{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:55:39Z","timestamp":1790787339485,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T00:00:00Z","timestamp":1484784000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T00:00:00Z","timestamp":1484784000000},"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":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Japanese encephalitis virus (JEV), which is a causative agent of sporadic encephalitis, harbours itself inside the neural stem\/progenitor cells. It is a well-known fact that JEV infects neural stem\/progenitor cells and decreases their proliferation capacity. With mass spectrometry-based quantitative proteomic study, it is possible to reveal the impact of virus on the stem cells at protein level. Our aim was to perceive the stem cell proteomic response upon viral challenge. We performed a two-dimensional gel electrophoresis-based proteomic study of the human neural stem cells (hNS1 cell line) post JEV infection and found that 13 proteins were differentially expressed. The altered proteome profile of hNS1 cell line revealed sustained endoplasmic reticulum stress, which deteriorated normal cellular activities leading to cell apoptosis. The proteomic changes found in hNS1 cell line were validated\n                    <jats:italic>in vivo<\/jats:italic>\n                    in the subventricular zone of JE infected BALB\/c mice. Congruent alterations were also witnessed in multipotent neural precursor cells isolated from human foetus and in autopsy samples of human brain clinically diagnosed as cases of JE patients. Endoplasmic reticulum resident chaperone GRP78, mitochondrial protein Prohibitin and heterogeneous nuclear ribonucleoprotein hnRNPC (C1\/C2) have been shown to interact with viral RNA. Hence it is proposed that these are the principle candidates governing endoplasmic reticulum stress-induced apoptosis in JEV infection.\n                  <\/jats:p>","DOI":"10.1038\/cddis.2016.394","type":"journal-article","created":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T10:35:07Z","timestamp":1484822107000},"page":"e2556-e2556","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Japanese encephalitis virus induces human neural stem\/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress"],"prefix":"10.1038","volume":"8","author":[{"given":"Sriparna","family":"Mukherjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noopur","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabonita","family":"Sengupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahar","family":"Fatima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Seth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Mahadevan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susarla Krishna","family":"Shankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arindam","family":"Bhattacharyya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anirban","family":"Basu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,19]]},"reference":[{"key":"BFcddis2016394_CR1","doi-asserted-by":"publisher","first-page":"4798","DOI":"10.1128\/JVI.02979-13","volume":"88","author":"MC Thounaojam","year":"2014","unstructured":"Thounaojam MC, Kundu K, Kaushik DK, Swaroop S, Mahadevan A, Shankar SK et al. MicroRNA 155 regulates Japanese encephalitis virus-induced inflammatory response by targeting Src homology 2-containing inositol phosphatase 1. J Virol 2014; 88: 4798\u20134810.","journal-title":"J Virol"},{"key":"BFcddis2016394_CR2","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1111\/j.1471-4159.2010.06951.x","volume":"115","author":"S Das","year":"2010","unstructured":"Das S, Chakraborty S, Basu A . Critical role of lipid rafts in virus entry and activation of phosphoinositide 3' kinase\/Akt signaling during early stages of Japanese encephalitis virus infection in neural stem\/progenitor cells. J Neurochem 2010; 115: 537\u2013549.","journal-title":"J Neurochem"},{"key":"BFcddis2016394_CR3","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1111\/j.1471-4159.2008.05511.x","volume":"106","author":"S