{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:29:10Z","timestamp":1791361750954,"version":"4.3.1"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T00:00:00Z","timestamp":1461542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T00:00:00Z","timestamp":1461542400000},"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>Disordered proteins, such as those central to Alzheimer\u2019s and Parkinson\u2019s, are particularly intractable for structure-targeted therapeutic design. Here we demonstrate the capacity of a synthetic foldamer to capture structure in a disease relevant peptide. Oligoquinoline amides have a defined fold with a solvent-excluded core that is independent of its outwardly projected, derivatizable moieties. Islet amyloid polypeptide (IAPP) is a peptide central to \u03b2-cell pathology in type II diabetes. A tetraquinoline is presented that stabilizes a pre-amyloid, \u03b1-helical conformation of IAPP. This charged, dianionic compound is readily soluble in aqueous buffer, yet crosses biological membranes without cellular assistance: an unexpected capability that is a consequence of its ability to reversibly fold. The tetraquinoline docks specifically with intracellular IAPP and rescues \u03b2-cells from toxicity. Taken together, our work here supports the thesis that stabilizing non-toxic conformers of a plastic protein is a viable strategy for cytotoxic rescue addressable using oligoquinoline amides.<\/jats:p>","DOI":"10.1038\/ncomms11412","type":"journal-article","created":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T06:51:53Z","timestamp":1461567113000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Foldamer-mediated manipulation of a pre-amyloid toxin"],"prefix":"10.1038","volume":"7","author":[{"given":"Sunil","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Birol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana E.","family":"Schlamadinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slawomir P.","family":"Wojcik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Rhoades","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Miranker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,4,25]]},"reference":[{"key":"BFncomms11412_CR1","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nchembio876","volume":"3","author":"CM Goodman","year":"2007","unstructured":"Goodman, C. M., Choi, S., Shandler, S. & DeGrado, W. F. Foldamers as versatile frameworks for the design and evolution of function. Nat. Chem. Biol. 3, 252\u2013262 (2007) .","journal-title":"Nat. Chem. Biol."},{"key":"BFncomms11412_CR2","doi-asserted-by":"publisher","first-page":"6968","DOI":"10.1073\/pnas.0811818106","volume":"106","author":"S Choi","year":"2009","unstructured":"Choi, S. et al. De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers. Proc. Natl Acad. Sci. USA 106, 6968\u20136973 (2009) .","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms11412_CR3","doi-asserted-by":"publisher","first-page":"5318","DOI":"10.1021\/ol402568j","volume":"15","author":"EV Denton","year":"2013","unstructured":"Denton, E. V. et al. A \u03b2-peptide agonist of the GLP-1 receptor, a class B GPCR. Org. Lett. 15, 5318\u20135321 (2013) .","journal-title":"Org. Lett."},{"key":"BFncomms11412_CR4","doi-asserted-by":"publisher","first-page":"14751","DOI":"10.1073\/pnas.0902663106","volume":"106","author":"WS Horne","year":"2009","unstructured":"Horne, W. S. et al. Structural and biological mimicry of protein surface recognition by \u03b1\/\u03b2-peptide foldamers. Proc. Natl Acad. Sci. USA 106, 14751\u201314756 (2009) .","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms11412_CR5","doi-asserted-by":"publisher","first-page":"5744","DOI":"10.1021\/ja711193x","volume":"130","author":"DG Udugamasooriya","year":"2008","unstructured":"Udugamasooriya, D. G., Dineen, S. P., Brekken, R. A. & Kodadek, T. A peptoid \"antibody surrogate\" that antagonizes VEGF receptor 2 activity. J. Am. Chem. Soc. 130, 5744\u20135752 (2008) .","journal-title":"J. Am. Chem. Soc."