Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal
Epidermal growth factor-like domain 7 (EGFL7) is a secreted factor implicated in cellular responses such as cell migration and blood vessel formation; however the molecular mechanisms underlying the effects of EGFL7 are largely unknown. Here we have identified transmembrane receptors of the Notch fa...
Gespeichert in:
| Veröffentlicht in: | Nature cell biology 2009-07, Vol.11 (7), p.873-880 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 880 |
|---|---|
| container_issue | 7 |
| container_start_page | 873 |
| container_title | Nature cell biology |
| container_volume | 11 |
| creator | Babuke, Tanja Dikic, Ivan Nikolic, Iva Schmidt, Mirko H.H Plate, Karl H Bicker, Frank Picuric, Srdjan Müller-Esterl, Werner Meister, Jeannette |
| description | Epidermal growth factor-like domain 7 (EGFL7) is a secreted factor implicated in cellular responses such as cell migration and blood vessel formation; however the molecular mechanisms underlying the effects of EGFL7 are largely unknown. Here we have identified transmembrane receptors of the Notch family as EGFL7-binding molecules. Secreted EGFL7 binds to a region in Notch involved in ligand-mediated receptor activation, thus acting as an antagonist of Notch signalling. Expression of EGFL7 in neural stem cells (NSCs) in vitro decreased Notch-specific signalling and consequently, reduced proliferation and self-renewal of NSCs. Such altered Notch signalling caused a shift in the differentiation pattern of cultured NSCs towards an excess of neurons and oligodendrocytes. We identified neurons as a source of EGFL7 in the brain, suggesting that brain-derived EGFL7 acts as an endogenous antagonist of Notch signalling that regulates proliferation and differentiation of subventricular zone-derived adult NSCs. |
| doi_str_mv | 10.1038/ncb1896 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_67437019</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A203660087</galeid><sourcerecordid>A203660087</sourcerecordid><originalsourceid>FETCH-LOGICAL-c493t-c18f93781f17c08409fe7ea58ed56ea4a2e285ec49c5029e243da0b7c15ed1643</originalsourceid><addsrcrecordid>eNqF0l1v1SAYB_DGaNycxk-gIZrodtEJhZZyuSxnc8mJJr5cNxz60DEpHIFm-u2l9uhy1MRwAYEff3iSpyieEnxKMG3fOLUhrWjuFYeE8aZkDRf353VTl5yK6qB4FOMNxoQxzB8WB0TUmGJOD4txtTU9hFFaNAR_m66Rlir5UFrzBVDvR2kc4uh4dXmx5ido9P1kZYKI3vmkrlE0g5PWGjcg6XoktQaVInIwhZwYE4xIgbUogINbaR8XD7S0EZ7s5qPi88Xq0_nbcv3-8ur8bF0qJmgqFWm1oLwlmnCFW4aFBg6ybqGvG5BMVlC1NWSsalwJqBjtJd5wRWroScPoUfFqyd0G_3WCmLrRxPkj0oGfYtdwRjkm4r-wwgRjznmGL_6AN34KufZsqooyUv989uWCBmmhM077FKSaE7uzCtOmwbido07_ofLoYTTKO9Am7-9dONm7kE2Cb2mQU4zd1ccP-_b1YlXwMQbQ3TaYUYbvHcHd3CrdrlWyfL6raNqM0N-5XW9kcLyAmI_cAOGu5L-zni3UyTQF-J316_wH3mHNGg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222341564</pqid></control><display><type>article</type><title>Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal</title><source>MEDLINE</source><source>Nature</source><source>Alma/SFX Local Collection</source><creator>Babuke, Tanja ; Dikic, Ivan ; Nikolic, Iva ; Schmidt, Mirko H.H ; Plate, Karl H ; Bicker, Frank ; Picuric, Srdjan ; Müller-Esterl, Werner ; Meister, Jeannette</creator><creatorcontrib>Babuke, Tanja ; Dikic, Ivan ; Nikolic, Iva ; Schmidt, Mirko H.H ; Plate, Karl H ; Bicker, Frank ; Picuric, Srdjan ; Müller-Esterl, Werner ; Meister, Jeannette</creatorcontrib><description>Epidermal growth factor-like domain 7 (EGFL7) is a secreted factor implicated in cellular responses such as cell migration and blood vessel formation; however the molecular mechanisms underlying the effects of EGFL7 are largely unknown. Here we have identified transmembrane receptors of the Notch family as EGFL7-binding molecules. Secreted EGFL7 binds to a region in Notch involved in ligand-mediated receptor activation, thus acting as an antagonist of Notch signalling. Expression of EGFL7 in neural stem cells (NSCs) in vitro decreased Notch-specific signalling and consequently, reduced proliferation and self-renewal of NSCs. Such altered Notch signalling caused a shift in the differentiation pattern of cultured NSCs towards an excess of neurons and oligodendrocytes. We identified neurons as a source of EGFL7 in the brain, suggesting that brain-derived EGFL7 acts as an endogenous antagonist of Notch signalling that regulates proliferation and differentiation of subventricular zone-derived adult NSCs.