Loading…
Structural basis for receptor recognition of pollen tube attraction peptides
Transportation of the immobile sperms directed by pollen tubes to the ovule-enclosed female gametophytes is important for plant sexual reproduction. The defensin-like (DEFL) cysteine-rich peptides (CRPs) LUREs play an essential role in pollen tube attraction to the ovule, though their receptors stil...
Saved in:
Published in: | Nature communications 2017-11, Vol.8 (1), p.1331-9, Article 1331 |
---|---|
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-c606t-9fac4aa54cf80b5af6f72e03a91e669765cf4a1a57ab93271c748b6444094f013 |
---|---|
cites | cdi_FETCH-LOGICAL-c606t-9fac4aa54cf80b5af6f72e03a91e669765cf4a1a57ab93271c748b6444094f013 |
container_end_page | 9 |
container_issue | 1 |
container_start_page | 1331 |
container_title | Nature communications |
container_volume | 8 |
creator | Zhang, Xiaoxiao Liu, Weijia Nagae, Takuya T. Takeuchi, Hidenori Zhang, Heqiao Han, Zhifu Higashiyama, Tetsuya Chai, Jijie |
description | Transportation of the immobile sperms directed by pollen tubes to the ovule-enclosed female gametophytes is important for plant sexual reproduction. The defensin-like (DEFL) cysteine-rich peptides (CRPs) LUREs play an essential role in pollen tube attraction to the ovule, though their receptors still remain controversial. Here we provide several lines of biochemical evidence showing that the extracellular domain of the leucine-rich repeat receptor kinase (LRR-RK) PRK6 from
Arabidopsis thaliana
directly interacts with AtLURE1 peptides. Structural study reveals that a C-terminal loop of the LRR domain (AtPRK6
LRR
) is responsible for recognition of AtLURE1.2, mediated by a set of residues largely conserved among PRK6 homologs from
Arabidopsis lyrata
and
Capsella rubella
, supported by in vitro mutagenesis and semi-in-vivo pollen tube growth assays. Our study provides evidence showing that PRK6 functions as a receptor of the LURE peptides in
A. thaliana
and reveals a unique ligand recognition mechanism of LRR-RKs.
The cysteine-rich peptides LUREs play an essential role in pollen tube attraction to the ovule for plant sexual reproduction. Here Zhang et al. show that PRK6 functions as a receptor of the LUREs in
Arabidopsis thaliana
and reveal the ligand recognition mechanism. |
doi_str_mv | 10.1038/s41467-017-01323-8 |
format | article |
fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_2cb0b1d61d3f492ca018b463981c9b16</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_2cb0b1d61d3f492ca018b463981c9b16</doaj_id><sourcerecordid>1961025651</sourcerecordid><originalsourceid>FETCH-LOGICAL-c606t-9fac4aa54cf80b5af6f72e03a91e669765cf4a1a57ab93271c748b6444094f013</originalsourceid><addsrcrecordid>eNp1kU1r3DAQhk1paEKSP9BDMfTSi1uNJMvWpVBCPwILPSQ9i5EsbbV4LVeSC_n31a7TsClUIDRo3nk0o7eqXgN5D4T1HxIHLrqGwGEzypr-RXVBCYcGOspensTn1XVKO1IWk9Bz_qo6pxKI5AAX1eYux8XkJeJYa0w-1S7EOlpj57wGYTv57MNUB1fPYRztVOdF2xpzjmiOmbmI_WDTVXXmcEz2-vG8rH58-Xx_863ZfP96e_Np0xhBRG6kQ8MRW25cT3SLTriOWsJQghVCdqI1jiNg26GWjHZgOt5rwTkvTbsy7WV1u3KHgDs1R7_H-KACenW8CHGrMGZvRquo0UTDIGBgjktqkECvuWCyByM1iML6uLLmRe_tYOxUxhqfQZ9nJv9TbcNv1YqO9VIWwLtHQAy_Fpuy2vtk7DjiZMOSFEhRnhGEHfp--490F5Y4la86qghtRXtQ0VVlYkgpWvfUDBB18F6t3qvivTp6r_pS9OZ0jKeSv04XAVsFqaSmrY0nb_8f-wdClbm6</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1961025651</pqid></control><display><type>article</type><title>Structural basis for receptor recognition of pollen tube attraction peptides</title><source>Open Access: PubMed Central</source><source>Nature Publishing Group</source><source>ProQuest - Publicly Available Content Database</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Zhang, Xiaoxiao ; Liu, Weijia ; Nagae, Takuya T. ; Takeuchi, Hidenori ; Zhang, Heqiao ; Han, Zhifu ; Higashiyama, Tetsuya ; Chai, Jijie</creator><creatorcontrib>Zhang, Xiaoxiao ; Liu, Weijia ; Nagae, Takuya T. ; Takeuchi, Hidenori ; Zhang, Heqiao ; Han, Zhifu ; Higashiyama, Tetsuya ; Chai, Jijie</creatorcontrib><description>Transportation of the immobile sperms directed by pollen tubes to the ovule-enclosed female gametophytes is important for plant sexual reproduction. The defensin-like (DEFL) cysteine-rich peptides (CRPs) LUREs play an essential role in pollen tube attraction to the ovule, though their receptors still remain controversial. Here we provide several lines of biochemical evidence showing that the extracellular domain of the leucine-rich repeat receptor kinase (LRR-RK) PRK6 from