},{"key":"BFncomms11412_CR6","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/nchem.2195","volume":"7","author":"N Chandramouli","year":"2015","unstructured":"Chandramouli, N. et al. Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose. Nat. Chem. 7, 334\u2013341 (2015) .","journal-title":"Nat. Chem."},{"key":"BFncomms11412_CR7","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1038\/nchembio.232","volume":"5","author":"DD Boehr","year":"2009","unstructured":"Boehr, D. D., Nussinov, R. & Wright, P. E. The role of dynamic conformational ensembles in biomolecular recognition. Nat. Chem. Biol. 5, 789\u2013796 (2009) .","journal-title":"Nat. Chem. Biol."},{"key":"BFncomms11412_CR8","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1126\/science.aaa1823","volume":"347","author":"C Wilson","year":"2015","unstructured":"Wilson, C. et al. Using ancient protein kinases to unravel a modern cancer drug\u2019s mechanism. Science 347, 882\u2013886 (2015) .","journal-title":"Science"},{"key":"BFncomms11412_CR9","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.molmed.2015.04.005","volume":"21","author":"A Mukherjee","year":"2015","unstructured":"Mukherjee, A., Morales-Scheihing, D., Butler, P. C. & Soto, C. Type 2 diabetes as a protein misfolding disease. Trends Mol. Med. 21, 439\u2013449 (2015) .","journal-title":"Trends Mol. Med."},{"key":"BFncomms11412_CR10","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1096\/fj.11-194613","volume":"26","author":"M Magzoub","year":"2012","unstructured":"Magzoub, M. & Miranker, A. D. Concentration-dependent transitions govern the subcellular localization of islet amyloid polypeptide. FASEB J. 26, 1228\u20131238 (2012) .","journal-title":"FASEB J."},{"key":"BFncomms11412_CR11","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1038\/ni.1935","volume":"11","author":"SL Masters","year":"2010","unstructured":"Masters, S. L. et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat. Immunol. 11, 897\u2013904 (2010) .","journal-title":"Nat. Immunol."},{"key":"BFncomms11412_CR12","doi-asserted-by":"publisher","first-page":"2559","DOI":"10.1016\/j.bpj.2014.09.047","volume":"107","author":"DE Schlamadinger","year":"2014","unstructured":"Schlamadinger, D. E. & Miranker, A. D. Fiber-dependent and -independent toxicity of islet amyloid polypeptide. Biophys. J. 107, 2559\u20132566 (2014) .","journal-title":"Biophys. J."},{"key":"BFncomms11412_CR13","first-page":"795","volume":"91","author":"P Westermark","year":"2011","unstructured":"Westermark, P., Andersson, A. & Westermark, G. T. Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Phys. Rev. 91, 795\u2013826 (2011) .","journal-title":"Phys. Rev."},{"key":"BFncomms11412_CR14","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1017\/S0033583505004014","volume":"37","author":"M Magzoub","year":"2004","unstructured":"Magzoub, M. & Gr\u00e4slund, A. Cell-penetrating peptides: small from inception to application. Q. Rev. Biophys. 37, 147\u2013195 (2004) .","journal-title":"Q. Rev. Biophys."},{"key":"BFncomms11412_CR15","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1002\/pro.2518","volume":"23","author":"JA Hebda","year":"2014","unstructured":"Hebda, J. A., Magzoub, M. & Miranker, A. D. Small molecule screening in context: lipid-catalyzed amyloid formation. Protein Sci. 23, 1341\u20131348 (2014) .","journal-title":"Protein Sci."},{"key":"BFncomms11412_CR16","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nrm2330","volume":"9","author":"G Van Meer","year":"2008","unstructured":"Van Meer, G., Voelkar, D. R. & Feigenson, G. W. Membrane lipids: where they are now and how they behave. Nat. Rev. Mol. Cell. Biol. 9, 112\u2013124 (2008) .","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"BFncomms11412_CR17","doi-asserted-by":"publisher","first-page":"11075","DOI":"10.1074\/jbc.M114.628420","volume":"290","author":"MJ MacDonald","year":"2015","unstructured":"MacDonald, M. J., Ade, L., Ntambi, J. M., Ansari, I. U. & Stoker, S. W. Characterization of phospholipids in insulin secretory granules and mitochondria in pancreatic beta cells and their changes with glucose stimulation. J. Biol. Chem. 290, 11075\u201311092 (2015) .","journal-title":"J. Biol. Chem."