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb1896</identifier><identifier>PMID: 19503073</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Biomedical and Life Sciences ; Blood vessels ; Cancer Research ; Cell Biology ; Cell Differentiation - genetics ; Cell Differentiation - physiology ; Cell Line ; Cell Proliferation ; Cell receptors ; Cells, Cultured ; Cellular signal transduction ; Developmental Biology ; Endothelial Growth Factors - genetics ; Endothelial Growth Factors - metabolism ; Endothelial Growth Factors - physiology ; Epidermal growth factor ; Genetic aspects ; Humans ; letter ; Life Sciences ; Ligands ; Mice ; Neurons - cytology ; Neurons - metabolism ; Physiological aspects ; Protein Binding ; Receptors, Notch - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction - genetics ; Signal Transduction - physiology ; Stem Cells ; Stem Cells - cytology ; Stem Cells - metabolism ; Two-Hybrid System Techniques</subject><ispartof>Nature cell biology, 2009-07, Vol.11 (7), p.873-880</ispartof><rights>Springer Nature Limited 2009</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-c18f93781f17c08409fe7ea58ed56ea4a2e285ec49c5029e243da0b7c15ed1643</citedby><cites>FETCH-LOGICAL-c493t-c18f93781f17c08409fe7ea58ed56ea4a2e285ec49c5029e243da0b7c15ed1643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19503073$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Babuke, Tanja</creatorcontrib><creatorcontrib>Dikic, Ivan</creatorcontrib><creatorcontrib>Nikolic, Iva</creatorcontrib><creatorcontrib>Schmidt, Mirko H.H</creatorcontrib><creatorcontrib>Plate, Karl H</creatorcontrib><creatorcontrib>Bicker, Frank</creatorcontrib><creatorcontrib>Picuric, Srdjan</creatorcontrib><creatorcontrib>Müller-Esterl, Werner</creatorcontrib><creatorcontrib>Meister, Jeannette</creatorcontrib><title>Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>Epidermal growth factor-like domain 7 (EGFL7) is a secreted factor implicated in cellular responses such as cell migration and blood vessel formation; however the molecular mechanisms underlying the effects of EGFL7 are largely unknown. Here we have identified transmembrane receptors of the Notch family as EGFL7-binding molecules. Secreted EGFL7 binds to a region in Notch involved in ligand-mediated receptor activation, thus acting as an antagonist of Notch signalling. Expression of EGFL7 in neural stem cells (NSCs) in vitro decreased Notch-specific signalling and consequently, reduced proliferation and self-renewal of NSCs. Such altered Notch signalling caused a shift in the differentiation pattern of cultured NSCs towards an excess of neurons and oligodendrocytes. We identified neurons as a source of EGFL7 in the brain, suggesting that brain-derived EGFL7 acts as an endogenous antagonist of Notch signalling that regulates proliferation and differentiation of subventricular zone-derived adult NSCs.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Blood vessels</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Line</subject><subject>Cell Proliferation</subject><subject>Cell receptors</subject><subject>Cells, Cultured</subject><subject>Cellular signal transduction</subject><subject>Developmental Biology</subject><subject>Endothelial Growth Factors - genetics</subject><subject>Endothelial Growth Factors - metabolism</subject><subject>Endothelial Growth Factors - physiology</subject><subject>Epidermal growth factor</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>letter</subject><subject>Life Sciences</subject><subject>Ligands</subject><subject>Mice</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Physiological aspects</subject><subject>Protein Binding</subject><subject>Receptors, Notch - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><subject>Stem Cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - metabolism</subject><subject>Two-Hybrid System Techniques</subject><issn>1465-7392</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</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><recordid>eNqF0l1v1SAYB_DGaNycxk-gIZrodtEJhZZyuSxnc8mJJr5cNxz60DEpHIFm-u2l9uhy1MRwAYEff3iSpyieEnxKMG3fOLUhrWjuFYeE8aZkDRf353VTl5yK6qB4FOMNxoQxzB8WB0TUmGJOD4txtTU9hFFaNAR_m66Rlir5UFrzBVDvR2kc4uh4dXmx5ido9P1kZYKI3vmkrlE0g5PWGjcg6XoktQaVInIwhZwYE4xIgbUogINbaR8XD7S0EZ7s5qPi88Xq0_nbcv3-8ur8bF0qJmgqFWm1oLwlmnCFW4aFBg6ybqGvG5BMVlC1NWSsalwJqBjtJd5wRWroScPoUfFqyd0G_3WCmLrRxPkj0oGfYtdwRjkm4r-wwgRjznmGL_6AN34KufZsqooyUv989uWCBmmhM077FKSaE7uzCtOmwbido07_ofLoYTTKO9Am7-9dONm7kE2Cb2mQU4zd1ccP-_b1YlXwMQbQ3TaYUYbvHcHd3CrdrlWyfL6raNqM0N-5XW9kcLyAmI_cAOGu5L-zni3UyTQF-J316_wH3mHNGg</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Babuke, Tanja</creator><creator>Dikic, Ivan</creator><creator>Nikolic, Iva</creator><creator>Schmidt, Mirko H.H</creator><creator>Plate, Karl H</creator><creator>Bicker, Frank</creator><creator>Picuric, Srdjan</creator><creator>Müller-Esterl, Werner</creator><creator>Meister, Jeannette</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</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>C1K</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>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20090701</creationdate><title>Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal</title><author>Babuke, Tanja ; Dikic, Ivan ; Nikolic, Iva ; Schmidt, Mirko H.H ; Plate, Karl H ; Bicker, Frank ; Picuric, Srdjan ; Müller-Esterl, Werner ; Meister, Jeannette</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-c18f93781f17c08409fe7ea58ed56ea4a2e285ec49c5029e243da0b7c15ed1643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Blood