{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T03:26:27Z","timestamp":1778124387532,"version":"3.51.4"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>In this paper we apply a novel JAVA version of a model on the homeostasis of human red blood cells (RBCs) to investigate the changes RBCs experience during single capillary transits. In the companion paper we apply a model extension to investigate the changes in RBC homeostasis over the approximately 200000 capillary transits during the ~120 days lifespan of the cells. These are topics inaccessible to direct experimentation but rendered mature for a computational modelling approach by the large body of recent and early experimental results which robustly constrain the range of parameter values and model outcomes, offering a unique opportunity for an in depth study of the mechanisms involved. Capillary transit times vary between 0.5 and 1.5s during which the red blood cells squeeze and deform in the capillary stream transiently opening stress-gated PIEZO1 channels allowing ion gradient dissipation and creating minuscule quantal changes in RBC ion contents and volume. Widely accepted views, based on the effects of experimental shear stress on human RBCs, suggested that quantal changes generated during capillary transits add up over time to develop the documented changes in RBC density and composition during their long circulatory lifespan, the quantal hypothesis. Applying the new red cell model (RCM) we investigated here the changes in homeostatic variables that may be expected during single capillary transits resulting from transient PIEZO1 channel activation. The predicted quantal volume changes were infinitesimal in magnitude, biphasic in nature, and essentially irreversible within inter-transit periods. A sub-second transient PIEZO1 activation triggered a sharp swelling peak followed by a much slower recovery period towards lower-than-baseline volumes. The peak response was caused by net CaCl<jats:sub>2<\/jats:sub> and fluid gain via PIEZO1 channels driven by the steep electrochemical inward Ca<jats:sup>2+<\/jats:sup> gradient. The ensuing dehydration followed a complex time-course with sequential, but partially overlapping contributions by KCl loss via Ca<jats:sup>2+<\/jats:sup>-activated Gardos channels, restorative Ca<jats:sup>2+<\/jats:sup> extrusion by the plasma membrane calcium pump, and chloride efflux by the Jacobs-Steward mechanism. The change in relative cell volume predicted for single capillary transits was around 10<jats:sup>\u22125<\/jats:sup>, an infinitesimal volume change incompatible with a functional role in capillary flow. The biphasic response predicted by the RCM appears to conform to the quantal hypothesis, but whether its cumulative effects could account for the documented changes in density during RBC senescence required an investigation of the effects of myriad transits over the full four months circulatory lifespan of the cells, the subject of the next paper.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008706","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T19:15:22Z","timestamp":1614798922000},"page":"e1008706","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Up-down biphasic volume response of human red blood cells to PIEZO1 activation during capillary transits"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3578-4477","authenticated-orcid":true,"given":"Simon","family":"Rogers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-2701","authenticated-orcid":true,"given":"Virgilio L.","family":"Lew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"pcbi.1008706.ref001","author":"S Rogers","year":"2021","journal-title":"PIEZO1 and the mechanism of the long circulatory longevity of human red blood cells."},{"key":"pcbi.1008706.ref002","first-page":"3","volume-title":"The Cellular Functions of Membrane Transport","author":"DC Tosteson","year":"1964"},{"key":"pcbi.1008706.ref003","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3109\/00365516609051812","article-title":"Potassium, sodium, and water in normal human red blood cells","volume":"18","author":"J Funder","year":"1966","journal-title":"Scand J clin Lab Invest"},{"key":"pcbi.1008706.ref004","first-page":"39","volume-title":"Membrane Transport in Red Cells","author":"L Beauge","year":"1977"},{"key":"pcbi.1008706.ref005","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3389\/fphys.2017.00977","article-title":"On the Mechanism of Human Red Blood Cell Longevity: Roles of Calcium, the Sodium Pump, PIEZO1, and Gardos Channels","volume":"8","author":"VL Lew","year":"2017","journal-title":"Front Physiol."