Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex
CXCR1, a member in G-protein coupled receptor (GPCR) family, binds to chemokine interleukin-8 (IL-8) specifically and transduces signals to mediate immune and inflammatory responses. Despite the importance of CXCR1, high-resolution structure determination is hindered by the challenges in crystalliza...
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| Veröffentlicht in: | Scientific reports 2019-03, Vol.9 (1), p.5317-11, Article 5317 |
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| creator | Wang, Yang Park, Jae-Hyun Lupala, Cecylia Severin Yun, Ji-Hye Jin, Zeyu Huang, Lanqing Li, Xuanxuan Tang, Leihan Lee, Weontae Liu, Haiguang |
| description | CXCR1, a member in G-protein coupled receptor (GPCR) family, binds to chemokine interleukin-8 (IL-8) specifically and transduces signals to mediate immune and inflammatory responses. Despite the importance of CXCR1, high-resolution structure determination is hindered by the challenges in crystallization. It has been shown that properly designed mutants with enhanced thermostability, together with fusion partner proteins, can be useful to form crystals for GPCR proteins. In this study,
in silico
protein design was carried out by using homology modeling and molecular dynamics simulations. To validate the computational modeling results, the thermostability of several mutants and the wild type were measured experimentally. Both computational results and experimental data suggest that the mutant L126W has a significant improvement in the thermostability. This study demonstrated that
in silico
design can guide protein engineering and potentially facilitate protein crystallography research. |
| doi_str_mv | 10.1038/s41598-019-41838-2 |
| format | Article |
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in silico
protein design was carried out by using homology modeling and molecular dynamics simulations. To validate the computational modeling results, the thermostability of several mutants and the wild type were measured experimentally. Both computational results and experimental data suggest that the mutant L126W has a significant improvement in the thermostability. This study demonstrated that
in silico
design can guide protein engineering and potentially facilitate protein crystallography research.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-41838-2</identifier><identifier>PMID: 30926935</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>119/118 ; 45/70 ; 631/535/1267 ; 631/57/2266 ; Amino Acid Sequence ; Binding Sites ; Chemokines ; Computer applications ; Crystallization ; Crystallography ; Crystals ; G protein-coupled receptors ; Homology ; Humanities and Social Sciences ; Inflammation ; Interleukin 8 ; Lysozyme ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; multidisciplinary ; Muramidase - chemistry ; Muramidase - genetics ; Muramidase - metabolism ; Mutation ; Protein Binding ; Protein Engineering ; Protein Interaction Domains and Motifs ; Protein Stability ; Proteins ; Receptors, Interleukin-8A - chemistry ; Receptors, Interleukin-8A - genetics ; Receptors, Interleukin-8A - metabolism ; Science ; Science (multidisciplinary) ; Structure-Activity Relationship ; Thermal stability ; Thermodynamics</subject><ispartof>Scientific reports, 2019-03, Vol.9 (1), p.5317-11, Article 5317</ispartof><rights>The Author(s) 2019</rights><rights>2019. 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-c511t-18af5de3dfcab1a8d371c78ddf6f8616bdcb41dda0ac1a4f586b896bf904ccd73</citedby><cites>FETCH-LOGICAL-c511t-18af5de3dfcab1a8d371c78ddf6f8616bdcb41dda0ac1a4f586b896bf904ccd73</cites><orcidid>0000-0001-7324-6632 ; 0000-0002-5504-9800</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441008/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441008/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30926935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Park, Jae-Hyun</creatorcontrib><creatorcontrib>Lupala, Cecylia Severin</creatorcontrib><creatorcontrib>Yun, Ji-Hye</creatorcontrib><creatorcontrib>Jin, Zeyu</creatorcontrib><creatorcontrib>Huang, Lanqing</creatorcontrib><creatorcontrib>Li, Xuanxuan</creatorcontrib><creatorcontrib>Tang, Leihan</creatorcontrib><creatorcontrib>Lee, Weontae</creatorcontrib><creatorcontrib>Liu, Haiguang</creatorcontrib><title>Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>CXCR1, a member in G-protein coupled receptor (GPCR) family, binds to chemokine interleukin-8 (IL-8) specifically and transduces signals to mediate immune and inflammatory responses. Despite the importance of CXCR1, high-resolution structure determination is hindered by the challenges in crystallization. It has been shown that properly designed mutants with enhanced thermostability, together with fusion partner proteins, can be useful to form crystals for GPCR proteins. In this study,
