EID3 directly associates with DNMT3A during transdifferentiation of human umbilical cord mesenchymal stem cells to NPC-like cells
There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-...
Gespeichert in:
Veröffentlicht in: | Scientific reports 2017-01, Vol.7 (1), p.40463-40463, Article 40463 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 40463 |
---|---|
container_issue | 1 |
container_start_page | 40463 |
container_title | Scientific reports |
container_volume | 7 |
creator | Luo, Liang Chen, Wen-Jin Yin, James Q. Xu, Ru-Xiang |
description | There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL
in vitro
. Before transdifferentiation of UMSCs into uNSCLs, high levels of EID3 and low levels of DNMT3A were detected; after transdifferentiation, low levels of EID3 and high levels of DNMT3A were detected. The current work showed that EID3 and DNMT3A co-localized in cell nuclei and EID3 interacted directly with DNMT3A in uNSCL. In summary, these results suggest that DNMT3A is probably directly regulated by EID3 during UMSC transdifferentiation into uNSCLs. These findings indicated a novel mechanism by which EID3, a p300 acetyltransferase inhibitor, could directly affect DNMT3A, this enzyme possesses dual methylation and demethylation abilities. These studies may be helpful for understanding a complex regulation mode of DNMT3A, which is a unique member of the methyltransferase family. |
doi_str_mv | 10.1038/srep40463 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5225425</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1899492297</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-32b42f869948a46459b60979dc1e1bbc16d2bda96cfff5ae2eabf4a79a598c573</originalsourceid><addsrcrecordid>eNplkc1u1DAUhS0EolXpghdAltgAUiD-S-INUjUtUKkUFmVtOc51xyWxp7YDmiVvjqMpowG8sXX96dxzdBB6Tuq3pGbduxRhw2vesEfomNZcVJRR-vjgfYROU7qryxFUciKfoiPa1S2XjByjXxeX5wwPLoLJ4xbrlIJxOkPCP11e4_PrzzfsDA9zdP4W56h9Gpy1EMHngrngcbB4PU_a43nq3eiMHrEJccATJPBmvZ3KIGWYsIFxTDgHfP11VY3uO-wmz9ATq8cEpw_3Cfr24eJm9am6-vLxcnV2VRnOulwx2nNqu0ZK3mnecCH7ppatHAwB0veGNAPtBy0bY60VGijo3nLdSi1kZ0TLTtD7ne5m7icYTEkQ9ag20U06blXQTv39491a3YYfSlAqOBVF4NWDQAz3M6SsJpeWCNpDmJMinWhbQTq5oC__Qe_CHH2JV6iSQFIqF0evd5SJIZUa7d4MqdXSrdp3W9gXh-735J8mC_BmB6TN0hXEg5X_qf0GNkCv1g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899492297</pqid></control><display><type>article</type><title>EID3 directly associates with DNMT3A during transdifferentiation of human umbilical cord mesenchymal stem cells to NPC-like cells</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature OA Free Journals</source><creator>Luo, Liang ; Chen, Wen-Jin ; Yin, James Q. ; Xu, Ru-Xiang</creator><creatorcontrib>Luo, Liang ; Chen, Wen-Jin ; Yin, James Q. ; Xu, Ru-Xiang</creatorcontrib><description>There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL
in vitro
. Before transdifferentiation of UMSCs into uNSCLs, high levels of EID3 and low levels of DNMT3A were detected; after transdifferentiation, low levels of EID3 and high levels of DNMT3A were detected. The current work showed that EID3 and DNMT3A co-localized in cell nuclei and EID3 interacted directly with DNMT3A in uNSCL. In summary, these results suggest that DNMT3A is probably directly regulated by EID3 during UMSC transdifferentiation into uNSCLs. These findings indicated a novel mechanism by which EID3, a p300 acetyltransferase inhibitor, could directly affect DNMT3A, this enzyme possesses dual methylation and demethylation abilities. These studies may be helpful for understanding a complex regulation mode of DNMT3A, which is a unique member of the methyltransferase family.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep40463</identifier><identifier>PMID: 28074931</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/100 ; 13/109 ; 13/31 ; 14/19 ; 14/34 ; 14/35 ; 38 ; 38/90 ; 631/532/2118/2074 ; 631/532/2128 ; Acetyltransferase ; Biomarkers - metabolism ; Carrier Proteins - metabolism ; Cell Transdifferentiation ; Demethylation ; DNA (Cytosine-5-)-Methyltransferases - metabolism ; DNA methyltransferase ; Epigenetics ; Event-related potentials ; HEK293 Cells ; Humanities and Social Sciences ; Humans ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; Mesenchyme ; multidisciplinary ; Neural Stem Cells - cytology ; Neural Stem Cells - metabolism ; Neurological