},{"issue":"27","key":"pcbi.1008706.ref006","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.1039\/C9SM00677J","article-title":"State diagram for wall adhesion of red blood cells in shear flow: from crawling to flipping","volume":"15","author":"AK Dasanna","year":"2019","journal-title":"Soft Matter"},{"issue":"1","key":"pcbi.1008706.ref007","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.bpj.2018.11.3130","article-title":"A Model of Piezo1-Based Regulation of Red Blood Cell Volume","volume":"116","author":"S Svetina","year":"2019","journal-title":"Biophys J"},{"issue":"2","key":"pcbi.1008706.ref008","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1152\/physrev.1988.68.2.503","article-title":"Senescence of red blood cells: progress and problems","volume":"68","author":"MR Clark","year":"1988","journal-title":"Physiol Rev"},{"key":"pcbi.1008706.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-4165(92)90120-J","article-title":"Density separation of human red blood cells on self forming Percoll gradients: correlation with cell age","volume":"1116","author":"HU Lutz","year":"1992","journal-title":"Biochim Biophys Acta"},{"issue":"5","key":"pcbi.1008706.ref010","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1172\/JCI103468","article-title":"The distribution of Fe59 tagged human erythrocytes in centrifuged specimens as a function of cell age","volume":"36","author":"ER Borun","year":"1957","journal-title":"J Clin Invest"},{"issue":"14","key":"pcbi.1008706.ref011","doi-asserted-by":"crossref","first-page":"8045","DOI":"10.1073\/pnas.130198797","article-title":"Identification and characterization of a newly recognized population of high-Na+, low-K+, low-density sickle and normal red cells","volume":"97","author":"RM Bookchin","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pcbi.1008706.ref012","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/ajh.23344","article-title":"Changes in the properties of normal human red blood cells during in vivo aging","volume":"88","author":"RS Franco","year":"2013","journal-title":"Am J Hematol"},{"key":"pcbi.1008706.ref013","first-page":"171","article-title":"The terminal density reversal phenomenon of aging human red blood cells","volume":"4","author":"VL Lew","year":"2013","journal-title":"Front Physiol"},{"issue":"1","key":"pcbi.1008706.ref014","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0047-6374(81)90008-7","article-title":"An age-specific cell antigen is present on senescent human red blood cell membranes. A brief note","volume":"15","author":"HU Lutz","year":"1981","journal-title":"Mech Ageing Dev"},{"key":"pcbi.1008706.ref015","first-page":"387","article-title":"Mechanisms tagging senescent red blood cells for clearance in healthy humans","volume":"4","author":"HU Lutz","year":"2013","journal-title":"Front Physiol"},{"issue":"1","key":"pcbi.1008706.ref016","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/iub.1703","article-title":"Molecular mechanism for the red blood cell senescence clock","volume":"70","author":"KE Badior","year":"2018","journal-title":"IUBMB Life"},{"issue":"8","key":"pcbi.1008706.ref017","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/nm.4146","article-title":"On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver","volume":"22","author":"I Theurl","year":"2016","journal-title":"Nat Med"},{"issue":"14","key":"pcbi.1008706.ref018","first-page":"1579","article-title":"Hemolysis in the spleen drives erythrocyte turnover","volume":"136","author":"TRL Klei","year":"2020","journal-title":"Blood"},{"issue":"14","key":"pcbi.1008706.ref019","first-page":"1569","article-title":"Turning over a new leaf on turning over RBCs","volume":"136","author":"JC Zimring","year":"2020","journal-title":"Blood"},{"issue":"2","key":"pcbi.1008706.ref020","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0005-2736(76)90349-7","article-title":"Biochemical characterization of density-separated human erythrocytes","volume":"419","author":"NS Cohen","year":"1976","journal-title":"Biochim Biophys Acta"},{"issue":"5","key":"pcbi.1008706.ref021","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1172\/JCI111600","article-title":"Mechanism