAXONOMY><TAXONOMY>NEWT:632957</TAXONOMY><TAXONOMY>NEWT:34073</TAXONOMY><TAXONOMY>NEWT:373995</TAXONOMY><TAXONOMY>NEWT:5689</TAXONOMY><TAXONOMY>NEWT:544404</TAXONOMY><TAXONOMY>NEWT:9925</TAXONOMY><TAXONOMY>NEWT:8839</TAXONOMY><TAXONOMY>NEWT:4232</TAXONOMY><TAXONOMY>NEWT:2758385</TAXONOMY><TAXONOMY>NEWT:4113</TAXONOMY><TAXONOMY>NEWT:837</TAXONOMY><TAXONOMY>NEWT:11298</TAXONOMY><TAXONOMY>NEWT:171101</TAXONOMY><TAXONOMY>NEWT:714</TAXONOMY><TAXONOMY>NEWT:36015</TAXONOMY><TAXONOMY>NEWT:421932</TAXONOMY><TAXONOMY>NEWT:196627</TAXONOMY><TAXONOMY>NEWT:5691</TAXONOMY><TAXONOMY>NEWT:48479</TAXONOMY><TAXONOMY>NEWT:627025</TAXONOMY><TAXONOMY>NEWT:1097677</TAXONOMY><TAXONOMY>NEWT:61674</TAXONOMY><TAXONOMY>NEWT:1117957</TAXONOMY><TAXONOMY>NEWT:9913</TAXONOMY><TAXONOMY>NEWT:4100</TAXONOMY><TAXONOMY>NEWT:1076</TAXONOMY><TAXONOMY>NEWT:6763</TAXONOMY><TAXONOMY>NEWT:803</TAXONOMY><TAXONOMY>NEWT:29722</TAXONOMY><TAXONOMY>NEWT:380394</TAXONOMY><TAXONOMY>NEWT:1692259</TAXONOMY><TAXONOMY>NEWT:180066</TAXONOMY><TAXONOMY>NEWT:135588</TAXONOMY><TAXONOMY>NEWT:1843183</TAXONOMY><TAXONOMY>NEWT:58002</TAXONOMY><TAXONOMY>NEWT:326423</TAXONOMY><TAXONOMY>NEWT:36111</TAXONOMY><TAXONOMY>NEWT:4577</TAXONOMY><TAXONOMY>NEWT:1416333</TAXONOMY><TAXONOMY>NEWT:5664</TAXONOMY><TAXONOMY>NEWT:2157</TAXONOMY><TAXONOMY>NEWT:1678078</TAXONOMY><TAXONOMY>NEWT:749906</TAXONOMY><TAXONOMY>NEWT:418985</TAXONOMY><TAXONOMY>NEWT:146479</TAXONOMY><TAXONOMY>NEWT:1911079</TAXONOMY><TAXONOMY>NEWT:69373</TAXONOMY><TAXONOMY>NEWT:264203</TAXONOMY><TAXONOMY>NEWT:1480154</TAXONOMY><TAXONOMY>NEWT:1274414</TAXONOMY><TAXONOMY>NEWT:27606</TAXONOMY><TAXONOMY>NEWT:59202</TAXONOMY><TAXONOMY>NEWT:9975</TAXONOMY><TAXONOMY>NEWT:9612</TAXONOMY><TAXONOMY>NEWT:38865</TAXONOMY><TAXONOMY>NEWT:51953</TAXONOMY><TAXONOMY>NEWT:3197</TAXONOMY><TAXONOMY>NEWT:9615</TAXONOMY><TAXONOMY>NEWT:10299</TAXONOMY><TAXONOMY>NEWT:860688</TAXONOMY><TAXONOMY>NEWT:36329</TAXONOMY><TAXONOMY>NEWT:1147787</TAXONOMY><TAXONOMY>NCBITaxon:3044782</TAXONOMY><TAXONOMY>NEWT:72407</TAXONOMY><TAXONOMY>NEWT:349741</TAXONOMY><TAXONOMY>NEWT:9605</TAXONOMY><TAXONOMY>NEWT:9606</TAXONOMY><TAXONOMY>NEWT:90371</TAXONOMY><TAXONOMY>NEWT:157295</TAXONOMY><TAXONOMY>NEWT:641501</TAXONOMY><TAXONOMY>NEWT:7668</TAXONOMY><TAXONOMY>NEWT:915099</TAXONOMY><TAXONOMY>NEWT:74940</TAXONOMY><TAXONOMY>NEWT:9721</TAXONOMY><TAXONOMY>NEWT:137221</TAXONOMY><TAXONOMY>NEWT:9600</TAXONOMY><TAXONOMY>NEWT:1450511</TAXONOMY><TAXONOMY>NEWT:1143193</TAXONOMY><TAXONOMY>NEWT:411901</TAXONOMY><TAXONOMY>NEWT:9838</TAXONOMY><TAXONOMY>NEWT:105884</TAXONOMY><TAXONOMY>NCBITaxon:9615</TAXONOMY><TAXONOMY>NEWT:9839</TAXONOMY><TAXONOMY>NEWT:58334</TAXONOMY><TAXONOMY>NEWT:1193501</TAXONOMY><TAXONOMY>NEWT:3055</TAXONOMY><TAXONOMY>NEWT:58331</TAXONOMY><TAXONOMY>NEWT:6326</TAXONOMY><TAXONOMY>NEWT:6689</TAXONOMY><TAXONOMY>NEWT:5476</TAXONOMY><TAXONOMY>NEWT:299767</TAXONOMY><TAXONOMY>NEWT:1274432</TAXONOMY><TAXONOMY>NEWT:1274426</TAXONOMY><TAXONOMY>NEWT:70448</TAXONOMY><TAXONOMY>NEWT:9825</TAXONOMY><TAXONOMY>NEWT:1274423</TAXONOMY><TAXONOMY>NEWT:393765</TAXONOMY><TAXONOMY>NEWT:698936</TAXONOMY><TAXONOMY>NEWT:39946</TAXONOMY><TAXONOMY>NEWT:9823</TAXONOMY><TAXONOMY>NEWT:9940</TAXONOMY><TAXONOMY>NEWT:521001</TAXONOMY><TAXONOMY>NEWT:39947</TAXONOMY><TAXONOMY>NEWT:1274420</TAXONOMY><TAXONOMY>NEWT:578458</TAXONOMY><pubmed>42286659</pubmed></cross_references></HashMap>