},{"key":"BFncomms11412_CR18","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/j.chembiol.2009.08.013","volume":"16","author":"JA Hebda","year":"2009","unstructured":"Hebda, J. A. et al. A peptidomimetic approach to targeting pre-amyloidogenic states in type II diabetes. Chem. Biol. 16, 943\u2013950 (2009) .","journal-title":"Chem. Biol."},{"key":"BFncomms11412_CR19","doi-asserted-by":"publisher","first-page":"6382","DOI":"10.1073\/pnas.1219059110","volume":"110","author":"NB Last","year":"2013","unstructured":"Last, N. B. & Miranker, A. D. Common mechanism unites membrane poration by amyloid and antimicrobial peptides. Proc. Natl Acad. Sci. U S A. 110, 6382\u20136387 (2013) .","journal-title":"Proc. Natl Acad. Sci. U S A."},{"key":"BFncomms11412_CR20","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.chembiol.2015.01.006","volume":"22","author":"S Kumar","year":"2015","unstructured":"Kumar, S. et al. Islet amyloid-induced cell death and bilayer integrity loss share a molecular origin targetable with oligopyridylamide-based \u03b1-helical mimetics. Chem. Biol. 22, 369\u2013378 (2015) .","journal-title":"Chem. Biol."},{"key":"BFncomms11412_CR21","doi-asserted-by":"publisher","first-page":"4267","DOI":"10.1038\/srep04267","volume":"4","author":"Y Bram","year":"2014","unstructured":"Bram, Y. et al. Apoptosis induced by islet amyloid polypeptide soluble oligomers is neutralized by diabetes-associated specific antibodies. Sci. Rep. 4, 4267 (2014) .","journal-title":"Sci. Rep."},{"key":"BFncomms11412_CR22","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.chembiol.2014.05.007","volume":"21","author":"S Kumar","year":"2014","unstructured":"Kumar, S., Brown, M. A., Nath, A. & Miranker, A. D. Folded small molecule manipulation of islet amyloid polypeptide. Chem. Biol. 21, 775\u2013781 (2014) .","journal-title":"Chem. Biol."},{"key":"BFncomms11412_CR23","doi-asserted-by":"publisher","first-page":"4749","DOI":"10.1039\/c3cc41452c","volume":"49","author":"S Kumar","year":"2013","unstructured":"Kumar, S. & Miranker, A. D. A foldamer approach to targeting membrane bound helical states of islet amyloid polypeptide. Chem. Commun. 49, 4749\u20134751 (2013) .","journal-title":"Chem. Commun."},{"key":"BFncomms11412_CR24","doi-asserted-by":"publisher","first-page":"8127","DOI":"10.1021\/bi100939a","volume":"49","author":"F Meng","year":"2010","unstructured":"Meng, F., Abedini, A., Plesner, A., Verchere, C. B. & Raleigh, D. P. The flavanol (-)-epigallocatechin 3-gallate inhibits amyloid formation by islet amyloid polypeptide, disaggregates amyloid fibrils, and protects cultured cells against iapp-induced toxicity. Biochemistry 49, 8127\u20138133 (2010) .","journal-title":"Biochemistry"},{"key":"BFncomms11412_CR25","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.jmb.2010.05.001","volume":"400","author":"F Meng","year":"2010","unstructured":"Meng, F. et al. The sulfated triphenyl methane derivative acid fuchsin is a potent inhibitor of amyloid formation by human islet amyloid polypeptide and protects against the toxic effects of amyloid formation. J. Mol. Biol. 400, 555\u2013566 (2010) .","journal-title":"J. Mol. Biol."},{"key":"BFncomms11412_CR26","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1002\/cbic.200800762","volume":"10","author":"R Mishra","year":"2009","unstructured":"Mishra, R., Sellin, D., Radovan, D., Gohlke, A. & Winter, R. Inhibiting islet amyloid polypeptide fibril formation by the red wine compound resveratrol. ChemBioChem 10, 445\u2013449 (2009) .","journal-title":"ChemBioChem"},{"key":"BFncomms11412_CR27","doi-asserted-by":"publisher","first-page":"17205","DOI":"10.1074\/jbc.M801383200","volume":"283","author":"M Apostolidou","year":"2008","unstructured":"Apostolidou, M., Jayasinghe, S. A. & Langen, R. Structure of \u03b1-helical membrane-bound human islet amyloid polypeptide and its implications for membrane-mediated misfolding. J. Biol. Chem. 283, 17205\u201317210 (2008) .","journal-title":"J. Biol. Chem."