Transcriptional repression of p27 is essential for murine embryonic development
The Nczf gene has been identified as one of Ncx target genes and encodes a novel KRAB zinc-finger protein, which functions as a sequence specific transcriptional repressor. In order to elucidate Nczf functions, we generated Nczf knockout (Nczf−/−) mice. Nczf−/− mice died around embryonic day 8.5 (E8...
Gespeichert in:
Veröffentlicht in: | Scientific reports 2016-05, Vol.6 (1), p.26244, Article 26244 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 1 |
container_start_page | 26244 |
container_title | Scientific reports |
container_volume | 6 |
creator | Teratake, Youichi Kuga, Chisa Hasegawa, Yuta Sato, Yoshiharu Kitahashi, Masayasu Fujimura, Lisa Watanabe-Takano, Haruko Sakamoto, Akemi Arima, Masafumi Tokuhisa, Takeshi Hatano, Masahiko |
description | The
Nczf
gene has been identified as one of Ncx target genes and encodes a novel KRAB zinc-finger protein, which functions as a sequence specific transcriptional repressor. In order to elucidate Nczf functions, we generated Nczf knockout (Nczf−/−) mice. Nczf−/− mice died around embryonic day 8.5 (E8.5) with small body size and impairment of axial rotation. Histopathological analysis revealed that the cell number decreased and pyknotic cells were occasionally observed. We examined the expression of cell cycle related genes in Nczf−/− mice.
p27
expression was increased in E8.0 Nczf−/− mice compared to that of wild type mice. Nczf knockdown by siRNA resulted in increased expression of
p27
in mouse embryonic fibroblasts (MEFs). Furthermore,
p27
promoter luciferase reporter gene analysis confirmed the regulation of
p27
mRNA expression by Nczf. Nczf−/−; p27−/− double knockout mice survived until E11.5 and the defect of axial rotation was restored. These data suggest that
p27
repression by Nczf is essential in the developing embryo. |
doi_str_mv | 10.1038/srep26244 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4872541</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1898668614</sourcerecordid><originalsourceid>FETCH-LOGICAL-c504t-99b338179c6d416f85b9b2addafc39f4022f75b333832d6ca7248b3776e22eee3</originalsourceid><addsrcrecordid>eNplkF1LwzAYhYMoTuYu_ANS8Eqh2rxJ83EjyPALBruZ1yFt05nRNjVZB_v3RjbHxNy8yXsezgkHoSuc3eOMiIfgTQ8MKD1BF5DRPAUCcHp0H6FJCKssnhwkxfIcjYBjyQjHF2i-8LoLpbf92rpON0l08yaE-EhcnfTAExuSuDDd2ka5dj5pB287k5i28FvX2TKpzMY0rm8jc4nOat0EM9nPMfp4eV5M39LZ_PV9-jRLyzyj61TKghCBuSxZRTGrRV7IAnRV6boksqYZQM3zyBBBoGKl5kBFQThnBsAYQ8bocefbD0VrqjJGe92o3ttW-61y2qq_Smc_1dJtFBUccoqjwc3ewLuvwYS1WrnBxwaCwkIKxgTDNFK3O6r0LsSm60MCztRP_epQf2Svj790IH_LjsDdDghR6pbGH0X-c_sGyZCQGw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1898668614</pqid></control><display><type>article</type><title>Transcriptional repression of p27 is essential for murine embryonic development</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Teratake, Youichi ; Kuga, Chisa ; Hasegawa, Yuta ; Sato, Yoshiharu ; Kitahashi, Masayasu ; Fujimura, Lisa ; Watanabe-Takano, Haruko ; Sakamoto, Akemi ; Arima, Masafumi ; Tokuhisa, Takeshi ; Hatano, Masahiko</creator><creatorcontrib>Teratake, Youichi ; Kuga, Chisa ; Hasegawa, Yuta ; Sato, Yoshiharu ; Kitahashi, Masayasu ; Fujimura, Lisa ; Watanabe-Takano, Haruko ; Sakamoto, Akemi ; Arima, Masafumi ; Tokuhisa, Takeshi ; Hatano, Masahiko</creatorcontrib><description>The
Nczf
gene has been identified as one of Ncx target genes and encodes a novel KRAB zinc-finger protein, which functions as a sequence specific transcriptional repressor. In order to elucidate Nczf functions, we generated Nczf knockout (Nczf−/−) mice. Nczf−/− mice died around embryonic day 8.5 (E8.5) with small body size and impairment of axial rotation. Histopathological analysis revealed that the cell number decreased and pyknotic cells were occasionally observed. We examined the expression of cell cycle related genes in Nczf−/− mice.
