{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:21:50Z","timestamp":1776954110331,"version":"3.51.4"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000881","name":"Lowe Syndrome Trust","doi-asserted-by":"publisher","award":["ML\/MU\/DEC07"],"award-info":[{"award-number":["ML\/MU\/DEC07"]}],"id":[{"id":"10.13039\/501100000881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000881","name":"Lowe Syndrome Trust","doi-asserted-by":"publisher","award":["NoMU\/ML\/1010"],"award-info":[{"award-number":["NoMU\/ML\/1010"]}],"id":[{"id":"10.13039\/501100000881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000881","name":"Lowe Syndrome Trust","doi-asserted-by":"publisher","award":["ML\/MU\/2012"],"award-info":[{"award-number":["ML\/MU\/2012"]}],"id":[{"id":"10.13039\/501100000881","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Endocytosis is a fundamentally important process through which material is internalized into cells from the extracellular environment. In the renal proximal tubule, endocytosis of the abundant scavenger receptor megalin and its co-receptor cubilin play a vital role in retrieving low molecular weight proteins from the renal filtrate. Although we know much about megalin and its ligands, the machinery and mechanisms by which the receptor is trafficked through the endosomal system remain poorly defined. In this study, we show that inositol phosphatase interacting protein of 27 kDa (Ipip27A), an interacting partner of the Lowe syndrome protein oculocerebrorenal syndrome of Lowe (OCRL), is required for endocytic traffic of megalin within the proximal renal tubule of zebrafish larvae. Knockout of Ipip27A phenocopies the endocytic phenotype seen upon loss of OCRL, with a deficit in uptake of both fluid-phase and protein cargo, which is accompanied by a reduction in megalin abundance and altered endosome morphology. Rescue and co-depletion experiments indicate that Ipip27A functions together with OCRL to support proximal tubule endocytosis. The results therefore identify Ipip27A as a new player in endocytic traffic in the proximal tubule in vivo and support the view that defective endocytosis underlies the renal tubulopathy in Lowe syndrome and Dent-2 disease.<\/jats:p>","DOI":"10.1093\/hmg\/ddab307","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T13:41:52Z","timestamp":1634650912000},"page":"1183-1196","source":"Crossref","is-referenced-by-count":5,"title":["IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule"],"prefix":"10.1093","volume":"31","author":[{"given":"Francesca","family":"Oltrabella","sequence":"first","affiliation":[{"name":"Medical Scientific Liaison-Nephrology, Astellas Pharma, Via Dante, Milano 20123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Jackson-Crawford","sequence":"additional","affiliation":[{"name":"Department of Blood Sciences, Grange University Hospital, Llanyravon, Gwent NP44 8YN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanhua","family":"Yan","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Rixham","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Starborg","sequence":"additional","affiliation":[{"name":"Rosalind Franklin Institute, Harwell Campus, Didcot OX11 0FA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9331-8143","authenticated-orcid":false,"given":"Martin","family":"Lowe","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"2022042214132451400_ref1","first-page":"223","article-title":"Endocytic receptors in the renal proximal tubule","volume":"27","author":"Christensen","year":"2012","journal-title":"Physiology (Bethesda)"},{"key":"2022042214132451400_ref2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-physiol-022516-034234","article-title":"Receptor-mediated endocytosis in the proximal tubule","volume":"79","author":"Eshbach","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"2022042214132451400_ref3","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/S0002-9440(10)65238-8","article-title":"Megalin knockout mice as an animal model of low molecular weight proteinuria","volume":"155","author":"Leheste","year":"1999","journal-title":"Am. J. Pathol."},{"key":"2022042214132451400_ref4","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1002\/dvdy.22624","article-title":"Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development","volume":"240","author":"Kur","year":"2011","journal-title":"Dev. Dyn."},{"key":"2022042214132451400_ref5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.kint.2015.11.007","article-title":"Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease","volume":"89","author":"Nielsen","year":"2016","journal-title":"Kidney Int."