{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:59:33Z","timestamp":1789174773643,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012692","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000}}],"reference-count":117,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001246","name":"Ambrose Monell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1AI068932"],"award-info":[{"award-number":["RO1AI068932"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI139525"],"award-info":[{"award-number":["R01 AI139525"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI163969"],"award-info":[{"award-number":["R21AI163969"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI163969"],"award-info":[{"award-number":["R21AI163969"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Tsetse flies (<jats:italic>Glossina<\/jats:italic> spp.) vector African trypanosomes that cause devastating diseases in humans and domestic animals. Within the <jats:italic>Glossina<\/jats:italic> genus, species in the <jats:italic>Palpalis<\/jats:italic> subgroup exhibit greater resistance to trypanosome infections compared to those in the <jats:italic>Morsitans<\/jats:italic> subgroup. Varying microbiota composition and species-specific genetic traits can significantly influence the efficiency of parasite transmission. Notably, infections with the endosymbiotic bacterium <jats:italic>Spiroplasma<\/jats:italic> have been documented in several <jats:italic>Palpalis<\/jats:italic> subgroup species, including <jats:italic>Glossina fuscipes fuscipes<\/jats:italic> (<jats:italic>Gff<\/jats:italic>). While <jats:italic>Spiroplasma<\/jats:italic> infections in <jats:italic>Gff<\/jats:italic> are known to hinder trypanosome transmission, the underlying mechanisms remain unknown. To investigate <jats:italic>Spiroplasma-<\/jats:italic>mediated factors affecting <jats:italic>Gff<\/jats:italic> vector competence, we conducted high-throughput RNA sequencing of the gut tissue along with functional assays. Our findings reveal elevated oxidative stress in the gut environment in the presence of <jats:italic>Spiroplasma<\/jats:italic>, evidenced by increased expression of <jats:italic>nitric oxide synthase<\/jats:italic>, which catalyzes the production of trypanocidal nitric oxide. Additionally, we observed impaired lipid biosynthesis leading to a reduction of this important class of nutrients essential for parasite and host physiologies. In contrast, trypanosome infections in <jats:italic>Gff\u2019s<\/jats:italic> midgut significantly upregulated various immunity-related genes, including a small peptide, <jats:italic>Stomoxyn-like<\/jats:italic>, homologous to <jats:italic>Stomoxyn<\/jats:italic> first discovered in the stable fly, <jats:italic>Stomoxys calcitrans<\/jats:italic>. We observed that the <jats:italic>Stomoxyn-like<\/jats:italic> locus is exclusive to the genomes of <jats:italic>Palpalis<\/jats:italic> subgroup tsetse species. <jats:italic>GffStomoxyn<\/jats:italic> is constitutively expressed in the cardia (proventriculus) and synthetic <jats:italic>Gff<\/jats:italic>Stomoxyn exhibits potent activity against <jats:italic>Escherichia coli<\/jats:italic> and bloodstream form of <jats:italic>Trypanosoma brucei<\/jats:italic> parasites, while showing no effect against insect stage procyclic forms or tsetse\u2019s commensal endosymbiont <jats:italic>Sodalis in vitro<\/jats:italic>. Reducing <jats:italic>Gff<\/jats:italic>Stomoxyn levels significantly increased trypanosome infection prevalence, indicating its potential trypanocidal role <jats:italic>in vivo<\/jats:italic>. Collectively, our results suggest that the enhanced resistance to trypanosomes observed in <jats:italic>Spiroplasma<\/jats:italic>-infected <jats:italic>Gff<\/jats:italic> may be due to the reduced lipid availability necessary for parasite metabolic maintenance. Furthermore, <jats:italic>Gff<\/jats:italic>Stomoxyn could play a crucial role in the initial immune response(s) against mammalian parasites early in the infection process in the gut and prevent gut colonization. We discuss the molecular characteristics of <jats:italic>Gff<\/jats:italic>Stomoxyn, its spatial and temporal expression regulation and its microbicidal activity against <jats:italic>Trypanosome<\/jats:italic> parasites. Our findings reinforce the nutritional influences of microbiota on host physiology and host-pathogen dynamics.