p27
expression was increased in E8.0 Nczf−/− mice compared to that of wild type mice. Nczf knockdown by siRNA resulted in increased expression of
p27
in mouse embryonic fibroblasts (MEFs). Furthermore,
p27
promoter luciferase reporter gene analysis confirmed the regulation of
p27
mRNA expression by Nczf. Nczf−/−; p27−/− double knockout mice survived until E11.5 and the defect of axial rotation was restored. These data suggest that
p27
repression by Nczf is essential in the developing embryo.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep26244</identifier><identifier>PMID: 27196371</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 38 ; 38/109 ; 38/15 ; 631/136/2091 ; 631/337/572 ; 64/110 ; 64/60 ; Animals ; Body size ; Cell Count ; Cell cycle ; Cell number ; Cyclin-Dependent Kinase Inhibitor p27 - genetics ; Cyclin-Dependent Kinase Inhibitor p27 - metabolism ; Embryo fibroblasts ; Embryo, Mammalian - abnormalities ; Embryogenesis ; Embryonic Development - genetics ; Embryonic growth stage ; Female ; Fibroblasts - metabolism ; Gene expression ; Gene silencing ; Genes ; Humanities and Social Sciences ; Male ; Mice ; Mice, Knockout ; multidisciplinary ; Pregnancy ; Reporter gene ; RNA Interference ; Rodents ; Science ; Science (multidisciplinary) ; siRNA ; Transcription, Genetic ; Zinc finger proteins</subject><ispartof>Scientific reports, 2016-05, Vol.6 (1), p.26244, Article 26244</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group May 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-99b338179c6d416f85b9b2addafc39f4022f75b333832d6ca7248b3776e22eee3</citedby><cites>FETCH-LOGICAL-c504t-99b338179c6d416f85b9b2addafc39f4022f75b333832d6ca7248b3776e22eee3</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/PMC4872541/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872541/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27196371$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teratake, Youichi</creatorcontrib><creatorcontrib>Kuga, Chisa</creatorcontrib><creatorcontrib>Hasegawa, Yuta</creatorcontrib><creatorcontrib>Sato, Yoshiharu</creatorcontrib><creatorcontrib>Kitahashi, Masayasu</creatorcontrib><creatorcontrib>Fujimura, Lisa</creatorcontrib><creatorcontrib>Watanabe-Takano, Haruko</creatorcontrib><creatorcontrib>Sakamoto, Akemi</creatorcontrib><creatorcontrib>Arima, Masafumi</creatorcontrib><creatorcontrib>Tokuhisa, Takeshi</creatorcontrib><creatorcontrib>Hatano, Masahiko</creatorcontrib><title>Transcriptional repression of p27 is essential for murine embryonic development</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The
Nczf
gene has been identified as one of Ncx target genes and encodes a novel KRAB zinc-finger protein, which functions as a sequence specific transcriptional repressor. In order to elucidate Nczf functions, we generated Nczf knockout (Nczf−/−) mice. Nczf−/− mice died around embryonic day 8.5 (E8.5) with small body size and impairment of axial rotation. Histopathological analysis revealed that the cell number decreased and pyknotic cells were occasionally observed. We examined the expression of cell cycle related genes in Nczf−/− mice.
