{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T07:09:07Z","timestamp":1775459347833,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Scho 503 20\/1"],"award-info":[{"award-number":["Scho 503 20\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Activating mutations in the human KIT receptor is known to drive severe hematopoietic disorders and tumor formation spanning various entities. The most common mutation is the substitution of aspartic acid at position 816 to valine (D816V), rendering the receptor constitutively active independent of ligand binding. As the role of the KIT receptor in placental signaling cascades is poorly understood, we analyzed the impact of KITD816V expression on placental development using a humanized mouse model. Placentas from KITD816V animals present with a grossly changed morphology, displaying a reduction in labyrinth and spongiotrophoblast layer and an increase in the Parietal Trophoblast Giant Cell (P-TGC) layer. Elevated differentiation to P-TGCs was accompanied with reduced differentiation to other Trophoblast Giant Cell (TGC) subtypes and by severe decrease in proliferation. The embryos display growth retardation and die in utero. KITD816V-trophoblast stem cells (TSC) differentiate much faster compared to wild type (WT) controls. In undifferentiated KITD816V-TSCs, levels of Phosphorylated Extracellular-signal Regulated Kinase (P-ERK) and Phosphorylated Protein Kinase B (P-AKT) are comparable to wildtype cultures differentiating for 3\u20136 days. Accordingly, P-TGC markers Placental Lactogen 1 (PL1) and Proliferin (PLF) are upregulated as well. The results reveal that KIT signaling orchestrates the fine-tuned differentiation of the placenta, with special emphasis on P-TGC differentiation. Appropriate control of KIT receptor action is therefore essential for placental development and nourishment of the embryo.<\/jats:p>","DOI":"10.3390\/ijms21155503","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T06:16:47Z","timestamp":1596435407000},"page":"5503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Persistent Human KIT Receptor Signaling Disposes Murine Placenta to Premature Differentiation Resulting in Severely Disrupted Placental Structure and Functionality"],"prefix":"10.3390","volume":"21","author":[{"given":"Franziska","family":"Kaiser","sequence":"first","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Hartweg","sequence":"additional","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"Department of Medicine II and IZKF Research Laboratory, W\u00fcrzburg University Hospital, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selina","family":"Jansky","sequence":"additional","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"Hopp Children\u2019s Cancer Center (KiTZ), 69120 Heidelberg, Germany"},{"name":"Division of Neuroblastoma Genomics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Pelusi","sequence":"additional","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"Department of Molecular Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Kubaczka","sequence":"additional","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"Division of Pediatric Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0589-503X","authenticated-orcid":false,"given":"Dominik","family":"Nitsche","sequence":"additional","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"Life &amp; Medical Sciences-Institute (LIMES), University of Bonn, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Langkabel","sequence":"additional","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-0076","authenticated-orcid":false,"given":"Hubert","family":"Schorle","sequence":"additional","affiliation":[{"name":"Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1530\/REP-09-0158","article-title":"Comparative aspects of implantation","volume":"138","author":"Bazer","year":"2009","journal-title":"Reproduction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1172\/JCI41229","article-title":"Making the blastocyst: Lessons from the mouse","volume":"120","author":"Cockburn","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3389\/fendo.2018.00570","article-title":"Regulation of Placental Development and Its Impact on Fetal Growth\u2014New Insights From Mouse Models","volume":"9","author":"Woods","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/S1357-2725(99)00076-X","article-title":"The biology of stem cell factor and its receptor C-kit","volume":"31","author":"Ashman","year":"1999","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/335088a0","article-title":"The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus","volume":"335","author":"Chabot","year":"1988","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0092-8674(90)90298-S","article-title":"Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles","volume":"63","author":"Copeland","year":"1990","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"435","DOI":"10.7150\/ijbs.6087","article-title":"The C-kit receptor-mediated signal transduction and tumor-related diseases","volume":"9","author":"Liang","year":"2013","journal-title":"Int. J. Biol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S1357-2725(99)00078-3","article-title":"Early signaling pathways activated by c-Kit in hematopoietic cells","volume":"31","author":"Linnekin","year":"1999","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2005.08.055","article-title":"Signaling by Kit protein-tyrosine kinase-The stem cell factor receptor","volume":"337","author":"Roskoski","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3634","DOI":"10.4161\/cc.7.23.7103","article-title":"Regulation of lymphocyte fate by Ras\/ERK signals","volume":"7","author":"Yasuda","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1095\/biolreprod47.4.614","article-title":"Expression of C-Kit Protein during Placental Development1","volume":"47","author":"Horie","year":"1992","journal-title":"Biol. