{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T13:20:40Z","timestamp":1779283240061,"version":"3.51.4"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2012,1,20]],"date-time":"2012-01-20T00:00:00Z","timestamp":1327017600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0030051","type":"journal-article","created":{"date-parts":[[2012,1,20]],"date-time":"2012-01-20T21:55:50Z","timestamp":1327096550000},"page":"e30051","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Activation Mobilizes the Cholesterol in the Late Endosomes-Lysosomes of Niemann Pick Type C Cells"],"prefix":"10.1371","volume":"7","author":[{"given":"Yvonne","family":"Lange","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore L.","family":"Steck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2012,1,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/S0022-2275(20)37704-X","article-title":"Differential Accumulation of Cholesterol in Golgi Compartments of Normal and Niemann-Pick Type-C Fibroblasts Incubated with LDL - a Cytochemical Freeze-Fracture Study.","volume":"34","author":"RA Coxey","year":"1993","journal-title":"Journal of Lipid Research"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/978-90-481-8622-8_11","article-title":"Cholesterol in Niemann-Pick Type C disease.","volume":"51","author":"X Bi","year":"2010","journal-title":"Subcell Biochem"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"15287","DOI":"10.1073\/pnas.0807328105","article-title":"NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes.","volume":"105","author":"RE Infante","year":"2008","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.cell.2009.03.049","article-title":"Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol.","volume":"137","author":"HJ Kwon","year":"2009","journal-title":"Cell"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.bbalip.2009.02.001","article-title":"Niemann-Pick C2 (NPC2) and intracellular cholesterol trafficking.","volume":"1791","author":"J Storch","year":"2009","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1194\/jlr.M003822","article-title":"Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion.","volume":"51","author":"M Abdul-Hammed","year":"2010","journal-title":"J Lipid Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.cell.2010.11.031","article-title":"Lipid Trafficking sans Vesicles: Where, Why, How?","volume":"143","author":"WA Prinz","year":"2010","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1097\/MOL.0b013e3283453e69","article-title":"Function of the Niemann-Pick type C proteins and their bypass by cyclodextrin.","volume":"22","author":"JE Vance","year":"2011","journal-title":"Curr Opin Lipidol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1194\/jlr.M000257","article-title":"Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid.","volume":"51","author":"B Liu","year":"2010","journal-title":"J Lipid Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1074\/jbc.275.6.4013","article-title":"Role of Niemann-Pick type C1 protein in intracellular trafficking of low density lipoprotein-derived cholesterol.","volume":"275","author":"JC Cruz","year":"2000","journal-title":"J Biol Chem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"17468","DOI":"10.1074\/jbc.M000875200","article-title":"Cholesterol movement in Niemann-Pick type C cells and in cells treated with amphiphiles.","volume":"275","author":"Y Lange","year":"2000","journal-title":"J Biol Chem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0022-2275(20)30161-9","article-title":"Dynamics of lysosomal cholesterol in Niemann-Pick type C and normal human fibroblasts.","volume":"43","author":"Y Lange","year":"2002","journal-title":"J Lipid Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1073\/pnas.0810895106","article-title":"Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1\u2212\/\u2212 mouse.","volume":"106","author":"B Liu","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e6951","DOI":"10.1371\/journal.pone.0006951","article-title":"Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression.","volume":"4","author":"CD Davidson","year":"2009","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"19316","DOI":"10.1073\/pnas.0910916106","article-title":"Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells.","volume":"106","author":"L Abi-Mosleh","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1073\/pnas.0914309107","article-title":"Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells.","volume":"107","author":"AI Rosenbaum","year":"2010","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1194\/jlr.M013789","article-title":"Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations.","volume":"52","author":"CM