{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:53:39Z","timestamp":1790380419573,"version":"4.1.0"},"reference-count":52,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI125929"],"award-info":[{"award-number":["R21AI125929"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103638"],"award-info":[{"award-number":["P20GM103638"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 630, project B9"],"award-info":[{"award-number":["SFB 630, project B9"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SPP1580"],"award-info":[{"award-number":["SPP1580"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Obligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of this domain revealed high similarity to mammalian deubiquitinases with a unique \u03b1-helix close to the substrate-binding pocket. We identified the apoptosis regulator Mcl-1 as a target that interacts with Cdu1 and is stabilized by deubiquitination at the chlamydial inclusion. A chlamydial transposon insertion mutant in the Cdu1-encoding gene exhibited increased Mcl-1 and inclusion ubiquitination and reduced Mcl-1 stabilization. Additionally, inactivation of Cdu1 led to increased sensitivity of C. trachomatis for IFN\u03b3 and impaired infection in mice. Thus, the chlamydial inclusion serves as an enriched site for a deubiquitinating activity exerting a function in selective stabilization of host proteins and protection from host defense.<\/jats:p>","DOI":"10.7554\/elife.21465","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T20:05:32Z","timestamp":1490645132000},"source":"Crossref","is-referenced-by-count":72,"title":["Chlamydia trachomatis-containing vacuole serves as deubiquitination platform to stabilize Mcl-1 and to interfere with host defense"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3979-9396","authenticated-orcid":true,"given":"Annette","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biocenter, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly S","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesid","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Rudolf Virchow Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Auer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biocenter, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvagata Roy","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biocenter, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7051-4670","authenticated-orcid":true,"given":"Bhupesh K","family":"Prusty","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biocenter, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Sauer","sequence":"additional","affiliation":[{"name":"Rudolf Virchow Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Dimond","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kisker","sequence":"additional","affiliation":[{"name":"Rudolf Virchow Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Scott","family":"Hefty","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4740-6991","authenticated-orcid":true,"given":"Thomas","family":"Rudel","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biocenter, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2017,3,28]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"6192","DOI":"10.1074\/jbc.M610643200","article-title":"Rapid turnover of mcl-1 couples translation to cell survival and apoptosis","volume":"282","author":"Adams","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallographica Section D Biological Crystallography"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.cell.2005.08.016","article-title":"The ubiquitin ligase HectH9 regulates transcriptional activation by myc and is essential for tumor cell proliferation","volume":"123","author":"Adhikary","year":"2005","journal-title":"Cell"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1046\/j.1462-5822.1999.00024.x","article-title":"Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells","volume":"1","author":"Al-Younes","year":"1999","journal-title":"Cellular Microbiology"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1093\/nar\/gkp1032","article-title":"Deep sequencing-based discovery of the Chlamydia trachomatis transcriptome","volume":"38","author":"Albrecht","year":"2010","journal-title":"Nucleic Acids Research"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","volume":"224","author":"Bolte","year":"2006","journal-title":"Journal of Microscopy"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1111\/j.1462-5822.2010.01473.x","article-title":"Chlamydia trachomatis-infected host cells resist dsRNA-induced apoptosis","volume":"12","author":"B\u00f6hme","year":"2010","journal-title":"Cellular Microbiology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"The CCP4 suite: programs for protein crystallography","volume":"50","author":"Collaborative Computational Project","year":"1994","journal-title":"Acta Crystallographica. Section D, Biological Crystallography"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"4006","DOI":"10.1128\/MCB.00620-06","article-title":"Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization","volume":"27","author":"Ding","year":"2007","journal-title":"Molecular and Cellular Biology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.bbadis.2008.08.010","article-title":"Ubiquitin and ubiquitin-like specific proteases targeted by infectious pathogens: emerging patterns and molecular principles","volume":"1782","author":"Edelmann","year":"2008","journal-title":"Biochimica Et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nrmicro.2016.30","article-title":"Chlamydia