{"id":"https://openalex.org/W7213454302","doi":"https://doi.org/10.64898/2026.09.13.751295","title":"Environmental stress promotes entry into a pre-existing latent state in Plasmodium falciparum","display_name":"Environmental stress promotes entry into a pre-existing latent state in Plasmodium falciparum","publication_year":2026,"publication_date":"2026-09-16","ids":{"openalex":"https://openalex.org/W7213454302","doi":"https://doi.org/10.64898/2026.09.13.751295"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.13.751295","doi":"https://doi.org/10.64898/2026.09.13.751295","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.13.751295","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/16/2026.09.13.751295.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/16/2026.09.13.751295.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5086860455","display_name":"Anush Aryal","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Anush Aryal","raw_affiliation_strings":["University of Virginia, Department of Biology"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Virginia, Department of Biology","institution_ids":["https://openalex.org/I51556381"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5119446577","display_name":"Kwesi Akonu Adom Mensah Forson","orcid":"https://orcid.org/0000-0001-6153-0935","observed_orcids":["https://orcid.org/0000-0001-6153-0935"]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kwesi Forson","raw_affiliation_strings":["University of Virginia, Department of Biology"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Virginia, Department of Biology","institution_ids":["https://openalex.org/I51556381"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5122701144","display_name":"Nadia Prasad","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nadia Prasad","raw_affiliation_strings":["University of Virginia, Department of Biology","University of Virginia, School of Medicine"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Virginia, Department of Biology","institution_ids":["https://openalex.org/I51556381"]},{"raw_affiliation_string":"University of Virginia, School of Medicine","institution_ids":["https://openalex.org/I51556381"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5078495656","display_name":"Jennifer L. G\u00fcler","orcid":"https://orcid.org/0000-0001-6301-4563","observed_orcids":["https://orcid.org/0000-0001-6301-4563"]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jennifer L. Guler","raw_affiliation_strings":["University of Virginia, Department of Biology","University of Virginia, Division of Infectious Disease and International Health"],"raw_orcid":"https://orcid.org/0000-0001-6301-4563","affiliations":[{"raw_affiliation_string":"University of Virginia, Department of Biology","institution_ids":["https://openalex.org/I51556381"]},{"raw_affiliation_string":"University of Virginia, Division of Infectious Disease and International Health","institution_ids":["https://openalex.org/I51556381"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5078495656"],"corresponding_institution_ids":["https://openalex.org/I51556381"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10091","display_name":"Malaria Research and Control","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10091","display_name":"Malaria Research and Control","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11155","display_name":"Toxoplasma gondii Research Studies","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2405","display_name":"Parasitology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12286","display_name":"Erythrocyte Function and Pathophysiology","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/plasmodium-falciparum","display_name":"Plasmodium falciparum","score":0.9990000128746033},{"id":"https://openalex.org/keywords/artemisinin-resistance","display_name":"artemisinin resistance","score":0.7770000100135803},{"id":"https://openalex.org/keywords/dihydroartemisinin","display_name":"dihydroartemisinin","score":0.9459999799728394},{"id":"https://openalex.org/keywords/environmental-stress","display_name":"environmental stress","score":0.9120000004768372},{"id":"https://openalex.org/keywords/nutrient-starvation","display_name":"nutrient deprivation","score":0.9810000061988831},{"id":"https://openalex.org/keywords/parasite-persistence","display_name":"parasite persistence","score":0.6309999823570251},{"id":"https://openalex.org/keywords/recrudescence","display_name":"recrudescence","score":0.8119999766349792},{"id":"https://openalex.org/keywords/transcriptional-remodeling","display_name":"transcriptional remodeling","score":0.9010000228881836},{"id":"https://openalex.org/keywords/mitochondrial-function","display_name":"mitochondrial function","score":0.7509999871253967},{"id":"https://openalex.org/keywords/redox-homeostasis","display_name":"redox homeostasis","score":0.8840000033378601},{"id":"https://openalex.org/keywords/maurer-s-clefts","display_name":"Maurer's clefts","score":0.8679999709129333},{"id":"https://openalex.org/keywords/antimalarial-drug-targets","display_name":"antimalarial drug