Loading…

Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway

A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investig...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2009-07, Vol.4 (7), p.e6234-e6234
Main Authors: Trisciuoglio, Lisa, Bianchi, Marco Emilio
Format: Article
Language:English
Subjects:
Citations: 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-c662t-a8b43c917f418838aabad4b39dfb93a00a065e20e86e07553bf2e3e60ebf83b93
cites
container_end_page e6234
container_issue 7
container_start_page e6234
container_title PloS one
container_volume 4
creator Trisciuoglio, Lisa
Bianchi, Marco Emilio
description A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investigate whether these events cluster together in pathways. We find that all depend directly or indirectly on caspase-3 activation. CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.
doi_str_mv 10.1371/journal.pone.0006234
format article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1291056692</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A472931605</galeid><doaj_id>oai_doaj_org_article_15de031c333f49008a5caf78fb891609</doaj_id><sourcerecordid>A472931605</sourcerecordid><originalsourceid>FETCH-LOGICAL-c662t-a8b43c917f418838aabad4b39dfb93a00a065e20e86e07553bf2e3e60ebf83b93</originalsourceid><addsrcrecordid>eNqNkl2L1DAUhoso7jr6D0QDwoIXHfPRpu3NwrL4MbCw4Kq34TQ9ncnQJrVJR_ffm3GqzogXkosmJ885p-fNmyTPGV0yUbA3WzeNFrrl4CwuKaWSi-xBcs4qwVPJqXh4tD9Lnni_pTQXpZSPkzNWyYxJzs6T_g53OEJH7KQ7hJHEow2eNNNo7JrA4IbgvIkBHNA2xFmiwQ_gMRUEdDA7CCYG6ymQxhHrAtHO-mDCFJBAPPR9vB4gbL7B_dPkUQudx2fzd5F8fvf20_WH9Ob2_er66ibVUvKQQllnQlesaDNWlqIEqKHJalE1bV0JoBSozJFTLCXSIs9F3XIUKCnWbSkiskheHuoOnfNqVsorxitGcykrHonVgWgcbNUwmh7Ge-XAqJ8BN64VjMFETRTLG6SCaSFEm1WUlpBraIuyrcuKSbrvdjl3m-oeGx0FjIqeFD29sWaj1m6neMFEFp9nkVzMBUb3dUIfVG-8xq4Di27ySha5yGTOIvjqL_Dfsy0P1Bri7xvbuthVx9Vgb-LrYGti_CoreCXiAHlMeH2SEJmA38MaJu_V6u7j_7O3X07ZiyN2g9CFjXfdtHeMPwWzA6hH5_2I7W_xGFV7t_-aU-3drma3x7QXx8L_SZrtLX4ApHz8Bw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1291056692</pqid></control><display><type>article</type><title>Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway</title><source>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</source><source>PubMed Central</source><creator>Trisciuoglio, Lisa ; Bianchi, Marco Emilio</creator><contributor>Goldman, Gustavo</contributor><creatorcontrib>Trisciuoglio, Lisa ; Bianchi, Marco Emilio ; Goldman, Gustavo</creatorcontrib><description>A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investigate whether these events cluster together in pathways. We find that all depend directly or indirectly on caspase-3 activation. CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0006234</identifier><identifier>PMID: 19641621</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Apoptosis ; Base Sequence ; Biochemistry ; Breast cancer ; Caspase ; Caspase 3 - metabolism ; Caspase 6 - metabolism ; Caspase-3 ; Cell Biology/Cellular Death and Stress Responses ; Cell Line ; Cell Nucleus - enzymology ; Chromatin ; Chromatin - metabolism ; Clusters ; Cytokines ; Deoxyribonucleic acid ; DNA ; DNA binding proteins ; DNA damage ; DNA fragmentation ; DNA Primers ; Enzyme Activation ; Epistasis ; Fluorescence ; Genetic research ; Histone H2A ; Histones ; Histones - metabolism ; HMGB1 protein ; HMGB1 Protein - metabolism ; Humans ; Microscopy ; Molecular Biology/Chromatin Structure ; Morphology ; Nuclease ; Nucleoproteins ; Pathogenesis ; Phosphorylation ; Proteins ; Recovery (Medical) ; Rodents</subject><ispartof>PloS one, 2009-07, Vol.4 (7), p.e6234-e6234</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Trisciuoglio, Bianchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Trisciuoglio, Bianchi. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c662t-a8b43c917f418838aabad4b39dfb93a00a065e20e86e07553bf2e3e60ebf83b93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1291056692/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1291056692?pq-origsite=primo$$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/19641621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Goldman, Gustavo</contributor><creatorcontrib>Trisciuoglio, Lisa</creatorcontrib><creatorcontrib>Bianchi, Marco Emilio</creatorcontrib><title>Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investigate whether these events cluster together in pathways. We find that all depend directly or indirectly on caspase-3 activation. CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.</description><subject>Activation</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Biochemistry</subject><subject>Breast cancer</subject><subject>Caspase</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase 6 - metabolism</subject><subject>Caspase-3</subject><subject>Cell Biology/Cellular Death and Stress Responses</subject><subject>Cell Line</subject><subject>Cell Nucleus - enzymology</subject><subject>Chromatin</subject><subject>Chromatin - metabolism</subject><subject>Clusters</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA binding proteins</subject><subject>DNA damage</subject><subject>DNA fragmentation</subject><subject>DNA Primers</subject><subject>Enzyme Activation</subject><subject>Epistasis</subject><subject>Fluorescence</subject><subject>Genetic research</subject><subject>Histone H2A</subject><subject>Histones</subject><subject>Histones - metabolism</subject><subject>HMGB1 protein</subject><subject>HMGB1 Protein - metabolism</subject><subject>Humans</subject><subject>Microscopy</subject><subject>Molecular Biology/Chromatin Structure</subject><subject>Morphology</subject><subject>Nuclease</subject><subject>Nucleoproteins</subject><subject>Pathogenesis</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Recovery (Medical)</subject><subject>Rodents</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7jr6D0QDwoIXHfPRpu3NwrL4MbCw4Kq34TQ9ncnQJrVJR_ffm3GqzogXkosmJ885p-fNmyTPGV0yUbA3WzeNFrrl4CwuKaWSi-xBcs4qwVPJqXh4tD9Lnni_pTQXpZSPkzNWyYxJzs6T_g53OEJH7KQ7hJHEow2eNNNo7JrA4IbgvIkBHNA2xFmiwQ_gMRUEdDA7CCYG6ymQxhHrAtHO-mDCFJBAPPR9vB4gbL7B_dPkUQudx2fzd5F8fvf20_WH9Ob2_er66ibVUvKQQllnQlesaDNWlqIEqKHJalE1bV0JoBSozJFTLCXSIs9F3XIUKCnWbSkiskheHuoOnfNqVsorxitGcykrHonVgWgcbNUwmh7Ge-XAqJ8BN64VjMFETRTLG6SCaSFEm1WUlpBraIuyrcuKSbrvdjl3m-oeGx0FjIqeFD29sWaj1m6neMFEFp9nkVzMBUb3dUIfVG-8xq4Di27ySha5yGTOIvjqL_Dfsy0P1Bri7xvbuthVx9Vgb-LrYGti_CoreCXiAHlMeH2SEJmA38MaJu_V6u7j_7O3X07ZiyN2g9CFjXfdtHeMPwWzA6hH5_2I7W_xGFV7t_-aU-3drma3x7QXx8L_SZrtLX4ApHz8Bw</recordid><startdate>20090729</startdate><enddate>20090729</enddate><creator>Trisciuoglio, Lisa</creator><creator>Bianchi, Marco Emilio</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090729</creationdate><title>Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway</title><author>Trisciuoglio, Lisa ; Bianchi, Marco Emilio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c662t-a8b43c917f418838aabad4b39dfb93a00a065e20e86e07553bf2e3e60ebf83b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Activation</topic><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Biochemistry</topic><topic>Breast cancer</topic><topic>Caspase</topic><topic>Caspase 3 - metabolism</topic><topic>Caspase 6 - metabolism</topic><topic>Caspase-3</topic><topic>Cell Biology/Cellular Death and Stress Responses</topic><topic>Cell Line</topic><topic>Cell Nucleus - enzymology</topic><topic>Chromatin</topic><topic>Chromatin - metabolism</topic><topic>Clusters</topic><topic>Cytokines</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA binding proteins</topic><topic>DNA damage</topic><topic>DNA fragmentation</topic><topic>DNA Primers</topic><topic>Enzyme