cell biology and pathogenesis","volume":"14","author":"Elwell","year":"2016","journal-title":"Nature Reviews Microbiology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1111\/cmi.12171","article-title":"The chlamydial OTU domain-containing protein ChlaOTU is an early type III secretion effector targeting ubiquitin and NDP52","volume":"15","author":"Furtado","year":"2013","journal-title":"Cellular Microbiology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.4049\/jimmunol.1103032","article-title":"CD4+ T cells are necessary and sufficient to confer protection against Chlamydia trachomatis infection in the murine upper genital tract","volume":"189","author":"Gondek","year":"2012","journal-title":"The Journal of Immunology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"435","DOI":"10.5483\/bmbrep.2008.41.6.435","article-title":"Structures of proteases for ubiqutin and ubiquitin-like modifiers","volume":"41","author":"Ha","year":"2008","journal-title":"BMB Reports"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"8604","DOI":"10.1021\/ac202028g","article-title":"High-throughput droplet digital PCR system for absolute quantitation of DNA copy number","volume":"83","author":"Hindson","year":"2011","journal-title":"Analytical Chemistry"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1006\/jmbi.1993.1489","article-title":"Protein structure comparison by alignment of distance matrices","volume":"233","author":"Holm","year":"1993","journal-title":"Journal of Molecular Biology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nature09732","article-title":"SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction","volume":"471","author":"Inuzuka","year":"2011","journal-title":"Nature"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1107\/S0567739476001873","article-title":"A solution for the best rotation to relate two sets of vectors","volume":"32","author":"Kabsch","year":"1976","journal-title":"Acta Crystallographica Section A"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","article-title":"XDS","volume":"66","author":"Kabsch","year":"2010","journal-title":"Acta Crystallographica. Section D, Biological Crystallography"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1093\/bioinformatics\/bts199","article-title":"Geneious basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data","volume":"28","author":"Kearse","year":"2012","journal-title":"Bioinformatics"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1038\/ncb1499","article-title":"Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies","volume":"8","author":"Kim","year":"2006","journal-title":"Nature Cell Biology"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1111\/j.1462-5822.2008.01178.x","article-title":"ChlaDub1 of Chlamydia trachomatis suppresses NF-kappaB activation and inhibits IkappaBalpha ubiquitination and degradation","volume":"10","author":"Le Negrate","year":"2008","journal-title":"Cellular Microbiology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/18457","article-title":"A new protease required for cell-cycle progression in yeast","volume":"398","author":"Li","year":"1999","journal-title":"Nature"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nmeth1010","article-title":"Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC","volume":"4","author":"Li","year":"2007","journal-title":"Nature Methods"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/j.1365-2958.2006.05199.x","article-title":"Chlamydia trachomatis-derived deubiquitinating enzymes in mammalian cells during infection","volume":"61","author":"Misaghi","year":"2006","journal-title":"Molecular Microbiology"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"418","DOI":"10.3390\/cells3020418","article-title":"Mcl-1 ubiquitination: unique regulation of an essential survival protein","volume":"3","author":"Mojsa","year":"2014","journal-title":"Cells"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"3845","DOI":"10.1128\/MCB.00279-09","article-title":"Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis","volume":"29","author":"Morel","year":"2009","journal-title":"Molecular and Cellular Biology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/S1097-2765(00)80326-3","article-title":"Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast","volume":"5","author":"Mossessova","year":"2000","journal-title":"Molecular Cell"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.cell.2005.11.007","article-title":"A genomic and functional inventory of deubiquitinating enzymes","volume":"123","author":"Nijman","year":"2005","journal-title":"Cell"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.molcel.2016.06.015","article-title":"The molecular basis for ubiquitin and Ubiquitin-like specificities in bacterial effector proteases","volume":"63","author":"Pruneda","year":"2016","journal-title":"Molecular Cell"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"e3102","DOI":"10.1371\/journal.pone.0003102","article-title":"Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells","volume":"3","author":"Rajalingam","year":"2008","journal-title":"PLoS One"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jmb.2004.10.022","article-title":"Structure of a complex between Nedd8 and the ulp\/Senp protease family member Den1","volume":"345","author":"Reverter","year":"2005","journal-title":"Journal of Molecular Biology"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.1016\/j.febslet.2010.05.012","article-title":"Post-translational modifications in host cells during bacterial