RXam2, a NLR from cassava (Manihot esculenta) contributes partially to the quantitative resistance to Xanthomonas phaseoli pv. manihotis

Key message The overexpression of RXam2, a cassava NLR (nucleotide-binding leucine-rich repeat) gene, by stable transformation and gene expression induction mediated by dTALEs, reduce cassava bacterial blight symptoms. Cassava ( Manihot esculenta ) is a tropical root crop affected by different patho...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Plant molecular biology 2022-06, Vol.109 (3), p.313-324
Hauptverfasser: Díaz-Tatis, Paula A., Ochoa, Juan C., Rico, Edgar M., Rodríguez, Catalina, Medina, Adriana, Szurek, Boris, Chavarriaga, Paul, López, Camilo E.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 324
container_issue 3
container_start_page 313
container_title Plant molecular biology
container_volume 109
creator Díaz-Tatis, Paula A.
Ochoa, Juan C.
Rico, Edgar M.
Rodríguez, Catalina
Medina, Adriana
Szurek, Boris
Chavarriaga, Paul
López, Camilo E.
description Key message The overexpression of RXam2, a cassava NLR (nucleotide-binding leucine-rich repeat) gene, by stable transformation and gene expression induction mediated by dTALEs, reduce cassava bacterial blight symptoms. Cassava ( Manihot esculenta ) is a tropical root crop affected by different pathogens including Xanthomonas phaseoli pv. manihotis ( Xpm ), the causal agent of cassava bacterial blight (CBB). Previous studies have reported resistance to CBB as a quantitative and polygenic character. This study sought to validate the functional role of a NLR (nucleotide-binding leucine-rich repeat) associated with a QTL to Xpm strain CIO151 called RXam2. Transgenic cassava plants overexpressing RXam2 were generated and analyzed. Plants overexpressing RXam2 showed a reduction in bacterial growth to Xpm strains CIO151, 232 and 226. In addition, designer TALEs (dTALEs) were developed to specifically bind to the RXam2 promoter region. The Xpm strain transformed with dTALEs allowed the induction of the RXam2 gene expression after inoculation in cassava plants and was associated with a diminution in CBB symptoms. These findings suggest that RXam2 contributes to the understanding of the molecular basis of quantitative disease resistance.
doi_str_mv 10.1007/s11103-021-01211-2
format Article
fullrecord <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2596022466</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A705890958</galeid><sourcerecordid>A705890958</sourcerecordid><originalsourceid>FETCH-LOGICAL-c414t-95f7661cf264c93bb1f1ead3bb3c8ddf9be9b2dd14607ab3ab0ec7ef33717e443</originalsourceid><addsrcrecordid>eNp9kc9u1DAQxiMEokvhBTggS1yKRBaP7cSbY1WVP9ICUgVSb9bEmXRdJfHWdlbqG_DYeEkBiQPywdbM75v55K8oXgJfA-f6XQQALksuoOQgAErxqFhBpWVZcbF5XKw41LpUCsRJ8SzGW86zTNZPixOpdKUraFbFj6trHMVbhuzL9or1wY_MYox4QHb2GSe384lRtPNAU8I3zPopBdfOiSLbY0gOh-GeJc_SjtjdjFNyCZM7EAsUXUw4WTq2r3Nn50c_YdbtMJIfHNsf1mxcdrj4vHjS4xDpxcN9Wnx_f_nt4mO5_frh08X5trQKVCqbqtd1DbYXtbKNbFvogbDLD2k3Xdc3LTWt6DpQNdfYSmw5WU29lBo0KSVPi7Nl7j74u5liMqOLloYBJ_JzNKJqai6EquuMvv4HvfVzmLI7I2otVCOBi0ytF-oGBzJu6n0KaPPpaHT5v6h3uX6uebVpeFNtskAsAht8jIF6sw9uxHBvgJtjsGYJ1uRgza9gzXHLqwcvcztS90fyO8kMyAWIuTXdUPhr9j9jfwJV369c</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2672493102</pqid></control><display><type>article</type><title>RXam2, a NLR from cassava (Manihot esculenta) contributes partially to the quantitative resistance to Xanthomonas phaseoli pv. manihotis</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Díaz-Tatis, Paula A. ; Ochoa, Juan C. ; Rico, Edgar M. ; Rodríguez, Catalina ; Medina, Adriana ; Szurek, Boris ; Chavarriaga, Paul ; López, Camilo E.</creator><creatorcontrib>Díaz-Tatis, Paula A. ; Ochoa, Juan C. ; Rico, Edgar M. ; Rodríguez, Catalina ; Medina, Adriana ; Szurek, Boris ; Chavarriaga, Paul ; López, Camilo E.