of alteration of sodium potassium pump of erythrocytes from patients with chronic renal failure","volume":"74","author":"JT Cheng","year":"1984","journal-title":"J Clin Invest"},{"issue":"3\u20134","key":"pcbi.1008706.ref022","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3109\/09687687809063847","article-title":"Ouabain binding and potassium transport in young and old populations of human red cells","volume":"1","author":"CH Joiner","year":"1978","journal-title":"Membr Biochem"},{"issue":"12","key":"pcbi.1008706.ref023","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1182\/blood-2003-06-1787","article-title":"Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells","volume":"102","author":"VL Lew","year":"2003","journal-title":"Blood"},{"key":"pcbi.1008706.ref024","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1182\/blood-2006-11-057232","article-title":"Effects of age-dependent membrane transport changes on the homeostasis of senescent human red blood cells","volume":"110","author":"VL Lew","year":"2007","journal-title":"Blood"},{"issue":"5","key":"pcbi.1008706.ref025","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0143-4160(97)90028-2","article-title":"Differences in Ca2+ pumping activity between sub-populations of human red cells","volume":"21","author":"PJ Romero","year":"1997","journal-title":"Cell Calcium"},{"issue":"3\u20134","key":"pcbi.1008706.ref026","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1054\/ceca.1999.0063","article-title":"Effect of cell ageing on Ca2+ influx into human red cells","volume":"26","author":"PJ Romero","year":"1999","journal-title":"Cell Calcium"},{"issue":"5","key":"pcbi.1008706.ref027","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1085\/jgp.200709766","article-title":"Age Decline in the Activity of the Ca2+-sensitive K+ Channel of Human Red Blood Cells","volume":"129","author":"T Tiffert","year":"2007","journal-title":"J Gen Physiol"},{"key":"pcbi.1008706.ref028","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/294667a0","article-title":"Physiological shear stresses enhance the Ca2+ permeability of human erythrocytes","volume":"294","author":"FL Larsen","year":"1981","journal-title":"Nature"},{"key":"pcbi.1008706.ref029","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/BF01869016","article-title":"Volume, pH and-ion content regulation in human red cells: analysis of transient behavior with an integrated model","volume":"92","author":"VL Lew","year":"1986","journal-title":"J Membrane Biol"},{"issue":"1","key":"pcbi.1008706.ref030","doi-asserted-by":"crossref","first-page":"e8732","DOI":"10.1371\/journal.pone.0008732","article-title":"Hypoxia activates a Ca2+-permeable cation conductance sensitive to carbon monoxide and to GsMTx-4 in human and mouse sickle erythrocytes","volume":"5","author":"DH Vandorpe","year":"2010","journal-title":"PLoS One"},{"issue":"2","key":"pcbi.1008706.ref031","doi-asserted-by":"crossref","first-page":"e9447","DOI":"10.1371\/journal.pone.0009447","article-title":"Local membrane deformations activate Ca2+-dependent K+ and anionic currents in intact human red blood cells","volume":"5","author":"A Dyrda","year":"2010","journal-title":"PLoS One"},{"issue":"29","key":"pcbi.1008706.ref032","doi-asserted-by":"crossref","first-page":"6295","DOI":"10.1021\/bi200770q","article-title":"The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4","volume":"50","author":"C Bae","year":"2011","journal-title":"Biochemistry"},{"issue":"4","key":"pcbi.1008706.ref033","doi-asserted-by":"crossref","first-page":"282","DOI":"10.4161\/chan.21064","article-title":"Gating the mechanical channel Piezo1: a comparison between whole-cell and patch recording.","volume":"6","author":"PA Gottlieb","year":"2012","journal-title":"Channels (Austin)"},{"issue":"19","key":"pcbi.1008706.ref034","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1182\/blood-2013-02-482489","article-title":"Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1","volume":"121","author":"I Andolfo","year":"2013","journal-title":"Blood"},{"issue":"11","key":"pcbi.1008706.ref035","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1182\/blood-2015-07-657957","article-title":"Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis","volume":"126","author":"E Glogowska","year":"2015","journal-title":"Blood"},{"key":"pcbi.1008706.ref036","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/bs.ctm.2017.01.001","article-title":"Genetic