targets","score":0.621999979019165},{"id":"https://openalex.org/keywords/single-cell-transcriptomics","display_name":"single-cell transcriptomics","score":0.7490000128746033}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.8201000094413757},{"id":"https://openalex.org/C2778371730","wikidata":"https://www.wikidata.org/wiki/Q311383","display_name":"Plasmodium falciparum","level":3,"score":0.7235000133514404},{"id":"https://openalex.org/C2778048844","wikidata":"https://www.wikidata.org/wiki/Q12156","display_name":"Malaria","level":2,"score":0.6389999985694885},{"id":"https://openalex.org/C2776120307","wikidata":"https://www.wikidata.org/wiki/Q426921","display_name":"Artemisinin","level":4,"score":0.5317000150680542},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.5113999843597412},{"id":"https://openalex.org/C71928629","wikidata":"https://www.wikidata.org/wiki/Q804206","display_name":"Parasite hosting","level":2,"score":0.4699000120162964},{"id":"https://openalex.org/C2986039202","wikidata":"https://www.wikidata.org/wiki/Q123414","display_name":"Environmental stress","level":2,"score":0.4609000086784363},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4287000000476837},{"id":"https://openalex.org/C2781160685","wikidata":"https://www.wikidata.org/wiki/Q5276420","display_name":"Dihydroartemisinin","level":5,"score":0.4196000099182129},{"id":"https://openalex.org/C82876162","wikidata":"https://www.wikidata.org/wiki/Q17096504","display_name":"Latency (audio)","level":2,"score":0.4047999978065491},{"id":"https://openalex.org/C11957725","wikidata":"https://www.wikidata.org/wiki/Q5533590","display_name":"Gentamicin protection assay","level":4,"score":0.39989998936653137},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.3474000096321106},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3425999879837036},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.3100000023841858},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.3034000098705292},{"id":"https://openalex.org/C166703698","wikidata":"https://www.wikidata.org/wiki/Q201993","display_name":"RNA interference","level":4,"score":0.27570000290870667},{"id":"https://openalex.org/C2776151105","wikidata":"https://www.wikidata.org/wiki/Q898814","display_name":"Oxidative stress","level":2,"score":0.26600000262260437},{"id":"https://openalex.org/C86339819","wikidata":"https://www.wikidata.org/wiki/Q407384","display_name":"Transcription factor","level":3,"score":0.26579999923706055},{"id":"https://openalex.org/C2778852064","wikidata":"https://www.wikidata.org/wiki/Q4115619","display_name":"Virus latency","level":4,"score":0.2526000142097473}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.13.751295","doi":"https://doi.org/10.64898/2026.09.13.751295","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.13.751295","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/16/2026.09.13.751295.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.13.751295","doi":"https://doi.org/10.64898/2026.09.13.751295","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.13.751295","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/16/2026.09.13.751295.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7213454302.pdf","grobid_xml":"https://content.openalex.org/works/W7213454302.grobid-xml"},"referenced_works_count":83,"referenced_works":["https://openalex.org/W1595322628","https://openalex.org/W1976977157","https://openalex.org/W1994459939","https://openalex.org/W2004803790","https://openalex.org/W2006740007","https://openalex.org/W2021609444","https://openalex.org/W2033985665","https://openalex.org/W2035826427","https://openalex.org/W2035939667","https://openalex.org/W2036041437","https://openalex.org/W2043274194","https://openalex.org/W2047565128","https://openalex.org/W2049016946","https://openalex.org/W2054995441","https://openalex.org/W2055809012","https://openalex.org/W2083822594","https://openalex.org/W2099767800","https://openalex.org/W2106198832","https://openalex.org/W2122534122","https://openalex.org/W2124634096","https://openalex.org/W2129428401","https://openalex.org/W2133913001","https://openalex.org/W2137529385","https://openalex.org/W2143977871","https://openalex.org/W2153136347","https://openalex.org/W2161311583","https://openalex.org/W2165081628","https://openalex.org/W2167868313","https://openalex.org/W2190545194","https://openalex.org/W2258757517","https://openalex.org/W2508378919","https://openalex.org/W2509122422","https://openalex.org/W2590767446","https://openalex.org/W2590802442","https://openalex.org/W2599977247","https://openalex.org/W2754965081","https://openalex.org/W2765242536","https://openalex.org/W2771484250","https://openalex.org/W2774947765","https://openalex.org/W2784489698","https://openalex.org/W2791358329","https://openalex.org/W2896506953","https://openalex.org/W2923635199","https://openalex.org/W2938680570","https://openalex.org/W2949444269","https://openalex.org/W2969974048","https://openalex.org/W2973731173","https://openalex.org/W2991059744","https://openalex.org/W2997424783","https://openalex.org/W3011407152","https://openalex.org/W3015794686","https://openalex.org/W3084316374","https://openalex