Ramirez","year":"2011","journal-title":"J Lipid Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1600-0854.2010.01046.x","article-title":"Improvement in lipid and protein trafficking in Niemann-Pick C1 cells by correction of a secondary enzyme defect.","volume":"11","author":"C Devlin","year":"2010","journal-title":"Traffic"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.plipres.2008.03.001","article-title":"Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol.","volume":"47","author":"Y Lange","year":"2008","journal-title":"Prog Lipid Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.tcb.2010.08.007","article-title":"Cell cholesterol homeostasis: Mediation by active cholesterol.","volume":"20","author":"TL Steck","year":"2010","journal-title":"Trends in Cell Biology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1194\/jlr.M900116-JLR200","article-title":"Regulation of fibroblast mitochondrial 27-hydroxycholesterol production by active plasma membrane cholesterol.","volume":"50","author":"Y Lange","year":"2009","journal-title":"J Lipid Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"9331","DOI":"10.1016\/S0021-9258(19)70566-3","article-title":"The effect of cholesterol and other intercalated amphipaths on the contour and stability of the isolated red cell membrane.","volume":"255","author":"Y Lange","year":"1980","journal-title":"J Biol Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"11664","DOI":"10.1073\/pnas.0404766101","article-title":"How cholesterol homeostasis is regulated by plasma membrane cholesterol in excess of phospholipids.","volume":"101","author":"Y Lange","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"36126","DOI":"10.1074\/jbc.M507149200","article-title":"Activation of membrane cholesterol by displacement from phospholipids.","volume":"280","author":"Y Lange","year":"2005","journal-title":"J Biol Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"8505","DOI":"10.1021\/bi900951r","article-title":"Activation of membrane cholesterol by 63 amphipaths.","volume":"48","author":"Y Lange","year":"2009","journal-title":"Biochemistry"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/0005-2736(84)90053-1","article-title":"Cholesterol oxidase susceptibility of the red cell membrane.","volume":"769","author":"Y Lange","year":"1984","journal-title":"Biochim Biophys Acta"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/0005-2736(89)90108-9","article-title":"Effects of sphingomyelin degradation on cell cholesterol oxidizability and steady-state distribution between the cell surface and the cell interior.","volume":"985","author":"JP Slotte","year":"1989","journal-title":"Biochim Biophys Acta"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1021\/bi6023397","article-title":"Scrambling of phospholipids activates red cell membrane cholesterol.","volume":"46","author":"Y Lange","year":"2007","journal-title":"Biochemistry"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S1388-1981(00)00055-X","article-title":"Intracellular cholesterol trafficking: role of the NPC1 protein.","volume":"1486","author":"EJ Blanchette-Mackie","year":"2000","journal-title":"Biochim Biophys Acta"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s10545-005-0117-7","article-title":"A comparative study of cytoplasmic granules imaged by the real-time microscope, Nile Red and Filipin in fibroblasts from patients with lipid storage diseases.","volume":"28","author":"NA Pham","year":"2005","journal-title":"Journal of Inherited Metabolic Disease"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/S0006-3495(98)77632-5","article-title":"Cholesterol distribution in living cells: fluorescence imaging using dehydroergosterol as a fluorescent cholesterol analog.","volume":"75","author":"S Mukherjee","year":"1998","journal-title":"Biophys J"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e15054","DOI":"10.1371\/journal.pone.0015054","article-title":"Cyclodextrin induces calcium-dependent lysosomal exocytosis.","volume":"5","author":"FW Chen","year":"2010","journal-title":"PLoS One"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/jbt.2570050407","article-title":"In vivo toxicity and pulmonary effects of promazine and chlorpromazine in rats.","volume":"5","author":"UP Kodavanti","year":"1990","journal-title":"J Biochem Toxicol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.tiv.2009.09.018","article-title":"Prediction of phospholipidosis-inducing potential of drugs by in vitro biochemical and physicochemical assays followed by multivariate analysis.","volume":"24","author":"Y Kuroda","year":"2010","journal-title":"Toxicol In