infection","volume":"584","author":"Ribet","year":"2010","journal-title":"FEBS Letters"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1128\/JCM.00622-13","article-title":"Development and evaluation of a next-generation digital PCR diagnostic assay for ocular Chlamydia trachomatis infections","volume":"51","author":"Roberts","year":"2013","journal-title":"Journal of Clinical Microbiology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1128\/IAI.05619-11","article-title":"Persistent Chlamydia trachomatis infection of HeLa cells mediates apoptosis resistance through a Chlamydia protease-like activity factor-independent mechanism and induces high mobility group box 1 release","volume":"80","author":"R\u00f6del","year":"2012","journal-title":"Infection and Immunity"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nature Methods"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1186\/1471-2105-11-274","article-title":"A high-level 3D visualization API for Java and ImageJ","volume":"11","author":"Schmid","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/nature08646","article-title":"Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival","volume":"463","author":"Schwickart","year":"2010","journal-title":"Nature"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/j.1574-695X.2008.00515.x","article-title":"Apoptosis resistance in Chlamydia-infected cells: a fate worse than death?","volume":"55","author":"Sharma","year":"2009","journal-title":"FEMS Immunology & Medical Microbiology"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1111\/j.1462-5822.2011.01642.x","article-title":"HIF-1\u03b1 is involved in mediating apoptosis resistance to Chlamydia trachomatis-infected cells","volume":"13","author":"Sharma","year":"2011","journal-title":"Cellular Microbiology"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1038\/ncomms3777","article-title":"Automatic protein structure solution from weak X-ray data","volume":"4","author":"Skub\u00e1k","year":"2013","journal-title":"Nature Communications"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"e1004846","DOI":"10.1371\/journal.ppat.1004846","article-title":"EphrinA2 receptor (EphA2) is an invasion and intracellular signaling receptor for Chlamydia trachomatis","volume":"11","author":"Subbarayal","year":"2015","journal-title":"PLOS Pathogens"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1111\/j.1365-2958.2005.04647.x","article-title":"A directed screen for chlamydial proteins secreted by a type III mechanism identifies a translocated protein and numerous other new candidates","volume":"56","author":"Subtil","year":"2005","journal-title":"Molecular Microbiology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1016\/j.febslet.2010.05.061","article-title":"Mcl-1; the molecular regulation of protein function","volume":"584","author":"Thomas","year":"2010","journal-title":"FEBS Letters"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/S0092-8674(94)90502-9","article-title":"Ubiquitin-dependent c-Jun degradation in vivo is mediated by the Delta domain","volume":"78","author":"Treier","year":"1994","journal-title":"Cell"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.mib.2008.01.003","article-title":"Chlamydia effector proteins and new insights into chlamydial cellular microbiology","volume":"11","author":"Valdivia","year":"2008","journal-title":"Current Opinion in Microbiology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/nrm3143","article-title":"Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death","volume":"12","author":"Vucic","year":"2011","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"e1002258","DOI":"10.1371\/journal.ppat.1002258","article-title":"Development of a transformation system for Chlamydia trachomatis: restoration of glycogen biosynthesis by acquisition of a plasmid shuttle vector","volume":"7","author":"Wang","year":"2011","journal-title":"PLoS Pathogens"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1038\/cdd.2014.42","article-title":"Role of Ku70 in deubiquitination of Mcl-1 and suppression of apoptosis","volume":"21","author":"Wang","year":"2014","journal-title":"Cell Death and Differentiation"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0378-1119(00)00139-6","article-title":"Ubiquitin-like proteins: new wines in new bottles","volume":"248","author":"Yeh","year":"2000","journal-title":"Gene"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1182\/blood.V99.6.1885","article-title":"Myeloid cell factor-1 is a critical survival factor for multiple myeloma","volume":"99","author":"Zhang","year":"2002","journal-title":"Blood"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/j.cell.2005.06.009","article-title":"Mule\/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis","volume":"121","author":"Zhong","year":"2005","journal-title":"Cell"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/21465\/elife-21465-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/21465\/elife-21465-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/21465","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:47:57Z","timestamp":1697057277000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/21465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,28]]},"references-count":52,"alternative-id":["10.7554\/eLife.21465"],"URL":"https:\/\/doi.org\/10.7554\/elife.21465","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.21465.039","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.21465.038","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,28]]},"article-number":"e21465"}}