{"id":"https://openalex.org/W2159536767","doi":null,"title":"Toll-like Receptor (TLR) Signaling and Differential Activation of PGC Family Genes in a Mouse Model of Staphylococcus aureus Sepsis","display_name":"Toll-like Receptor (TLR) Signaling and Differential Activation of PGC Family Genes in a Mouse Model of Staphylococcus aureus Sepsis","publication_year":2010,"publication_date":"2010-01-01","ids":{"openalex":"https://openalex.org/W2159536767","mag":"2159536767"},"language":"en","primary_location":{"id":"pmh:oai:dukespace.lib.duke.edu:10161/3022","doi":null,"is_oa":false,"landing_page_url":"http://hdl.handle.net/10161/3022","pdf_url":null,"source":{"id":"https://openalex.org/S4306400687","display_name":"DukeSpace (Duke University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I170897317","host_organization_name":"Duke University","host_organization_lineage":["https://openalex.org/I170897317"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Dissertation"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5058341211","display_name":"Timothy E. Sweeney","orcid":"https://orcid.org/0000-0002-3596-1093","observed_orcids":["https://orcid.org/0000-0002-3596-1093"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Timothy E. Sweeney","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-3596-1093","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5058341211"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"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/T10218","display_name":"Sepsis Diagnosis and Treatment","score":0.7401999831199646,"subfield":{"id":"https://openalex.org/subfields/2706","display_name":"Critical Care and Intensive Care Medicine"},"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/T10218","display_name":"Sepsis Diagnosis and Treatment","score":0.7401999831199646,"subfield":{"id":"https://openalex.org/subfields/2706","display_name":"Critical Care and Intensive Care Medicine"},"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/T10371","display_name":"Immune Response and Inflammation","score":0.10199999809265137,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"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/T14165","display_name":"Inflammation biomarkers and pathways","score":0.03799999877810478,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/sepsis","display_name":"sepsis","score":0.902999997138977},{"id":"https://openalex.org/keywords/staphylococcus-aureus","display_name":"Staphylococcus aureus","score":0.9980000257492065},{"id":"https://openalex.org/keywords/tlr2","display_name":"TLR2","score":0.9480000138282776},{"id":"https://openalex.org/keywords/tlr4","display_name":"TLR4","score":0.9980000257492065},{"id":"https://openalex.org/keywords/mitochondrial-biogenesis","display_name":"mitochondrial biogenesis","score":0.8949999809265137},{"id":"https://openalex.org/keywords/pgc-1alpha","display_name":"PGC-1\u03b1","score":0.9409999847412109},{"id":"https://openalex.org/keywords/pgc-1beta","display_name":"PGC-1\u03b2","score":0.9990000128746033},{"id":"https://openalex.org/keywords/ppargamma-coactivator","display_name":"PPAR\u03b3 coactivator","score":0.7599999904632568},{"id":"https://openalex.org/keywords/myd88-independent-signaling","display_name":"MyD88-independent signaling","score":0.921999990940094},{"id":"https://openalex.org/keywords/innate-immune-response","display_name":"innate immune response","score":0.75},{"id":"https://openalex.org/keywords/hepatic-gene-expression","display_name":"hepatic gene expression","score":0.7319999933242798},{"id":"https://openalex.org/keywords/mouse-sepsis-model","display_name":"mouse sepsis model","score":0.6179999709129333}],"concepts":[{"id":"https://openalex.org/C2779489039","wikidata":"https://www.wikidata.org/wiki/Q188121","display_name":"Staphylococcus aureus","level":3,"score":0.789945125579834},{"id":"https://openalex.org/C2776709828","wikidata":"https://www.wikidata.org/wiki/Q408004","display_name":"Toll-like