{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T19:53:43Z","timestamp":1773690823136,"version":"3.50.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The ability to induce reversible phase transitions between homogeneous solutions and biphasic liquid-liquid systems, at pre-defined and suitable operating temperatures, is of crucial relevance in the design of separation processes. Ionic-liquid-based aqueous biphasic systems (IL-based ABS) have demonstrated superior performance as alternative extraction platforms and their thermoreversible behaviour is here disclosed by the use of protic ILs. The applicability of the temperature-induced phase switching is further demonstrated with the complete extraction of two value-added proteins, achieved in a single-step. It is shown that these temperature-induced mono(bi)phasic systems are significantly more versatile than classical liquid-liquid systems which are constrained by their critical temperatures. IL-based ABS allow to work in a wide range of temperatures and compositions which can be tailored to fit the requirements of a given separation process.<\/jats:p>","DOI":"10.1038\/srep20276","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T10:21:04Z","timestamp":1454581264000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Thermoreversible (Ionic-Liquid-Based) Aqueous Biphasic Systems"],"prefix":"10.1038","volume":"6","author":[{"given":"Helena","family":"Passos","sequence":"first","affiliation":[]},{"given":"Andreia","family":"Lu\u00eds","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o A. P.","family":"Coutinho","sequence":"additional","affiliation":[]},{"given":"Mara G.","family":"Freire","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,2,4]]},"reference":[{"key":"BFsrep20276_CR1","doi-asserted-by":"publisher","first-page":"9058","DOI":"10.1021\/ja001708g","volume":"122","author":"DE Bergbreiter","year":"2000","unstructured":"Bergbreiter, D. E., Osburn, P. L., Wilson, A. & Sink, E. M. Palladium-catalyzed C\u2212C coupling under thermomorphic conditions. J. Am. Chem. Soc. 122, 9058\u20139064 (2000).","journal-title":"J. Am. Chem. Soc."},{"key":"BFsrep20276_CR2","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1002\/adsc.200606094","volume":"348","author":"A Behr","year":"2006","unstructured":"Behr, A., Henze, G. & Schom\u00e4cker, R. Thermoregulated liquid\/liquid catalyst separation and recycling. Adv. Synth. Catal. 348, 1485\u20131495 (2006).","journal-title":"Adv. Synth. Catal."},{"key":"BFsrep20276_CR3","doi-asserted-by":"publisher","first-page":"7119","DOI":"10.1039\/c2cc31638b","volume":"48","author":"Y Kohno","year":"2012","unstructured":"Kohno, Y. & Ohno, H. Ionic liquid\/water mixtures: from hostility to conciliation. Chem. Commun. 48, 7119\u20137130 (2012).","journal-title":"Chem. Commun."},{"key":"BFsrep20276_CR4","doi-asserted-by":"publisher","first-page":"7240","DOI":"10.1039\/c2ee02912j","volume":"5","author":"PG Jessop","year":"2012","unstructured":"Jessop, P. G., Mercer, S. M. & Heldebrant, D. J. CO2-triggered switchable solvents, surfactants and other materials. Energy Environ. Sci. 5, 7240\u20137253 (2012).","journal-title":"Energy Environ. Sci."},{"key":"BFsrep20276_CR5","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1039\/C2NJ40890B","volume":"37","author":"J Luo","year":"2013","unstructured":"Luo, J., Xin, T. & Wang, Y. A PEG bridged tertiary amine functionalized ionic liquid exhibiting thermoregulated reversible biphasic behavior with cyclohexane\/isopropanol: synthesis and application in Knoevenagel condensation. New J. Chem. 37, 269\u2013273 (2013).","journal-title":"New J. Chem."},{"key":"BFsrep20276_CR6","doi-asserted-by":"publisher","first-page":"4772","DOI":"10.1039\/c1cc10613a","volume":"47","author":"Y Kohno","year":"2011","unstructured":"Kohno, Y., Arai, H. & Ohno, H. Dual stimuli-responsive phase transition of an ionic liquid\/water mixture. Chem. Commun. 47, 4772\u20134774 (2011).","journal-title":"Chem. Commun."