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012692","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T18:46:43Z","timestamp":1738349203000},"page":"e1012692","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Spiroplasma endosymbiont reduction of host lipid synthesis and Stomoxyn-like peptide contribute to trypanosome resistance in the tsetse fly Glossina fuscipes"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1330-8296","authenticated-orcid":true,"given":"Erick O.","family":"Awuoche","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen","family":"Smallenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Bruzzese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Orfano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-143X","authenticated-orcid":true,"given":"Serap","family":"Aksoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ppat.1012692.ref001","article-title":"Trypanosomiasis, Human African (Sleeping Sickness)","author":"WHO","year":"2019"},{"key":"ppat.1012692.ref002","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13071-016-1336-5","article-title":"Assessment of animal African trypanosomiasis (AAT) vulnerability in cattle-owning communities of sub-Saharan Africa.","volume":"9","author":"HR Holt","year":"2016","journal-title":"Parasites & vectors."},{"key":"ppat.1012692.ref003","volume-title":"CAB International.","author":"I Maudlin","year":"2004"},{"issue":"1","key":"ppat.1012692.ref004","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pt.2021.07.012","article-title":"Evolution of the variant surface glycoprotein family in African trypanosomes","volume":"38","author":"S Silva Pereira","year":"2022","journal-title":"Trends in parasitology"},{"issue":"Suppl","key":"ppat.1012692.ref005","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1016\/j.jip.2012.07.014","article-title":"Tsetse-transmitted trypanosomes\u2014their biology, disease impact and control","volume":"112","author":"P. Holmes","year":"2013","journal-title":"J Invertebr Pathol"},{"issue":"4","key":"ppat.1012692.ref006","first-page":"e0005454","article-title":"Human African trypanosomiasis control: Achievements and challenges.","volume":"11","author":"S Aksoy","year":"2017","journal-title":"PubMed Central PMCID"},{"issue":"12","key":"ppat.1012692.ref007","doi-asserted-by":"crossref","first-page":"e0007903","DOI":"10.1371\/journal.pntd.0007903","article-title":"The impact of vector migration on the effectiveness of strategies to control gambiense human African trypanosomiasis.","volume":"13","author":"ML Ndeffo-Mbah","year":"2019","journal-title":"PLoS neglected tropical diseases."},{"issue":"1","key":"ppat.1012692.ref008","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1016\/S2214-109X(16)30237-6","article-title":"Seeing beyond 2020: an economic evaluation of contemporary and emerging strategies for elimination of Trypanosoma brucei gambiense","volume":"5","author":"CS Sutherland","year":"2017","journal-title":"Lancet Glob Health"},{"issue":"2","key":"ppat.1012692.ref009","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0001-706X(98)00013-8","article-title":"Factors influencing the prevalence of trypanosome infection of Glossina pallidipes on the Ruvu flood plain of Eastern Tanzania","volume":"70","author":"AR Msangi","year":"1998","journal-title":"Acta tropica"},{"key":"ppat.1012692.ref010","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.dci.2019.05.003","article-title":"Innate immunity in the tsetse fly (Glossina), vector of African trypanosomes.","volume":"98","author":"I Matetovici","year":"2019","journal-title":"Developmental and comparative immunology"},{"issue":"7","key":"ppat.1012692.ref011","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/ismej.2014.236","article-title":"Adult blood-feeding tsetse flies, trypanosomes, microbiota and the fluctuating environment in sub-","volume":"9","author":"A Geiger","year":"2015","journal-title":"Saharan Africa. The ISME