</creatorcontrib><description>Key message The overexpression of RXam2, a cassava NLR (nucleotide-binding leucine-rich repeat) gene, by stable transformation and gene expression induction mediated by dTALEs, reduce cassava bacterial blight symptoms. Cassava ( Manihot esculenta ) is a tropical root crop affected by different pathogens including Xanthomonas phaseoli pv. manihotis ( Xpm ), the causal agent of cassava bacterial blight (CBB). Previous studies have reported resistance to CBB as a quantitative and polygenic character. This study sought to validate the functional role of a NLR (nucleotide-binding leucine-rich repeat) associated with a QTL to Xpm strain CIO151 called RXam2. Transgenic cassava plants overexpressing RXam2 were generated and analyzed. Plants overexpressing RXam2 showed a reduction in bacterial growth to Xpm strains CIO151, 232 and 226. In addition, designer TALEs (dTALEs) were developed to specifically bind to the RXam2 promoter region. The Xpm strain transformed with dTALEs allowed the induction of the RXam2 gene expression after inoculation in cassava plants and was associated with a diminution in CBB symptoms. These findings suggest that RXam2 contributes to the understanding of the molecular basis of quantitative disease resistance.</description><identifier>ISSN: 0167-4412</identifier><identifier>EISSN: 1573-5028</identifier><identifier>DOI: 10.1007/s11103-021-01211-2</identifier><identifier>PMID: 34757519</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Analysis ; Bacteria ; Biochemistry ; Biomedical and Life Sciences ; Blight ; Cassava ; Cassava Molecular Biology ; Disease resistance ; Gene expression ; Genes ; Genetic engineering ; Genetic transformation ; Inoculation ; Leucine ; Life Sciences ; Manihot - genetics ; Manihot esculenta ; Nucleotides ; Plant Diseases - microbiology ; Plant Pathology ; Plant Sciences ; Polygenic inheritance ; Quantitative genetics ; Quantitative trait loci ; Transgenic plants ; Xanthomonas ; Xanthomonas phaseoli</subject><ispartof>Plant molecular biology, 2022-06, Vol.109 (3), p.313-324</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature B.V.</rights><rights>COPYRIGHT 2022 Springer</rights><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-95f7661cf264c93bb1f1ead3bb3c8ddf9be9b2dd14607ab3ab0ec7ef33717e443</citedby><cites>FETCH-LOGICAL-c414t-95f7661cf264c93bb1f1ead3bb3c8ddf9be9b2dd14607ab3ab0ec7ef33717e443</cites><orcidid>0000-0003-4592-8614</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11103-021-01211-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11103-021-01211-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34757519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Díaz-Tatis, Paula A.</creatorcontrib><creatorcontrib>Ochoa, Juan C.</creatorcontrib><creatorcontrib>Rico, Edgar M.</creatorcontrib><creatorcontrib>Rodríguez, Catalina</creatorcontrib><creatorcontrib>Medina, Adriana</creatorcontrib><creatorcontrib>Szurek, Boris</creatorcontrib><creatorcontrib>Chavarriaga, Paul</creatorcontrib><creatorcontrib>López, Camilo E.</creatorcontrib><title>RXam2, a NLR from cassava (Manihot esculenta) contributes partially to the quantitative resistance to Xanthomonas phaseoli pv. manihotis</title><title>Plant molecular biology</title><addtitle>Plant Mol Biol</addtitle><addtitle>Plant Mol Biol</addtitle><description>Key message The overexpression of RXam2, a cassava NLR (nucleotide-binding leucine-rich repeat) gene, by stable transformation and gene expression induction mediated by dTALEs, reduce cassava bacterial blight symptoms. Cassava ( Manihot esculenta ) is a tropical root crop affected by different pathogens including Xanthomonas phaseoli pv. manihotis ( Xpm ), the causal agent of cassava bacterial blight (CBB). Previous studies have reported resistance to CBB as a quantitative and polygenic character. This study sought to validate the functional role of a NLR (nucleotide-binding leucine-rich repeat) associated with a QTL to Xpm strain CIO151 called RXam2. Transgenic cassava plants overexpressing RXam2 were generated and analyzed. Plants overexpressing RXam2 showed a reduction in bacterial growth to Xpm strains CIO151, 232 and 226. In addition, designer TALEs (dTALEs) were developed to specifically bind to the RXam2 promoter region. The Xpm strain transformed with dTALEs allowed the induction of the RXam2 gene expression after inoculation in cassava plants and was associated with a diminution in CBB symptoms. These findings suggest that RXam2 contributes to the understanding of the molecular basis of quantitative disease resistance.