},{"key":"BFsrep20276_CR7","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1002\/cssc.201200307","volume":"5","author":"D Xiong","year":"2012","unstructured":"Xiong, D., Wang, H., Li, Z. & Wang, J. Recovery of ionic liquids with aqueous two-phase systems induced by carbon dioxide. Chem. Sus. Chem. 5, 2255\u20132261 (2012).","journal-title":"Chem. Sus. Chem"},{"key":"BFsrep20276_CR8","doi-asserted-by":"publisher","first-page":"8988","DOI":"10.1039\/c3cc45302b","volume":"49","author":"S Saita","year":"2013","unstructured":"Saita, S., Kohno, Y., Nakamura, N. & Ohno, H. Ionic liquids showing phase separation with water prepared by mixing hydrophilic and polar amino acid ionic liquids. Chem. Commun. 49, 8988\u20138990 (2013).","journal-title":"Chem. Commun."},{"key":"BFsrep20276_CR9","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S1381-1169(02)00653-2","volume":"197","author":"A Behr","year":"2003","unstructured":"Behr, A. & F\u00e4ngewisch, C. Rhodium-catalysed synthesis of branched fatty compounds in temperature-dependent solvent systems. J. Mol. Catal. A: Chem. 197, 115\u2013126 (2003).","journal-title":"J. Mol. Catal. A: Chem"},{"key":"BFsrep20276_CR10","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1039\/b505588a","volume":"7","author":"A Riisager","year":"2005","unstructured":"Riisager, A., Fehrmann, R., Berg, R. W., van Hal, R. & Wasserscheid, P. Thermomorphic phase separation in ionic liquid-organic liquid systems-conductivity and spectroscopic characterization. Phys. Chem. Chem. Phys. 7, 3052\u20133058 (2005).","journal-title":"Phys. Chem. Chem. Phys."},{"key":"BFsrep20276_CR11","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1021\/jp808993t","volume":"113","author":"P Nockemann","year":"2009","unstructured":"Nockemann, P. et al. Temperature-driven mixing-demixing behavior of binary mixtures of the ionic liquid choline bis(trifluoromethylsulfonyl)imide and water. J. Phys. Chem. B 113, 1429\u20131437 (2009).","journal-title":"J. Phys. Chem. B"},{"key":"BFsrep20276_CR12","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/cphc.201000808","volume":"12","author":"Z-L Xie","year":"2011","unstructured":"Xie, Z.-L. & Taubert, A. Thermomorphic behavior of the ionic liquids [C4mim][FeCl4] and [C12mim][FeCl4]. ChemPhysChem 12, 364\u2013368 (2011).","journal-title":"ChemPhysChem"},{"key":"BFsrep20276_CR13","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1002\/chem.201202707","volume":"19","author":"W Zhu","year":"2013","unstructured":"Zhu, W. et al. Cooperative effects in catalytic hydrogenation regulated by both the cation and anion of an ionic liquid. Chem. Eur. J. 19, 2059\u20132066 (2013).","journal-title":"Chem. Eur. J"},{"key":"BFsrep20276_CR14","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1021\/jz4005366","volume":"4","author":"TV Hoogerstraete","year":"2013","unstructured":"Hoogerstraete, T. V., Onghena, B. & Binnemans, K. Homogeneous liquid\u2013liquid extraction of metal ions with a functionalized ionic liquid. J. Phys. Chem. Lett. 4, 1659\u20131663 (2013).","journal-title":"J. Phys. Chem. Lett."},{"key":"BFsrep20276_CR15","doi-asserted-by":"crossref","unstructured":"Onghena, B., Opsomer, T. & Binnemans, K. Separation of cobalt and nickel using a thermomorphic ionic-liquid-based aqueous biphasic system. Chem. Commun., doi: 10.1039\/C1035CC06595J (2015).","DOI":"10.1039\/C5CC06595J"},{"key":"BFsrep20276_CR16","doi-asserted-by":"publisher","first-page":"20978","DOI":"10.1021\/jp0642995","volume":"110","author":"P Nockemann","year":"2006","unstructured":"Nockemann, P. et al. Task-specific ionic liquid for solubilizing metal oxides. J. Phys. Chem. B 110, 20978\u201320992 (2006).","journal-title":"J. Phys. Chem. B"},{"key":"BFsrep20276_CR17","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1002\/anie.200604402","volume":"46","author":"K Fukumoto","year":"2007","unstructured":"Fukumoto, K. & Ohno, H. LCST-type phase changes of a mixture of water and ionic liquids derived from amino acids. Angew. Chem. Int. Ed. 46, 1852\u20131855 (2007).","journal-title":"Angew. Chem. Int. Ed."