{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:11:35Z","timestamp":1790262695679,"version":"4.1.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a whole-joint disease characterized by cartilage destruction and other whole-joint pathological changes. There is currently no effective disease-modifying therapy. Here we investigate the post-transcriptional mRNA regulation of OA-modulating proteins in chondrocytes and show that the ZFP36 family member, ZFP36L1, is specifically upregulated in OA chondrocytes and OA cartilage of humans and mice. Adenovirus-mediated overexpression of ZFP36L1 alone in mouse knee-joint tissue does not modulate OA pathogenesis. However, genetic ablation or silencing of Zfp36l1 significantly abrogates experimental OA in mice. Knockdown of Zfp36l1 increases the mRNA expression of two heat shock protein 70 (HSP70) family members, which act as its direct targets. Furthermore, overexpression of HSPA1A in joint tissues protects mice against experimental OA by inhibiting chondrocyte apoptosis. Our results indicate that the RNA-binding protein, ZFP36L1, regulates HSP70 family members that appear to protect against OA pathogenesis by inhibiting chondrocyte apoptosis.<\/jats:p>","DOI":"10.1038\/s41467-018-08035-7","type":"journal-article","created":{"date-parts":[[2019,1,2]],"date-time":"2019-01-02T09:30:32Z","timestamp":1546421432000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["RNA-binding protein ZFP36L1 regulates osteoarthritis by modulating members of the heat shock protein 70 family"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0154-4061","authenticated-orcid":false,"given":"Young-Ok","family":"Son","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Eun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Su","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Churl-Hong","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang-Soo","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,8]]},"reference":[{"key":"8035_CR1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nrrheum.2014.44","volume":"17","author":"DJ Hunter","year":"2014","unstructured":"Hunter, D. J., Schofield, D. & Callander, E. The individual and socioeconomic impact of osteoarthritis. Nat. Rev. Rheumatol. 17, 437\u2013441 (2014).","journal-title":"Nat. Rev. Rheumatol."},{"key":"8035_CR2","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1002\/art.34453","volume":"64","author":"RF Loeser","year":"2012","unstructured":"Loeser, R. F. et al. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 64, 1697\u20131707 (2012).","journal-title":"Arthritis Rheum."},{"key":"8035_CR3","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1007\/s11926-015-0524-1","volume":"17","author":"PM Moon","year":"2015","unstructured":"Moon, P. M. & Beirer, F. Novel insights into osteoarthritis joint pathology from studies in mice. Curr. Rheumatol. Rep. 17, 50 (2015).","journal-title":"Curr. Rheumatol. Rep."},{"key":"8035_CR4","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.bbapap.2011.06.020","volume":"1824","author":"L Troeberg","year":"2012","unstructured":"Troeberg, L. & Nagase, H. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim. Biophys. Acta 1824, 133\u2013145 (2012).","journal-title":"Biochim. Biophys. Acta"},{"key":"8035_CR5","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1002\/art.22337","volume":"56","author":"AB Blom","year":"2007","unstructured":"Blom, A. B. et al. Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3. Arthritis Rheum. 56, 147\u2013157 (2007).","journal-title":"Arthritis Rheum."},{"key":"8035_CR6","doi-asserted-by":"publisher","first-page":"3723","DOI":"10.1002\/art.25002","volume":"60","author":"CB Little","year":"2009","unstructured":"Little, C. B. et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum. 60, 3723\u20133733 (2009).","journal-title":"Arthritis Rheum."},{"key":"8035_CR7","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/nature03369","volume":"434","author":"SS Glasson","year":"2005","unstructured":"Glasson, S. S. et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 434, 644\u2013648 (2005).","journal-title":"Nature"},{"key":"8035_CR8","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1080\/03008207.2016.1183667","volume":"58","author":"V Lefebvre","year":"2017","unstructured":"Lefebvre, V. & Dvir-Ginzberg, M. SOX9 and the many facets of its regulation in the chondrocyte lineage. Connect. Tissue Res. 58, 2\u201314 (2017).","journal-title":"Connect. Tissue Res."},{"key":"8035_CR9","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.3390\/ijms17122146","volume":"17","author":"E Charlier","year":"2016","unstructured":"Charlier, E. et al. Insights on molecular mechanisms of chondrocytes death in osteoarthritis. Int. J. Mol. Sci. 17, 2146 (2016).","journal-title":"Int. J. Mol. Sci."