.org/W3127608790","https://openalex.org/W3164247466","https://openalex.org/W3165864006","https://openalex.org/W3178899039","https://openalex.org/W3184062432","https://openalex.org/W3205045213","https://openalex.org/W4223500345","https://openalex.org/W4223956095","https://openalex.org/W4289963744","https://openalex.org/W4293771028","https://openalex.org/W4316506457","https://openalex.org/W4318026477","https://openalex.org/W4321457682","https://openalex.org/W4327597823","https://openalex.org/W4366983927","https://openalex.org/W4367047658","https://openalex.org/W4385396215","https://openalex.org/W4387966591","https://openalex.org/W4391515379","https://openalex.org/W4391600435","https://openalex.org/W4391787255","https://openalex.org/W4396574522","https://openalex.org/W4399990341","https://openalex.org/W4401999444","https://openalex.org/W4402783520","https://openalex.org/W4407298631","https://openalex.org/W4415256731","https://openalex.org/W7162795821","https://openalex.org/W7163892741","https://openalex.org/W7164825215","https://openalex.org/W7203704166"],"related_works":["https://openalex.org/W4401999444","https://openalex.org/W4318567125","https://openalex.org/W4391884346","https://openalex.org/W2122534122","https://openalex.org/W2153136347","https://openalex.org/W3164247466","https://openalex.org/W2168039618","https://openalex.org/W2001456353","https://openalex.org/W2934930341","https://openalex.org/W3084440238"],"abstract_inverted_index":{"Abstract":[0],"Artemisinin":[1],"treatment":[2,35],"eliminates":[3],"most":[4],"Plasmodium":[5],"falciparum":[6],"malaria":[7],"parasites":[8,42,153,174,211],"but":[9],"leaves":[10],"behind":[11],"a":[12,114,161,269,281],"small":[13],"population":[14,119],"capable":[15],"of":[16,82,138,160,221,263,280],"long-term":[17,107],"survival":[18,52,274],"and":[19,77,101,125,191,207,216,233,285],"eventual":[20],"recrudescence.":[21],"Although":[22],"these":[23],"survivors":[24],"have":[25],"been":[26],"associated":[27,229],"with":[28,106,170,219,230],"latency,":[29],"it":[30],"remains":[31],"unclear":[32],"whether":[33],"drug":[34],"induces":[36],"this":[37,83,139,241],"state":[38,84,242],"or":[39],"selectively":[40,196],"enriches":[41],"already":[43,165],"predisposed":[44,166],"for":[45,167,292],"persistence.":[46,168],"Environmental":[47,236],"stress":[48,58,72,237,252],"also":[49,149,212],"enhances":[50],"parasite":[51,108,163],"following":[53,97,141],"artemisinin":[54,142,273],"exposure,":[55,100],"suggesting":[56,157,250],"that":[57,70,120,185,251],"may":[59],"promote":[60],"persistence":[61],"by":[62,189],"increasing":[63],"entry":[64,74,239],"into":[65,75,240],"latency.":[66],"Here,":[67],"we":[68],"show":[69],"environmental":[71],"promotes":[73],"latency":[76,92,102,186,224,258,264,291],"define":[78],"the":[79,128,158,222,231,254,261],"molecular":[80],"features":[81],"using":[85],"single-cell":[86],"transcriptomics.":[87],"Mild":[88],"nutrient":[89,202],"deprivation":[90],"increased":[91,238],"formation":[93],"2-":[94],"to":[95,256,289],"3-fold":[96],"dihydroartemisinin":[98],"(DHA)":[99],"frequency":[103],"positively":[104],"correlated":[105],"recovery.":[109],"Single-cell":[110],"RNA":[111],"sequencing":[112],"revealed":[113,184],"transcriptionally":[115],"distinct":[116],"early":[117],"trophozoite":[118],"emerged":[121],"after":[122],"DHA":[123],"exposure":[124,143],"diverged":[126],"from":[127],"normal":[129],"developmental":[130],"trajectory.":[131],"A":[132],"200-gene":[133],"classifier":[134,148],"confirmed":[135],"strong":[136],"enrichment":[137,279],"signature":[140],"across":[144],"independent":[145],"datasets.":[146],"The":[147],"detected":[150],"rare":[151,162],"latent-like":[152],"in":[154,178,271,276],"untreated":[155],"populations,":[156],"presence":[159],"subpopulation":[164,284],"Consistent":[169],"previous":[171],"studies,":[172],"latent":[173,283],"exhibited":[175],"reduced":[176],"investment":[177],"growth-associated":[179],"functions;":[180],"however,":[181],"our":[182],"analyses":[183],"is":[187],"accompanied":[188],"extensive":[190],"coordinated":[192],"transcriptional":[193,248],"remodeling;":[194],"they":[195],"maintained":[197],"mitochondrial":[198],"functions,":[199],"redox":[200],"homeostasis,":[201],"acquisition":[203],"pathways,":[204],"lipid":[205],"metabolism,":[206],"stress-responsive":[208],"signaling.":[209],"Latent":[210],"preserved":[213],"invasion":[214],"functions":[215],"host-cell":[217],"interactions,":[218],"many":[220],"strongest":[223],"markers":[225],"encoding":[226],"exported":[227],"proteins":[228],"erythrocyte":[232],"Maurer\u2019s":[234],"clefts.":[235],"without":[243],"substantially":[244],"altering":[245],"its":[246],"core":[247],"architecture,":[249],"influences":[253],"decision":[255],"enter":[257],"more":[259],"than":[260],"biology":[262],"itself.":[265],"These":[266],"findings":[267],"support":[268],"model":[270],"which":[272],"arises,":[275],"part,":[277],"through":[278],"pre-existing":[282],"identify":[286],"promising":[287],"candidates":[288],"target":[290],"future":[293],"antimalarial":[294],"interventions.":[295]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-09-17T00:00:00"}