},{"key":"BFsrep20276_CR18","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1039\/c0py00364f","volume":"2","author":"Y Kohno","year":"2011","unstructured":"Kohno, Y., Saita, S., Murata, K., Nakamura, N. & Ohno, H. Extraction of proteins with temperature sensitive and reversible phase change of ionic liquid\/water mixture. Polym. Chem. 2, 862\u2013867 (2011).","journal-title":"Polym. Chem"},{"key":"BFsrep20276_CR19","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1038\/4361102a","volume":"436","author":"PG Jessop","year":"2005","unstructured":"Jessop, P. G., Heldebrant, D. J., Li, X., Eckert, C. A. & Liotta, C. L. Green chemistry: Reversible nonpolar-to-polar solvent. Nature 436, 1102\u20131102 (2005).","journal-title":"Nature"},{"key":"BFsrep20276_CR20","doi-asserted-by":"crossref","unstructured":"Huddleston G., J. & Rogers, D. R. Room temperature ionic liquids as novel media for \u2018clean\u2019 liquid-liquid extraction. Chem. Commun., 1765\u20131766 (1998).","DOI":"10.1039\/A803999B"},{"key":"BFsrep20276_CR21","doi-asserted-by":"publisher","first-page":"6632","DOI":"10.1021\/ja0351802","volume":"125","author":"KE Gutowski","year":"2003","unstructured":"Gutowski, K. E. et al. Controlling the aqueous miscibility of ionic liquids: aqueous biphasic systems of water-miscible ionic liquids and water-structuring salts for recycle, metathesis and separations. J. Am. Chem. Soc. 125, 6632\u20136633 (2003).","journal-title":"J. Am. Chem. Soc."},{"key":"BFsrep20276_CR22","doi-asserted-by":"publisher","first-page":"4966","DOI":"10.1039\/c2cs35151j","volume":"41","author":"MG Freire","year":"2012","unstructured":"Freire, M. G. et al. Aqueous biphasic systems: a boost brought about by using ionic liquids. Chem. Soc. Rev. 41, 4966\u20134995 (2012).","journal-title":"Chem. Soc. Rev."},{"key":"BFsrep20276_CR23","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1039\/c0gc00179a","volume":"12","author":"MG Freire","year":"2010","unstructured":"Freire, M. G. et al. High-performance extraction of alkaloids using aqueous two-phase systems with ionic liquids. Green Chem. 12, 1715\u20131718 (2010).","journal-title":"Green Chem."},{"key":"BFsrep20276_CR24","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1039\/c1gc15110j","volume":"13","author":"MG Freire","year":"2011","unstructured":"Freire, M. G., Louros, C. L. S., Rebelo, L. P. N. & Coutinho, J. A. P. Aqueous biphasic systems composed of a water-stable ionic liquid+carbohydrates and their applications. Green Chem. 13, 1536\u20131545 (2011).","journal-title":"Green Chem."},{"key":"BFsrep20276_CR25","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/182709a0","volume":"182","author":"P-A Albertsson","year":"1958","unstructured":"Albertsson, P.-A. Partition of Proteins in Liquid Polymer-Polymer Two-Phase Systems. Nature 182, 709\u2013711 (1958).","journal-title":"Nature"},{"key":"BFsrep20276_CR26","doi-asserted-by":"publisher","first-page":"8826","DOI":"10.1016\/j.chroma.2011.06.051","volume":"1218","author":"JA Asenjo","year":"2011","unstructured":"Asenjo, J. A. & Andrews, B. A. Aqueous two-phase systems for protein separation: A perspective. J. Chromatogr. A 1218, 8826\u20138835 (2011).","journal-title":"J. Chromatogr. A"},{"key":"BFsrep20276_CR27","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.seppur.2012.02.032","volume":"90","author":"P Selvakumar","year":"2012","unstructured":"Selvakumar, P., Ling, T. C., Walker, S. & Lyddiatt, A. Partitioning of haemoglobin and bovine serum albumin from whole bovine blood using aqueous two-phase systems. Sep. Pur. Technol. 90, 182\u2013188 (2012).","journal-title":"Sep. Pur. Technol"},{"key":"BFsrep20276_CR28","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.seppur.2014.03.020","volume":"135","author":"J-K Yan","year":"2014","unstructured":"Yan, J.-K., Ma, H.-L., Pei, J.-J., Wang, Z.-B. & Wu, J.-Y. Facile and effective separation of polysaccharides and proteins from Cordyceps sinensis mycelia by ionic liquid aqueous two-phase system. Sep. Pur. Technol. 135, 278\u2013284 (2014).","journal-title":"Sep. Pur. Technol"},{"key":"BFsrep20276_CR29","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jbiotec.2015.03.028","volume":"206","author":"MM Pereira","year":"2015","unstructured":"Pereira, M. M. et al. Enhanced extraction of bovine serum albumin with aqueous biphasic systems of phosphonium- and ammonium-based ionic liquids. J. Biotechnol. 