in silico
protein design was carried out by using homology modeling and molecular dynamics simulations. To validate the computational modeling results, the thermostability of several mutants and the wild type were measured experimentally. Both computational results and experimental data suggest that the mutant L126W has a significant improvement in the thermostability. This study demonstrated that
in silico
design can guide protein engineering and potentially facilitate protein crystallography research.</description><subject>119/118</subject><subject>45/70</subject><subject>631/535/1267</subject><subject>631/57/2266</subject><subject>Amino Acid Sequence</subject><subject>Binding Sites</subject><subject>Chemokines</subject><subject>Computer applications</subject><subject>Crystallization</subject><subject>Crystallography</subject><subject>Crystals</subject><subject>G protein-coupled receptors</subject><subject>Homology</subject><subject>Humanities and Social Sciences</subject><subject>Inflammation</subject><subject>Interleukin 8</subject><subject>Lysozyme</subject><subject>Molecular Docking Simulation</subject><subject>Molecular Dynamics Simulation</subject><subject>multidisciplinary</subject><subject>Muramidase - chemistry</subject><subject>Muramidase - genetics</subject><subject>Muramidase - metabolism</subject><subject>Mutation</subject><subject>Protein Binding</subject><subject>Protein Engineering</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Protein Stability</subject><subject>Proteins</subject><subject>Receptors, Interleukin-8A - chemistry</subject><subject>Receptors, Interleukin-8A - genetics</subject><subject>Receptors, Interleukin-8A - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Structure-Activity Relationship</subject><subject>Thermal stability</subject><subject>Thermodynamics</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><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>eNp9kUFrFTEQx4Motjz7BTxIwIuX1UyS3U0ugixWhYJQKniL2ST7Xspusia7xddPb9pXa-vBhDAT8p__ZPgh9BLIWyBMvMscaikqArLiIJio6BN0TAmvK8ooffogP0InOV-SsmoqOcjn6IgRSRvJ6mP0o4vTvC4uYe2ts3hOcXE-YBe2PjiXfNjiJZbrTgfj8LK7PWmKVV5070e_7HEccPe9O4cKX3A87nO83k8Om2I8ul8v0LNBj9md3MUN-nb68aL7XJ19_fSl-3BWmRpgqUDoobaO2cHoHrSwrAXTCmuHZhANNL01PQdrNdEGNB9q0fRCNv0gCTfGtmyD3h9857WfnDUuLEmPak5-0mmvovbq8UvwO7WNV6rhHAgRxeDNnUGKP1eXFzX5bNw46uDimhWlhLSCQdkb9Pof6WVcUyjjKQpSipZyyYqKHlQmxZyTG-4_A0TdMFQHhqowVLcMFS1Frx6OcV_yh1gRsIMgzzdwXPrb-z-2vwHm8KlH</recordid><startdate>20190329</startdate><enddate>20190329</enddate><creator>Wang, Yang</creator><creator>Park, Jae-Hyun</creator><creator>Lupala, Cecylia Severin</creator><creator>Yun, Ji-Hye</creator><creator>Jin, Zeyu</creator><creator>Huang, Lanqing</creator><creator>Li, Xuanxuan</creator><creator>Tang, Leihan</creator><creator>Lee, Weontae</creator><creator>Liu, Haiguang</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</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>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7324-6632</orcidid><orcidid>https://orcid.org/0000-0002-5504-9800</orcidid></search><sort><creationdate>20190329</creationdate><title>Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex</title><author>Wang, Yang ; Park, Jae-Hyun ; Lupala, Cecylia Severin ; Yun, Ji-Hye ; Jin, Zeyu ; Huang, Lanqing ; Li, Xuanxuan ; Tang, Leihan ; Lee, Weontae ; Liu, Haiguang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-18af5de3dfcab1a8d371c78ddf6f8616bdcb41dda0ac1a4f586b896bf904ccd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>119/118</topic><topic>45/70</topic><topic>631/535/1267</topic><topic>631/57/2266</topic><topic>Amino Acid Sequence</topic><topic>Binding