{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:11:08Z","timestamp":1791040268978,"version":"4.1.0"},"reference-count":60,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T00:00:00Z","timestamp":1373932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T00:00:00Z","timestamp":1373932800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T00:00:00Z","timestamp":1373932800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AG029430"],"award-info":[{"award-number":["AG029430"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"US Department of Energy","award":["DE-FC02-02ER63421"],"award-info":[{"award-number":["DE-FC02-02ER63421"]}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Amyloid protein aggregates are associated with dozens of devastating diseases including Alzheimer\u2019s, Parkinson\u2019s, ALS, and diabetes type 2. While structure-based discovery of compounds has been effective in combating numerous infectious and metabolic diseases, ignorance of amyloid structure has hindered similar approaches to amyloid disease. Here we show that knowledge of the atomic structure of one of the adhesive, steric-zipper segments of the amyloid-beta (A\u03b2) protein of Alzheimer\u2019s disease, when coupled with computational methods, identifies eight diverse but mainly flat compounds and three compound derivatives that reduce A\u03b2 cytotoxicity against mammalian cells by up to 90%. Although these compounds bind to A\u03b2 fibers, they do not reduce fiber formation of A\u03b2. Structure-activity relationship studies of the fiber-binding compounds and their derivatives suggest that compound binding increases fiber stability and decreases fiber toxicity, perhaps by shifting the equilibrium of A\u03b2 from oligomers to fibers.<\/jats:p>","DOI":"10.7554\/elife.00857","type":"journal-article","created":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T13:52:28Z","timestamp":1373982748000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.00857","source":"Crossref","is-referenced-by-count":94,"title":["Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta"],"prefix":"10.7554","volume":"2","author":[{"given":"Lin","family":"Jiang","sequence":"first","affiliation":[{"name":"Departments of Chemistry and Biochemistry and Biological Chemistry, Howard Hughes Medical Institute, UCLA\u2013DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry and Biological Chemistry, Howard Hughes Medical Institute, UCLA\u2013DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Leibly","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry and Biological Chemistry, Howard Hughes Medical Institute, UCLA\u2013DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meytal","family":"Landau","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry and Biological Chemistry, Howard Hughes Medical Institute, UCLA\u2013DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry and Biological Chemistry, Howard Hughes Medical Institute, UCLA\u2013DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P","family":"Hughes","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry and Biological Chemistry, Howard Hughes Medical Institute, UCLA\u2013DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry and Biological Chemistry, Howard Hughes Medical Institute, UCLA\u2013DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2013,7,16]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature09873","article-title":"Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan","volume":"472","author":"Alavez","year":"2011","journal-title":"Nature"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1002\/cbic.200900666","article-title":"Strategies for the inhibition of protein aggregation in human diseases","volume":"11","author":"Bartolini","year":"2010","journal-title":"Chembiochem"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/nchembio.719","article-title":"Small-molecule conversion of toxic oligomers to nontoxic beta-sheet-rich amyloid fibrils","volume":"8","author":"Bieschke","year":"2011","journal-title":"Nat Chem Biol"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/S1093-3263(02)00204-8","article-title":"Assessing the performance of OMEGA with respect to retrieving bioactive conformations","volume":"21","author":"Bostrom","year":"2003","journal-title":"J Mol Graph Model"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"17015","DOI":"10.1021\/ja107552s","article-title":"Small molecule microarrays enable the discovery of compounds that bind the alzheimer\u2019s abeta peptide and reduce its cytotoxicity","volume":"132","author":"Chen","year":"2010","journal-title":"J Am Chem Soc"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1038\/nchem.1433","article-title":"Amyloid beta-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity","volume":"4","author":"Cheng","year":"2012","journal-title":"Nat Chem"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","article-title":"Protein misfolding, functional amyloid, and human disease","volume":"75","author":"Chiti","year":"2006","journal-title":"Annu Rev Biochem"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nn1372","article-title":"Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function","volume":"8","author":"Cleary","year":"2005","journal-title":"Nat Neurosci"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"16938","DOI":"10.1073\/pnas.1112600108","article-title":"Molecular basis for amyloid-beta polymorphism","volume":"108","author":"Colletier","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/j.cell.2012.03.037","article-title":"Direct observation of the interconversion of normal and toxic forms of alpha-synuclein","volume":"149","author":"Cremades","year":"2012","journal-title":"Cell"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.expneurol.2009.08.032","article-title":"Amyloid-beta fibrillogenesis: structural insight and therapeutic intervention","volume":"223","author":"Dasilva","year":"2010","journal-title":"Exp Neurol"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.jmb.2008.11.010","article-title":"RosettaLigand docking with full ligand and receptor flexibility","volume":"385","author":"Davis","year":"2009","journal-title":"J