Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans
Secondary metabolism and development are linked in Aspergillus through the conserved regulatory velvet complex composed of VeA, VelB, and LaeA. The founding member of the velvet complex, VeA, shuttles between the cytoplasm and nucleus in response to alterations in light. Here we describe a new inter...
Gespeichert in:
Veröffentlicht in: | PLoS genetics 2013-01, Vol.9 (1), p.e1003193-e1003193 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | e1003193 |
---|---|
container_issue | 1 |
container_start_page | e1003193 |
container_title | PLoS genetics |
container_volume | 9 |
creator | Palmer, Jonathan M Theisen, Jeffrey M Duran, Rocio M Grayburn, W Scott Calvo, Ana M Keller, Nancy P |
description | Secondary metabolism and development are linked in Aspergillus through the conserved regulatory velvet complex composed of VeA, VelB, and LaeA. The founding member of the velvet complex, VeA, shuttles between the cytoplasm and nucleus in response to alterations in light. Here we describe a new interaction partner of VeA identified through a reverse genetics screen looking for LaeA-like methyltransferases in Aspergillus nidulans. One of the putative LaeA-like methyltransferases identified, LlmF, is a negative regulator of sterigmatocystin production and sexual development. LlmF interacts directly with VeA and the repressive function of LlmF is mediated by influencing the localization of VeA, as over-expression of llmF decreases the nuclear to cytoplasmic ratio of VeA while deletion of llmF results in an increased nuclear accumulation of VeA. We show that the methyltransferase domain of LlmF is required for function; however, LlmF does not directly methylate VeA in vitro. This study identifies a new interaction partner for VeA and highlights the importance of cellular compartmentalization of VeA for regulation of development and secondary metabolism. |
doi_str_mv | 10.1371/journal.pgen.1003193 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1314341857</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A320264526</galeid><doaj_id>oai_doaj_org_article_9a8f5a82460f443eacbcc009d8100595</doaj_id><sourcerecordid>A320264526</sourcerecordid><originalsourceid>FETCH-LOGICAL-c792t-ddf4f8b172017526ba27c648482fffdd4edce8ca4f975c284f86bbb6eb0acc523</originalsourceid><addsrcrecordid>eNqVk01v1DAQhiMEoqXwDxBYQkJw2CX-SOxckFYVhZVWVKLQq-X4I-vKsZc4qVp-PQ6bVhvUAygHR55nXo_f8WTZS5gvIabww1UYOi_cctdov4R5jmGFH2XHsCjwgpKcPD74P8qexXiVmIJV9Gl2hDAmkFJ2nN1caBm8Et0taHUv6uBsbIHwCih9rV3Ytdr3wMYUVVb0WoH6FmxcewZSWt8FB4IBl3oF4lBL7dzgRAdckMLZX6K3wQPrwSrudNfYFI3AW5UYH59nT4xwUb-Y1pPsx9mn76dfFpvzz-vT1WYhaYX6hVKGGFZDinJIC1TWAlFZEkYYMsYoRbSSmklBTEULiViCy7quS13nQsoC4ZPs9V5350Lkk2mRQwxJ8oAVNBHrPaGCuOK7zrbJDR6E5X82Qtdw0fVWOs0rwUwhGCJlbgjBWshayjyvFEsNKKoiaX2cThvqdiwteSTcTHQe8XbLm3DNcUEow2O57yaBLvwcdOx5a-NorPA6DKluRDGDhNIqoW_-Qh--3UQ1Il3AehPSuXIU5SuMclSS5Gqilg9Q6VO6tanT2ti0P0t4P0sYX4O-6RsxxMjXF9_-g_367-z55Zx9e8ButXD9NgY3jM8uzkGyB2UXYuy0uW8IzPk4THfO8XGY-DRMKe3VYTPvk-6mB_8GGcgaqw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1314341857</pqid></control><display><type>article</type><title>Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans</title><source>PLoS</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed (Medline)</source><source>EZB Electronic Journals Library</source><creator>Palmer, Jonathan M ; Theisen, Jeffrey M ; Duran, Rocio M ; Grayburn, W Scott ; Calvo, Ana M ; Keller, Nancy P</creator><contributor>Heitman, Joseph</contributor><creatorcontrib>Palmer, Jonathan M ; Theisen, Jeffrey M ; Duran, Rocio M ; Grayburn, W Scott ; Calvo, Ana M ; Keller, Nancy P ; Heitman, Joseph</creatorcontrib><description>Secondary metabolism and development are linked