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1242\/dev.113.4.1207","article-title":"Contiguous patterns of c-kit and steel expression: Analysis of mutations at the W and Sl loci","volume":"113","author":"Motro","year":"1991","journal-title":"Development"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.devcel.2005.02.001","article-title":"The Murine Placenta Contains Hematopoietic Stem Cells within the Vascular Labyrinth Region","volume":"8","author":"Ottersbach","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.placenta.2018.04.007","article-title":"Mechanism of hematopoiesis and vasculogenesis in mouse placenta","volume":"69","year":"2018","journal-title":"Placenta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3941 LP","DOI":"10.1242\/dev.051359","article-title":"Regulation of hematopoietic cell clusters in the placental niche through SCF\/Kit signaling in embryonic mouse","volume":"137","author":"Sasaki","year":"2010","journal-title":"Development"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/jid.2009.281","article-title":"Pediatric mastocytosis is a clonal disease associated with D 816 v and other activating c-KIT mutations","volume":"130","author":"Bodemer","year":"2010","journal-title":"J. Invest. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0002-9440(10)63120-3","article-title":"KIT mutations are common in testicular seminomas","volume":"164","author":"Kemmer","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0002-9440(10)65250-9","article-title":"Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas","volume":"154","author":"Lasota","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11899-009-0011-8","article-title":"Clinical implications of c-Kit mutations in acute myelogenous leukemia","volume":"4","author":"Malaise","year":"2009","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/01.pai.0000173054.83414.22","article-title":"KIT (CD117): A Review on Expression in Normal and Neoplastic Tissues, and Mutations and Their Clinicopathologic Correlation","volume":"13","author":"Miettinen","year":"2005","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11039","DOI":"10.1074\/jbc.M808058200","article-title":"The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction","volume":"284","author":"Sun","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/S0002-9440(10)65419-3","article-title":"Activating c-kit gene mutations in human germ cell tumors","volume":"154","author":"Tian","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5736","DOI":"10.1073\/pnas.76.11.5736","article-title":"Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta","volume":"76","author":"Fleischman","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.V90.4.1345","article-title":"Stem Cell Factor and Hematopoiesis","volume":"90","author":"Broudy","year":"1997","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31515","DOI":"10.1038\/srep31515","article-title":"Disruption of c-Kit Signaling in KitW-sh\/W-sh Growing Mice Increases Bone Turnover","volume":"6","author":"Lotinun","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1074-7613(02)00386-2","article-title":"Viable c-KitW\/W Mutants Reveal Pivotal Role for c-Kit in the Maintenance of Lymphopoiesis","volume":"17","author":"Waskow","year":"2002","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/cdd.2014.172","article-title":"Kit transduced signals counteract erythroid maturation by MAPK-dependent modulation of erythropoietin signaling and apoptosis induction in mouse fetal liver","volume":"22","author":"Haas","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1128\/MCB.01153-06","article-title":"Neoplasia driven by mutant c-KIT is mediated by intracellular, not plasma membrane, receptor signaling","volume":"27","author":"Xiang","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"41427","DOI":"10.1038\/srep41427","article-title":"The spleen microenvironment influences disease transformation in a mouse model of KITD816V-dependent myeloproliferative neoplasm","volume":"7","author":"Pelusi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1159\/000078196","article-title":"Expression of the proliferation marker Ki-67 during early mouse development","volume":"105","author":"Winking","year":"2004","journal-title":"Cytogenet. Genome Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1387\/ijdb.082768dh","article-title":"Development and function of trophoblast giant cells in the rodent placenta","volume":"54","author":"Hu","year":"2010","journal-title":"Int. J. Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ydbio.2006.08.018","article-title":"R-spondin3 is required for mouse placental development","volume":"301","author":"Aoki","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1E.4.1","DOI":"10.1002\/9780470151808.sc01e04s7","article-title":"Isolation and Manipulation of Mouse Trophoblast Stem Cells","volume":"7","author":"Himeno","year":"2008","journal-title":"Curr. Protoc. Stem Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3310","DOI":"10.1128\/MCB.01215-09","article-title":"The Transcription Factor TCFAP2C\/AP-2\u03b3 Cooperates with CDX2 To Maintain Trophectoderm Formation","volume":"30","author":"Kuckenberg","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"530 LP","DOI":"10.1128\/MCB.20.2.530-541.2000","article-title":"The HAND1 Basic Helix-Loop-Helix Transcription Factor Regulates Trophoblast Differentiation via Multiple Mechanisms","volume":"20","author":"Scott","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/cdd.2010.110","article-title":"The Notch2-Jagged1 interaction mediates stem cell factor signaling in erythropoiesis","volume":"18","author":"Zeuner","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.ydbio.2007.01.009","article-title":"Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta","volume":"304","author":"Simmons","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ydbio.2004.03.040","article-title":"Trophoblast stem cells differentiate in vitro into invasive trophoblast giant cells","volume":"271","author":"Hemberger","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ydbio.2014.01.015","article-title":"Development of the hemochorial maternal vascular spaces in the placenta through endothelial and vasculogenic mimicry","volume":"387","author":"Rai","year":"2014","journal-title":"Dev. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1182\/blood.V86.2.572.bloodjournal862572","article-title":"Stem cell factor retards differentiation of normal human erythroid progenitor cells while stimulating proliferation","volume":"86","author":"Muta","year":"1995","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1242\/dev.124.4.907","article-title":"GATA-2 and GATA-3 regulate trophoblast-specific gene expression in vivo","volume":"124","author":"Ma","year":"1997","journal-title":"Development"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1242\/dev.120.11.3257","article-title":"GATA factor activity is required for the trophoblast-specific transcriptional regulation of the mouse placental lactogen I gene","volume":"120","author":"Ng","year":"1994","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3650 LP","DOI":"10.1242\/dev.133462","article-title":"From the stem of the placental tree: Trophoblast stem cells and their progeny","volume":"143","author":"Latos","year":"2016","journal-title":"Development"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ydbio.2005.05.010","article-title":"Determinants of trophoblast lineage and cell subtype specification in the mouse placenta","volume":"284","author":"Simmons","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2072 LP","DOI":"10.1126\/science.282.5396.2072","article-title":"Promotion of Trophoblast Stem Cell Proliferation by FGF4","volume":"282","author":"Tanaka","year":"1998","journal-title":"Science (80-)"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1006\/dbio.2001.0300","article-title":"Retinoic acid promotes differentiation of trophoblast stem cells to a giant cell fate","volume":"235","author":"Yan","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ydbio.2014.10.020","article-title":"Retinoic acid regulates Kit translation during spermatogonial differentiation in the mouse","volume":"397","author":"Busada","year":"2015","journal-title":"Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e1005501","DOI":"10.1371\/journal.pgen.1005501","article-title":"Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor","volume":"11","author":"Raverdeau","year":"2015","journal-title":"PLoS Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1071\/RD15145","article-title":"Retinoic acid triggers c-kit gene expression in spermatogonial stem cells through an enhanceosome constituted between transcription factor binding sites for retinoic acid response element (RARE), spleen focus forming virus proviral integration onco","volume":"29","author":"Koli","year":"2017","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e25155","DOI":"10.4161\/jkst.25155","article-title":"LIF-STAT signaling and trophoblast biology","volume":"2","author":"Suman","year":"2013","journal-title":"JAK-STAT"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1210\/me.2008-0058","article-title":"Leukemia Inhibitory Factor Regulates Trophoblast Giant Cell Differentiation via Janus Kinase 1-Signal Transducer and Activator of Transcription 3-Suppressor of Cytokine Signaling 3 Pathway","volume":"22","author":"Takahashi","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1093\/emboj\/cdg057","article-title":"SOCS3: An essential regulator of LIF receptor signaling in trophoblast giant cell differentiation","volume":"22","author":"Takahashi","year":"2003","journal-title":"EMBO J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1158\/1078-0432.CCR-06-2313","article-title":"Regulation of Metastases by Signal Transducer and Activator of Transcription 3 Signaling Pathway: Clinical Implications","volume":"13","author":"Huang","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1093\/nar\/23.24.5080","article-title":"A cre -transgenic mouse strain for the ubiquitous deletion of loxP -flanked gene segments including deletion in germ cells","volume":"23","author":"Schwenk","year":"1995","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5503\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:53:29Z","timestamp":1760176409000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,31]]},"references-count":54,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21155503"],"URL":"https:\/\/doi.org\/10.3390\/ijms21155503","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,31]]}}}