Loading…
Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons
Mutations in the gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regula...
Saved in:
| Published in: | eLife 2016-10, Vol.5 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c572t-77fa014915612d96fddde1c7fc940549f22037f3429fbad37c86eaf9a56940293 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c572t-77fa014915612d96fddde1c7fc940549f22037f3429fbad37c86eaf9a56940293 |
| container_end_page | |
| container_issue | |
| container_start_page | |
| container_title | eLife |
| container_volume | 5 |
| creator | Sampathkumar, Charanya Wu, Yuan-Ju Vadhvani, Mayur Trimbuch, Thorsten Eickholt, Britta Rosenmund, Christian |
| description | Mutations in the
gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons
and
. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system. |
| doi_str_mv | 10.7554/elife.19374 |
| format | article |
| fullrecord | <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_eaa0f71ce81f47009aafd08b447f1eb0</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A470149881</galeid><doaj_id>oai_doaj_org_article_eaa0f71ce81f47009aafd08b447f1eb0</doaj_id><sourcerecordid>A470149881</sourcerecordid><originalsourceid>FETCH-LOGICAL-c572t-77fa014915612d96fddde1c7fc940549f22037f3429fbad37c86eaf9a56940293</originalsourceid><addsrcrecordid>eNptktuPEyEYxSdG427WffLdkPiiMa3AQIEXk7W62qRe4iXxjVDmY6SZgS7MGP3vZdp13RrhgdvvO4TDqaqHBM8F5-w5dN7BnKhasDvVKcUcz7Bk3-7emp9U5zlvcWmCSUnU_eqECiGpFOq02qxjzig69A6WHylqfE7jbsjIQtchMw4xxD6OGZnQ7Jc2-QDo5av3lyj7NpjOhxb5gCYIUNuNg-nNAKn1FgUYUwz5QXXPmS7D-fV4Vn29fP1l-Xa2_vBmtbxYzywXdJgJ4QwmTBG-ILRRC9c0DRArnFUMc6YcpbgWrmZUuY1pamHlAoxThi8KQFV9Vq0Ouk00W71Lvjfpl47G6_1GTK02afC2Aw3GYCeIBUkcExgrY1yD5YYx4QhscNF6cdDajZseGgthSKY7Ej0-Cf67buMPzQmWXE0CT64FUrwaIQ-693ky1QQoVmkia44x4UwU9PE_6DaOqVhbKMXrmlAm-V-qNeUBPrhY7rWTqL4oTyjGlb8t1Pw_VOkN9N7GAM6X_aOCp0cFhRng59CaMWe9-vzpmH12YG0qoUngbvwgWE9p1LAuadT7NBb60W0Lb9g_2at_A_Qo2U4</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1953312485</pqid></control><display><type>article</type><title>Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons</title><source>Open Access: PubMed Central</source><source>ProQuest - Publicly Available Content Database</source><creator>Sampathkumar, Charanya ; Wu, Yuan-Ju ; Vadhvani, Mayur ; Trimbuch, Thorsten ; Eickholt, Britta ; Rosenmund, Christian</creator><creatorcontrib>Sampathkumar, Charanya ; Wu, Yuan-Ju ; Vadhvani, Mayur ; Trimbuch, Thorsten ; Eickholt, Britta ; Rosenmund, Christian</creatorcontrib><description>Mutations in the
gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons
and
. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system.</description><identifier>ISSN: 2050-084X</identifier><identifier>EISSN: 2050-084X</identifier><identifier>DOI: 10.7554/elife.19374</identifier><identifier>PMID: 27782879</identifier><language>eng</language><publisher>England: eLife Science Publications, Ltd</publisher><subject>Acids ; Animals ; Autocrine signalling ; Axonogenesis ; BDNF ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - metabolism ; cell autonomous ; Cell Differentiation ; Cell Proliferation ; Cellular signal transduction ; Disease Models, Animal ; Gene mutation ; Genetic aspects ; glutamatergic ; Glutamatergic transmission ; Health aspects ; Male ; MeCP2 protein ; Methyl-CpG binding protein ; Methyl-CpG-Binding Protein 2 - genetics ; Methyl-CpG-Binding Protein 2 - metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular modelling ; Morphology ; Mutation ; Nervous system ; Neural circuitry ; Neurodevelopmental disorders ; Neurons ; Neurons - physiology ; Neuroscience ; Rett syndrome ; Rett Syndrome - physiopathology ; Rodents ; Signal Transduction ; Synapses ; synaptic transmission ; Synaptogenesis ; Transcription ; TrkB receptors</subject><ispartof>eLife, 2016-10, Vol.5</ispartof><rights>COPYRIGHT 2016 eLife Science Publications, Ltd.</rights><rights>2016, Sampathkumar et al. This work is licensed under the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/3.0/ ) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016, Sampathkumar et al 2016 Sampathkumar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c572t-77fa014915612d96fddde1c7fc940549f22037f3429fbad37c86eaf9a56940293</citedby><cites>FETCH-LOGICAL-c572t-77fa014915612d96fddde1c7fc940549f22037f3429fbad37c86eaf9a56940293</cites><orcidid>0000-0002-3905-2444</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1953312485/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1953312485?