},{"key":"8035_CR10","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","volume":"7","author":"M Kapoor","year":"2010","unstructured":"Kapoor, M. et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat. Rev. Rheumatol. 7, 33\u201342 (2010).","journal-title":"Nat. Rev. Rheumatol."},{"key":"8035_CR11","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/nm.2153","volume":"16","author":"S Yang","year":"2010","unstructured":"Yang, S. et al. Hypoxia-inducible factor-2\u03b1 is a catabolic regulator of osteoarthritic cartilage destruction. Nat. Med. 16, 687\u2013693 (2010).","journal-title":"Nat. Med."},{"key":"8035_CR12","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.cell.2014.01.007","volume":"156","author":"JH Kim","year":"2014","unstructured":"Kim, J. H. et al. Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-MTF1 axis. Cell 156, 730\u2013743 (2014).","journal-title":"Cell"},{"key":"8035_CR13","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ceb.2018.02.011","volume":"52","author":"AH Corbett","year":"2018","unstructured":"Corbett, A. H. Post-transcriptional regulation of gene expression and human disease. Curr. Opin. Cell Biol. 52, 96\u2013104 (2018).","journal-title":"Curr. Opin. Cell Biol."},{"key":"8035_CR14","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.tibs.2016.12.003","volume":"42","author":"ML Wells","year":"2017","unstructured":"Wells, M. L. et al. An ancient family of RNA-binding proteins: still important! Trends Biochem. Sci. 42, 285\u2013296 (2017).","journal-title":"Trends Biochem. Sci."},{"key":"8035_CR15","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.bbagrm.2013.02.003","volume":"1829","author":"SA Brooks","year":"2013","unstructured":"Brooks, S. A. & Blackshear, P. J. Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochim. Biophys. Acta 1829, 666\u2013679 (2013).","journal-title":"Biochim. Biophys. Acta"},{"key":"8035_CR16","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/wrna.28","volume":"2","author":"S Sanduja","year":"2010","unstructured":"Sanduja, S. et al. The roles of TTP and BRF proteins in regulated mRNA decay. Wiley Interdiscip. Rev. RNA 2, 42\u201357 (2010).","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"8035_CR17","doi-asserted-by":"publisher","first-page":"634520","DOI":"10.1155\/2009\/634520","volume":"2009","author":"M Baou","year":"2009","unstructured":"Baou, M. et al. TIS11 family proteins and their roles in posttranslational gene regulation. J. Biomed. Biotechnol. 2009, 634520 (2009).","journal-title":"J. Biomed. Biotechnol."},{"key":"8035_CR18","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41590-017-0028-4","volume":"19","author":"M Turner","year":"2018","unstructured":"Turner, M. & Diaz-Munoz, M. D. RNA-binding proteins control gene expression and cell fate in the immune system. Nat. Immunol. 19, 120\u2013129 (2018).","journal-title":"Nat. Immunol."},{"key":"8035_CR19","doi-asserted-by":"publisher","first-page":"3741","DOI":"10.1172\/JCI94029","volume":"127","author":"EJ Tarling","year":"2017","unstructured":"Tarling, E. J. et al. RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism. J. Clin. Invest. 127, 3741\u20133754 (2017).","journal-title":"J. Clin. Invest."},{"key":"8035_CR20","doi-asserted-by":"publisher","unstructured":"Galloway, A. & Turner, M. Cell cycle RNA regulons coordinating early lymphocyte development. Wiley Iinterdiscip. Rev. RNA 8, https:\/\/doi.org\/10.1002\/wrna.1419 (2017).","DOI":"10.1002\/wrna.1419"},{"key":"8035_CR21","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S1074-7613(00)80411-2","volume":"4","author":"GA Taylor","year":"1996","unstructured":"Taylor, G. A. et al. A pathogenetic role of TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 4, 445\u2013454 (1996).","journal-title":"Immunity"},{"key":"8035_CR22","doi-asserted-by":"publisher","first-page":"6445","DOI":"10.1128\/MCB.24.14.6445-6455.2004","volume":"24","author":"DJ Stumpo","year":"2004","unstructured":"Stumpo, D. J. et al. Chorioallantoic fusion defects and embryonic lethality resulting fromdisruption of Zfl36l1, a gene encoding a CCCH tandem zinc finger protein of the tristetraprolin family. Mol. Cell. Biol. 24, 6445\u20136455 (2004).","journal-title":"Mol. Cell. Biol."},{"key":"8035_CR23","doi-asserted-by":"publisher","first-page":"4883","DOI":"10.1242\/dev.01336","volume":"131","author":"SB Ramos","year":"2004","unstructured":"Ramos, S. B. et al. The CCCH tandem zinc-finger protein ZFP36L2 is crucial for female fertility and early embryonic development. Development 131, 4883\u20134893 (2004).","journal-title":"Development"},{"key":"8035_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01868-8","volume":"8","author":"YO Son","year":"2017","unstructured":"Son, Y. O. et al. Estrogen-related receptor gamma causes osteoarthritis by upregulating extracellular matrix-degrading enzymes. Nat. Commun. 