journal"},{"issue":"3","key":"ppat.1012692.ref012","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.pt.2015.11.008","article-title":"Beyond Tsetse\u2014Implications for Research and Control of Human African Trypanosomiasis Epidemics","volume":"32","author":"SC Welburn","year":"2016","journal-title":"Trends in parasitology"},{"issue":"3","key":"ppat.1012692.ref013","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1365-2915.1988.tb00192.x","article-title":"Comparative study on the infection rates of different laboratory strains of Glossina species by Trypanosoma congolense","volume":"2","author":"SK Moloo","year":"1988","journal-title":"Medical and veterinary entomology"},{"issue":"2","key":"ppat.1012692.ref014","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/ana.21429","article-title":"The continuing problem of human African trypanosomiasis (sleeping sickness).","volume":"64","author":"PG Kennedy","year":"2008","journal-title":"Ann Neurol"},{"issue":"14","key":"ppat.1012692.ref015","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1017\/S0031182009006416","article-title":"Controlling sleeping sickness\u2014a review","volume":"136","author":"SC Welburn","year":"2009","journal-title":"Parasitology"},{"key":"ppat.1012692.ref016","doi-asserted-by":"crossref","first-page":"109613","DOI":"10.1016\/j.vetpar.2021.109613","article-title":"World Association for the Advancement of Veterinary Parasitology (WAAVP) second edition: Guideline for evaluating the efficacy of parasiticides against ectoparasites of ruminants.","volume":"302","author":"P Holdsworth","year":"2022","journal-title":"Veterinary parasitology"},{"issue":"4","key":"ppat.1012692.ref017","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1365-2915.2008.00747.x","article-title":"Land cover and tsetse fly distributions in sub-Saharan Africa","volume":"22","author":"G Cecchi","year":"2008","journal-title":"Medical and veterinary entomology"},{"issue":"9","key":"ppat.1012692.ref018","doi-asserted-by":"crossref","first-page":"e1332","DOI":"10.1371\/journal.pntd.0001332","article-title":"Towards an optimal design of target for tsetse control: comparisons of novel targets for the control of Palpalis group tsetse in West Africa.","volume":"5","author":"JB Rayaisse","year":"2011","journal-title":"PLoS neglected tropical diseases."},{"issue":"3","key":"ppat.1012692.ref019","doi-asserted-by":"crossref","first-page":"e632","DOI":"10.1371\/journal.pntd.0000632","article-title":"Prospects for the development of odour baits to control the tsetse flies Glossina tachinoides and G. palpalis s.l.","volume":"4","author":"JB Rayaisse","year":"2010","journal-title":"PLoS neglected tropical diseases"},{"issue":"1","key":"ppat.1012692.ref020","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s13059-019-1768-2","article-title":"Comparative genomic analysis of six Glossina genomes, vectors of African trypanosomes","volume":"20","author":"GM Attardo","year":"2019","journal-title":"Genome Biol"},{"issue":"12","key":"ppat.1012692.ref021","doi-asserted-by":"crossref","first-page":"e1006017","DOI":"10.1371\/journal.ppat.1006017","article-title":"PIWIs Go Viral: Arbovirus-Derived piRNAs in Vector Mosquitoes.","volume":"12","author":"P Miesen","year":"2016","journal-title":"PLoS pathogens."},{"issue":"12","key":"ppat.1012692.ref022","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/S0965-1748(02)00106-6","article-title":"Proventriculus-specific cDNAs characterized from the tsetse, Glossina morsitans morsitans","volume":"32","author":"Z Hao","year":"2002","journal-title":"Insect biochemistry and molecular biology"},{"issue":"4","key":"ppat.1012692.ref023","doi-asserted-by":"crossref","first-page":"e2691","DOI":"10.1371\/journal.pntd.0002691","article-title":"An investigation into the protein composition of the teneral Glossina morsitans morsitans peritrophic matrix","volume":"8","author":"C Rose","year":"2014","journal-title":"PLoS neglected tropical diseases"},{"issue":"2","key":"ppat.1012692.ref024","doi-asserted-by":"crossref","first-page":"773","DOI":"10.4049\/jimmunol.1400163","article-title":"The peritrophic matrix mediates differential infection outcomes in the tsetse fly gut following challenge with commensal, pathogenic, and parasitic microbes","volume":"193","author":"BL Weiss","year":"2014","journal-title":"Journal of immunology (Baltimore, Md: 1950)."