Vitro"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0022-2275(20)39826-6","article-title":"Studies on drug-induced lipidosis: subcellular localization of phospholipid and cholesterol in the liver of rats treated with chloroquine or 4,4\u2032-bis (diethylaminoethoxy)alpha, beta-diethyldiphenylethane.","volume":"21","author":"Y Matsuzawa","year":"1980","journal-title":"J Lipid Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"18915","DOI":"10.1074\/jbc.273.30.18915","article-title":"Circulation of cholesterol between lysosomes and the plasma membrane.","volume":"273","author":"Y Lange","year":"1998","journal-title":"J Biol Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1016\/j.cellsig.2006.04.006","article-title":"Cellular mechanism of U18666A-mediated apoptosis in cultured murine cortical neurons: Bridging Niemann-Pick disease type C and Alzheimer's disease.","volume":"18","author":"CHV Koh","year":"2006","journal-title":"Cellular Signalling"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s11745-009-3305-7","article-title":"Cholesterol synthesis inhibitor U18666A and the role of sterol metabolism and trafficking in numerous pathophysiological processes.","volume":"44","author":"RJ Cenedella","year":"2009","journal-title":"Lipids"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1021\/bi035697q","article-title":"Cholesterol oxidase senses subtle changes in lipid bilayer structure.","volume":"43","author":"KW Ahn","year":"2004","journal-title":"Biochemistry"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"15130","DOI":"10.1016\/S0021-9258(17)43782-3","article-title":"Analysis of the distribution of cholesterol in the intact cell.","volume":"258","author":"Y Lange","year":"1983","journal-title":"J Biol Chem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.plipres.2007.06.002","article-title":"Non-vesicular sterol transport in cells.","volume":"46","author":"WA Prinz","year":"2007","journal-title":"Prog Lipid Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.bbalip.2009.03.002","article-title":"Intracellular sterol dynamics.","volume":"1791","author":"B Mesmin","year":"2009","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.1600-0854.2010.01142.x","article-title":"Role of ORPs in Sterol Transport from Plasma Membrane to ER and Lipid Droplets in Mammalian Cells.","volume":"12","author":"M Jansen","year":"2011","journal-title":"Traffic"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1016\/S0021-9258(18)69086-6","article-title":"Type-C Niemann-Pick Disease - Lysosomal Accumulation and Defective Intracellular Mobilization of Low-Density Lipoprotein Cholesterol.","volume":"263","author":"J Sokol","year":"1988","journal-title":"Journal of Biological Chemistry"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1194\/jlr.P000331","article-title":"The National Niemann-Pick Type C1 Disease Database: correlation of lipid profiles, mutations, and biochemical phenotypes.","volume":"51","author":"WS Garver","year":"2010","journal-title":"J Lipid Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1086\/324068","article-title":"Niemann-Pick disease type C: spectrum of HE1 mutations and genotype\/phenotype correlations in the NPC2 group.","volume":"69","author":"G Millat","year":"2001","journal-title":"Am J Hum Genet"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1111\/j.1471-4159.2010.07014.x","article-title":"Regulation of the NPC2 protein-mediated cholesterol trafficking by membrane lipids.","volume":"116","author":"HD Gallala","year":"2011","journal-title":"J Neurochem"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"25517","DOI":"10.1074\/jbc.M302588200","article-title":"NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols.","volume":"278","author":"A Frolov","year":"2003","journal-title":"J Biol Chem"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.1021\/ja8095224","article-title":"Perturbations of Membrane Structure by Cholesterol and Cholesterol Derivatives Are Determined by Sterol Orientation.","volume":"131","author":"BN Olsen","year":"2009","journal-title":"Journal of the American Chemical Society"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.bpj.2010.12.3728","article-title":"25-hydroxycholesterol increases the availability of cholesterol in phospholipid membranes.","volume":"100","author":"BN Olsen","year":"2011","journal-title":"Biophys J"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1016\/S0022-2275(20)32101-5","article-title":"Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol.","volume":"40","author":"Y Lange","year":"1999","journal-title":"J Lipid Res"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/S0022-2275(20)39867-9","article-title":"Movement of 