8, 2133 (2017).","journal-title":"Nat. Commun."},{"key":"8035_CR25","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1136\/annrheumdis-2015-208406","volume":"75","author":"Y Won","year":"2016","unstructured":"Won, Y. et al. Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis. Ann. Rheum. Dis. 75, 2045\u20132052 (2016).","journal-title":"Ann. Rheum. Dis."},{"key":"8035_CR26","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1136\/annrheumdis-2015-208953","volume":"76","author":"J Rhee","year":"2017","unstructured":"Rhee, J. et al. Inhibition of BATF\/JUN transcriptional activity protects against osteoarthritic cartilage destruction. Ann. Rheum. Dis. 76, 427\u2013434 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"8035_CR27","doi-asserted-by":"publisher","first-page":"e0174294","DOI":"10.1371\/journal.pone.0174294","volume":"12","author":"P Das Neves Borges","year":"2017","unstructured":"Das Neves Borges, P. et al. Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis. PLoS ONE 12, e0174294 (2017).","journal-title":"PLoS ONE"},{"key":"8035_CR28","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1007\/s00018-004-4464-6","volume":"62","author":"MP Mayer","year":"2005","unstructured":"Mayer, M. P. & Bukau, B. Hsp70 chaperones: cellular functions and molecular mechanisms. Mol. Life Sci. 62, 670\u2013684 (2005).","journal-title":"Mol. Life Sci."},{"key":"8035_CR29","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s12192-008-0068-7","volume":"14","author":"HH Kampinga","year":"2009","unstructured":"Kampinga, H. H. et al. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones. 14, 105\u2013111 (2009).","journal-title":"Cell Stress Chaperones."},{"key":"8035_CR30","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1074\/jbc.M107231200","volume":"277","author":"SJ Kim","year":"2001","unstructured":"Kim, S. J. et al. ERK-1\/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status. J. Biol. Chem. 277, 1332\u20131339 (2001).","journal-title":"J. Biol. Chem."},{"key":"8035_CR31","doi-asserted-by":"publisher","first-page":"4991","DOI":"10.1242\/jcs.01373","volume":"117","author":"XC Zeng","year":"2004","unstructured":"Zeng, X. C. et al. Hsp70 dynamics in vivo: effect of heat shock and protein aggregation. J. Cell Sci. 117, 4991\u20135000 (2004).","journal-title":"J. Cell Sci."},{"key":"8035_CR32","doi-asserted-by":"publisher","first-page":"7146","DOI":"10.1128\/MCB.20.19.7146-7159.2000","volume":"20","author":"DD Mosser","year":"2000","unstructured":"Mosser, D. D. et al. The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol. Cell. Biol. 20, 7146\u20137159 (2000).","journal-title":"Mol. Cell. Biol."},{"key":"8035_CR33","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1126\/science.aad5978","volume":"352","author":"A Galloway","year":"2016","unstructured":"Galloway, A. et al. RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science 352, 453\u2013459 (2016).","journal-title":"Science"},{"key":"8035_CR34","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/ni.1901","volume":"11","author":"DJ Hodson","year":"2010","unstructured":"Hodson, D. J. et al. Deletion of the RNA-binding proteins Zfp36l1 and Zfp36l2 leads to perturbed thymic development and T-lymphoblastic leukemia. Nat. Immunol. 11, 717\u2013724 (2010).","journal-title":"Nat. Immunol."},{"key":"8035_CR35","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/j.joca.2016.01.988","volume":"24","author":"BT McDermott","year":"2016","unstructured":"McDermott, B. T. et al. RNA binding proteins regulates anabolic and catabolic gene expression in chondrocytes. Osteoarthritis Cartilage 24, 1263\u20131273 (2016).","journal-title":"Osteoarthritis Cartilage"},{"key":"8035_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/srep16229","volume":"5","author":"MT Chen","year":"2015","unstructured":"Chen, M. T. et al. ZFP36L1 promotes monocyte\/macrophage differentiation by repressing CDK6. Sci. Rep. 5, 16229 (2015).","journal-title":"Sci. Rep."},{"key":"8035_CR37","doi-asserted-by":"publisher","first-page":"e102625","DOI":"10.1371\/journal.pone.0102625","volume":"9","author":"A Zekavati","year":"2014","unstructured":"Zekavati, A. et al. Post-transcriptional regulation of BCL2 mRNA by the RNA-binding protein ZFP36L1 in malignant B cells. PLoS ONE 9, e102625 (2014).","journal-title":"PLoS ONE"},{"key":"8035_CR38","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1210\/me.2008-0296","volume":"23","author":"H Duan","year":"2009","unstructured":"Duan, H. et al. cAMP-dependent posttranscriptional regulation of steroidoenic acute regulatory (STAR) protein by the zinc finger protein ZFP36L1\/TIS11b. Mol. Endocrinol. 23, 497\u2013509 (2009).","journal-title":"Mol. Endocrinol."