206, 17\u201325 (2015).","journal-title":"J. Biotechnol."},{"key":"BFsrep20276_CR30","doi-asserted-by":"publisher","first-page":"4781","DOI":"10.1002\/chem.201405693","volume":"21","author":"M Taha","year":"2015","unstructured":"Taha, M. et al. Novel biocompatible and self-buffering ionic liquids for biopharmaceutical applications. Chem. Eur. J. 21, 4781\u20134788 (2015).","journal-title":"Chem. Eur. J"},{"key":"BFsrep20276_CR31","doi-asserted-by":"publisher","first-page":"3149","DOI":"10.1039\/C4GC00328D","volume":"16","author":"M Taha","year":"2014","unstructured":"Taha, M. et al. Good\u2019s buffers as a basis for developing self-buffering and biocompatible ionic liquids for biological research. Green Chem. 16, 3149\u20133159 (2014).","journal-title":"Green Chem."},{"key":"BFsrep20276_CR32","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1039\/c2gc16428k","volume":"14","author":"SPM Ventura","year":"2012","unstructured":"Ventura, S. P. M. et al. Production and purification of an extracellular lipolytic enzyme using ionic liquid-based aqueous two-phase systems. Green Chem. 14, 734\u2013740 (2012).","journal-title":"Green Chem."},{"key":"BFsrep20276_CR33","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1002\/biot.201500003","volume":"10","author":"MV Quental","year":"2015","unstructured":"Quental, M. V. et al. Enhanced extraction of proteins using cholinium-based ionic liquids as phase-forming components of aqueous biphasic systems. Biotechnol. J. 10, 1457\u20131466 (2015).","journal-title":"Biotechnol. J"},{"key":"BFsrep20276_CR34","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1021\/cr068040u","volume":"108","author":"TL Greaves","year":"2008","unstructured":"Greaves, T. L. & Drummond, C. J. Protic ionic liquids: properties and applications. Chem. Rev. 108, 206\u2013237 (2008).","journal-title":"Chem. Rev."},{"key":"BFsrep20276_CR35","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1002\/chem.201101780","volume":"18","author":"MG Freire","year":"2012","unstructured":"Freire, M. G. et al. Insight into the interactions that control the phase behaviour of new aqueous biphasic systems composed of polyethylene glycol polymers and ionic liquids. Chem. Eur. J 18, 1831\u20131839 (2012).","journal-title":"Chem. Eur. J"},{"key":"BFsrep20276_CR36","doi-asserted-by":"publisher","first-page":"15925","DOI":"10.1021\/jp1093788","volume":"114","author":"MG Freire","year":"2010","unstructured":"Freire, M. G. et al. Mutual solubility of water and structural\/positional isomers of n-alkylpyridinium-based ionic liquids. J. Phys. Chem. B 114, 15925\u201315934 (2010).","journal-title":"J. Phys. Chem. B"},{"key":"BFsrep20276_CR37","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1039\/b513308d","volume":"8","author":"J \u0141achwa","year":"2006","unstructured":"\u0141achwa, J. et al. Changing from an unusual high-temperature demixing to a UCST-type in mixtures of 1-alkyl-3-methylimidazolium bis{(trifluoromethyl)sulfonyl}amide and arenes. Green Chem. 8, 262\u2013267 (2006).","journal-title":"Green Chem."},{"key":"BFsrep20276_CR38","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1039\/C2CC37006A","volume":"49","author":"S Saita","year":"2013","unstructured":"Saita, S., Kohno, Y. & Ohno, H. Detection of small differences in the hydrophilicity of ions using the LCST-type phase transition of an ionic liquid-water mixture. Chem. Commun. 49, 93\u201395 (2013).","journal-title":"Chem. Commun."},{"key":"BFsrep20276_CR39","doi-asserted-by":"publisher","first-page":"875","DOI":"10.2116\/analsci.14.875","volume":"14","author":"H Tani","year":"1998","unstructured":"Tani, H., Kamidate, T. & Watanabe, H. Aqueous micellar two-phase systems for protein separation. Anal. Sci. 14, 875\u2013888 (1998).","journal-title":"Anal. Sci."