Arabidopsis thaliana
directly interacts with AtLURE1 peptides. Structural study reveals that a C-terminal loop of the LRR domain (AtPRK6
LRR
) is responsible for recognition of AtLURE1.2, mediated by a set of residues largely conserved among PRK6 homologs from
Arabidopsis lyrata
and
Capsella rubella
, supported by in vitro mutagenesis and semi-in-vivo pollen tube growth assays. Our study provides evidence showing that PRK6 functions as a receptor of the LURE peptides in
A. thaliana
and reveals a unique ligand recognition mechanism of LRR-RKs.
The cysteine-rich peptides LUREs play an essential role in pollen tube attraction to the ovule for plant sexual reproduction. Here Zhang et al. show that PRK6 functions as a receptor of the LUREs in
Arabidopsis thaliana
and reveal the ligand recognition mechanism.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/s41467-017-01323-8</identifier><identifier>PMID: 29109411</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/449/2679/2113 ; 631/535/1266 ; Attraction ; Gametophytes ; Homology ; Humanities and Social Sciences ; Leucine ; multidisciplinary ; Mutagenesis ; Peptides ; Pollen ; Pollen tubes ; Receptors ; Recognition ; Reproduction (biology) ; Rubella ; Science ; Science (multidisciplinary) ; Sexual reproduction ; Tubes</subject><ispartof>Nature communications, 2017-11, Vol.8 (1), p.1331-9, Article 1331</ispartof><rights>The Author(s) 2017</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c606t-9fac4aa54cf80b5af6f72e03a91e669765cf4a1a57ab93271c748b6444094f013</citedby><cites>FETCH-LOGICAL-c606t-9fac4aa54cf80b5af6f72e03a91e669765cf4a1a57ab93271c748b6444094f013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1961025651/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1961025651?pq-origsite=primo$$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/29109411$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xiaoxiao</creatorcontrib><creatorcontrib>Liu, Weijia</creatorcontrib><creatorcontrib>Nagae, Takuya T.</creatorcontrib><creatorcontrib>Takeuchi, Hidenori</creatorcontrib><creatorcontrib>Zhang, Heqiao</creatorcontrib><creatorcontrib>Han, Zhifu</creatorcontrib><creatorcontrib>Higashiyama, Tetsuya</creatorcontrib><creatorcontrib>Chai, Jijie</creatorcontrib><title>Structural basis for receptor recognition of pollen tube attraction peptides</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Transportation of the immobile sperms directed by pollen tubes to the ovule-enclosed female gametophytes is important for plant sexual reproduction. The defensin-like (DEFL) cysteine-rich peptides (CRPs) LUREs play an essential role in pollen tube attraction to the ovule, though their receptors still remain controversial. Here we provide several lines of biochemical evidence showing that the extracellular domain of the leucine-rich repeat receptor kinase (LRR-RK) PRK6 from
Arabidopsis thaliana
directly interacts with AtLURE1 peptides. Structural study reveals that a C-terminal loop of the LRR domain (AtPRK6
LRR
) is responsible for recognition of AtLURE1.2, mediated by a set of residues largely conserved among PRK6 homologs from
Arabidopsis lyrata
and
Capsella rubella
, supported by in vitro mutagenesis and semi-in-vivo pollen tube growth assays. Our study provides evidence showing that PRK6 functions as a receptor of the LURE peptides in
A. thaliana
and reveals a unique ligand recognition mechanism of LRR-RKs.