},{"key":"BFncomms11412_CR28","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.jmb.2009.07.077","volume":"393","author":"JA Williamson","year":"2009","unstructured":"Williamson, J. A., Loria, J. P. & Miranker, A. D. Helix stabilization precedes aqueous and bilayer-catalyzed fiber formation in islet amyloid polypeptide. J. Mol. Biol. 393, 383\u2013396 (2009) .","journal-title":"J. Mol. Biol."},{"key":"BFncomms11412_CR29","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.jmb.2009.06.026","volume":"393","author":"AM Ruschak","year":"2009","unstructured":"Ruschak, A. M. & Miranker, A. D. The role of prefibrillar structures in the assembly of a peptide amyloid. J. Mol. Biol. 393, 214\u2013226 (2009) .","journal-title":"J. Mol. Biol."},{"key":"BFncomms11412_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gku1303","volume":"43","author":"P Agrawal","year":"2015","unstructured":"Agrawal, P. et al. CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides. Nucleic Acids Res. 43, 1\u20136 (2015) .","journal-title":"Nucleic Acids Res."},{"key":"BFncomms11412_CR31","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.tibs.2015.10.004","volume":"40","author":"WB Kauffman","year":"2015","unstructured":"Kauffman, W. B., Fuselier, T., He, J. & Wimley, W. C. Mechanism matters: a taxonomy of cell penetrating peptides. Trends Biochem Sci. 40, 749\u2013764 (2015) .","journal-title":"Trends Biochem Sci."},{"key":"BFncomms11412_CR32","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1002\/cbic.201000256","volume":"11","author":"J Iriondo-Alberdi","year":"2010","unstructured":"Iriondo-Alberdi, J. et al. Cellular internalization of water-soluble helical aromatic amide foldamers. Chembiochem 11, 1679\u20131685 (2010) .","journal-title":"Chembiochem"},{"key":"BFncomms11412_CR33","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/nprot.2012.059","volume":"7","author":"E Sezgin","year":"2012","unstructured":"Sezgin, E. et al. Elucidating membrane structure and protein behavior using giant plasma membrane vesicles. Nat. Protoc. 7, 1042\u20131051 (2012) .","journal-title":"Nat. Protoc."},{"key":"BFncomms11412_CR34","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1002\/cphc.200800310","volume":"9","author":"N Delsuc","year":"2013","unstructured":"Delsuc, N. et al. Kinetics of helix-handedness inversion: folding and unfolding in aromatic amide oligomers. Chemphyschem 9, 1882\u20131890 (2013) .","journal-title":"Chemphyschem"},{"key":"BFncomms11412_CR35","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1021\/jo1019442","volume":"76","author":"AM Kendhale","year":"2011","unstructured":"Kendhale, A. M. et al. Absolute control of helical handedness in quinoline oligoamides. J. Org. Chem. 76, 195\u2013200 (2011) .","journal-title":"J. Org. Chem."},{"key":"BFncomms11412_CR36","doi-asserted-by":"publisher","first-page":"8365","DOI":"10.1016\/j.tet.2003.08.058","volume":"59","author":"H Jiang","year":"2003","unstructured":"Jiang, H., L\u00e9ger, J., Dolain, C., Guionneau, P. & Huc, I. Aromatic \u03b4-peptides: design, synthesis and structural studies of helical, quinoline-derived oligoamide foldamers. Tetrahedron 59, 8365\u20138374 (2003) .","journal-title":"Tetrahedron"},{"key":"BFncomms11412_CR37","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.cbpa.2010.06.169","volume":"14","author":"SJ Metallo","year":"2010","unstructured":"Metallo, S. J. Intrinsically disordered proteins are potential drug targets. Curr. Opin. Chem. Biol. 14, 481\u2013488 (2010) .","journal-title":"Curr. Opin. Chem. Biol."},{"key":"BFncomms11412_CR38","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1016\/j.febslet.2015.06.003","volume":"589","author":"RB Berlow","year":"2015","unstructured":"Berlow, R. B., Dyson, H. J. & Wright, P. E. Functional advantages of dynamic protein disorder. FEBS Lett. 589, 2433\u20132440 (2015) .","journal-title":"FEBS Lett."