Das","year":"2008","unstructured":"Das S, Basu A . Japanese encephalitis virus infects neural progenitor cells and decreases their proliferation. J Neurochem 2008; 106: 1624\u20131636.","journal-title":"J Neurochem"},{"key":"BFcddis2016394_CR4","doi-asserted-by":"publisher","first-page":"e8134","DOI":"10.1371\/journal.pone.0008134","volume":"4","author":"S Das","year":"2009","unstructured":"Das S, Ghosh D, Basu A . Japanese encephalitis virus induce immuno-competency in neural stem\/progenitor cells. PloS One 2009; 4: e8134.","journal-title":"PloS One"},{"key":"BFcddis2016394_CR5","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1002\/pmic.201100488","volume":"12","author":"DC Munday","year":"2012","unstructured":"Munday DC, Surtees R, Emmott E, Dove BK, Digard P, Barr JN et al. Using SILAC and quantitative proteomics to investigate the interactions between viral and host proteomes. Proteomics 2012; 12: 666\u2013672.","journal-title":"Proteomics"},{"key":"BFcddis2016394_CR6","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.jprot.2014.06.003","volume":"108","author":"TH Issac","year":"2014","unstructured":"Issac TH, Tan EL, Chu JJ . Proteomic profiling of chikungunya virus-infected human muscle cells: reveal the role of cytoskeleton network in CHIKV replication. J Proteomics 2014; 108: 445\u2013464.","journal-title":"J Proteomics"},{"key":"BFcddis2016394_CR7","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jprot.2014.06.029","volume":"111","author":"V Pando-Robles","year":"2014","unstructured":"Pando-Robles V, Oses-Prieto JA, Rodriguez-Gandarilla M, Meneses-Romero E, Burlingame AL, Batista CV . Quantitative proteomic analysis of Huh-7 cells infected with Dengue virus by label-free LC-MS. J Proteomics 2014; 111: 16\u201329.","journal-title":"J Proteomics"},{"key":"BFcddis2016394_CR8","doi-asserted-by":"publisher","first-page":"e90211","DOI":"10.1371\/journal.pone.0090211","volume":"9","author":"N Sengupta","year":"2014","unstructured":"Sengupta N, Ghosh S, Vasaikar SV, Gomes J, Basu A . Modulation of neuronal proteome profile in response to Japanese encephalitis virus infection. PloS One 2014; 9: e90211.","journal-title":"PloS One"},{"key":"BFcddis2016394_CR9","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/nrd2755","volume":"7","author":"I Kim","year":"2008","unstructured":"Kim I, Xu W, Reed JC . Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov 2008; 7: 1013\u20131030.","journal-title":"Nat Rev Drug Discov"},{"key":"BFcddis2016394_CR10","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.toxlet.2010.11.019","volume":"201","author":"TH Lu","year":"2011","unstructured":"Lu TH, Su CC, Chen YW, Yang CY, Wu CC, Hung DZ et al. Arsenic induces pancreatic beta-cell apoptosis via the oxidative stress-regulated mitochondria-dependent and endoplasmic reticulum stress-triggered signaling pathways. Toxicol Lett 2011; 201: 15\u201326.","journal-title":"Toxicol Lett"},{"key":"BFcddis2016394_CR11","doi-asserted-by":"publisher","first-page":"4162","DOI":"10.1128\/JVI.76.9.4162-4171.2002","volume":"76","author":"HL Su","year":"2002","unstructured":"Su HL, Liao CL, Lin YL . Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response. J Virol 2002; 76: 4162\u20134171.","journal-title":"J Virol"},{"key":"BFcddis2016394_CR12","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.stem.2016.02.016","volume":"18","author":"H Tang","year":"2016","unstructured":"Tang H, Hammack C, Ogden SC, Wen Z, Qian X, Li Y et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell 2016; 18: 587\u2013590.","journal-title":"Cell Stem Cell"},{"key":"BFcddis2016394_CR13","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1186\/1756-0500-7-757","volume":"7","author":"J Xu","year":"2014","unstructured":"Xu J, Nash RJ, Frey TK . Cellular responses to Sindbis virus infection of neural progenitors derived from human embryonic stem cells. BMC Res Notes 2014; 7: 757.","journal-title":"BMC Res