vessels</topic><topic>Cancer Research</topic><topic>Cell Biology</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Line</topic><topic>Cell Proliferation</topic><topic>Cell receptors</topic><topic>Cells, Cultured</topic><topic>Cellular signal transduction</topic><topic>Developmental Biology</topic><topic>Endothelial Growth Factors - genetics</topic><topic>Endothelial Growth Factors - metabolism</topic><topic>Endothelial Growth Factors - physiology</topic><topic>Epidermal growth factor</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>letter</topic><topic>Life Sciences</topic><topic>Ligands</topic><topic>Mice</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>Physiological aspects</topic><topic>Protein Binding</topic><topic>Receptors, Notch - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - physiology</topic><topic>Stem Cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - metabolism</topic><topic>Two-Hybrid System Techniques</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Babuke, Tanja</creatorcontrib><creatorcontrib>Dikic, Ivan</creatorcontrib><creatorcontrib>Nikolic, Iva</creatorcontrib><creatorcontrib>Schmidt, Mirko H.H</creatorcontrib><creatorcontrib>Plate, Karl H</creatorcontrib><creatorcontrib>Bicker, Frank</creatorcontrib><creatorcontrib>Picuric, Srdjan</creatorcontrib><creatorcontrib>Müller-Esterl, Werner</creatorcontrib><creatorcontrib>Meister, Jeannette</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</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>ProQuest Pharma Collection</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 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>Environmental Sciences and Pollution Management</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>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Babuke, Tanja</au><au>Dikic, Ivan</au><au>Nikolic, Iva</au><au>Schmidt, Mirko H.H</au><au>Plate, Karl H</au><au>Bicker, Frank</au><au>Picuric, Srdjan</au><au>Müller-Esterl, Werner</au><au>Meister, Jeannette</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>11</volume><issue>7</issue><spage>873</spage><epage>880</epage><pages>873-880</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>Epidermal growth factor-like domain 7 (EGFL7) is a secreted factor implicated in cellular responses such as cell migration and blood vessel formation; however the molecular mechanisms underlying the effects of EGFL7 are largely unknown. Here we have identified transmembrane receptors of the Notch family as EGFL7-binding molecules. Secreted EGFL7 binds to a region in Notch involved in ligand-mediated receptor activation, thus acting as an antagonist of Notch signalling. Expression of EGFL7 in neural stem cells (NSCs) in vitro decreased Notch-specific signalling and consequently, reduced proliferation and self-renewal of NSCs. Such altered Notch signalling caused a shift in the differentiation pattern of cultured NSCs towards an excess of neurons and oligodendrocytes. We identified neurons as a source of EGFL7 in the brain, suggesting that brain-derived EGFL7 acts as an endogenous antagonist of Notch signalling that regulates proliferation and differentiation of subventricular zone-derived adult NSCs.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19503073</pmid><doi>10.1038/ncb1896</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-7392 |
| ispartof | Nature cell biology, 2009-07, Vol.11 (7), p.873-880 |
| issn | 1465-7392 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67437019 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | Animals Biomedical and Life Sciences Blood vessels Cancer Research Cell Biology Cell Differentiation - genetics Cell Differentiation - physiology Cell Line Cell Proliferation Cell receptors Cells, Cultured Cellular signal transduction Developmental Biology Endothelial Growth Factors - genetics Endothelial Growth Factors - metabolism Endothelial Growth Factors - physiology Epidermal growth factor Genetic aspects Humans letter Life Sciences Ligands Mice Neurons - cytology Neurons - metabolism Physiological aspects Protein Binding Receptors, Notch - metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction - genetics Signal Transduction - physiology Stem Cells Stem Cells - cytology Stem Cells - metabolism Two-Hybrid System Techniques |
| title | Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T18%3A40%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Epidermal%20growth%20factor-like%20domain%207%20(EGFL7)%20modulates%20Notch%20signalling%20and%20affects%20neural%20stem%20cell%20renewal&rft.jtitle=Nature%20cell%20biology&rft.au=Babuke,%20Tanja&rft.date=2009-07-01&rft.volume=11&rft.issue=7&rft.spage=873&rft.epage=880&rft.pages=873-880&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/ncb1896&rft_dat=%3Cgale_proqu%3EA203660087%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222341564&rft_id=info:pmid/19503073&rft_galeid=A203660087&rfr_iscdi=true |