Diseases of PIEZO1 and PIEZO2 Dysfunction","volume":"79","author":"SL Alper","year":"2017","journal-title":"Curr Top Membr"},{"issue":"5","key":"pcbi.1008706.ref037","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/mrc.4416","article-title":"Anisotropic diffusion in stretched hydrogels containing erythrocytes: evidence of cell-shape distortion recorded by PGSE NMR spectroscopy","volume":"55","author":"D Shishmarev","year":"2017","journal-title":"Magn Reson Chem"},{"key":"pcbi.1008706.ref038","doi-asserted-by":"crossref","first-page":"979","DOI":"10.3389\/fphys.2017.00979","article-title":"Red Blood Cell Passage of Small Capillaries Is Associated with Transient Ca(2+)-mediated Adaptations","volume":"8","author":"JG Danielczok","year":"2017","journal-title":"Front Physiol"},{"issue":"6","key":"pcbi.1008706.ref039","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.neuron.2016.01.046","article-title":"Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels","volume":"89","author":"Q Zhao","year":"2016","journal-title":"Neuron"},{"issue":"4","key":"pcbi.1008706.ref040","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.bcmd.2010.02.014","article-title":"Anion conductance of the human red cell is carried by a maxi-anion channel","volume":"44","author":"E Glogowska","year":"2010","journal-title":"Blood Cells Mol Dis"},{"issue":"5","key":"pcbi.1008706.ref041","doi-asserted-by":"crossref","first-page":"e0125503","DOI":"10.1371\/journal.pone.0125503","article-title":"Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels","volume":"10","author":"R Gnanasambandam","year":"2015","journal-title":"PLoS One"},{"issue":"6","key":"pcbi.1008706.ref042","doi-asserted-by":"crossref","first-page":"C1169","DOI":"10.1152\/ajpcell.1990.258.6.C1169","article-title":"Voltage-activated cation permeability in high-potassium but not low-potassium red blood cells","volume":"258","author":"JA Halperin","year":"1990","journal-title":"Am J Physiol"},{"issue":"1","key":"pcbi.1008706.ref043","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0005-2736(91)90017-3","article-title":"Evidence for a voltage-gated, non-selective cation channel in the human red cell membrane","volume":"1065","author":"P Christophersen","year":"1991","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"pcbi.1008706.ref044","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0005-2736(93)90328-W","article-title":"The voltage-gated non-selective cation channel from human red cells is sensitive to acetylcholine","volume":"1147","author":"P. Bennekou","year":"1993","journal-title":"Biochim Biophys Acta"},{"key":"pcbi.1008706.ref045","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1085\/jgp.81.1.127","article-title":"Chloride net efflux from intact erythrocytes under slippage conditions","volume":"81","author":"O Frohlich","year":"1983","journal-title":"J Gen Physiol"},{"key":"pcbi.1008706.ref046","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1085\/jgp.84.6.877","article-title":"Relative contributions of the slippage and tunneling mechanisms to anion net efflux from human erythrocytes","volume":"84","author":"O. Frohlich","year":"1984","journal-title":"J Gen Physiol"},{"issue":"4","key":"pcbi.1008706.ref047","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.bcmd.2011.02.007","article-title":"Ion channels in human red blood cell membrane: actors or relics?","volume":"46","author":"SL Thomas","year":"2011","journal-title":"Blood Cells Mol Dis"},{"issue":"2","key":"pcbi.1008706.ref048","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bioelechem.2003.08.006","article-title":"Voltage activation and hysteresis of the non-selective voltage-dependent channel in the intact human red cell","volume":"62","author":"P Bennekou","year":"2004","journal-title":"Bioelectrochemistry"},{"issue":"1","key":"pcbi.1008706.ref049","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00232-003-2036-6","article-title":"The human red cell voltage-regulated cation channel. The interplay with the chloride conductance, the Ca(2+)-activated K(+) channel and the Ca(2+) pump","volume":"195","author":"P Bennekou","year":"2003","journal-title":"J Membr Biol"},{"issue":"2","key":"pcbi.1008706.ref050","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/0005-2736(78)90253-5","article-title":"Erythrocyte