Notes"},{"key":"BFcddis2016394_CR14","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/2042-4280-4-2","volume":"4","author":"H Nakamura","year":"2013","unstructured":"Nakamura H, Liao H, Minami K, Toyoda M, Akutsu H, Miyagawa Y et al. Human cytomegalovirus induces apoptosis in neural stem\/progenitor cells derived from induced pluripotent stem cells by generating mitochondrial dysfunction and endoplasmic reticulum stress. Herpesviridae 2013; 4: 2.","journal-title":"Herpesviridae"},{"key":"BFcddis2016394_CR15","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.stem.2016.04.009","volume":"18","author":"JJ Miner","year":"2016","unstructured":"Miner JJ, Diamond MS . Understanding how Zika virus enters and infects neural target cells. Cell Stem Cell 2016; 18: 559\u2013560.","journal-title":"Cell Stem Cell"},{"key":"BFcddis2016394_CR16","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1016\/S0002-9440(10)63496-7","volume":"163","author":"R Feuer","year":"2003","unstructured":"Feuer R, Mena I, Pagarigan RR, Harkins S, Hassett DE, Whitton JL . Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am J Pathol 2003; 163: 1379\u20131393.","journal-title":"Am J Pathol"},{"key":"BFcddis2016394_CR17","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1523\/JNEUROSCI.4517-04.2005","volume":"25","author":"R Feuer","year":"2005","unstructured":"Feuer R, Pagarigan RR, Harkins S, Liu F, Hunziker IP, Whitton JL . Coxsackievirus targets proliferating neuronal progenitor cells in the neonatal CNS. J Neuroscience: The Official Journal of the Society for Neuroscience 2005; 25: 2434\u20132444.","journal-title":"J Neuroscience: The Official Journal of the Society for Neuroscience"},{"key":"BFcddis2016394_CR18","doi-asserted-by":"publisher","first-page":"7319","DOI":"10.1128\/JVI.78.14.7319-7328.2004","volume":"78","author":"DM Lawrence","year":"2004","unstructured":"Lawrence DM, Durham LC, Schwartz L, Seth P, Maric D, Major EO . Human immunodeficiency virus type 1 infection of human brain-derived progenitor cells. J Virol 2004; 78: 7319\u20137328.","journal-title":"J Virol"},{"key":"BFcddis2016394_CR19","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1172\/JCI0216886","volume":"110","author":"RJ Kaufman","year":"2002","unstructured":"Kaufman RJ . Orchestrating the unfolded protein response in health and disease. J Clin Invest 2002; 110: 1389\u20131398.","journal-title":"J Clin Invest"},{"key":"BFcddis2016394_CR20","doi-asserted-by":"publisher","first-page":"10849","DOI":"10.1128\/JVI.01151-07","volume":"81","author":"GR Medigeshi","year":"2007","unstructured":"Medigeshi GR, Lancaster AM, Hirsch AJ, Briese T, Lipkin WI, Defilippis V et al. West Nile virus infection activates the unfolded protein response, leading to CHOP induction and apoptosis. J Virol 2007; 81: 10849\u201310860.","journal-title":"J Virol"},{"key":"BFcddis2016394_CR21","first-page":"233","volume":"5","author":"SW Chan","year":"2014","unstructured":"Chan SW . Unfolded protein response in hepatitis C virus infection. Front Microbiol 2014; 5: 233.","journal-title":"Front Microbiol"},{"key":"BFcddis2016394_CR22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/1743-422X-4-91","volume":"4","author":"I Umareddy","year":"2007","unstructured":"Umareddy I, Pluquet O, Wang QY, Vasudevan SG, Chevet E, Gu F . Dengue virus serotype infection specifies the activation of the unfolded protein response. Virol J 2007; 4: 91.","journal-title":"Virol J"},{"key":"BFcddis2016394_CR23","doi-asserted-by":"publisher","first-page":"17794","DOI":"10.1038\/srep17794","volume":"5","author":"S Bhattacharyya","year":"2015","unstructured":"Bhattacharyya S, Vrati S . The Malat1 long non-coding RNA is upregulated by signalling through the PERK axis of unfolded protein response during flavivirus infection. Sci Rep 2015; 5: 17794.","journal-title":"Sci Rep"},{"issue":"Pt 1","key":"BFcddis2016394_CR24","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1099\/vir.0.057265-0","volume":"95","author":"S Bhattacharyya","year":"2014","unstructured":"Bhattacharyya