p27
expression was increased in E8.0 Nczf−/− mice compared to that of wild type mice. Nczf knockdown by siRNA resulted in increased expression of
p27
in mouse embryonic fibroblasts (MEFs). Furthermore,
p27
promoter luciferase reporter gene analysis confirmed the regulation of
p27
mRNA expression by Nczf. Nczf−/−; p27−/− double knockout mice survived until E11.5 and the defect of axial rotation was restored. These data suggest that
p27
repression by Nczf is essential in the developing embryo.</description><subject>13</subject><subject>38</subject><subject>38/109</subject><subject>38/15</subject><subject>631/136/2091</subject><subject>631/337/572</subject><subject>64/110</subject><subject>64/60</subject><subject>Animals</subject><subject>Body size</subject><subject>Cell Count</subject><subject>Cell cycle</subject><subject>Cell number</subject><subject>Cyclin-Dependent Kinase Inhibitor p27 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p27 - metabolism</subject><subject>Embryo fibroblasts</subject><subject>Embryo, Mammalian - abnormalities</subject><subject>Embryogenesis</subject><subject>Embryonic Development - genetics</subject><subject>Embryonic growth stage</subject><subject>Female</subject><subject>Fibroblasts - metabolism</subject><subject>Gene expression</subject><subject>Gene silencing</subject><subject>Genes</subject><subject>Humanities and Social Sciences</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>multidisciplinary</subject><subject>Pregnancy</subject><subject>Reporter gene</subject><subject>RNA Interference</subject><subject>Rodents</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>siRNA</subject><subject>Transcription, Genetic</subject><subject>Zinc finger proteins</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkF1LwzAYhYMoTuYu_ANS8Eqh2rxJ83EjyPALBruZ1yFt05nRNjVZB_v3RjbHxNy8yXsezgkHoSuc3eOMiIfgTQ8MKD1BF5DRPAUCcHp0H6FJCKssnhwkxfIcjYBjyQjHF2i-8LoLpbf92rpON0l08yaE-EhcnfTAExuSuDDd2ka5dj5pB287k5i28FvX2TKpzMY0rm8jc4nOat0EM9nPMfp4eV5M39LZ_PV9-jRLyzyj61TKghCBuSxZRTGrRV7IAnRV6boksqYZQM3zyBBBoGKl5kBFQThnBsAYQ8bocefbD0VrqjJGe92o3ttW-61y2qq_Smc_1dJtFBUccoqjwc3ewLuvwYS1WrnBxwaCwkIKxgTDNFK3O6r0LsSm60MCztRP_epQf2Svj790IH_LjsDdDghR6pbGH0X-c_sGyZCQGw</recordid><startdate>20160519</startdate><enddate>20160519</enddate><creator>Teratake, Youichi</creator><creator>Kuga, Chisa</creator><creator>Hasegawa, Yuta</creator><creator>Sato, Yoshiharu</creator><creator>Kitahashi, Masayasu</creator><creator>Fujimura, Lisa</creator><creator>Watanabe-Takano, Haruko</creator><creator>Sakamoto, Akemi</creator><creator>Arima, Masafumi</creator><creator>Tokuhisa, Takeshi</creator><creator>Hatano, Masahiko</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>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>5PM</scope></search><sort><creationdate>20160519</creationdate><title>Transcriptional repression of p27 is essential for murine embryonic development</title><author>Teratake, Youichi ; Kuga, Chisa ; Hasegawa, Yuta ; Sato, Yoshiharu ; Kitahashi, Masayasu ; Fujimura, Lisa ; Watanabe-Takano, Haruko ; Sakamoto, Akemi ; Arima, Masafumi ; Tokuhisa, Takeshi ; Hatano, Masahiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-99b338179c6d416f85b9b2addafc39f4022f75b333832d6ca7248b3776e22eee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13</topic><topic>38</topic><topic>38/109</topic><topic>38/15</topic><topic>631/136/2091</topic><topic>631/337/572</topic><topic>64/110</topic><topic>64/60</topic><topic>Animals</topic><topic>Body size</topic><topic>Cell Count</topic><topic>Cell cycle</topic><topic>Cell number</topic><topic>Cyclin-Dependent Kinase Inhibitor p27 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p27 - metabolism</topic><topic>Embryo fibroblasts</topic><topic>Embryo, Mammalian - abnormalities</topic><topic>Embryogenesis</topic><topic>Embryonic Development - genetics</topic><topic>Embryonic growth stage</topic><topic>Female</topic><topic>Fibroblasts - metabolism</topic><topic>Gene expression</topic><topic>Gene silencing</topic><topic>Genes</topic><topic>Humanities and Social Sciences</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>multidisciplinary</topic><topic>Pregnancy</topic><topic>Reporter