},{"key":"2022042214132451400_ref6","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/ng2063","article-title":"Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes","volume":"39","author":"Kantarci","year":"2007","journal-title":"Nat. Genet."},{"issue":"Pt 3","key":"2022042214132451400_ref7","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1042\/bj3470613","article-title":"Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600\/megalin","volume":"347","author":"Oleinikov","year":"2000","journal-title":"Biochem. J."},{"key":"2022042214132451400_ref8","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1073\/pnas.0813002106","article-title":"Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct","volume":"106","author":"Yu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022042214132451400_ref9","first-page":"6257","volume-title":"Metabolic and Molecular Basis of Inherited Diseases","author":"Nussbaum","year":"2001"},{"key":"2022042214132451400_ref10","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.2215\/CJN.00520108","article-title":"Renal phenotype in Lowe syndrome: a selective proximal tubular dysfunction","volume":"3","author":"Bockenhauer","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"2022042214132451400_ref11","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jpeds.2009.01.049","article-title":"Dent-2 disease: a mild variant of Lowe syndrome","volume":"155","author":"Bokenkamp","year":"2009","journal-title":"J. Pediatr."},{"key":"2022042214132451400_ref12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/358239a0","article-title":"The Lowe\u2019s oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase","volume":"358","author":"Attree","year":"1992","journal-title":"Nature"},{"key":"2022042214132451400_ref13","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1086\/427887","article-title":"Dent disease with mutations in OCRL1","volume":"76","author":"Hoopes","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"2022042214132451400_ref14","doi-asserted-by":"crossref","first-page":"3467","DOI":"10.1091\/mbc.e05-02-0120","article-title":"Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network","volume":"16","author":"Choudhury","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"2022042214132451400_ref15","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.devcel.2007.08.004","article-title":"A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway","volume":"13","author":"Erdmann","year":"2007","journal-title":"Dev. Cell"},{"key":"2022042214132451400_ref16","doi-asserted-by":"crossref","first-page":"F335","DOI":"10.1152\/ajprenal.00453.2009","article-title":"OCRL1 function in renal epithelial membrane traffic","volume":"298","author":"Cui","year":"2010","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"2022042214132451400_ref17","doi-asserted-by":"crossref","first-page":"4970","DOI":"10.1038\/emboj.2011.354","article-title":"OCRL controls trafficking through early endosomes via PtdIns4,5P(2)-dependent regulation of endosomal actin","volume":"30","author":"Vicinanza","year":"2011","journal-title":"EMBO J."},{"key":"2022042214132451400_ref18","doi-asserted-by":"crossref","first-page":"5019","DOI":"10.1093\/hmg\/dds343","article-title":"The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module","volume":"21","author":"Rahden","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132451400_ref19","doi-asserted-by":"crossref","first-page":"e02975","DOI":"10.7554\/eLife.02975","article-title":"A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells","volume":"3","author":"Nandez","year":"2014","journal-title":"elife"},{"key":"2022042214132451400_ref20","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1093\/hmg\/ddy449","article-title":"OCRL deficiency impairs endolysosomal function in a humanized mouse model for Lowe syndrome and Dent disease","volume":"28","author":"Festa","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132451400_ref21","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/ncb3386","article-title":"Autophagosome-lysosome fusion triggers a lysosomal response mediated by TLR9 and controlled by OCRL","volume":"18","author":"De Leo","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"2022042214132451400_ref22","doi-asserted-by":"crossref","first-page":"e52173","DOI":"10.15252\/embr.202052173","article-title":"OCRL regulates lysosome positioning and mTORC1 activity through SSX2IP-mediated microtubule anchoring","volume":"22","author":"Wang","year":"2021","journal-title":"EMBO Rep."},{"key":"2022042214132451400_ref23","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/ncb2279","article-title":"Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis","volume":"13","author":"Dambournet","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"2022042214132451400_ref24","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4161\/cib.19914","article-title":"The unexpected role of Drosophila OCRL during cytokinesis","volume":"5","author":"Ben El Kadhi","year":"2012","journal-title":"Commun. Integr. Biol."