</description><subject>Analysis</subject><subject>Bacteria</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Blight</subject><subject>Cassava</subject><subject>Cassava Molecular Biology</subject><subject>Disease resistance</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic engineering</subject><subject>Genetic transformation</subject><subject>Inoculation</subject><subject>Leucine</subject><subject>Life Sciences</subject><subject>Manihot - genetics</subject><subject>Manihot esculenta</subject><subject>Nucleotides</subject><subject>Plant Diseases - microbiology</subject><subject>Plant Pathology</subject><subject>Plant Sciences</subject><subject>Polygenic inheritance</subject><subject>Quantitative genetics</subject><subject>Quantitative trait loci</subject><subject>Transgenic plants</subject><subject>Xanthomonas</subject><subject>Xanthomonas phaseoli</subject><issn>0167-4412</issn><issn>1573-5028</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc9u1DAQxiMEokvhBTggS1yKRBaP7cSbY1WVP9ICUgVSb9bEmXRdJfHWdlbqG_DYeEkBiQPywdbM75v55K8oXgJfA-f6XQQALksuoOQgAErxqFhBpWVZcbF5XKw41LpUCsRJ8SzGW86zTNZPixOpdKUraFbFj6trHMVbhuzL9or1wY_MYox4QHb2GSe384lRtPNAU8I3zPopBdfOiSLbY0gOh-GeJc_SjtjdjFNyCZM7EAsUXUw4WTq2r3Nn50c_YdbtMJIfHNsf1mxcdrj4vHjS4xDpxcN9Wnx_f_nt4mO5_frh08X5trQKVCqbqtd1DbYXtbKNbFvogbDLD2k3Xdc3LTWt6DpQNdfYSmw5WU29lBo0KSVPi7Nl7j74u5liMqOLloYBJ_JzNKJqai6EquuMvv4HvfVzmLI7I2otVCOBi0ytF-oGBzJu6n0KaPPpaHT5v6h3uX6uebVpeFNtskAsAht8jIF6sw9uxHBvgJtjsGYJ1uRgza9gzXHLqwcvcztS90fyO8kMyAWIuTXdUPhr9j9jfwJV369c</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Díaz-Tatis, Paula A.</creator><creator>Ochoa, Juan C.</creator><creator>Rico, Edgar M.</creator><creator>Rodríguez, Catalina</creator><creator>Medina, Adriana</creator><creator>Szurek, Boris</creator><creator>Chavarriaga, Paul</creator><creator>López, Camilo E.</creator><general>Springer Netherlands</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7TM</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>8G5</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>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4592-8614</orcidid></search><sort><creationdate>20220601</creationdate><title>RXam2, a NLR from cassava (Manihot esculenta) contributes partially to the quantitative resistance to Xanthomonas phaseoli pv. manihotis</title><author>Díaz-Tatis, Paula A. ; Ochoa, Juan C. ; Rico, Edgar M. ; Rodríguez, Catalina ; Medina, Adriana ; Szurek, Boris ; Chavarriaga, Paul ; López, Camilo E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-95f7661cf264c93bb1f1ead3bb3c8ddf9be9b2dd14607ab3ab0ec7ef33717e443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Bacteria</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Blight</topic><topic>Cassava</topic><topic>Cassava Molecular Biology</topic><topic>Disease resistance</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic engineering</topic><topic>Genetic transformation</topic><topic>Inoculation</topic><topic>Leucine</topic><topic>Life Sciences</topic><topic>Manihot - genetics</topic><topic>Manihot esculenta</topic><topic>Nucleotides</topic><topic>Plant Diseases - microbiology</topic><topic>Plant Pathology</topic><topic>Plant Sciences</topic><topic>Polygenic inheritance</topic><topic>Quantitative genetics</topic><topic>Quantitative trait loci</topic><topic>Transgenic plants</topic><topic>Xanthomonas</topic><topic>Xanthomonas phaseoli</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Díaz-Tatis, Paula A.</creatorcontrib><creatorcontrib>Ochoa, Juan C.</creatorcontrib><creatorcontrib>Rico, Edgar M.</creatorcontrib><creatorcontrib>Rodríguez, Catalina</creatorcontrib><creatorcontrib>Medina, Adriana</creatorcontrib><creatorcontrib>Szurek, Boris</creatorcontrib><creatorcontrib>Chavarriaga, Paul</creatorcontrib><creatorcontrib>López, Camilo E.