Sites</topic><topic>Chemokines</topic><topic>Computer applications</topic><topic>Crystallization</topic><topic>Crystallography</topic><topic>Crystals</topic><topic>G protein-coupled receptors</topic><topic>Homology</topic><topic>Humanities and Social Sciences</topic><topic>Inflammation</topic><topic>Interleukin 8</topic><topic>Lysozyme</topic><topic>Molecular Docking Simulation</topic><topic>Molecular Dynamics Simulation</topic><topic>multidisciplinary</topic><topic>Muramidase - chemistry</topic><topic>Muramidase - genetics</topic><topic>Muramidase - metabolism</topic><topic>Mutation</topic><topic>Protein Binding</topic><topic>Protein Engineering</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Protein Stability</topic><topic>Proteins</topic><topic>Receptors, Interleukin-8A - chemistry</topic><topic>Receptors, Interleukin-8A - genetics</topic><topic>Receptors, Interleukin-8A - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Structure-Activity Relationship</topic><topic>Thermal stability</topic><topic>Thermodynamics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Park, Jae-Hyun</creatorcontrib><creatorcontrib>Lupala, Cecylia Severin</creatorcontrib><creatorcontrib>Yun, Ji-Hye</creatorcontrib><creatorcontrib>Jin, Zeyu</creatorcontrib><creatorcontrib>Huang, Lanqing</creatorcontrib><creatorcontrib>Li, Xuanxuan</creatorcontrib><creatorcontrib>Tang, Leihan</creatorcontrib><creatorcontrib>Lee, Weontae</creatorcontrib><creatorcontrib>Liu, Haiguang</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</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>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 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>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yang</au><au>Park, Jae-Hyun</au><au>Lupala, Cecylia Severin</au><au>Yun, Ji-Hye</au><au>Jin, Zeyu</au><au>Huang, Lanqing</au><au>Li, Xuanxuan</au><au>Tang, Leihan</au><au>Lee, Weontae</au><au>Liu, Haiguang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-03-29</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>5317</spage><epage>11</epage><pages>5317-11</pages><artnum>5317</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>CXCR1, a member in G-protein coupled receptor (GPCR) family, binds to chemokine interleukin-8 (IL-8) specifically and transduces signals to mediate immune and inflammatory responses. Despite the importance of CXCR1, high-resolution structure determination is hindered by the challenges in crystallization. It has been shown that properly designed mutants with enhanced thermostability, together with fusion partner proteins, can be useful to form crystals for GPCR proteins. In this study,
in silico
protein design was carried out by using homology modeling and molecular dynamics simulations. To validate the computational modeling results, the thermostability of several mutants and the wild type were measured experimentally. Both computational results and experimental data suggest that the mutant L126W has a significant improvement in the thermostability. This study demonstrated that
in silico
design can guide protein engineering and potentially facilitate protein crystallography research.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30926935</pmid><doi>10.1038/s41598-019-41838-2</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7324-6632</orcidid><orcidid>https://orcid.org/0000-0002-5504-9800</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 119/118 45/70 631/535/1267 631/57/2266 Amino Acid Sequence Binding Sites Chemokines Computer applications Crystallization Crystallography Crystals G protein-coupled receptors Homology Humanities and Social Sciences Inflammation Interleukin 8 Lysozyme Molecular Docking Simulation Molecular Dynamics Simulation multidisciplinary Muramidase - chemistry Muramidase - genetics Muramidase - metabolism Mutation Protein Binding Protein Engineering Protein Interaction Domains and Motifs Protein Stability Proteins Receptors, Interleukin-8A - chemistry Receptors, Interleukin-8A - genetics Receptors, Interleukin-8A - metabolism Science Science (multidisciplinary) Structure-Activity Relationship Thermal stability Thermodynamics |
| title | Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex |
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