S, Sen U, Vrati S . Regulated IRE1-dependent decay pathway is activated during Japanese encephalitis virus-induced unfolded protein response and benefits viral replication. J Gen Virol 2014; 95 (Pt 1): 71\u201379.","journal-title":"J Gen Virol"},{"key":"BFcddis2016394_CR25","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.1242\/jcs.112.23.4185","volume":"112 Pt 23","author":"K Romisch","year":"1999","unstructured":"Romisch K . Surfing the Sec61 channel: bidirectional protein translocation across the ER membrane. J Cell Sci 1999; 112 Pt 23 4185\u20134191.","journal-title":"J Cell Sci"},{"key":"BFcddis2016394_CR26","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1002\/jmv.23403","volume":"84","author":"P Wintachai","year":"2012","unstructured":"Wintachai P, Wikan N, Kuadkitkan A, Jaimipuk T, Ubol S, Pulmanausahakul R et al. Identification of prohibitin as a Chikungunya virus receptor protein. J Med Virol 2012; 84: 1757\u20131770.","journal-title":"J Med Virol"},{"key":"BFcddis2016394_CR27","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1128\/JVI.01641-09","volume":"84","author":"V Emerson","year":"2010","unstructured":"Emerson V, Holtkotte D, Pfeiffer T, Wang IH, Schnolzer M, Kempf T et al. Identification of the cellular prohibitin 1\/prohibitin 2 heterodimer as an interaction partner of the C-terminal cytoplasmic domain of the HIV-1 glycoprotein. J Virol 2010; 84: 1355\u20131365.","journal-title":"J Virol"},{"key":"BFcddis2016394_CR28","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1186\/1743-422X-8-424","volume":"8","author":"SS Dang","year":"2011","unstructured":"Dang SS, Sun MZ, Yang E, Xun M, Ma L, Jia ZS et al. Prohibitin is overexpressed in Huh-7-HCV and Huh-7.5-HCV cells harboring in vitro transcribed full-length hepatitis C virus RNA. Virol J 2011; 8: 424.","journal-title":"Virol J"},{"key":"BFcddis2016394_CR29","doi-asserted-by":"publisher","first-page":"4229","DOI":"10.1128\/JVI.02198-09","volume":"84","author":"KJ Ertel","year":"2010","unstructured":"Ertel KJ, Brunner JE, Semler BL . Mechanistic consequences of hnRNP C binding to both RNA termini of poliovirus negative-strand RNA intermediates. J Virol 2010; 84: 4229\u20134242.","journal-title":"J Virol"},{"key":"BFcddis2016394_CR30","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12985-014-0219-7","volume":"12","author":"T Dechtawewat","year":"2015","unstructured":"Dechtawewat T, Songprakhon P, Limjindaporn T, Puttikhunt C, Kasinrerk W, Saitornuang S et al. Role of human heterogeneous nuclear ribonucleoprotein C1\/C2 in dengue virus replication. Virol J 2015; 12: 14.","journal-title":"Virol J"},{"key":"BFcddis2016394_CR31","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/sj.embor.7400779","volume":"7","author":"E Szegezdi","year":"2006","unstructured":"Szegezdi E, Logue SE, Gorman AM, Samali A . Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 2006; 7: 880\u2013885.","journal-title":"EMBO Rep"},{"key":"BFcddis2016394_CR32","doi-asserted-by":"publisher","first-page":"3803","DOI":"10.7314\/APJCP.2012.13.8.3803","volume":"13","author":"L Zhang","year":"2012","unstructured":"Zhang L, Ji Q, Ni ZH, Sun J . Prohibitin induces apoptosis in BGC823 gastric cancer cells through the mitochondrial pathway. Asian Pac J Cancer Prev: APJCP 2012; 13: 3803\u20133807.","journal-title":"Asian Pac J Cancer Prev: APJCP"},{"key":"BFcddis2016394_CR33","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1128\/JVI.76.2.633-643.2002","volume":"76","author":"K Triantafilou","year":"2002","unstructured":"Triantafilou K, Fradelizi D, Wilson K, Triantafilou M . GRP78, a coreceptor for coxsackievirus A9, interacts with major histocompatibility complex class I molecules which mediate virus internalization. J Virol 2002; 76: 633\u2013643.","journal-title":"J Virol"},{"key":"BFcddis2016394_CR34","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1743-422X-8-128","volume":"8","author":"YP Wu","year":"2011","unstructured":"Wu YP, Chang CM, Hung CY, Tsai MC, Schuyler SC, Wang RY . Japanese