Activation</topic><topic>Epistasis</topic><topic>Fluorescence</topic><topic>Genetic research</topic><topic>Histone H2A</topic><topic>Histones</topic><topic>Histones - metabolism</topic><topic>HMGB1 protein</topic><topic>HMGB1 Protein - metabolism</topic><topic>Humans</topic><topic>Microscopy</topic><topic>Molecular Biology/Chromatin Structure</topic><topic>Morphology</topic><topic>Nuclease</topic><topic>Nucleoproteins</topic><topic>Pathogenesis</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Recovery (Medical)</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trisciuoglio, Lisa</creatorcontrib><creatorcontrib>Bianchi, Marco Emilio</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_Opposing Viewpoints In Context</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies &amp; Aerospace Database‎ (1962 - current)</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</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 (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Trisciuoglio, Lisa</au><au>Bianchi, Marco Emilio</au><au>Goldman, Gustavo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-07-29</date><risdate>2009</risdate><volume>4</volume><issue>7</issue><spage>e6234</spage><epage>e6234</epage><pages>e6234-e6234</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A number of nuclear events occur during apoptosis, including DNA laddering, nuclear lamina breakdown, phosphorylation of histones H2B and histone H2AX, and the tight binding to chromatin of HMGB1 and CAD, the nuclease responsible for DNA laddering. We have performed an epistasis analysis to investigate whether these events cluster together in pathways. We find that all depend directly or indirectly on caspase-3 activation. CAD activation, H2AX phosphorylation and DNA laddering cluster together into a pathway, but all other events appear to be independent of each other downstream of caspase-3, and likely evolved subject to different functional pressures.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19641621</pmid><doi>10.1371/journal.pone.0006234</doi><tpages>e6234</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2009-07, Vol.4 (7), p.e6234-e6234
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1291056692
source Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central
subjects Activation
Apoptosis
Base Sequence
Biochemistry
Breast cancer
Caspase
Caspase 3 - metabolism
Caspase 6 - metabolism
Caspase-3
Cell Biology/Cellular Death and Stress Responses
Cell Line
Cell Nucleus - enzymology
Chromatin
Chromatin - metabolism
Clusters
Cytokines
Deoxyribonucleic acid
DNA
DNA binding proteins
DNA damage
DNA fragmentation
DNA Primers
Enzyme Activation
Epistasis
Fluorescence
Genetic research
Histone H2A
Histones
Histones - metabolism
HMGB1 protein
HMGB1 Protein - metabolism
Humans
Microscopy
Molecular Biology/Chromatin Structure
Morphology
Nuclease
Nucleoproteins
Pathogenesis
Phosphorylation
Proteins
Recovery (Medical)
Rodents
title Several nuclear events during apoptosis depend on caspase-3 activation but do not constitute a common pathway
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T14%3A47%3A16IST&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=Several%20nuclear%20events%20during%20apoptosis%20depend%20on%20caspase-3%20activation%20but%20do%20not%20constitute%20a%20common%20pathway&rft.jtitle=PloS%20one&rft.au=Trisciuoglio,%20Lisa&rft.date=2009-07-29&rft.volume=4&rft.issue=7&rft.spage=e6234&rft.epage=e6234&rft.pages=e6234-e6234&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0006234&rft_dat=%3Cgale_plos_%3EA472931605%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c662t-a8b43c917f418838aabad4b39dfb93a00a065e20e86e07553bf2e3e60ebf83b93%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1291056692&rft_id=info:pmid/19641621&rft_galeid=A472931605&rfr_iscdi=true