},{"key":"2022042214132451400_ref25","doi-asserted-by":"crossref","first-page":"4478","DOI":"10.1093\/hmg\/ddp407","article-title":"Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase","volume":"18","author":"Coon","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132451400_ref26","doi-asserted-by":"crossref","first-page":"e24044","DOI":"10.1371\/journal.pone.0024044","article-title":"Lowe syndrome protein OCRL1 supports maturation of polarized epithelial cells","volume":"6","author":"Grieve","year":"2011","journal-title":"PLoS One"},{"key":"2022042214132451400_ref27","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1111\/j.1600-0854.2012.01387.x","article-title":"OCRL1 modulates cilia length in renal epithelial cells","volume":"13","author":"Rbaibi","year":"2012","journal-title":"Traffic"},{"key":"2022042214132451400_ref28","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1093\/hmg\/dds163","article-title":"OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome","volume":"21","author":"Luo","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132451400_ref29","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1093\/hmg\/ddr615","article-title":"The Lowe syndrome protein OCRL1 is involved in primary cilia assembly","volume":"21","author":"Coon","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132451400_ref30","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/tra.12160","article-title":"The cellular and physiological functions of the Lowe syndrome protein OCRL1","volume":"15","author":"Mehta","year":"2014","journal-title":"Traffic"},{"key":"2022042214132451400_ref31","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrneph.2017.83","article-title":"The 5-phosphatase OCRL in Lowe syndrome and Dent disease 2","volume":"13","author":"De Matteis","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"2022042214132451400_ref32","doi-asserted-by":"crossref","first-page":"e1005058","DOI":"10.1371\/journal.pgen.1005058","article-title":"The Lowe syndrome protein OCRL1 is required for endocytosis in the zebrafish pronephric tubule","volume":"11","author":"Oltrabella","year":"2015","journal-title":"PLoS Genet."},{"key":"2022042214132451400_ref33","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/ki.2008.37","article-title":"The zebrafish pronephros: a model to study nephron segmentation","volume":"73","author":"Wingert","year":"2008","journal-title":"Kidney Int."},{"key":"2022042214132451400_ref34","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/B978-0-12-384892-5.00009-8","article-title":"Zebrafish kidney development","volume":"100","author":"Drummond","year":"2010","journal-title":"Methods Cell Biol."},{"key":"2022042214132451400_ref35","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1681\/ASN.2016080913","article-title":"Kidney tubular ablation of Ocrl\/Inpp5b phenocopies Lowe syndrome tubulopathy","volume":"28","author":"Inoue","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"2022042214132451400_ref36","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1681\/ASN.2010050565","article-title":"Mouse model for Lowe syndrome\/Dent disease 2 renal tubulopathy","volume":"22","author":"Bothwell","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"2022042214132451400_ref37","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.1073\/pnas.0914658107","article-title":"Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1","volume":"107","author":"Swan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022042214132451400_ref38","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1091\/mbc.e10-08-0730","article-title":"The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway","volume":"22","author":"Noakes","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"2022042214132451400_ref39","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1091\/mbc.E15-06-0329","article-title":"OCRL1 engages with the F-BAR protein pacsin 2 to promote biogenesis of membrane-trafficking intermediates","volume":"27","author":"Billcliff","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"2022042214132451400_ref40","doi-asserted-by":"crossref","first-page":"dmm041913","DOI":"10.1242\/dmm.041913","article-title":"Deficiency in the endocytic adaptor proteins PHETA1\/2 impairs renal and craniofacial development","volume":"13","author":"Ates","year":"2020","journal-title":"Dis. Model. Mech."