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27782879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sampathkumar, Charanya</creatorcontrib><creatorcontrib>Wu, Yuan-Ju</creatorcontrib><creatorcontrib>Vadhvani, Mayur</creatorcontrib><creatorcontrib>Trimbuch, Thorsten</creatorcontrib><creatorcontrib>Eickholt, Britta</creatorcontrib><creatorcontrib>Rosenmund, Christian</creatorcontrib><title>Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons</title><title>eLife</title><addtitle>Elife</addtitle><description>Mutations in the
gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons
and
. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system.</description><subject>Acids</subject><subject>Animals</subject><subject>Autocrine signalling</subject><subject>Axonogenesis</subject><subject>BDNF</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>cell autonomous</subject><subject>Cell Differentiation</subject><subject>Cell Proliferation</subject><subject>Cellular signal transduction</subject><subject>Disease Models, Animal</subject><subject>Gene mutation</subject><subject>Genetic aspects</subject><subject>glutamatergic</subject><subject>Glutamatergic transmission</subject><subject>Health aspects</subject><subject>Male</subject><subject>MeCP2 protein</subject><subject>Methyl-CpG binding protein</subject><subject>Methyl-CpG-Binding Protein 2 - genetics</subject><subject>Methyl-CpG-Binding Protein 2 - metabolism</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Molecular modelling</subject><subject>Morphology</subject><subject>Mutation</subject><subject>Nervous system</subject><subject>Neural circuitry</subject><subject>Neurodevelopmental disorders</subject><subject>Neurons</subject><subject>Neurons - physiology</subject><subject>Neuroscience</subject><subject>Rett syndrome</subject><subject>Rett Syndrome - physiopathology</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Synapses</subject><subject>synaptic transmission</subject><subject>Synaptogenesis</subject><subject>Transcription</subject><subject>TrkB receptors</subject><issn>2050-084X</issn><issn>2050-084X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptktuPEyEYxSdG427WffLdkPiiMa3AQIEXk7W62qRe4iXxjVDmY6SZgS7MGP3vZdp13RrhgdvvO4TDqaqHBM8F5-w5dN7BnKhasDvVKcUcz7Bk3-7emp9U5zlvcWmCSUnU_eqECiGpFOq02qxjzig69A6WHylqfE7jbsjIQtchMw4xxD6OGZnQ7Jc2-QDo5av3lyj7NpjOhxb5gCYIUNuNg-nNAKn1FgUYUwz5QXXPmS7D-fV4Vn29fP1l-Xa2_vBmtbxYzywXdJgJ4QwmTBG-ILRRC9c0DRArnFUMc6YcpbgWrmZUuY1pamHlAoxThi8KQFV9Vq0Ouk00W71Lvjfpl47G6_1GTK02afC2Aw3GYCeIBUkcExgrY1yD5YYx4QhscNF6cdDajZseGgthSKY7Ej0-Cf67buMPzQmWXE0CT64FUrwaIQ-693ky1QQoVmkia44x4UwU9PE_6DaOqVhbKMXrmlAm-V-qNeUBPrhY7rWTqL4oTyjGlb8t1Pw_VOkN9N7GAM6X_aOCp0cFhRng59CaMWe9-vzpmH12YG0qoUngbvwgWE9p1LAuadT7NBb60W0Lb9g_2at_A_Qo2U4</recordid><startdate>20161026</startdate><enddate>20161026</enddate><creator>Sampathkumar, Charanya</creator><creator>Wu, Yuan-Ju</creator><creator>Vadhvani, Mayur</creator><creator>Trimbuch, Thorsten</creator><creator>Eickholt, Britta</creator><creator>Rosenmund, Christian</creator><general>eLife Science Publications, Ltd</general><general>eLife Sciences Publications Ltd</general><general>eLife Sciences Publications, Ltd</general><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>ISR</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</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>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3905-2444</orcidid></search><sort><creationdate>20161026</creationdate><title>Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons</title><author>Sampathkumar, Charanya ; Wu, Yuan-Ju ; Vadhvani, Mayur ; Trimbuch, Thorsten ; Eickholt, Britta ; Rosenmund, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-77fa014915612d96fddde1c7fc940549f22037f3429fbad37c86eaf9a56940293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acids</topic><topic>Animals</topic><topic>Autocrine signalling</topic><topic>Axonogenesis</topic><topic>BDNF</topic><topic>Brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - metabolism</topic><topic>cell