gene</topic><topic>RNA Interference</topic><topic>Rodents</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>siRNA</topic><topic>Transcription, Genetic</topic><topic>Zinc finger proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teratake, Youichi</creatorcontrib><creatorcontrib>Kuga, Chisa</creatorcontrib><creatorcontrib>Hasegawa, Yuta</creatorcontrib><creatorcontrib>Sato, Yoshiharu</creatorcontrib><creatorcontrib>Kitahashi, Masayasu</creatorcontrib><creatorcontrib>Fujimura, Lisa</creatorcontrib><creatorcontrib>Watanabe-Takano, Haruko</creatorcontrib><creatorcontrib>Sakamoto, Akemi</creatorcontrib><creatorcontrib>Arima, Masafumi</creatorcontrib><creatorcontrib>Tokuhisa, Takeshi</creatorcontrib><creatorcontrib>Hatano, Masahiko</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 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>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teratake, Youichi</au><au>Kuga, Chisa</au><au>Hasegawa, Yuta</au><au>Sato, Yoshiharu</au><au>Kitahashi, Masayasu</au><au>Fujimura, Lisa</au><au>Watanabe-Takano, Haruko</au><au>Sakamoto, Akemi</au><au>Arima, Masafumi</au><au>Tokuhisa, Takeshi</au><au>Hatano, Masahiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptional repression of p27 is essential for murine embryonic development</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-05-19</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>26244</spage><pages>26244-</pages><artnum>26244</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The
Nczf
gene has been identified as one of Ncx target genes and encodes a novel KRAB zinc-finger protein, which functions as a sequence specific transcriptional repressor. In order to elucidate Nczf functions, we generated Nczf knockout (Nczf−/−) mice. Nczf−/− mice died around embryonic day 8.5 (E8.5) with small body size and impairment of axial rotation. Histopathological analysis revealed that the cell number decreased and pyknotic cells were occasionally observed. We examined the expression of cell cycle related genes in Nczf−/− mice.
p27
expression was increased in E8.0 Nczf−/− mice compared to that of wild type mice. Nczf knockdown by siRNA resulted in increased expression of
p27
in mouse embryonic fibroblasts (MEFs). Furthermore,
p27
promoter luciferase reporter gene analysis confirmed the regulation of
p27
mRNA expression by Nczf. Nczf−/−; p27−/− double knockout mice survived until E11.5 and the defect of axial rotation was restored. These data suggest that
p27
repression by Nczf is essential in the developing embryo.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27196371</pmid><doi>10.1038/srep26244</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2045-2322 |
ispartof | Scientific reports, 2016-05, Vol.6 (1), p.26244, Article 26244 |
issn | 2045-2322 2045-2322 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4872541 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | 13 38 38/109 38/15 631/136/2091 631/337/572 64/110 64/60 Animals Body size Cell Count Cell cycle Cell number Cyclin-Dependent Kinase Inhibitor p27 - genetics Cyclin-Dependent Kinase Inhibitor p27 - metabolism Embryo fibroblasts Embryo, Mammalian - abnormalities Embryogenesis Embryonic Development - genetics Embryonic growth stage Female Fibroblasts - metabolism Gene expression Gene silencing Genes Humanities and Social Sciences Male Mice Mice, Knockout multidisciplinary Pregnancy Reporter gene RNA Interference Rodents Science Science (multidisciplinary) siRNA Transcription, Genetic Zinc finger proteins |
title | Transcriptional repression of p27 is essential for murine embryonic development |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T08%3A59%3A41IST&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=Transcriptional%20repression%20of%20p27%20is%20essential%20for%20murine%20embryonic%20development&rft.jtitle=Scientific%20reports&rft.au=Teratake,%20Youichi&rft.date=2016-05-19&rft.volume=6&rft.issue=1&rft.spage=26244&rft.pages=26244-&rft.artnum=26244&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep26244&rft_dat=%3Cproquest_pubme%3E1898668614%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=1898668614&rft_id=info:pmid/27196371&rfr_iscdi=true |