{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:34:32Z","timestamp":1772120072924,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Quant. Biol."],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Microbes live in dynamic environments where nutrient concentrations fluctuate. Quantifying fitness in terms of birth rate and death rate in a wide range of environments is critical for understanding microbial evolution and ecology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, using high\u2010throughput time\u2010lapse microscopy, we have quantified how\n                      <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                      mutants incapable of synthesizing an essential metabolite (auxotrophs) grow or die in various concentrations of the required metabolite. We establish that cells normally expressing fluorescent proteins lose fluorescence upon death and that the total fluorescence in an imaging frame is proportional to the number of live cells even when cells form multiple layers. We validate our microscopy approach of measuring birth and death rates using flow cytometry, cell counting, and chemostat culturing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For lysine\u2010requiring cells, very low concentrations of lysine are not detectably consumed and do not support cell birth, but delay the onset of death phase and reduce the death rate compared to no lysine. In contrast, in low hypoxanthine, hypoxanthine\u2010requiring cells can produce new cells, yet also die faster than in the absence of hypoxanthine. For both strains, birth rates under various metabolite concentrations are better described by the sigmoidal\u2010shaped Moser model than the well\u2010known Monod model, while death rates can vary with metabolite concentration and time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our work reveals how time\u2010lapse microscopy can be used to discover non\u2010intuitive microbial birth and death dynamics and to quantify growth rates in many environments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40484-018-0160-7","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T04:35:15Z","timestamp":1547699715000},"page":"69-81","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["High\u2010throughput quantification of microbial birth and death dynamics using fluorescence microscopy"],"prefix":"10.1002","volume":"7","author":[{"given":"Samuel F. M.","family":"Hart","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Research Center Seattle WA 98109 USA"}]},{"given":"David","family":"Skelding","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center Seattle WA 98109 USA"}]},{"given":"Adam J.","family":"Waite","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center Seattle WA 98109 USA"}]},{"given":"Justin C.","family":"Burton","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center Seattle WA 98109 USA"}]},{"given":"Wenying","family":"Shou","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center Seattle WA 98109 USA"}]}],"member":"311","published-online":{"date-parts":[[2019,3]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.110"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mst138"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.181"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.007"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.03.100149.002103"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260211014"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.62.3.646-666.1998"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610575104"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010011\u20100649\u2010y"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1210190109"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00230"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00960"},{"key":"e_1_2_9_14_2","doi-asserted-by":"crossref","unstructured":"Hart S. F. M. Mi H. Green R. Pineda J. M. B. Momeni B. Shou W.(2018)Resolving challenges in quantitative modeling of microbial community dynamics. bioRxiv 356519 doi:https:\/\/doi.org\/10.1101\/356519","DOI":"10.1101\/356519"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00455924"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40484\u2010018\u20100143\u20108"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802601105"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202547200"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00190.2003"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00214a020"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.09.025"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100854.2011.01314.x"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20100554\u20106_2"},{"key":"e_1_2_9_24_2","volume-title":"Guide to Yeast Genetics and Molecular Biology","author":"Guthrie C.","year":"1991"},{"key":"e_1_2_9_25_2","article-title":"An extensive empirical evaluation of focus measures for digital photography","volume":"9023","author":"Mir H.","year":"2014","journal-title":"In\u2002Proceedings of SPIE \u2013The International Society for Optical Engineering"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/24.1.1254907"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009\u20102509(99)00500\u2010X"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1364\/OE.24.006996"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1008"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb1415s102"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1109\/MC.1983.1654163"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0734\u2010189X(85)90125\u20102"},{"key":"e_1_2_9_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1109\/TSMC.1978.4310039"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/sb500165g"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.36.12.708"}],"container-title":["Quantitative Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40484-018-0160-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40484-018-0160-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40484-018-0160-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s40484-018-0160-7","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T04:58:11Z","timestamp":1735880291000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s40484-018-0160-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1007\/s40484-018-0160-7"],"URL":"https:\/\/doi.org\/10.1007\/s40484-018-0160-7","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/324269","asserted-by":"object"}]},"ISSN":["2095-4689","2095-4697"],"issn-type":[{"value":"2095-4689","type":"print"},{"value":"2095-4697","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"16 June 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}