membrane potentials determined by hydrogen ion distribution","volume":"512","author":"RI Macey","year":"1978","journal-title":"Biochim Biophys Acta"},{"key":"pcbi.1008706.ref051","first-page":"384P","article-title":"Variation of anion exchange turnover among red cells from individual human donors","volume":"459","author":"JE Raftos","year":"1993","journal-title":"J Physiol"},{"key":"pcbi.1008706.ref052","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/BF01869305","article-title":"K-permeabilized human red cells lose an alkaline, hypertonic fluid containing excess K over diffusible anions","volume":"96","author":"CJ Freeman","year":"1987","journal-title":"J Membrane Biol"},{"key":"pcbi.1008706.ref053","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1113\/jphysiol.1996.sp021256","article-title":"Distribution of chloride permeabilities in normal human red cells","volume":"491","author":"JE Raftos","year":"1996","journal-title":"J Physiol"},{"key":"pcbi.1008706.ref054","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1113\/jphysiol.1988.sp017428","article-title":"Detection and separation of human red cells with different calcium contents following uniform calcium permeabilization","volume":"407","author":"J Garc\u00eda-Sancho","year":"1988","journal-title":"J Physiol"},{"key":"pcbi.1008706.ref055","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1113\/jphysiol.1977.sp011845","article-title":"Human erythrocyte anion permeabilities measured under conditions of net charge transfer","volume":"268","author":"MJ Hunter","year":"1977","journal-title":"J Physiol"},{"key":"pcbi.1008706.ref056","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1085\/jgp.81.1.95","article-title":"Relationship of net chloride flow across the human erythrocyte membrane to the anion exchange mechanism","volume":"81","author":"PA Knauf","year":"1983","journal-title":"J Gen Physiol"},{"key":"pcbi.1008706.ref057","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3389\/fphys.2020.00392","article-title":"Heterogeneity of Red Blood Cells: Causes and Consequences","volume":"11","author":"A Bogdanova","year":"2020","journal-title":"Front Physiol"},{"issue":"3","key":"pcbi.1008706.ref058","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0041-0101(03)00141-7","article-title":"cDNA sequence and in vitro folding of GsMTx4, a specific peptide inhibitor of mechanosensitive channels","volume":"42","author":"KL Ostrow","year":"2003","journal-title":"Toxicon"},{"key":"pcbi.1008706.ref059","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S1063-5823(06)59004-0","article-title":"Properties and Mechanism of the Mechanosensitive Ion Channel Inhibitor GsMTx4, a Therapeutic Peptide Derived from Tarantula Venom","volume":"59","author":"PA Gottlieb","year":"2007","journal-title":"Curr Top Membr"},{"issue":"2","key":"pcbi.1008706.ref060","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1113\/jphysiol.2008.162453","article-title":"The plasma membrane calcium ATPase (PMCA) of neurones is electroneutral and exchanges 2 H+ for each Ca2+ or Ba2+ ion extruded","volume":"587","author":"RC Thomas","year":"2009","journal-title":"J Physiol"},{"issue":"2","key":"pcbi.1008706.ref061","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.bbamem.2004.01.011","article-title":"Properties of the basal calcium influx in human red blood cells","volume":"1661","author":"R Hudec","year":"2004","journal-title":"Biochim Biophys Acta"},{"issue":"5","key":"pcbi.1008706.ref062","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1016\/S0021-9258(18)34929-9","article-title":"The purified Ca2+ pump of human erythrocyte membranes catalyzes an electroneutral Ca2+-H+ exchange in reconstituted liposomal systems","volume":"257","author":"V Niggli","year":"1982","journal-title":"J Biol Chem"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1008862","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008706","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T19:16:15Z","timestamp":1614798975000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008706"}},"subtitle":[],"editor":[{"given":"Daniel A.","family":"Beard","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,3]]},"references-count":62,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1008706","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1008862","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,3]]}}}