diseases ; Protein Binding ; Science ; Science (multidisciplinary) ; Skin & tissue grafts ; Stem cells ; Umbilical cord ; Umbilical Cord - cytology</subject><ispartof>Scientific reports, 2017-01, Vol.7 (1), p.40463-40463, Article 40463</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Jan 2017</rights><rights>Copyright © 2017, The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-32b42f869948a46459b60979dc1e1bbc16d2bda96cfff5ae2eabf4a79a598c573</citedby><cites>FETCH-LOGICAL-c438t-32b42f869948a46459b60979dc1e1bbc16d2bda96cfff5ae2eabf4a79a598c573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225425/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225425/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28074931$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Liang</creatorcontrib><creatorcontrib>Chen, Wen-Jin</creatorcontrib><creatorcontrib>Yin, James Q.</creatorcontrib><creatorcontrib>Xu, Ru-Xiang</creatorcontrib><title>EID3 directly associates with DNMT3A during transdifferentiation of human umbilical cord mesenchymal stem cells to NPC-like cells</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL
in vitro
. Before transdifferentiation of UMSCs into uNSCLs, high levels of EID3 and low levels of DNMT3A were detected; after transdifferentiation, low levels of EID3 and high levels of DNMT3A were detected. The current work showed that EID3 and DNMT3A co-localized in cell nuclei and EID3 interacted directly with DNMT3A in uNSCL. In summary, these results suggest that DNMT3A is probably directly regulated by EID3 during UMSC transdifferentiation into uNSCLs. These findings indicated a novel mechanism by which EID3, a p300 acetyltransferase inhibitor, could directly affect DNMT3A, this enzyme possesses dual methylation and demethylation abilities. These studies may be helpful for understanding a complex regulation mode of DNMT3A, which is a unique member of the methyltransferase family.</description><subject>13/1</subject><subject>13/100</subject><subject>13/109</subject><subject>13/31</subject><subject>14/19</subject><subject>14/34</subject><subject>14/35</subject><subject>38</subject><subject>38/90</subject><subject>631/532/2118/2074</subject><subject>631/532/2128</subject><subject>Acetyltransferase</subject><subject>Biomarkers - metabolism</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Transdifferentiation</subject><subject>Demethylation</subject><subject>DNA (Cytosine-5-)-Methyltransferases - metabolism</subject><subject>DNA methyltransferase</subject><subject>Epigenetics</subject><subject>Event-related potentials</subject><subject>HEK293 Cells</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Mesenchyme</subject><subject>multidisciplinary</subject><subject>Neural Stem Cells - cytology</subject><subject>Neural Stem Cells - metabolism</subject><subject>Neurological diseases</subject><subject>Protein Binding</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Skin & tissue grafts</subject><subject>Stem cells</subject><subject>Umbilical cord</subject><subject>Umbilical Cord - cytology</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkc1u1DAUhS0EolXpghdAltgAUiD-S-INUjUtUKkUFmVtOc51xyWxp7YDmiVvjqMpowG8sXX96dxzdBB6Tuq3pGbduxRhw2vesEfomNZcVJRR-vjgfYROU7qryxFUciKfoiPa1S2XjByjXxeX5wwPLoLJ4xbrlIJxOkPCP11e4_PrzzfsDA9zdP4W56h9Gpy1EMHngrngcbB4PU_a43nq3eiMHrEJccATJPBmvZ3KIGWYsIFxTDgHfP11VY3uO-wmz9ATq8cEpw_3Cfr24eJm9am6-vLxcnV2VRnOulwx2nNqu0ZK3mnecCH7ppatHAwB0veGNAPtBy0bY60VGijo3nLdSi1kZ0TLTtD7ne5m7icYTEkQ9ag20U06blXQTv39491a3YYfSlAqOBVF4NWDQAz3M6SsJpeWCNpDmJMinWhbQTq5oC__Qe_CHH2JV6iSQFIqF0evd5SJIZUa7d4MqdXSrdp3W9gXh-735J8mC_BmB6TN0hXEg5X_qf0GNkCv1g</recordid><startdate>20170111</startdate><enddate>20170111</enddate><creator>Luo, Liang</creator><creator>Chen, Wen-Jin</creator><creator>Yin, James Q.