autonomous</topic><topic>Cell Differentiation</topic><topic>Cell Proliferation</topic><topic>Cellular signal transduction</topic><topic>Disease Models, Animal</topic><topic>Gene mutation</topic><topic>Genetic aspects</topic><topic>glutamatergic</topic><topic>Glutamatergic transmission</topic><topic>Health aspects</topic><topic>Male</topic><topic>MeCP2 protein</topic><topic>Methyl-CpG binding protein</topic><topic>Methyl-CpG-Binding Protein 2 - genetics</topic><topic>Methyl-CpG-Binding Protein 2 - metabolism</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Molecular modelling</topic><topic>Morphology</topic><topic>Mutation</topic><topic>Nervous system</topic><topic>Neural circuitry</topic><topic>Neurodevelopmental disorders</topic><topic>Neurons</topic><topic>Neurons - physiology</topic><topic>Neuroscience</topic><topic>Rett syndrome</topic><topic>Rett Syndrome - physiopathology</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Synapses</topic><topic>synaptic transmission</topic><topic>Synaptogenesis</topic><topic>Transcription</topic><topic>TrkB receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sampathkumar, Charanya</creatorcontrib><creatorcontrib>Wu, Yuan-Ju</creatorcontrib><creatorcontrib>Vadhvani, Mayur</creatorcontrib><creatorcontrib>Trimbuch, Thorsten</creatorcontrib><creatorcontrib>Eickholt, Britta</creatorcontrib><creatorcontrib>Rosenmund, Christian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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>ProQuest Biological Science Journals</collection><collection>ProQuest - 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 China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>eLife</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sampathkumar, Charanya</au><au>Wu, Yuan-Ju</au><au>Vadhvani, Mayur</au><au>Trimbuch, Thorsten</au><au>Eickholt, Britta</au><au>Rosenmund, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons</atitle><jtitle>eLife</jtitle><addtitle>Elife</addtitle><date>2016-10-26</date><risdate>2016</risdate><volume>5</volume><issn>2050-084X</issn><eissn>2050-084X</eissn><abstract>Mutations in the
gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons
and
. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system.</abstract><cop>England</cop><pub>eLife Science Publications, Ltd</pub><pmid>27782879</pmid><doi>10.7554/elife.19374</doi><orcidid>https://orcid.org/0000-0002-3905-2444</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2050-084X |
| ispartof | eLife, 2016-10, Vol.5 |
| issn | 2050-084X 2050-084X |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_eaa0f71ce81f47009aafd08b447f1eb0 |
| source | Open Access: PubMed Central; ProQuest - Publicly Available Content Database |
| subjects | Acids Animals Autocrine signalling Axonogenesis BDNF Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism cell autonomous Cell Differentiation Cell Proliferation Cellular signal transduction Disease Models, Animal Gene mutation Genetic aspects glutamatergic Glutamatergic transmission Health aspects Male MeCP2 protein Methyl-CpG binding protein Methyl-CpG-Binding Protein 2 - genetics Methyl-CpG-Binding Protein 2 - metabolism Mice, Inbred C57BL Mice, Knockout Molecular modelling Morphology Mutation Nervous system Neural circuitry Neurodevelopmental disorders Neurons Neurons - physiology Neuroscience Rett syndrome Rett Syndrome - physiopathology Rodents Signal Transduction Synapses synaptic transmission Synaptogenesis Transcription TrkB receptors |
| title | Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T06%3A49%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Loss%20of%20MeCP2%20disrupts%20cell%20autonomous%20and%20autocrine%20BDNF%20signaling%20in%20mouse%20glutamatergic%20neurons&rft.jtitle=eLife&rft.au=Sampathkumar,%20Charanya&rft.date=2016-10-26&rft.volume=5&rft.issn=2050-084X&rft.eissn=2050-084X&rft_id=info:doi/10.7554/elife.19374&rft_dat=%3Cgale_doaj_%3EA470149881%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c572t-77fa014915612d96fddde1c7fc940549f22037f3429fbad37c86eaf9a56940293%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1953312485&rft_id=info:pmid/27782879&rft_galeid=A470149881&rfr_iscdi=true |