{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:51:33Z","timestamp":1790841093633,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2016,2,12]],"date-time":"2016-02-12T00:00:00Z","timestamp":1455235200000},"content-version":"tdm","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 Differ"],"published-print":{"date-parts":[[2016,7]]},"DOI":"10.1038\/cdd.2015.176","type":"journal-article","created":{"date-parts":[[2016,2,12]],"date-time":"2016-02-12T13:05:24Z","timestamp":1455282324000},"page":"1219-1231","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":282,"title":["Inflammasome-dependent IL-1\u03b2 release depends upon membrane permeabilisation"],"prefix":"10.1038","volume":"23","author":[{"given":"F","family":"Mart\u00edn-S\u00e1nchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Zeitler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A I","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Baroja-Mazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Bagnall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Spiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J D","family":"Daniels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Mortellaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pe\u00f1alver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Paszek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P","family":"Steringer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Nickel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Brough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Pelegr\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,12]]},"reference":[{"key":"BFcdd2015176_CR1","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1016\/j.immuni.2013.11.010","volume":"39","author":"C Garlanda","year":"2013","unstructured":"Garlanda C, Dinarello CA, Mantovani A . The interleukin-1 family: back to the future. Immunity 2013; 39: 1003\u20131018.","journal-title":"Immunity"},{"key":"BFcdd2015176_CR2","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","volume":"140","author":"O Takeuchi","year":"2010","unstructured":"Takeuchi O, Akira S . Pattern recognition receptors and inflammation. Cell 2010; 140: 805\u2013820.","journal-title":"Cell"},{"key":"BFcdd2015176_CR3","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nri3452","volume":"13","author":"E Latz","year":"2013","unstructured":"Latz E, Xiao TS, Stutz A . Activation and regulation of the inflammasomes. Nat Rev Immunol 2013; 13: 397\u2013411.","journal-title":"Nat Rev Immunol"},{"key":"BFcdd2015176_CR4","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1002\/eji.200940207","volume":"40","author":"SL Cassel","year":"2010","unstructured":"Cassel SL, Sutterwala FS . Sterile inflammatory responses mediated by the NLRP3 inflammasome. Eur J Immunol 2010; 40: 607\u2013611.","journal-title":"Eur J Immunol"},{"key":"BFcdd2015176_CR5","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.cytogfr.2011.10.001","volume":"22","author":"G Lopez-Castejon","year":"2011","unstructured":"Lopez-Castejon G, Brough D . Understanding the mechanism of IL-1beta secretion. Cytokine Growth Factor Rev 2011; 22: 189\u2013195.","journal-title":"Cytokine Growth Factor Rev"},{"key":"BFcdd2015176_CR6","doi-asserted-by":"publisher","first-page":"9745","DOI":"10.1073\/pnas.0308558101","volume":"101","author":"C Andrei","year":"2004","unstructured":"Andrei C, Margiocco P, Poggi A, Lotti LV, Torrisi MR, Rubartelli A . Phospholipases C and A2 control lysosome-mediated IL-1 beta secretion: Implications for inflammatory processes. Proc Natl Acad Sci USA 2004; 101: 9745\u20139750.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcdd2015176_CR7","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/S1074-7613(01)00229-1","volume":"15","author":"A MacKenzie","year":"2001","unstructured":"MacKenzie A, Wilson HL, Kiss-Toth E, Dower SK, North RA, Surprenant A . Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 2001; 15: 825\u2013835.","journal-title":"Immunity"},{"key":"BFcdd2015176_CR8","doi-asserted-by":"publisher","first-page":"4736","DOI":"10.1038\/srep04736","volume":"4","author":"Y Shirasaki","year":"2014","unstructured":"Shirasaki Y, Yamagishi M, Suzuki N, Izawa K, Nakahara A, Mizuno J et al. Real-time single-cell imaging of protein secretion. Sci Rep 2014; 4: 4736.","journal-title":"Sci Rep"},{"key":"BFcdd2015176_CR9","doi-asserted-by":"publisher","first-page":"27659","DOI":"10.1074\/jbc.M112.381939","volume":"287","author":"JP Steringer","year":"2012","unstructured":"Steringer JP, Bleicken S, Andreas H, Zacherl S, Laussmann M, Temmerman K et al. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion. J Biol Chem 2012; 287: 27659\u201327669.","journal-title":"J Biol Chem"},{"key":"BFcdd2015176_CR10","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/j.1460-2075.1988.tb02818.x","volume":"7","author":"JP Priestle","year":"1988","unstructured":"Priestle JP, Schar HP, Grutter MG . Crystal structure of the cytokine interleukin-1 beta. EMBO J 1988; 7: 339\u2013343.","journal-title":"EMBO J"},{"key":"BFcdd2015176_CR11","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1126\/science.1702556","volume":"251","author":"X Zhu","year":"1991","unstructured":"Zhu X, Komiya H, Chirino A, Faham S, Fox GM, Arakawa T et al. Three-dimensional structures of acidic and basic fibroblast growth factors. Science 1991; 251: 90\u201393.","journal-title":"Science"},{"key":"BFcdd2015176_CR12","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1242\/jcs.03377","volume":"120","author":"D Brough","year":"2007","unstructured":"Brough D, Rothwell NJ . Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death. J Cell Sci 2007; 120: 772\u2013781.","journal-title":"J Cell Sci"},{"key":"BFcdd2015176_CR13","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fimmu.2015.00054","volume":"6","author":"M Stoffels","year":"2015","unstructured":"Stoffels M, Zaal R, Kok N, van der Meer JW, Dinarello CA, Simon A . ATP-Induced IL-1beta Specific Secretion: True Under Stringent Conditions. Front Immunol 2015; 6: 54.","journal-title":"Front Immunol"},{"key":"BFcdd2015176_CR14","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.celrep.2014.06.028","volume":"8","author":"KW Chen","year":"2014","unstructured":"Chen KW, Gro\u00df CJ, Sotomayor FV, Stacey KJ, Tschopp J, Sweet MJ et al. The neutrophil NLRC4 inflammasome selectively promotes IL-1beta maturation without pyroptosis during acute Salmonella challenge. Cell Rep 2014; 8: 570\u2013582.","journal-title":"Cell Rep"},{"key":"BFcdd2015176_CR15","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1111\/j.1600-0854.2008.00749.x","volume":"9","author":"K Temmerman","year":"2008","unstructured":"Temmerman K, Ebert AD, M\u00fcller HM, Sinning I, Tews I, Nickel W . A direct role for phosphatidylinositol-4,5-bisphosphate in unconventional secretion of fibroblast growth factor 2. Traffic 2008; 9: 1204\u20131217.","journal-title":"Traffic"},{"key":"BFcdd2015176_CR16","doi-asserted-by":"publisher","first-page":"8925","DOI":"10.1074\/jbc.M114.622456","volume":"290","author":"HM M\u00fcller","year":"2015","unstructured":"M\u00fcller HM, Steringer JP, Wegehingel S, Bleicken S, M\u00fcnster M, Dimou E et al. Formation of disulfide bridges drives oligomerization, membrane pore formation and translocation of fibroblast growth factor 2 to cell surfaces. J Biol Chem 2015; 290: 8925\u20138937.","journal-title":"J Biol Chem"},{"key":"BFcdd2015176_CR17","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1111\/j.1600-0854.2010.01059.x","volume":"11","author":"AD Ebert","year":"2010","unstructured":"Ebert AD, Laussmann M, Wegehingel S, Kaderali L, Erfle H, Reichert J et al. Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic 2010; 11: 813\u2013826.","journal-title":"Traffic"},{"key":"BFcdd2015176_CR18","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1194\/jlr.D800043-JLR200","volume":"50","author":"K Temmerman","year":"2009","unstructured":"Temmerman K, Nickel W . A novel flow cytometric assay to quantify interactions between proteins and membrane lipids. J Lipid Res 2009; 50: 1245\u20131254.","journal-title":"J Lipid Res"},{"key":"BFcdd2015176_CR19","doi-asserted-by":"publisher","first-page":"7907","DOI":"10.1073\/pnas.81.24.7907","volume":"81","author":"PE Auron","year":"1984","unstructured":"Auron PE, Webb AC, Rosenwasser LJ, Mucci SF, Rich A, Wolff SM et al. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci USA 1984; 81: 7907\u20137911.