},{"key":"2022042214132451400_ref41","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cub.2019.01.043","article-title":"IPIP27 coordinates PtdIns(4,5)P2 homeostasis for successful cytokinesis","volume":"29","author":"Carim","year":"2019","journal-title":"Curr. Biol."},{"key":"2022042214132451400_ref42","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/nature03025","article-title":"Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype","volume":"431","author":"Jaillon","year":"2004","journal-title":"Nature"},{"key":"2022042214132451400_ref43","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.gep.2010.10.002","article-title":"Transgenic labeling of the zebrafish pronephric duct and tubules using a promoter from the enpep gene","volume":"11","author":"Seiler","year":"2010","journal-title":"Gene Expr. Patterns"},{"key":"2022042214132451400_ref44","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1038\/emboj.2009.155","article-title":"A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism","volume":"28","author":"Mao","year":"2009","journal-title":"EMBO J."},{"key":"2022042214132451400_ref45","doi-asserted-by":"crossref","first-page":"9965","DOI":"10.1074\/jbc.M807442200","article-title":"Differential clathrin binding and subcellular localization of OCRL1 splice isoforms","volume":"284","author":"Choudhury","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2022042214132451400_ref46","doi-asserted-by":"crossref","first-page":"e1000604","DOI":"10.1371\/journal.pbio.1000604","article-title":"A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis","volume":"9","author":"Taylor","year":"2011","journal-title":"PLoS Biol."},{"key":"2022042214132451400_ref47","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1126\/science.aar2131","article-title":"Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease","volume":"360","author":"Park","year":"2018","journal-title":"Science"},{"key":"2022042214132451400_ref48","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/ki.2012.379","article-title":"The cytoplasmic protein Pacsin 2 in kidney development and injury repair","volume":"83","author":"Yao","year":"2013","journal-title":"Kidney Int."},{"key":"2022042214132451400_ref49","doi-asserted-by":"crossref","first-page":"dev186452","DOI":"10.1242\/dev.186452","article-title":"Transcriptional adaptation: a mechanism underlying genetic robustness","volume":"147","author":"Sztal","year":"2020","journal-title":"Development"},{"key":"2022042214132451400_ref50","doi-asserted-by":"crossref","DOI":"10.1515\/revac-2016-0019","article-title":"Urine oligosaccharide tests for the diagnosis of oligosaccharidoses","volume":"36","author":"Casado","year":"2017","journal-title":"Rev. Anal. Chem."},{"key":"2022042214132451400_ref51","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1681\/ASN.2019020125","article-title":"Effects of proximal tubule shortening on protein excretion in a Lowe syndrome model","volume":"31","author":"Gliozzi","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"2022042214132451400_ref52","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1093\/hmg\/ddr608","article-title":"Impaired neural development in a zebrafish model for Lowe syndrome","volume":"21","author":"Ramirez","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132451400_ref53","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1083\/jcb.200207045","article-title":"The coiled-coil membrane protein golgin-84 is a novel rab effector required for Golgi ribbon formation","volume":"160","author":"Diao","year":"2003","journal-title":"J. Cell Biol."},{"key":"2022042214132451400_ref54","doi-asserted-by":"crossref","first-page":"e82","DOI":"10.1093\/nar\/gkr218","article-title":"Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting","volume":"39","author":"Cermak","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2022042214132451400_ref55","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1038\/nprot.2009.209","article-title":"Targeted mutagenesis in zebrafish using customized zinc-finger nucleases","volume":"4","author":"Foley","year":"2009","journal-title":"Nat. Protoc."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddab307\/41364257\/ddab307.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/8\/1183\/43408415\/ddab307.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/8\/1183\/43408415\/ddab307.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T14:14:26Z","timestamp":1650636866000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/31\/8\/1183\/6406900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,21]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,10,21]]},"published-print":{"date-parts":[[2022,4,22]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddab307","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,15]]},"published":{"date-parts":[[2021,10,21]]}}}