Mol Biol"},{"key":"bib13","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1096\/fj.00-0676fje","article-title":"Inhibition of alzheimer\u2019s disease beta-amyloid aggregation, neurotoxicity, and in vivo deposition by nitrophenols: implications for alzheimer\u2019s therapy","volume":"15","author":"De Felice","year":"2001","journal-title":"FASEB J"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/nsmb.1437","article-title":"EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers","volume":"15","author":"Ehrnhoefer","year":"2008","journal-title":"Nat Struct Mol Biol"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1016\/j.cell.2012.02.022","article-title":"The amyloid state of proteins in human diseases","volume":"148","author":"Eisenberg","year":"2012","journal-title":"Cell"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"33182","DOI":"10.1074\/jbc.M606192200","article-title":"Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro","volume":"281","author":"Evans","year":"2006","journal-title":"J Biol Chem"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1023\/A:1011115820450","article-title":"DOCK 4.0: search strategies for automated molecular docking of flexible molecule databases","volume":"15","author":"Ewing","year":"2001","journal-title":"J Comput Aided Mol Des"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"417","DOI":"10.2174\/1568026024607508","article-title":"Peptide inhibitors of beta amyloid aggregation","volume":"2","author":"Findeis","year":"2002","journal-title":"Curr Top Med Chem"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jmb.2009.12.016","article-title":"The recombinant amyloid-beta peptide Abeta1-42 aggregates faster and is more neurotoxic than synthetic Abeta1-42","volume":"396","author":"Finder","year":"2010","journal-title":"J Mol Biol"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.brainresrev.2006.08.001","article-title":"Congo red and protein aggregation in neurodegenerative diseases","volume":"53","author":"Frid","year":"2007","journal-title":"Brain Res Rev"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1021\/ci050400b","article-title":"The blue obelisk-interoperability in chemical informatics","volume":"46","author":"Guha","year":"2006","journal-title":"J Chem Inf Model"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.jmb.2011.12.062","article-title":"Inhibition of amyloid formation","volume":"421","author":"Hard","year":"2012","journal-title":"J Mol Biol"},{"key":"bib23","doi-asserted-by":"crossref","first-page":"8876","DOI":"10.1523\/JNEUROSCI.19-20-08876.1999","article-title":"Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons","volume":"19","author":"Hartley","year":"1999","journal-title":"J Neurosci"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.jmr.2006.10.014","article-title":"Water suppression that works. excitation sculpting using arbitrary waveforms and pulsed field gradients","volume":"112","author":"Hwang","year":"1995","journal-title":"J Magn Reson"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"ZINC\u2013a free database of commercially available compounds for virtual screening","volume":"45","author":"Irwin","year":"2005","journal-title":"J Chem Inf Model"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1126\/science.1079469","article-title":"Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis","volume":"300","author":"Kayed","year":"2003","journal-title":"Science"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1002\/ana.20009","article-title":"Imaging brain amyloid in alzheimer\u2019s disease with pittsburgh compound-B","volume":"55","author":"Klunk","year":"2004","journal-title":"Ann Neurol"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"9906","DOI":"10.1021\/bi060837s","article-title":"N-Methylated peptide inhibitors of beta-amyloid aggregation and toxicity. Optimization of the inhibitor structure","volume":"45","author":"Kokkoni","year":"2006","journal-title":"Biochemistry"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/S0022-2836(03)00021-4","article-title":"An orientation-dependent hydrogen bonding potential improves prediction of specificity and structure for proteins and protein-protein complexes","volume":"326","author":"Kortemme","year":"2003","journal-title":"J Mol Biol"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"11172","DOI":"10.1073\/pnas.1209527109","article-title":"Conserved features of intermediates in amyloid assembly determine their benign or toxic states","volume":"109","author":"Krishnan","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"34786","DOI":"10.1074\/jbc.M112.357665","article-title":"Discovery and structure activity relationship of small molecule inhibitors of toxic beta-amyloid-42 fibril formation","volume":"287","author":"Kroth","year":"2012","journal-title":"J Biol Chem"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"10383","DOI":"10.1073\/pnas.97.19.10383","article-title":"Native protein sequences are close to optimal for their structures","volume":"97","author":"Kuhlman","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"19965","DOI":"10.1073\/pnas.1208797109","article-title":"Rational design of potent domain antibody inhibitors of amyloid fibril assembly","volume":"109","author":"Ladiwala","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1074\/jbc.M110.173856","article-title":"Aromatic small molecules remodel toxic soluble oligomers of amyloid beta through three independent pathways","volume":"286","author":"Ladiwala","year":"2011","journal-title":"J Biol Chem"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1126\/science.1213151","article-title":"Atomic view of a toxic amyloid small oligomer","volume":"335","author":"Laganowsky","year":"2012","journal-title":"Science"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"e1001080","DOI":"10.1371\/journal.pbio.1001080","article-title":"Towards a pharmacophore for amyloid","volume":"9","author":"Landau","year":"2011","journal-title":"PLOS BIOL"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1006\/jmbi.1993.1648","article-title":"Shape complementarity at protein\/protein interfaces","volume":"234","author":"Lawrence","year":"1993","journal-title":"J