},{"key":"BFsrep20276_CR40","doi-asserted-by":"publisher","first-page":"2902","DOI":"10.1021\/bm7006136","volume":"8","author":"Y Liu","year":"2007","unstructured":"Liu, Y. & Guo, R. Interaction between casein and the oppositely charged surfactant. Biomacromolecules 8, 2902\u20132908 (2007).","journal-title":"Biomacromolecules"},{"key":"BFsrep20276_CR41","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1039\/b302570e","volume":"5","author":"MB Turner","year":"2003","unstructured":"Turner, M. B., Spear, S. K., Huddleston, J. G., Holbrey, J. D. & Rogers, R. D. Ionic liquid salt-induced inactivation and unfolding of cellulase from Trichoderma reesei. Green Chem. 5, 443\u2013447 (2003).","journal-title":"Green Chem."},{"key":"BFsrep20276_CR42","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1021\/bm050847t","volume":"7","author":"K Shimojo","year":"2006","unstructured":"Shimojo, K., Nakashima, K., Kamiya, N. & Goto, M. Crown ether-mediated extraction and functional conversion of cytochrome c in ionic liquids. Biomacromolecules 7, 2\u20135 (2006).","journal-title":"Biomacromolecules"},{"key":"BFsrep20276_CR43","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1039\/C3GC41999A","volume":"16","author":"AFM Cl\u00e1udio","year":"2014","unstructured":"Cl\u00e1udio, A. F. M., Marques, C. F. C., Boal-Palheiros, I., Freire, M. G. & Coutinho, J. A. P. Development of back-extraction and recyclability routes for ionic-liquid-based aqueous two-phase systems. Green Chem. 16, 259\u2013268 (2014).","journal-title":"Green Chem."},{"key":"BFsrep20276_CR44","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1039\/c3gc40437d","volume":"15","author":"AFM Cl\u00e1udio","year":"2013","unstructured":"Cl\u00e1udio, A. F. M., Ferreira, A. M., Freire, M. G. & Coutinho, J. A. P. Enhanced extraction of caffeine from guarana seeds using aqueous solutions of ionic liquids. Green Chem. 15, 2002\u20132010 (2013).","journal-title":"Green Chem."},{"key":"BFsrep20276_CR45","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.seppur.2014.02.036","volume":"128","author":"AM Ferreira","year":"2014","unstructured":"Ferreira, A. M., Coutinho, J. A. P., Fernandes, A. M. & Freire, M. G. Complete removal of textile dyes from aqueous media using ionic-liquid-based aqueous two-phase systems. Sep. Pur. Technol. 128, 58\u201366 (2014).","journal-title":"Sep. Pur. Technol"},{"key":"BFsrep20276_CR46","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.bbabio.2007.06.004","volume":"1767","author":"A Barth","year":"2007","unstructured":"Barth, A. Infrared spectroscopy of proteins. Biochim. Biophys. Acta 1767, 1073\u20131101 (2007).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFsrep20276_CR47","doi-asserted-by":"crossref","unstructured":"Fujita, K., MacFarlane, D. R. & Forsyth, M. Protein solubilising and stabilising ionic liquids. Chem. Commun., 4804\u20134806 (2005).","DOI":"10.1039\/b508238b"},{"key":"BFsrep20276_CR48","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1021\/bm070041o","volume":"8","author":"K Fujita","year":"2007","unstructured":"Fujita, K. et al. Solubility and stability of cytochrome c in hydrated ionic liquids: effect of oxo acid residues and kosmotropicity. Biomacromolecules 8, 2080\u20132086 (2007).","journal-title":"Biomacromolecules"},{"key":"BFsrep20276_CR49","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/S0378-4347(97)00594-X","volume":"711","author":"JC Merchuk","year":"1998","unstructured":"Merchuk, J. C., Andrews, B. A. & Asenjo, J. A. Aqueous two-phase systems for protein separation: studies on phase inversion. J. Chromatogr. B, Biomed.Sci. Appl. 711, 285\u2013293 (1998).","journal-title":"J. Chromatogr. B, Biomed.Sci. Appl"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep20276","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep20276.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep20276.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:37:47Z","timestamp":1672839467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep20276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,4]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,22]]}},"alternative-id":["BFsrep20276"],"URL":"https:\/\/doi.org\/10.1038\/srep20276","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,4]]},"assertion":[{"value":"14 July 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2016","order":3,"name":"first_online","label":"First Online","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":"20276"}}