},{"issue":"22","key":"ppat.1012692.ref025","doi-asserted-by":"crossref","first-page":"12648","DOI":"10.1073\/pnas.221363798","article-title":"Tsetse immune responses and trypanosome transmission: implications for the development of tsetse-based strategies to reduce trypanosomiasis","volume":"98","author":"Z Hao","year":"2001","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"5","key":"ppat.1012692.ref026","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1111\/j.1365-2958.2006.05180.x","article-title":"Innate immune responses regulate trypanosome parasite infection of the tsetse fly Glossina morsitans morsitans","volume":"60","author":"C Hu","year":"2006","journal-title":"Molecular microbiology"},{"issue":"2","key":"ppat.1012692.ref027","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ibmb.2004.10.007","article-title":"An antimicrobial peptide with trypanocidal activity characterized from Glossina morsitans morsitans","volume":"35","author":"Y Hu","year":"2005","journal-title":"Insect biochemistry and molecular biology"},{"issue":"3","key":"ppat.1012692.ref028","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1365-2583.2008.00805.x","article-title":"Characterization of the antimicrobial peptide attacin loci from Glossina morsitans","volume":"17","author":"J Wang","year":"2008","journal-title":"Insect molecular biology"},{"issue":"2","key":"ppat.1012692.ref029","doi-asserted-by":"crossref","first-page":"e239","DOI":"10.1371\/journal.pone.0000239","article-title":"Factors affecting trypanosome maturation in tsetse flies.","volume":"2","author":"ET Macleod","year":"2007","journal-title":"PloS one."},{"issue":"Pt 6","key":"ppat.1012692.ref030","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1017\/S0031182007002247","article-title":"Antioxidants promote establishment of trypanosome infections in tsetse","volume":"134","author":"ET MacLeod","year":"2007","journal-title":"Parasitology"},{"issue":"3","key":"ppat.1012692.ref031","doi-asserted-by":"crossref","first-page":"e1000793","DOI":"10.1371\/journal.ppat.1000793","article-title":"Tsetse EP protein protects the fly midgut from trypanosome establishment.","volume":"6","author":"LR Haines","year":"2010","journal-title":"PLoS pathogens"},{"key":"ppat.1012692.ref032","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1017\/S003118200006056X","article-title":"Identification of trypanolysin and trypanoagglutinin in Glossina palpalis sspp. (Diptera: Glossinidae).","volume":"101","author":"JK Stiles","year":"1990","journal-title":"Parasitology"},{"key":"ppat.1012692.ref033","first-page":"26","article-title":"Lysis of Trypanosoma brucei brucei by Tsetse Trypanolysin","volume":"14","author":"B Nyambega","year":"2011","journal-title":"Kenya Journal of Science (B series)."},{"key":"ppat.1012692.ref034","unstructured":"Osir EO, Abakar M, Abubakar L, editors. The role of trypanolysin in the development of trypanosomes in tsetse. Proceedings of the 25th Meeting of the International Council for Trypanosomiasis Research Control (ISCTRC); 1999; Mombasa, Kenya."},{"issue":"29","key":"ppat.1012692.ref035","doi-asserted-by":"crossref","first-page":"12133","DOI":"10.1073\/pnas.0901226106","article-title":"Interactions between mutualist Wigglesworthia and tsetse peptidoglycan recognition protein (PGRP-LB) influence trypanosome transmission.","volume":"106","author":"J Wang","year":"2009","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"4","key":"ppat.1012692.ref036","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/BF00931529","article-title":"Properties of a blood-meal-induced midgut lectin from the tsetse fly Glossina morsitans","volume":"81","author":"L Abubakar","year":"1995","journal-title":"Parasitology research"},{"issue":"4","key":"ppat.1012692.ref037","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ibmb.2006.01.010","article-title":"Molecular characterization of a tsetse fly midgut proteolytic lectin that mediates differentiation of African