in Aspergillus through the conserved regulatory velvet complex composed of VeA, VelB, and LaeA. The founding member of the velvet complex, VeA, shuttles between the cytoplasm and nucleus in response to alterations in light. Here we describe a new interaction partner of VeA identified through a reverse genetics screen looking for LaeA-like methyltransferases in Aspergillus nidulans. One of the putative LaeA-like methyltransferases identified, LlmF, is a negative regulator of sterigmatocystin production and sexual development. LlmF interacts directly with VeA and the repressive function of LlmF is mediated by influencing the localization of VeA, as over-expression of llmF decreases the nuclear to cytoplasmic ratio of VeA while deletion of llmF results in an increased nuclear accumulation of VeA. We show that the methyltransferase domain of LlmF is required for function; however, LlmF does not directly methylate VeA in vitro. This study identifies a new interaction partner for VeA and highlights the importance of cellular compartmentalization of VeA for regulation of development and secondary metabolism.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1003193</identifier><identifier>PMID: 23341778</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetylesterase - genetics ; Acetylesterase - metabolism ; Aspergillus ; Aspergillus nidulans - genetics ; Aspergillus nidulans - growth & development ; Aspergillus nidulans - metabolism ; Biology ; Cell Nucleus - metabolism ; Computational Biology ; Cytoplasm - metabolism ; Fungal Proteins - genetics ; Fungal Proteins - metabolism ; Gene expression ; Gene Expression Regulation, Fungal ; Genes ; Genetic aspects ; Health aspects ; Humans ; Medical research ; Metabolism ; Metabolites ; Microbial genetics ; Microbiology ; Phylogeny ; Physiological aspects ; Proteins</subject><ispartof>PLoS genetics, 2013-01, Vol.9 (1), p.e1003193-e1003193</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Palmer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Palmer JM, Theisen JM, Duran RM, Grayburn WS, Calvo AM, et al. (2013) Secondary Metabolism and Development Is Mediated by LlmF Control of VeA Subcellular Localization in Aspergillus nidulans. PLoS Genet 9(1): e1003193. doi:10.1371/journal.pgen.1003193</rights><rights>2013 Palmer et al 2013 Palmer et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c792t-ddf4f8b172017526ba27c648482fffdd4edce8ca4f975c284f86bbb6eb0acc523</citedby><cites>FETCH-LOGICAL-c792t-ddf4f8b172017526ba27c648482fffdd4edce8ca4f975c284f86bbb6eb0acc523</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/PMC3547832/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547832/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23341778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Heitman, Joseph</contributor><creatorcontrib>Palmer, Jonathan M</creatorcontrib><creatorcontrib>Theisen, Jeffrey M</creatorcontrib><creatorcontrib>Duran, Rocio M</creatorcontrib><creatorcontrib>Grayburn, W Scott</creatorcontrib><creatorcontrib>Calvo, Ana M</creatorcontrib><creatorcontrib>Keller, Nancy P</creatorcontrib><title>Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Secondary metabolism and development are linked in Aspergillus through the conserved regulatory velvet complex composed of VeA, VelB, and LaeA. The founding member of the velvet complex, VeA, shuttles between the cytoplasm and nucleus in response to alterations in light. Here we describe a new interaction partner of VeA identified through a reverse genetics screen looking for LaeA-like methyltransferases in Aspergillus nidulans. One of the putative LaeA-like methyltransferases identified, LlmF, is a negative regulator of sterigmatocystin production and sexual