25-hydroxycholesterol from the plasma membrane to the rough endoplasmic reticulum in cultured hepatoma cells.","volume":"36","author":"Y Lange","year":"1995","journal-title":"J Lipid Res"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"29371","DOI":"10.1016\/S0021-9258(18)43886-0","article-title":"Cholesterol homeostasis. Modulation by amphiphiles.","volume":"269","author":"Y Lange","year":"1994","journal-title":"J Biol Chem"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1476-511X-9-33","article-title":"Alterations in the homeostasis of phospholipids and cholesterol by antitumor alkylphospholipids.","volume":"9","author":"J Jimenez-Lopez","year":"2010","journal-title":"Lipids in Health and Disease"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.molcel.2004.06.019","article-title":"Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain.","volume":"15","author":"A Radhakrishnan","year":"2004","journal-title":"Mol Cell"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"10647","DOI":"10.1073\/pnas.1534833100","article-title":"Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles.","volume":"100","author":"CM Adams","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/S0022-2275(20)39138-0","article-title":"Quantitative analysis of hydrophobic amine inhibition of intracellular cholesterol transport.","volume":"37","author":"KW Underwood","year":"1996","journal-title":"J Lipid Res"},{"key":"ref58","article-title":"Principles and techniques of electron microscopy: Biological applications","author":"MA Hayat","year":"2000"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1016\/S0006-3495(02)73972-6","article-title":"Probing red cell membrane cholesterol movement with cyclodextrin.","volume":"83","author":"TL Steck","year":"2002","journal-title":"Biophys J"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ceb.2011.04.006","article-title":"Lipid transfer and signaling at organelle contact sites: the tip of the iceberg.","volume":"23","author":"A Toulmay","year":"2011","journal-title":"Curr Opin Cell Biol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1083\/jcb.201004142","article-title":"A role for oxysterol-binding protein\u2013related protein 5 in endosomal cholesterol trafficking.","volume":"192","author":"X Du","year":"2011","journal-title":"The Journal of Cell Biology"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0079-6468(08)70140-1","article-title":"The biological uses and importance of glutaraldehyde.","volume":"13","author":"AD Russell","year":"1976","journal-title":"Prog Med Chem"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0022-2275(20)32113-1","article-title":"Cell cholesterol efflux: integration of old and new observations provides new insights.","volume":"40","author":"GH Rothblat","year":"1999","journal-title":"J Lipid Res"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0005-2760(91)90132-2","article-title":"Cholesterol transport between cells and high-density lipoproteins.","volume":"1085","author":"WJ Johnson","year":"1991","journal-title":"Biochim Biophys Acta"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"7662","DOI":"10.1021\/bi992686h","article-title":"Lysosomal membrane cholesterol dynamics.","volume":"39","author":"JK Schoer","year":"2000","journal-title":"Biochemistry"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"13103","DOI":"10.1074\/jbc.272.20.13103","article-title":"Quantitation of the pool of cholesterol associated with acyl-CoA:cholesterol acyltransferase in human fibroblasts.","volume":"272","author":"Y Lange","year":"1997","journal-title":"J Biol Chem"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S0163-7827(01)00020-0","article-title":"Cholesterol interactions with phospholipids in membranes.","volume":"41","author":"H Ohvo-Rekila","year":"2002","journal-title":"Prog Lipid Res"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"21439","DOI":"10.1016\/S0021-9258(18)54658-5","article-title":"Movement of zymosterol, a precursor of cholesterol, among three membranes in human fibroblasts.","volume":"266","author":"Y Lange","year":"1991","journal-title":"J Biol Chem"},{"key":"ref69","article-title":"Compartmental analysis in biology and medicine","author":"JA Jacquez","year":"1985"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0030051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T17:36:37Z","timestamp":1640540197000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0030051"}},"subtitle":[],"editor":[{"given":"Maria","family":"Gasset","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2012,1,20]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0030051","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,20]]}}}