receptor","level":4,"score":0.6679855585098267},{"id":"https://openalex.org/C2778384902","wikidata":"https://www.wikidata.org/wiki/Q183134","display_name":"Sepsis","level":2,"score":0.644739031791687},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5379785299301147},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.49531951546669006},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.47316890954971313},{"id":"https://openalex.org/C89423630","wikidata":"https://www.wikidata.org/wiki/Q7193","display_name":"Microbiology","level":1,"score":0.4533616006374359},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.4444453716278076},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.42441850900650024},{"id":"https://openalex.org/C2778025104","wikidata":"https://www.wikidata.org/wiki/Q408004","display_name":"Toll","level":2,"score":0.41447803378105164},{"id":"https://openalex.org/C93226319","wikidata":"https://www.wikidata.org/wiki/Q193137","display_name":"Differential (mechanical device)","level":2,"score":0.41400086879730225},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.40746188163757324},{"id":"https://openalex.org/C136449434","wikidata":"https://www.wikidata.org/wiki/Q428253","display_name":"Innate immune system","level":3,"score":0.33116012811660767},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.22261017560958862},{"id":"https://openalex.org/C523546767","wikidata":"https://www.wikidata.org/wiki/Q10876","display_name":"Bacteria","level":2,"score":0.1831163763999939},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.0},{"id":"https://openalex.org/C146978453","wikidata":"https://www.wikidata.org/wiki/Q3798668","display_name":"Aerospace engineering","level":1,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:dukespace.lib.duke.edu:10161/3022","doi":null,"is_oa":false,"landing_page_url":"http://hdl.handle.net/10161/3022","pdf_url":null,"source":{"id":"https://openalex.org/S4306400687","display_name":"DukeSpace (Duke University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I170897317","host_organization_name":"Duke University","host_organization_lineage":["https://openalex.org/I170897317"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Dissertation"},{"id":"mag:2159536767","doi":null,"is_oa":false,"landing_page_url":"https://dukespace.lib.duke.edu/dspace/bitstream/10161/3022/1/D_Sweeney_Timothy_a_201008.pdf","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":164,"referenced_works":["https://openalex.org/W10482017","https://openalex.org/W45369538","https://openalex.org/W112745552","https://openalex.org/W144423133","https://openalex.org/W166801957","https://openalex.org/W1523213544","https://openalex.org/W1582241183","https://openalex.org/W1587157283","https://openalex.org/W1600472471","https://openalex.org/W1607829491","https://openalex.org/W1628984902","https://openalex.org/W1805967757","https://openalex.org/W1840693165","https://openalex.org/W1861227972","https://openalex.org/W1916491745","https://openalex.org/W1965361671","https://openalex.org/W1966210473","https://openalex.org/W1968336033","https://openalex.org/W1969394188","https://openalex.org/W1970100427","https://openalex.org/W1970216382","https://openalex.org/W1971082641","https://openalex.org/W1972285445","https://openalex.org/W1972752943","https://openalex.org/W1978231462","https://openalex.org/W1978337436","https://openalex.org/W1979463052","https://openalex.org/W1980269624","https://openalex.org/W1983800969","https://openalex.org/W1987093392","https://openalex.org/W1987383242","https://openalex.org/W1987410025","https://openalex.org/W1987935765","https://openalex.org/W1992223192","https://openalex.org/W1992969522","https://openalex.org/W1993451325","https://openalex.org/W1993799748","https://openalex.org/W1995354490","https://openalex.org/W1996155397","https://openalex.org/W1997640131","https://openalex.org/W1999742427","https://openalex.org/W2003060606","https://openalex.org/W2003385732","https://openalex.org/W2003807404","https://openalex.org/W2004052382","https://openalex.org/W2005792688","https://openalex.org/W2007222211","https://openalex.org/W2007241912","https://openalex.org/W2007456673","https://openalex.org/W2009707997","https://openalex.org/W2009818318","https://openalex.org/W2010094123","https://openalex.org/W2011984413","https://openalex.org/W2013601771","https://openalex.org/W2014333801","https://openalex.org/W2015011627","https://openalex.org/W2015069256","https://openalex.org/W2015242572","https://openalex.org/W2015415445","https://openalex.org/W2017883909","https://openalex.org/W2018011543","https://openalex.org/W2