trypanosomes","volume":"36","author":"LU Abubakar","year":"2006","journal-title":"Insect biochemistry and molecular biology"},{"key":"ppat.1012692.ref038","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/BF00931530","article-title":"Purification and characterization of a midgut lectin-trypsin complex from the tsetse fly Glossina Iongipennis","volume":"81","author":"EO Osir","year":"1995","journal-title":"Parasitology research"},{"issue":"4","key":"ppat.1012692.ref039","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/BF00937083","article-title":"Inhibitory effect of Trypanosoma brucei brucei on Glossina morsitans midgut trypsin in vitro","volume":"78","author":"MO Imbuga","year":"1992","journal-title":"Parasitology research"},{"key":"ppat.1012692.ref040","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/BF00936174","article-title":"Studies on tsetse midgut factors that induce differentiation of bloodstream Trypanosoma brucei brucei in vitro","volume":"78","author":"MO Imbuga","year":"1992","journal-title":"Parasitol Res"},{"issue":"10","key":"ppat.1012692.ref041","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0169-4758(99)01512-4","article-title":"Tsetse-trypanosome interactions: rites of passage.","volume":"15","author":"SC Welburn","year":"1999","journal-title":"Parasitology today (Personal ed)."},{"issue":"1","key":"ppat.1012692.ref042","doi-asserted-by":"crossref","first-page":"4699","DOI":"10.1038\/s41598-017-04740-3","article-title":"Challenging the Wigglesworthia, Sodalis, Wolbachia symbiosis dogma in tsetse flies: Spiroplasma is present in both laboratory and natural populations","volume":"7","author":"V Doudoumis","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"ppat.1012692.ref043","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s12866-023-03005-6","article-title":"Molecular detection of Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts in wild population of tsetse flies collected in Cameroon, Chad and Nigeria.","volume":"23","author":"YM Mfopit","year":"2023","journal-title":"BMC microbiology"},{"key":"ppat.1012692.ref044","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1051\/parasite\/2023064","article-title":"Prevalence of Spiroplasma and interaction with wild Glossina tachinoides microbiota.","volume":"30","author":"KM Dera","year":"2023","journal-title":"Parasite (Paris, France)."},{"issue":"8","key":"ppat.1012692.ref045","doi-asserted-by":"crossref","first-page":"e0007340","DOI":"10.1371\/journal.pntd.0007340","article-title":"Spatio-temporal distribution of Spiroplasma infections in the tsetse fly (Glossina fuscipes fuscipes) in northern Uganda.","volume":"13","author":"DI Schneider","year":"2019","journal-title":"PLoS neglected tropical diseases."},{"issue":"9","key":"ppat.1012692.ref046","doi-asserted-by":"crossref","first-page":"e1009539","DOI":"10.1371\/journal.ppat.1009539","article-title":"Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis.","volume":"17","author":"JH Son","year":"2021","journal-title":"PLoS pathogens."},{"key":"ppat.1012692.ref047","doi-asserted-by":"crossref","first-page":"e02964","DOI":"10.7554\/eLife.02964","article-title":"Insect endosymbiont proliferation is limited by lipid availability.","volume":"3","author":"JK Herren","year":"2014","journal-title":"eLife"},{"issue":"3","key":"ppat.1012692.ref048","doi-asserted-by":"crossref","first-page":"e192","DOI":"10.1371\/journal.pntd.0000192","article-title":"Infections with immunogenic trypanosomes reduce tsetse reproductive fitness: potential impact of different parasite strains on vector population structure","volume":"2","author":"C Hu","year":"2008","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"ppat.1012692.ref049","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1111\/jeb.12260","article-title":"Protection against a fungal pathogen conferred by the aphid facultative endosymbionts Rickettsia and Spiroplasma is expressed in multiple host genotypes and species and is not influenced by co-infection with another symbiont","volume":"26","author":"P \u0141ukasik","year":"2013","journal-title":"J Evol Biol"},{"issue":"2","key":"ppat.1012692.ref050","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1073\/pnas.1518648113","article-title":"A