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcdd2015176_CR20","doi-asserted-by":"publisher","first-page":"787","DOI":"10.4049\/jimmunol.0901363","volume":"183","author":"FG Bauernfeind","year":"2009","unstructured":"Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 2009; 183: 787\u2013791.","journal-title":"J Immunol"},{"key":"BFcdd2015176_CR21","doi-asserted-by":"publisher","first-page":"15942","DOI":"10.1074\/jbc.M114.557561","volume":"289","author":"H England","year":"2014","unstructured":"England H, Summersgill HR, Edye ME, Rothwell NJ, Brough D . Release of interleukin-1alpha or interleukin-1beta depends on mechanism of cell death. J Biol Chem 2014; 289: 15942\u201315950.","journal-title":"J Biol Chem"},{"key":"BFcdd2015176_CR22","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1152\/physrev.00015.2002","volume":"82","author":"RA North","year":"2002","unstructured":"North RA . Molecular physiology of P2X receptors. Physiol Rev 2002; 82: 1013\u20131067.","journal-title":"Physiol Rev"},{"key":"BFcdd2015176_CR23","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1126\/science.272.5259.227","volume":"272","author":"JE Rothman","year":"1996","unstructured":"Rothman JE, Wieland FT . Protein sorting by transport vesicles. Science 1996; 272: 227\u2013234.","journal-title":"Science"},{"key":"BFcdd2015176_CR24","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1146\/annurev.cellbio.24.110707.175320","volume":"24","author":"W Nickel","year":"2008","unstructured":"Nickel W, Seedorf M . Unconventional mechanisms of protein transport to the cell surface of eukaryotic cells. Annu Rev Cell Dev Biol 2008; 24: 287\u2013308.","journal-title":"Annu Rev Cell Dev Biol"},{"key":"BFcdd2015176_CR25","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/nrm2617","volume":"10","author":"W Nickel","year":"2009","unstructured":"Nickel W, Rabouille C . Mechanisms of regulated unconventional protein secretion. Nat Rev Mol Cell Biol 2009; 10: 148\u2013155.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcdd2015176_CR26","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1002\/j.1460-2075.1990.tb08268.x","volume":"9","author":"A Rubartelli","year":"1990","unstructured":"Rubartelli A, Cozzolino F, Talio M, Sitia R . A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence. EMBO J 1990; 9: 1503\u20131510.","journal-title":"EMBO J"},{"key":"BFcdd2015176_CR27","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/nrd3800","volume":"11","author":"CA Dinarello","year":"2012","unstructured":"Dinarello CA, Simon A, van der Meer JW . Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 2012; 11: 633\u2013652.","journal-title":"Nat Rev Drug Discov"},{"key":"BFcdd2015176_CR28","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1016\/j.celrep.2015.05.003","volume":"11","author":"SP Cullen","year":"2015","unstructured":"Cullen SP, Kearney CJ, Clancy DM, Martin SJ . Diverse activators of the NLRP3 inflammasome promote IL-1beta secretion by triggering necrosis. Cell Rep 2015; 11: 1535\u20131548.","journal-title":"Cell Rep"},{"key":"BFcdd2015176_CR29","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.4049\/jimmunol.179.3.1913","volume":"179","author":"Y Qu","year":"2007","unstructured":"Qu Y, Franchi L, Nunez G, Dubyak GR . Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. J Immunol 2007; 179: 1913\u20131925.","journal-title":"J Immunol"},{"key":"BFcdd2015176_CR30","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1091\/mbc.10.5.1463","volume":"10","author":"C Andrei","year":"1999","unstructured":"Andrei C, Dazzi C, Lotti L, Torrisi MR, Chimini G, Rubartelli A . The secretory route of the leaderless protein interleukin 1beta involves exocytosis of endolysosome-related vesicles. Mol Biol Cell 1999; 10: 1463\u20131475.","journal-title":"Mol Biol Cell"},{"key":"BFcdd2015176_CR31","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/35011084","volume":"405","author":"VA Fadok","year":"2000","unstructured":"Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM . A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 2000; 405: 85\u201390.","journal-title":"Nature"},{"key":"BFcdd2015176_CR32","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1038\/ncb1279","volume":"7","author":"JI Elliott","year":"2005","unstructured":"Elliott JI, Surprenant A, Marelli-Berg FM, Cooper JC, Cassady-Cain RL, Wooding C et al. Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes. Nat Cell Biol 2005; 7: 808\u2013816.","journal-title":"Nat Cell Biol"},{"key":"BFcdd2015176_CR33","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1038\/ni.2919","volume":"15","author":"A Baroja-Mazo","year":"2014","unstructured":"Baroja-Mazo A, Mart\u00edn-S\u00e1nchez F, Gomez AI, Mart\u00ednez CM, Amores-Iniesta J, Compan V et al. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol 2014; 15: 738\u2013748.","journal-title":"Nat Immunol"},{"key":"BFcdd2015176_CR34","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/ni.2913","volume":"15","author":"BS Franklin","year":"2014","unstructured":"Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G et al. The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation. Nat Immunol 2014; 15: 727\u2013737.","journal-title":"Nat Immunol"},{"key":"BFcdd2015176_CR35","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1124\/mol.66.4.909","volume":"66","author":"PA Verhoef","year":"2004","unstructured":"Verhoef PA, Kertesy SB, Estacion M, Schilling WP, Dubyak GR . Maitotoxin induces biphasic interleukin-1beta secretion and membrane blebbing in murine macrophages. Mol Pharmacol 2004; 66: 909\u2013920.","journal-title":"Mol Pharmacol"},{"key":"BFcdd2015176_CR36","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/nature15541","volume":"526","author":"N Kayagaki","year":"2015","unstructured":"Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K, Warming S et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 2015; 526: 666\u2013671.","journal-title":"Nature"},{"key":"BFcdd2015176_CR37","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/nature15514","volume":"526","author":"J Shi","year":"2015","unstructured":"Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 2015; 526: 660\u2013665.","journal-title":"Nature"},{"key":"BFcdd2015176_CR38","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1038\/cr.2015.139","volume":"25","author":"WT He","year":"2015","unstructured":"He WT, Wan H, Hu L, Chen P, Wang X, Huang Z et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion. Cell Res 2015; 25: 1285\u20131298.","journal-title":"Cell Res"},{"key":"BFcdd2015176_CR39","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nature04516","volume":"440","author":"F Martinon","year":"2006","unstructured":"Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J . Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440: 237\u2013241.","journal-title":"Nature"},{"key":"BFcdd2015176_CR40","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.1126\/science.7535475","volume":"267","author":"K Kuida","year":"1995","unstructured":"Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS et al. Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science 1995; 267: 2000\u20132003.","journal-title":"Science"},{"key":"BFcdd2015176_CR41","doi-asserted-by":"publisher","first-page":"2951","DOI":"10.1096\/fj.12-205765","volume":"26","author":"M Barbera-Cremades","year":"2012","unstructured":"Barbera-Cremades M, Baroja-Mazo A, Gomez AI, Machado F, Di Virgilio F, Pelegr\u00edn P . P2X7 receptor-stimulation causes fever via PGE2 and IL-1beta release. FASEB J 2012; 26: 2951\u20132962.","journal-title":"FASEB J"},{"key":"BFcdd2015176_CR42","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1098\/rsif.2006.0137","volume":"3","author":"H Shen","year":"2006","unstructured":"Shen H, Nelson G, Nelson DE, Kennedy S, Spiller DG, Griffiths T et al. Automated tracking of gene expression in individual cells and cell compartments. J R Soc Interface 2006; 3: 787\u2013794.","journal-title":"J R Soc Interface"},{"key":"BFcdd2015176_CR43","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.immuni.2012.06.013","volume":"37","author":"V Compan","year":"2012","unstructured":"Compan V, Baroja-Mazo A, L\u00f3pez-Castej\u00f3n G, Gomez AI, Mart\u00ednez CM, Angosto D et al. Cell volume regulation modulates NLRP3 inflammasome activation. Immunity 2012; 37: 487\u2013500.","journal-title":"Immunity"}],"container-title":["Cell Death & Differentiation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/cdd2015176.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cdd2015176","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cdd2015176.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T13:09:08Z","timestamp":1684415348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cdd2015176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,12]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["BFcdd2015176"],"URL":"https:\/\/doi.org\/10.1038\/cdd.2015.176","relation":{},"ISSN":["1350-9047","1476-5403"],"issn-type":[{"value":"1350-9047","type":"print"},{"value":"1476-5403","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,12]]},"assertion":[{"value":"28 April 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MP is an employee of Probelte Biotechnology S.L. The other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}