020062408","https://openalex.org/W2025310815","https://openalex.org/W2028419507","https://openalex.org/W2029078679","https://openalex.org/W2029571074","https://openalex.org/W2029857264","https://openalex.org/W2029948570","https://openalex.org/W2033693969","https://openalex.org/W2033801757","https://openalex.org/W2034172998","https://openalex.org/W2037454778","https://openalex.org/W2038267036","https://openalex.org/W2038535939","https://openalex.org/W2039096764","https://openalex.org/W2039358381","https://openalex.org/W2044433375","https://openalex.org/W2046395583","https://openalex.org/W2046677011","https://openalex.org/W2046864190","https://openalex.org/W2049927822","https://openalex.org/W2052779789","https://openalex.org/W2052833946","https://openalex.org/W2056183846","https://openalex.org/W2056402897","https://openalex.org/W2057809738","https://openalex.org/W2059793806","https://openalex.org/W2060725412","https://openalex.org/W2061203855","https://openalex.org/W2061460256","https://openalex.org/W2065596509","https://openalex.org/W2067678108","https://openalex.org/W2067683753","https://openalex.org/W2070743921","https://openalex.org/W2074827635","https://openalex.org/W2076361525","https://openalex.org/W2077648685","https://openalex.org/W2079222412","https://openalex.org/W2079605309","https://openalex.org/W2082890018","https://openalex.org/W2083364750","https://openalex.org/W2083381199","https://openalex.org/W2083812577","https://openalex.org/W2083944116","https://openalex.org/W2084527080","https://openalex.org/W2084880831","https://openalex.org/W2087203965","https://openalex.org/W2094045593","https://openalex.org/W2095017048","https://openalex.org/W2095809865","https://openalex.org/W2098901296","https://openalex.org/W2099281097","https://openalex.org/W2100876902","https://openalex.org/W2107324877","https://openalex.org/W2109056923","https://openalex.org/W2109110671","https://openalex.org/W2109491705","https://openalex.org/W2110217901","https://openalex.org/W2111428445","https://openalex.org/W2111922856","https://openalex.org/W2112708549","https://openalex.org/W2113549988","https://openalex.org/W2113999599","https://openalex.org/W2115185894","https://openalex.org/W2116890805","https://openalex.org/W2117408241","https://openalex.org/W2117888940","https://openalex.org/W2117991391","https://openalex.org/W2120444833","https://openalex.org/W2122242846","https://openalex.org/W2123115740","https://openalex.org/W2126060886","https://openalex.org/W2127367800","https://openalex.org/W2129438003","https://openalex.org/W2131117779","https://openalex.org/W2131406530","https://openalex.org/W2135807050","https://openalex.org/W2139871065","https://openalex.org/W2140375278","https://openalex.org/W2140751228","https://openalex.org/W2141157874","https://openalex.org/W2144787399","https://openalex.org/W2144794300","https://openalex.org/W2149649111","https://openalex.org/W2150010602","https://openalex.org/W2152906228","https://openalex.org/W2154074258","https://openalex.org/W2155192432","https://openalex.org/W2157260713","https://openalex.org/W2158728030","https://openalex.org/W2159650080","https://openalex.org/W2160012920","https://openalex.org/W2161493785","https://openalex.org/W2166234597","https://openalex.org/W2166628824","https://openalex.org/W2166739041","https://openalex.org/W2167059596","https://openalex.org/W2167276755","https://openalex.org/W2171594721","https://openalex.org/W2194951460","https://openalex.org/W2336216244","https://openalex.org/W2336572885","https://openalex.org/W2768146862","https://openalex.org/W4322574849"],"related_works":["https://openalex.org/W7096293047","https://openalex.org/W1999468353","https://openalex.org/W2120444833","https://openalex.org/W2483821833","https://openalex.org/W2947570164","https://openalex.org/W4313384784","https://openalex.org/W1967774301","https://openalex.org/W2051769972","https://openalex.org/W2788621659","https://openalex.org/W2120773723"],"abstract_inverted_index":{"Sepsis":[0],"is":[1,18,44,80,83,331,339,347,353,389],"a":[2,84,131,154,348,377],"major":[3,155],"cause":[4],"of":[5,54,60,68,96,105,121,145,157,182,214,242,249,316,327,333,380,395,432,439],"morbidity":[6],"and":[7,13,37,41,70,78,82,133,141,269,278,283,291,338,397,403,406,422,441],"mortality":[8],"in":[9,73,88,109,116,170,191,221