Mol Biol"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1002\/(SICI)1097-0134(19990501)35:23.0.CO;2-N","article-title":"Effective energy function for proteins in solution","volume":"35","author":"Lazaridis","year":"1999","journal-title":"Proteins"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/B978-0-12-381270-4.00019-6","article-title":"ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules","volume":"487","author":"Leaver-Fay","year":"2011","journal-title":"Methods Enzymol"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"20913","DOI":"10.1073\/pnas.1218792109","article-title":"Out-of-register beta-sheets suggest a pathway to toxic amyloid aggregates","volume":"109","author":"Liu","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"17342","DOI":"10.1073\/pnas.0506723102","article-title":"3D structure of Alzheimer\u2019s amyloid-beta(1-42) fibrils","volume":"102","author":"Luhrs","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/nm1423","article-title":"Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse alzheimer phenotype in a mouse model","volume":"12","author":"McLaurin","year":"2006","journal-title":"Nat Med"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1002\/prot.21086","article-title":"ROSETTALIGAND: protein-small molecule docking with full side-chain flexibility","volume":"65","author":"Meiler","year":"2006","journal-title":"Proteins"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J Comput Chem"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"10311","DOI":"10.1074\/jbc.M608207200","article-title":"Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct","volume":"282","author":"Necula","year":"2007","journal-title":"J Biol Chem"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/nature03680","article-title":"Structure of the cross-beta spine of amyloid-like fibrils","volume":"435","author":"Nelson","year":"2005","journal-title":"Nature"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"14631","DOI":"10.1074\/jbc.M111.325456","article-title":"Phenolic compounds prevent amyloid beta-protein oligomerization and synaptic dysfunction by site-specific binding","volume":"287","author":"Ono","year":"2012","journal-title":"J Biol Chem"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1126\/science.1105850","article-title":"Self-propagating, molecular-level polymorphism in Alzheimer\u2019s beta-amyloid fibrils","volume":"307","author":"Petkova","year":"2005","journal-title":"Science"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1021\/bi051952q","article-title":"Experimental constraints on quaternary structure in Alzheimer\u2019s beta-amyloid fibrils","volume":"45","author":"Petkova","year":"2006","journal-title":"Biochemistry"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/j.1747-0285.2005.00318.x","article-title":"Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism","volume":"67","author":"Porat","year":"2006","journal-title":"Chem Biol Drug Des"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/nrd769","article-title":"Therapeutic strategies for human amyloid diseases","volume":"1","author":"Sacchettini","year":"2002","journal-title":"Nat Rev Drug Discov"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nature05695","article-title":"Atomic structures of amyloid cross-beta spines reveal varied steric zippers","volume":"447","author":"Sawaya","year":"2007","journal-title":"Nature"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"5956","DOI":"10.1002\/anie.201008276","article-title":"The amyloid-Congo red interface at atomic resolution","volume":"50","author":"Schutz","year":"2011","journal-title":"Angew Chem Int Ed Engl"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"11665","DOI":"10.1074\/jbc.M111.282533","article-title":"Microcin amyloid fibrils A are reservoir of toxic oligomeric species","volume":"287","author":"Shahnawaz","year":"2012","journal-title":"J Biol Chem"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/nature03989","article-title":"The most infectious prion protein particles","volume":"437","author":"Silveira","year":"2005","journal-title":"Nature"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1021\/ar8000475","article-title":"Peptide and protein mimetics inhibiting amyloid beta-peptide aggregation","volume":"41","author":"Takahashi","year":"2008","journal-title":"Acc Chem Res"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"7115","DOI":"10.1073\/pnas.0408582102","article-title":"Structural properties of Abeta protofibrils stabilized by a small molecule","volume":"102","author":"Williams","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"4086","DOI":"10.1074\/jbc.271.48.30392","article-title":"Selective inhibition of Abeta fibril formation","volume":"271","author":"Wood","year":"1996","journal-title":"J Biol Chem"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"34272","DOI":"10.1074\/jbc.M109.049809","article-title":"Fibril fragmentation enhances amyloid cytotoxicity","volume":"284","author":"Xue","year":"2009","journal-title":"J Biol Chem"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"5892","DOI":"10.1074\/jbc.M404751200","article-title":"Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo","volume":"280","author":"Yang","year":"2005","journal-title":"J Biol Chem"}],"updated-by":[{"DOI":"10.7554\/elife.01252","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T00:00:00Z","timestamp":1374537600000}}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/00857\/elife-00857-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/00857\/elife-00857-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/00857","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:40:40Z","timestamp":1697056840000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/00857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,16]]},"references-count":60,"alternative-id":["10.7554\/eLife.00857"],"URL":"https:\/\/doi.org\/10.7554\/elife.00857","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.00857.039","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.00857.040","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,16]]},"article-number":"e00857"}}