encephalitis virus co-opts the ER-stress response protein GRP78 for viral infectivity. Virol J 2011; 8: 128.","journal-title":"Virol J"},{"key":"BFcddis2016394_CR35","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1161\/CIRCRESAHA.111.243212","volume":"110","author":"PE Kolattukudy","year":"2012","unstructured":"Kolattukudy PE, Niu J . Inflammation, endoplasmic reticulum stress, autophagy, and the monocyte chemoattractant protein-1\/CCR2 pathway. Circ Res 2012; 110: 174\u2013189.","journal-title":"Circ Res"},{"key":"BFcddis2016394_CR36","doi-asserted-by":"publisher","first-page":"3077","DOI":"10.1210\/en.2012-2138","volume":"154","author":"CM O\u2019Neill","year":"2013","unstructured":"O\u2019Neill CM, Lu C, Corbin KL, Sharma PR, Dula SB, Carter JD et al. Circulating levels of IL-1B+IL-6 cause ER stress and dysfunction in islets from prediabetic male mice. Endocrinology 2013; 154: 3077\u20133088.","journal-title":"Endocrinology"},{"key":"BFcddis2016394_CR37","doi-asserted-by":"publisher","first-page":"12804","DOI":"10.1074\/jbc.M609031200","volume":"282","author":"AL Theiss","year":"2007","unstructured":"Theiss AL, Obertone TS, Merlin D, Sitaraman SV . Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells. J Biol Chem 2007; 282: 12804\u201312812.","journal-title":"J Biol Chem"},{"key":"BFcddis2016394_CR38","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.yexcr.2003.11.025","volume":"294","author":"A Villa","year":"2004","unstructured":"Villa A, Navarro-Galve B, Bueno C, Franco S, Blasco MA, Martinez-Serrano A . Long-term molecular and cellular stability of human neural stem cell lines. Exp Cell Res 2004; 294: 559\u2013570.","journal-title":"Exp Cell Res"},{"key":"BFcddis2016394_CR39","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/S0361-9230(01)00776-6","volume":"57","author":"A Villa","year":"2002","unstructured":"Villa A, Navarro B, Martinez-Serrano A . Genetic perpetuation of in vitro expanded human neural stem cells: cellular properties and therapeutic potential. Brain Res Bull 2002; 57: 789\u2013794.","journal-title":"Brain Res Bull"},{"key":"BFcddis2016394_CR40","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/cdd.2015.138","volume":"23","author":"M Fatima","year":"2016","unstructured":"Fatima M, Kumari R, Schwamborn JC, Mahadevan A, Shankar SK, Raja R et al. Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration. Cell Death Differ 2016; 23: 776\u2013786.","journal-title":"Cell Death Differ"},{"key":"BFcddis2016394_CR41","doi-asserted-by":"publisher","first-page":"32593","DOI":"10.1038\/srep32593","volume":"6","author":"S Ghosh","year":"2016","unstructured":"Ghosh S, Mukherjee S, Sengupta N, Roy A, Dey D, Chakraborty S et al. Network analysis reveals common host protein\/s modulating pathogenesis of neurotropic viruses. Sci Rep 2016; 6: 32593.","journal-title":"Sci Rep"},{"key":"BFcddis2016394_CR42","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.nbd.2014.05.036","volume":"69","author":"A Nazmi","year":"2014","unstructured":"Nazmi A, Mukherjee S, Kundu K, Dutta K, Mahadevan A, Shankar SK et al. TLR7 is a key regulator of innate immunity against Japanese encephalitis virus infection. Neurobiol Dis 2014; 69: 235\u2013247.","journal-title":"Neurobiol Dis"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis2016394.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016394","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016394.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T18:37:24Z","timestamp":1718995044000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2016394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,19]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,1]]}},"alternative-id":["BFcddis2016394"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2016.394","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727222787.793567008","asserted-by":"object"}]},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,19]]},"assertion":[{"value":"18 July 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}