development. LlmF interacts directly with VeA and the repressive function of LlmF is mediated by influencing the localization of VeA, as over-expression of llmF decreases the nuclear to cytoplasmic ratio of VeA while deletion of llmF results in an increased nuclear accumulation of VeA. We show that the methyltransferase domain of LlmF is required for function; however, LlmF does not directly methylate VeA in vitro. This study identifies a new interaction partner for VeA and highlights the importance of cellular compartmentalization of VeA for regulation of development and secondary metabolism.</description><subject>Acetylesterase - genetics</subject><subject>Acetylesterase - metabolism</subject><subject>Aspergillus</subject><subject>Aspergillus nidulans - genetics</subject><subject>Aspergillus nidulans - growth & development</subject><subject>Aspergillus nidulans - metabolism</subject><subject>Biology</subject><subject>Cell Nucleus - metabolism</subject><subject>Computational Biology</subject><subject>Cytoplasm - metabolism</subject><subject>Fungal Proteins - genetics</subject><subject>Fungal Proteins - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Fungal</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Medical research</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Microbial genetics</subject><subject>Microbiology</subject><subject>Phylogeny</subject><subject>Physiological aspects</subject><subject>Proteins</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVk01v1DAQhiMEoqXwDxBYQkJw2CX-SOxckFYVhZVWVKLQq-X4I-vKsZc4qVp-PQ6bVhvUAygHR55nXo_f8WTZS5gvIabww1UYOi_cctdov4R5jmGFH2XHsCjwgpKcPD74P8qexXiVmIJV9Gl2hDAmkFJ2nN1caBm8Et0taHUv6uBsbIHwCih9rV3Ytdr3wMYUVVb0WoH6FmxcewZSWt8FB4IBl3oF4lBL7dzgRAdckMLZX6K3wQPrwSrudNfYFI3AW5UYH59nT4xwUb-Y1pPsx9mn76dfFpvzz-vT1WYhaYX6hVKGGFZDinJIC1TWAlFZEkYYMsYoRbSSmklBTEULiViCy7quS13nQsoC4ZPs9V5350Lkk2mRQwxJ8oAVNBHrPaGCuOK7zrbJDR6E5X82Qtdw0fVWOs0rwUwhGCJlbgjBWshayjyvFEsNKKoiaX2cThvqdiwteSTcTHQe8XbLm3DNcUEow2O57yaBLvwcdOx5a-NorPA6DKluRDGDhNIqoW_-Qh--3UQ1Il3AehPSuXIU5SuMclSS5Gqilg9Q6VO6tanT2ti0P0t4P0sYX4O-6RsxxMjXF9_-g_367-z55Zx9e8ButXD9NgY3jM8uzkGyB2UXYuy0uW8IzPk4THfO8XGY-DRMKe3VYTPvk-6mB_8GGcgaqw</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Palmer, Jonathan M</creator><creator>Theisen, Jeffrey M</creator><creator>Duran, Rocio M</creator><creator>Grayburn, W Scott</creator><creator>Calvo, Ana M</creator><creator>Keller, Nancy P</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130101</creationdate><title>Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans</title><author>Palmer, Jonathan M ; Theisen, Jeffrey M ; Duran, Rocio M ; Grayburn, W Scott ; Calvo, Ana M ; Keller, Nancy P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c792t-ddf4f8b172017526ba27c648482fffdd4edce8ca4f975c284f86bbb6eb0acc523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetylesterase - genetics</topic><topic>Acetylesterase - metabolism</topic><topic>Aspergillus</topic><topic>Aspergillus nidulans - genetics</topic><topic>Aspergillus nidulans - growth & development</topic><topic>Aspergillus nidulans - metabolism</topic><topic>Biology</topic><topic>Cell Nucleus - metabolism</topic><topic>Computational Biology</topic><topic>Cytoplasm - metabolism</topic><topic>Fungal Proteins - genetics</topic><topic>Fungal Proteins - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Fungal</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Medical research</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Microbial genetics</topic><topic>Microbiology</topic><topic>Phylogeny</topic><topic>Physiological aspects</topic><topic>Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Palmer, Jonathan M</creatorcontrib><creatorcontrib>Theisen, Jeffrey