,227,235,245,266,288,299,341,356,360,384,400,419,435],"the":[10,19,30,33,38,52,66,93,101,137,142,149,158,201,247,272,296,303,324,328,334,357,385,393,430,436],"United":[11],"States,":[12],"Staphylococcus":[14],"aureus":[15,225],"(S.":[16],"aureus)":[17],"bacteria":[20],"most":[21],"commonly":[22],"cultured":[23],"from":[24],"septic":[25],"patients.":[26],"In":[27,264,280,375],"severe":[28],"sepsis,":[29,127],"relationship":[31],"between":[32,136],"systemic":[34],"inflammatory":[35],"response":[36,87,117,140,192,222,275],"resulting":[39],"mitochondrial":[40,55,61,114,122,146,168,188,219,254,273,443],"metabolic":[42,69],"dysfunction":[43],"not":[45,370],"fully":[46],"understood,":[47],"especially":[48],"with":[49,392],"respect":[50],"to":[51,65,118,180,193,204,212,223,366,409],"mechanisms":[53,297],"damage":[56],"resolution.":[57],"The":[58,229],"process":[59],"biogenesis,":[62,255],"which":[63,246,388],"leads":[64],"restoration":[67],"anti-oxidative":[71],"functions":[72],"damaged":[74],"or":[75],"stressed":[76],"cells":[77],"tissues,":[79],"pro-survival":[81],"critical":[85],"protective":[86],"sepsis.":[89,172],"Mitochondrial":[90],"biogenesis":[91,115,169,189,220,274],"requires":[92],"coordinated":[94],"expression":[95,394],"multiple":[97],"regulatory":[98,251],"proteins,":[99],"including":[100,256],"PPARgamma-coactivator":[102],"(PGC)":[103],"family":[104,260,330],"proteins.":[106],"Previous":[107],"work":[108,174],"sepsis":[110,226,230,440],"has":[111],"focused":[112],"on":[113],"late":[119],"signals":[120],"damage;":[123],"however,":[124],"for":[125,187,253,311,372,429],"acute":[126],"we":[128,162],"have":[129],"hypothesized":[130,163],"direct":[132],"early":[134],"link":[135],"innate":[138,159],"immune":[139,160],"transcriptional":[143],"activation":[144,312],"biogenesis.":[147,444],"Since":[148],"Toll-like":[150],"receptors":[151],"(TLRs)":[152],"are":[153,417],"part":[156,342],"response,":[161],"that":[164,176,323,352],"they":[165],"could":[166],"activate":[167,218],"bacterial":[171],"Earlier":[173],"showed":[175],"TLR4":[177],"(which":[178,210],"responds":[179,211],"components":[181,213],"Gram-negative":[183],"bacteria)":[184,216],"was":[185,203,232,262,276,364,382,407],"necessary":[186,368],"induction":[190,301],"heat-killed":[194],"E.":[195],"coli":[196],"challenge.":[197],"For":[198],"this":[199,300,361],"work,":[200],"objective":[202],"investigate":[205],"whether":[206],"signaling":[207,306],"by":[208,239,343],"TLR2":[209],"Gram-positive":[215],"would":[217],"S.":[224],"mice.":[228,293,319],"model":[231],"initially":[233],"characterized":[234],"wild-type":[236],"(WT)":[237],"mice":[238,405],"PCR":[240],"analysis":[241],"hepatic":[243],"RNA,":[244],"up-regulation":[248,431],"several":[250,314],"proteins":[252],"all":[257],"three":[258],"PGC":[259,329],"members,":[261],"observed.":[263],"contrast,":[265],"both":[267],"TLR2-/-":[268],"TLR4-/-":[270,292,404],"mice,":[271],"deficient":[277],"delayed.":[279],"addition,":[281,376],"PGC-1alpha":[282,396,412],"PGC-1beta":[284,398],"were":[285,308],"differentially":[286],"regulated":[287],"WT,":[289,401],"TLR2-/-,":[290,402],"To":[294],"identify":[295],"involved":[298,355],"pattern,":[302],"known":[304],"TLR":[305],"pathways":[307],"systematically":[309],"probed":[310],"using":[313],"strains":[315],"genetic":[317],"knockout":[318],"These":[320],"data":[321],"demonstrated":[322],"differential":[325],"regulation":[326,381],"independent":[332],"MyD88":[335],"adapter":[336],"protein":[337],"caused":[340],"IRF7":[344,346,363,421],"signaling.":[345],"pro-inflammatory":[349],"transcription":[350],"factor":[351],"normally":[354],"interferon":[358],"response;":[359],"case,":[362],"found":[365],"be":[367,425],"but":[369],"sufficient":[371],"PGC-1alpha/beta":[373,433],"induction.":[374],"second":[378],"level":[379],"identified":[383],"microRNA":[386],"mmu-mir-202-3p,":[387],"inversely":[390],"correlated":[391],"mRNA":[399],"shown":[408],"functionally":[410],"decrease":[411],"mRNA.":[413],"If":[414],"these":[415],"observations":[416],"confirmed":[418],"humans,":[420],"mir-202-3p":[423],"may":[424],"potential":[426],"therapeutic":[427],"targets":[428],"levels":[434],"clinical":[437],"setting":[438],"impaired":[442]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2016-06-24T00:00:00"}