</creatorcontrib><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>Nucleic Acids Abstracts</collection><collection>Health &amp; 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>Research Library (Alumni Edition)</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>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Plant molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Díaz-Tatis, Paula A.</au><au>Ochoa, Juan C.</au><au>Rico, Edgar M.</au><au>Rodríguez, Catalina</au><au>Medina, Adriana</au><au>Szurek, Boris</au><au>Chavarriaga, Paul</au><au>López, Camilo E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RXam2, a NLR from cassava (Manihot esculenta) contributes partially to the quantitative resistance to Xanthomonas phaseoli pv. manihotis</atitle><jtitle>Plant molecular biology</jtitle><stitle>Plant Mol Biol</stitle><addtitle>Plant Mol Biol</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>109</volume><issue>3</issue><spage>313</spage><epage>324</epage><pages>313-324</pages><issn>0167-4412</issn><eissn>1573-5028</eissn><abstract>Key message The overexpression of RXam2, a cassava NLR (nucleotide-binding leucine-rich repeat) gene, by stable transformation and gene expression induction mediated by dTALEs, reduce cassava bacterial blight symptoms. Cassava ( Manihot esculenta ) is a tropical root crop affected by different pathogens including Xanthomonas phaseoli pv. manihotis ( Xpm ), the causal agent of cassava bacterial blight (CBB). Previous studies have reported resistance to CBB as a quantitative and polygenic character. This study sought to validate the functional role of a NLR (nucleotide-binding leucine-rich repeat) associated with a QTL to Xpm strain CIO151 called RXam2. Transgenic cassava plants overexpressing RXam2 were generated and analyzed. Plants overexpressing RXam2 showed a reduction in bacterial growth to Xpm strains CIO151, 232 and 226. In addition, designer TALEs (dTALEs) were developed to specifically bind to the RXam2 promoter region. The Xpm strain transformed with dTALEs allowed the induction of the RXam2 gene expression after inoculation in cassava plants and was associated with a diminution in CBB symptoms. These findings suggest that RXam2 contributes to the understanding of the molecular basis of quantitative disease resistance.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>34757519</pmid><doi>10.1007/s11103-021-01211-2</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4592-8614</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 0167-4412
ispartof Plant molecular biology, 2022-06, Vol.109 (3), p.313-324
issn 0167-4412
1573-5028
language eng
recordid cdi_proquest_miscellaneous_2596022466
source MEDLINE; SpringerNature Journals
subjects Analysis
Bacteria
Biochemistry
Biomedical and Life Sciences
Blight
Cassava
Cassava Molecular Biology
Disease resistance
Gene expression
Genes
Genetic engineering
Genetic transformation
Inoculation
Leucine
Life Sciences
Manihot - genetics
Manihot esculenta
Nucleotides
Plant Diseases - microbiology
Plant Pathology
Plant Sciences
Polygenic inheritance
Quantitative genetics
Quantitative trait loci
Transgenic plants
Xanthomonas
Xanthomonas phaseoli
title RXam2, a NLR from cassava (Manihot esculenta) contributes partially to the quantitative resistance to Xanthomonas phaseoli pv. manihotis
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T09%3A44%3A03IST&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=RXam2,%20a%20NLR%20from%20cassava%20(Manihot%20esculenta)%20contributes%20partially%20to%20the%20quantitative%20resistance%20to%20Xanthomonas%20phaseoli%20pv.%20manihotis&rft.jtitle=Plant%20molecular%20biology&rft.au=D%C3%ADaz-Tatis,%20Paula%20A.&rft.date=2022-06-01&rft.volume=109&rft.issue=3&rft.spage=313&rft.epage=324&rft.pages=313-324&rft.issn=0167-4412&rft.eissn=1573-5028&rft_id=info:doi/10.1007/s11103-021-01211-2&rft_dat=%3Cgale_proqu%3EA705890958%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=2672493102&rft_id=info:pmid/34757519&rft_galeid=A705890958&rfr_iscdi=true