</creator><creator>Xu, Ru-Xiang</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170111</creationdate><title>EID3 directly associates with DNMT3A during transdifferentiation of human umbilical cord mesenchymal stem cells to NPC-like cells</title><author>Luo, Liang ; Chen, Wen-Jin ; Yin, James Q. ; Xu, Ru-Xiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-32b42f869948a46459b60979dc1e1bbc16d2bda96cfff5ae2eabf4a79a598c573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>13/1</topic><topic>13/100</topic><topic>13/109</topic><topic>13/31</topic><topic>14/19</topic><topic>14/34</topic><topic>14/35</topic><topic>38</topic><topic>38/90</topic><topic>631/532/2118/2074</topic><topic>631/532/2128</topic><topic>Acetyltransferase</topic><topic>Biomarkers - metabolism</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Transdifferentiation</topic><topic>Demethylation</topic><topic>DNA (Cytosine-5-)-Methyltransferases - metabolism</topic><topic>DNA methyltransferase</topic><topic>Epigenetics</topic><topic>Event-related potentials</topic><topic>HEK293 Cells</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Mesenchyme</topic><topic>multidisciplinary</topic><topic>Neural Stem Cells - cytology</topic><topic>Neural Stem Cells - metabolism</topic><topic>Neurological diseases</topic><topic>Protein Binding</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Skin & tissue grafts</topic><topic>Stem cells</topic><topic>Umbilical cord</topic><topic>Umbilical Cord - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Liang</creatorcontrib><creatorcontrib>Chen, Wen-Jin</creatorcontrib><creatorcontrib>Yin, James Q.</creatorcontrib><creatorcontrib>Xu, Ru-Xiang</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Liang</au><au>Chen, Wen-Jin</au><au>Yin, James Q.</au><au>Xu, Ru-Xiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EID3 directly associates with DNMT3A during transdifferentiation of human umbilical cord mesenchymal stem cells to NPC-like cells</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-01-11</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>40463</spage><epage>40463</epage><pages>40463-40463</pages><artnum>40463</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL
in vitro
. Before transdifferentiation of UMSCs into uNSCLs, high levels of EID3 and low levels of DNMT3A were detected; after transdifferentiation, low levels of EID3 and high levels of DNMT3A were detected. The current work showed that EID3 and DNMT3A co-localized in cell nuclei and EID3 interacted directly with DNMT3A in uNSCL. In summary, these results suggest that DNMT3A is probably directly regulated by EID3 during UMSC transdifferentiation into uNSCLs. These findings indicated a novel mechanism by which EID3, a p300 acetyltransferase inhibitor, could directly affect DNMT3A, this enzyme possesses dual methylation and demethylation abilities. These studies may be helpful for understanding a complex regulation mode of DNMT3A, which is a unique member of the methyltransferase family.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28074931</pmid><doi>10.1038/srep40463</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2045-2322 |
ispartof | Scientific reports, 2017-01, Vol.7 (1), p.40463-40463, Article 40463 |
issn | 2045-2322 2045-2322 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5225425 |
source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
subjects | 13/1 13/100 13/109 13/31 14/19 14/34 14/35 38 38/90 631/532/2118/2074 631/532/2128 Acetyltransferase Biomarkers - metabolism Carrier Proteins - metabolism Cell Transdifferentiation Demethylation DNA (Cytosine-5-)-Methyltransferases - metabolism DNA methyltransferase Epigenetics Event-related potentials HEK293 Cells Humanities and Social Sciences Humans Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Mesenchyme multidisciplinary Neural Stem Cells - cytology Neural Stem Cells - metabolism Neurological diseases Protein Binding Science Science (multidisciplinary) Skin & tissue grafts Stem cells Umbilical cord Umbilical Cord - cytology |
title | EID3 directly associates with DNMT3A during transdifferentiation of human umbilical cord mesenchymal stem cells to NPC-like cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T11%3A23%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=EID3%20directly%20associates%20with%20DNMT3A%20during%20transdifferentiation%20of%20human%20umbilical%20cord%20mesenchymal%20stem%20cells%20to%20NPC-like%20cells&rft.jtitle=Scientific%20reports&rft.au=Luo,%20Liang&rft.date=2017-01-11&rft.volume=7&rft.issue=1&rft.spage=40463&rft.epage=40463&rft.pages=40463-40463&rft.artnum=40463&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep40463&rft_dat=%3Cproquest_pubme%3E1899492297%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1899492297&rft_id=info:pmid/28074931&rfr_iscdi=true |