},{"key":"BFncomms11412_CR39","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nature13999","volume":"519","author":"A Bah","year":"2015","unstructured":"Bah, A. et al. Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch. Nature 519, 106\u2013109 (2015) .","journal-title":"Nature"},{"key":"BFncomms11412_CR40","doi-asserted-by":"publisher","first-page":"e87133","DOI":"10.1371\/journal.pone.0087133","volume":"9","author":"G T\u00f3th","year":"2014","unstructured":"T\u00f3th, G. et al. Targeting the intrinsically disordered structural ensemble of \u03b1-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease. PLOS ONE 9, e87133 (2014) .","journal-title":"PLOS ONE"},{"key":"BFncomms11412_CR41","doi-asserted-by":"publisher","first-page":"035101","DOI":"10.1063\/1.4811831","volume":"139","author":"M Zhu","year":"2013","unstructured":"Zhu, M. et al. Identification of small-molecule binding pockets in the soluble monomeric form of the A\u03b242 peptide. J. Chem. Phys. 139, 035101 (2013) .","journal-title":"J. Chem. Phys."},{"key":"BFncomms11412_CR42","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1021\/acs.biochem.5b00052","volume":"54","author":"A Nath","year":"2015","unstructured":"Nath, A., Schlamadinger, D. E., Rhoades, E. & Miranker, A. D. Structure-based small molecule modulation of a pre-amyloid state: pharmacological enhancement of iapp membrane-binding and toxicity. Biochemistry 54, 3555\u20133564 (2015) .","journal-title":"Biochemistry"},{"key":"BFncomms11412_CR43","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1021\/ac60119a033","volume":"28","author":"PS Chen","year":"1956","unstructured":"Chen, P. S., Toribara, T. Y. & Warner, H. Microdetermination of phosphorus. Anal. Chem. 28, 1756\u20131758 (1956) .","journal-title":"Anal. Chem."},{"key":"BFncomms11412_CR44","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1016\/j.bpj.2010.07.056","volume":"99","author":"ER Middleton","year":"2010","unstructured":"Middleton, E. R. & Rhoades, E. Effects of curvature and composition on \u03b1-synuclein binding to lipid vesicles. Biophys. J. 99, 2279\u20132288 (2010) .","journal-title":"Biophys. J."},{"key":"BFncomms11412_CR45","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1016\/S0006-3495(99)77065-7","volume":"77","author":"P Schwille","year":"1999","unstructured":"Schwille, P., Haupts, U., Maiti, S. & Webb, W. W. Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. Biophys. J. 77, 2251\u20132265 (1999) .","journal-title":"Biophys. J."},{"key":"BFncomms11412_CR46","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671\u2013675 (2012) .","journal-title":"Nat. Methods"},{"key":"BFncomms11412_CR47","doi-asserted-by":"publisher","first-page":"7931","DOI":"10.1021\/jo0603577","volume":"71","author":"ER Gillies","year":"2006","unstructured":"Gillies, E. R., Dolain, C., Leger, J. & Huc, I. Amphipathic helices from aromatic amino acid oligomers. J. Org. Chem. 71, 7931\u20137939 (2006) .","journal-title":"J. Org. Chem."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms11412.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms11412","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms11412.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T06:18:03Z","timestamp":1672813083000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms11412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,25]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,1]]}},"alternative-id":["BFncomms11412"],"URL":"https:\/\/doi.org\/10.1038\/ncomms11412","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,25]]},"assertion":[{"value":"28 August 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2016","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This paper was updated shortly after publication, following a technical error that meant the HTML linked to incorrect article and supplementary information PDFs. The error has now been fixed.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11412"}}