The cysteine-rich peptides LUREs play an essential role in pollen tube attraction to the ovule for plant sexual reproduction. Here Zhang et al. show that PRK6 functions as a receptor of the LUREs in
Arabidopsis thaliana
and reveal the ligand recognition mechanism.</description><subject>631/449/2679/2113</subject><subject>631/535/1266</subject><subject>Attraction</subject><subject>Gametophytes</subject><subject>Homology</subject><subject>Humanities and Social Sciences</subject><subject>Leucine</subject><subject>multidisciplinary</subject><subject>Mutagenesis</subject><subject>Peptides</subject><subject>Pollen</subject><subject>Pollen tubes</subject><subject>Receptors</subject><subject>Recognition</subject><subject>Reproduction (biology)</subject><subject>Rubella</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sexual reproduction</subject><subject>Tubes</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp1kU1r3DAQhk1paEKSP9BDMfTSi1uNJMvWpVBCPwILPSQ9i5EsbbV4LVeSC_n31a7TsClUIDRo3nk0o7eqXgN5D4T1HxIHLrqGwGEzypr-RXVBCYcGOspensTn1XVKO1IWk9Bz_qo6pxKI5AAX1eYux8XkJeJYa0w-1S7EOlpj57wGYTv57MNUB1fPYRztVOdF2xpzjmiOmbmI_WDTVXXmcEz2-vG8rH58-Xx_863ZfP96e_Np0xhBRG6kQ8MRW25cT3SLTriOWsJQghVCdqI1jiNg26GWjHZgOt5rwTkvTbsy7WV1u3KHgDs1R7_H-KACenW8CHGrMGZvRquo0UTDIGBgjktqkECvuWCyByM1iML6uLLmRe_tYOxUxhqfQZ9nJv9TbcNv1YqO9VIWwLtHQAy_Fpuy2vtk7DjiZMOSFEhRnhGEHfp--490F5Y4la86qghtRXtQ0VVlYkgpWvfUDBB18F6t3qvivTp6r_pS9OZ0jKeSv04XAVsFqaSmrY0nb_8f-wdClbm6</recordid><startdate>20171106</startdate><enddate>20171106</enddate><creator>Zhang, Xiaoxiao</creator><creator>Liu, Weijia</creator><creator>Nagae, Takuya T.</creator><creator>Takeuchi, Hidenori</creator><creator>Zhang, Heqiao</creator><creator>Han, Zhifu</creator><creator>Higashiyama, Tetsuya</creator><creator>Chai, Jijie</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</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>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20171106</creationdate><title>Structural basis for receptor recognition of pollen tube attraction peptides</title><author>Zhang, Xiaoxiao ; Liu, Weijia ; Nagae, Takuya T. ; Takeuchi, Hidenori ; Zhang, Heqiao ; Han, Zhifu ; Higashiyama, Tetsuya ; Chai, Jijie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c606t-9fac4aa54cf80b5af6f72e03a91e669765cf4a1a57ab93271c748b6444094f013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/449/2679/2113</topic><topic>631/535/1266</topic><topic>Attraction</topic><topic>Gametophytes</topic><topic>Homology</topic><topic>Humanities and Social Sciences</topic><topic>Leucine</topic><topic>multidisciplinary</topic><topic>Mutagenesis</topic><topic>Peptides</topic><topic>Pollen</topic><topic>Pollen tubes</topic><topic>Receptors</topic><topic>Recognition</topic><topic>Reproduction (biology)</topic><topic>Rubella</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sexual reproduction</topic><topic>Tubes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Xiaoxiao</creatorcontrib><creatorcontrib>Liu, Weijia</creatorcontrib><creatorcontrib>Nagae, Takuya T.</creatorcontrib><creatorcontrib>Takeuchi, Hidenori</creatorcontrib><creatorcontrib>Zhang, Heqiao</creatorcontrib><creatorcontrib>Han, Zhifu</creatorcontrib><creatorcontrib>Higashiyama, Tetsuya</creatorcontrib><creatorcontrib>Chai, Jijie</creatorcontrib><collection>SpringerOpen(OpenAccess)</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: 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 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>ProQuest Biological Science Journals</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xiaoxiao</au><au>Liu, Weijia</au><au>Nagae, Takuya T.