},{"key":"8035_CR39","doi-asserted-by":"publisher","first-page":"3340","DOI":"10.1091\/mbc.e10-01-0040","volume":"21","author":"T Vignudelli","year":"2010","unstructured":"Vignudelli, T. et al. ZFP36L1 negatively regulates erythoid differentiation of CD34+ hematopoietic stem cells by interfering with the Stat5b pathway. Mol. Biol. Cell 21, 3340\u20133351 (2010).","journal-title":"Mol. Biol. Cell"},{"key":"8035_CR40","doi-asserted-by":"publisher","first-page":"10037","DOI":"10.1093\/nar\/gku652","volume":"42","author":"S Adachi","year":"2014","unstructured":"Adachi, S. et al. ZFP36L1 and ZFP36L2 control LDLR mRNA stability via the ERK-RSK pathway. Nucleic Acids Res. 42, 10037\u201310049 (2014).","journal-title":"Nucleic Acids Res."},{"key":"8035_CR41","doi-asserted-by":"publisher","first-page":"368","DOI":"10.3109\/03009749709065701","volume":"26","author":"K Takahashi","year":"1997","unstructured":"Takahashi, K. et al. Localization of heat shock protein in osteoarthritic cartilage. Scand. J. Rheumatol. 26, 368\u2013375 (1997).","journal-title":"Scand. J. Rheumatol."},{"key":"8035_CR42","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/S1063-4584(97)80036-2","volume":"5","author":"K Takahashi","year":"1997","unstructured":"Takahashi, K. et al. Analysis of heat shock proteins and cytokines expressed during early stages of osteoarthritis in a mouse model. Osteoarthritis Cartilage 5, 321\u2013329 (1997).","journal-title":"Osteoarthritis Cartilage"},{"key":"8035_CR43","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.joca.2005.12.008","volume":"14","author":"H Tonomura","year":"2006","unstructured":"Tonomura, H. et al. Glutamine protects articular chondrocytes from heat stress and NO-induced apoptosis with HSP70 expression. Osteoarthritis Cartilage 14, 545\u2013553 (2006).","journal-title":"Osteoarthritis Cartilage"},{"key":"8035_CR44","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1002\/jor.22235","volume":"31","author":"SW Ueng","year":"2013","unstructured":"Ueng, S. W. et al. Hyperbaric oxygen treatment prevents nitric oxide-induced apoptosis in articular cartilage injury via enhancement of the expression of heat shock protein 70. J. Orthop. Res. 31, 376\u2013384 (2013).","journal-title":"J. Orthop. Res."},{"key":"8035_CR45","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1254\/jphs.09076FP","volume":"110","author":"H Kimura","year":"2009","unstructured":"Kimura, H. et al. The chondroprotective agent ITZ-1 inhibits interleukin-1beta-induced matrix metalloproteinase-13 production and suppresses nitric oxide-induced chondrocyte death. J. Pharmacol. Sci. 110, 201\u2013211 (2009).","journal-title":"J. Pharmacol. Sci."},{"key":"8035_CR46","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1002\/art.11040","volume":"48","author":"R Terauchi","year":"2003","unstructured":"Terauchi, R. et al. Hsp70 prevents nitric oxide-induced apoptosis in articular chondrocytes. Arthritis Rheum. 48, 1562\u20131568 (2003).","journal-title":"Arthritis Rheum."},{"key":"8035_CR47","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1096\/fj.04-2889com","volume":"20","author":"L Grossin","year":"2006","unstructured":"Grossin, L. et al. Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis. FASEB J. 20, 65\u201375 (2006).","journal-title":"FASEB J."},{"key":"8035_CR48","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","volume":"18","author":"SS Glasson","year":"2010","unstructured":"Glasson, S. S. et al. The OARSI histopathology initiative\u2014recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage 18, S17\u2013S23 (2010).","journal-title":"Osteoarthritis Cartilage"},{"key":"8035_CR49","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1038\/nprot.2008.95","volume":"3","author":"M Gosset","year":"2008","unstructured":"Gosset, M. et al. Primary culture and phenotyping of murine chondrocytes. Nat. Protoc. 3, 1253\u20131260 (2008).","journal-title":"Nat. Protoc."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-08035-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-08035-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-08035-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T13:39:26Z","timestamp":1671197966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-08035-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,8]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["8035"],"URL":"https:\/\/doi.org\/10.1038\/s41467-018-08035-7","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734831197.793562450","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.734831197.793561194","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,8]]},"assertion":[{"value":"29 March 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 December 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"77"}}