M</creatorcontrib><creatorcontrib>Duran, Rocio M</creatorcontrib><creatorcontrib>Grayburn, W Scott</creatorcontrib><creatorcontrib>Calvo, Ana M</creatorcontrib><creatorcontrib>Keller, Nancy P</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: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</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 UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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 China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Palmer, Jonathan M</au><au>Theisen, Jeffrey M</au><au>Duran, Rocio M</au><au>Grayburn, W Scott</au><au>Calvo, Ana M</au><au>Keller, Nancy P</au><au>Heitman, Joseph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>9</volume><issue>1</issue><spage>e1003193</spage><epage>e1003193</epage><pages>e1003193-e1003193</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Secondary metabolism and development are linked in Aspergillus through the conserved regulatory velvet complex composed of VeA, VelB, and LaeA. The founding member of the velvet complex, VeA, shuttles between the cytoplasm and nucleus in response to alterations in light. Here we describe a new interaction partner of VeA identified through a reverse genetics screen looking for LaeA-like methyltransferases in Aspergillus nidulans. One of the putative LaeA-like methyltransferases identified, LlmF, is a negative regulator of sterigmatocystin production and sexual development. LlmF interacts directly with VeA and the repressive function of LlmF is mediated by influencing the localization of VeA, as over-expression of llmF decreases the nuclear to cytoplasmic ratio of VeA while deletion of llmF results in an increased nuclear accumulation of VeA. We show that the methyltransferase domain of LlmF is required for function; however, LlmF does not directly methylate VeA in vitro. This study identifies a new interaction partner for VeA and highlights the importance of cellular compartmentalization of VeA for regulation of development and secondary metabolism.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23341778</pmid><doi>10.1371/journal.pgen.1003193</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1553-7404 |
ispartof | PLoS genetics, 2013-01, Vol.9 (1), p.e1003193-e1003193 |
issn | 1553-7404 1553-7390 1553-7404 |
language | eng |
recordid | cdi_plos_journals_1314341857 |
source | PLoS; MEDLINE; DOAJ Directory of Open Access Journals; PubMed (Medline); EZB Electronic Journals Library |
subjects | Acetylesterase - genetics Acetylesterase - metabolism Aspergillus Aspergillus nidulans - genetics Aspergillus nidulans - growth & development Aspergillus nidulans - metabolism Biology Cell Nucleus - metabolism Computational Biology Cytoplasm - metabolism Fungal Proteins - genetics Fungal Proteins - metabolism Gene expression Gene Expression Regulation, Fungal Genes Genetic aspects Health aspects Humans Medical research Metabolism Metabolites Microbial genetics Microbiology Phylogeny Physiological aspects Proteins |
title | Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T21%3A37%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Secondary%20metabolism%20and%20development%20is%20mediated%20by%20LlmF%20control%20of%20VeA%20subcellular%20localization%20in%20Aspergillus%20nidulans&rft.jtitle=PLoS%20genetics&rft.au=Palmer,%20Jonathan%20M&rft.date=2013-01-01&rft.volume=9&rft.issue=1&rft.spage=e1003193&rft.epage=e1003193&rft.pages=e1003193-e1003193&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1003193&rft_dat=%3Cgale_plos_%3EA320264526%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1314341857&rft_id=info:pmid/23341778&rft_galeid=A320264526&rft_doaj_id=oai_doaj_org_article_9a8f5a82460f443eacbcc009d8100595&rfr_iscdi=true |