</au><au>Takeuchi, Hidenori</au><au>Zhang, Heqiao</au><au>Han, Zhifu</au><au>Higashiyama, Tetsuya</au><au>Chai, Jijie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural basis for receptor recognition of pollen tube attraction peptides</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2017-11-06</date><risdate>2017</risdate><volume>8</volume><issue>1</issue><spage>1331</spage><epage>9</epage><pages>1331-9</pages><artnum>1331</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Transportation of the immobile sperms directed by pollen tubes to the ovule-enclosed female gametophytes is important for plant sexual reproduction. The defensin-like (DEFL) cysteine-rich peptides (CRPs) LUREs play an essential role in pollen tube attraction to the ovule, though their receptors still remain controversial. Here we provide several lines of biochemical evidence showing that the extracellular domain of the leucine-rich repeat receptor kinase (LRR-RK) PRK6 from
Arabidopsis thaliana
directly interacts with AtLURE1 peptides. Structural study reveals that a C-terminal loop of the LRR domain (AtPRK6
LRR
) is responsible for recognition of AtLURE1.2, mediated by a set of residues largely conserved among PRK6 homologs from
Arabidopsis lyrata
and
Capsella rubella
, supported by in vitro mutagenesis and semi-in-vivo pollen tube growth assays. Our study provides evidence showing that PRK6 functions as a receptor of the LURE peptides in
A. thaliana
and reveals a unique ligand recognition mechanism of LRR-RKs.
The cysteine-rich peptides LUREs play an essential role in pollen tube attraction to the ovule for plant sexual reproduction. Here Zhang et al. show that PRK6 functions as a receptor of the LUREs in
Arabidopsis thaliana
and reveal the ligand recognition mechanism.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29109411</pmid><doi>10.1038/s41467-017-01323-8</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2041-1723 |
ispartof | Nature communications, 2017-11, Vol.8 (1), p.1331-9, Article 1331 |
issn | 2041-1723 2041-1723 |
language | eng |
recordid | cdi_doaj_primary_oai_doaj_org_article_2cb0b1d61d3f492ca018b463981c9b16 |
source | Open Access: PubMed Central; Nature Publishing Group; ProQuest - Publicly Available Content Database; Springer Nature - nature.com Journals - Fully Open Access |
subjects | 631/449/2679/2113 631/535/1266 Attraction Gametophytes Homology Humanities and Social Sciences Leucine multidisciplinary Mutagenesis Peptides Pollen Pollen tubes Receptors Recognition Reproduction (biology) Rubella Science Science (multidisciplinary) Sexual reproduction Tubes |
title | Structural basis for receptor recognition of pollen tube attraction peptides |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T12%3A44%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structural%20basis%20for%20receptor%20recognition%20of%20pollen%20tube%20attraction%20peptides&rft.jtitle=Nature%20communications&rft.au=Zhang,%20Xiaoxiao&rft.date=2017-11-06&rft.volume=8&rft.issue=1&rft.spage=1331&rft.epage=9&rft.pages=1331-9&rft.artnum=1331&rft.issn=2041-1723&rft.eissn=2041-1723&rft_id=info:doi/10.1038/s41467-017-01323-8&rft_dat=%3Cproquest_doaj_%3E1961025651%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c606t-9fac4aa54cf80b5af6f72e03a91e669765cf4a1a57ab93271c748b6444094f013%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1961025651&rft_id=info:pmid/29109411&rfr_iscdi=true |