ribosome-inactivating protein in a Drosophila defensive symbiont","volume":"113","author":"PT Hamilton","year":"2016","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ppat.1012692.ref051","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cois.2018.10.004","article-title":"The defensive Spiroplasma.","volume":"32","author":"MJ Ballinger","year":"2019","journal-title":"Curr Opin Insect Sci"},{"issue":"2","key":"ppat.1012692.ref052","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41579-019-0309-z","article-title":"Microorganisms in the reproductive tissues of arthropods","volume":"18","author":"JI Perlmutter","year":"2020","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1012692.ref053","doi-asserted-by":"crossref","first-page":"103919","DOI":"10.1016\/j.jinsphys.2019.103919","article-title":"Tsetse peritrophic matrix influences for trypanosome transmission","volume":"118","author":"S. Aksoy","year":"2019","journal-title":"Journal of insect physiology"},{"issue":"4","key":"ppat.1012692.ref054","article-title":"Identification and RNAi-Based Functional Analysis of Four Chitin Deacetylase Genes in Sogatella furcifera (Hemiptera: Delphacidae).","volume":"21","author":"XB Yang","year":"2021","journal-title":"J Insect Sci."},{"issue":"8","key":"ppat.1012692.ref055","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ibmb.2010.06.003","article-title":"A gut-specific chitinase gene essential for regulation of chitin content of peritrophic matrix and growth of Ostrinia nubilalis larvae","volume":"40","author":"C Khajuria","year":"2010","journal-title":"Insect biochemistry and molecular biology"},{"key":"ppat.1012692.ref056","first-page":"206","article-title":"Chitin metabolism in insects: structure, function and regulation of chitin synthases and chitinases","author":"H Merzendorfer","year":"2003","journal-title":"The Journal of experimental biology"},{"key":"ppat.1012692.ref057","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3389\/fmicb.2017.00540","article-title":"Comparative Genomics of Glossina palpalis gambiensis and G. morsitans morsitans to Reveal Gene Orthologs Involved in Infection by Trypanosoma brucei gambiense","volume":"8","author":"I Hamidou Soumana","year":"2017","journal-title":"Front Microbiol"},{"issue":"25","key":"ppat.1012692.ref058","doi-asserted-by":"crossref","first-page":"6961","DOI":"10.1073\/pnas.1600304113","article-title":"Mammalian African trypanosome VSG coat enhances tsetse\u2019s vector competence","volume":"113","author":"E Aksoy","year":"2016","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"4","key":"ppat.1012692.ref059","doi-asserted-by":"crossref","first-page":"e1006972","DOI":"10.1371\/journal.ppat.1006972","article-title":"A fine-tuned vector-parasite dialogue in tsetse\u2019s cardia determines peritrophic matrix integrity and trypanosome transmission success","volume":"14","author":"A Vigneron","year":"2018","journal-title":"PLoS pathogens"},{"issue":"6","key":"ppat.1012692.ref060","doi-asserted-by":"crossref","first-page":"e1009475","DOI":"10.1371\/journal.ppat.1009475","article-title":"Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly\u2019s midgut environment.","volume":"17","author":"L Yang","year":"2021","journal-title":"PLoS pathogens."},{"issue":"10","key":"ppat.1012692.ref061","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/ni1001-907","article-title":"Nitric oxide and the immune response","volume":"2","author":"C. Bogdan","year":"2001","journal-title":"Nature immunology"},{"issue":"11","key":"ppat.1012692.ref062","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.ibmb.2003.07.001","article-title":"Proventriculus (cardia) plays a crucial role in immunity in tsetse fly (Diptera: Glossinidiae).","volume":"33","author":"Z Hao","year":"2003","journal-title":"Insect biochemistry and molecular biology"},{"issue":"5591","key":"ppat.1012692.ref063","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1126\/science.1077136","article-title":"Immunity-related genes and gene families in Anopheles gambiae","volume":"298","author":"GK Christophides","year":"2002","journal-title":"Science"},{"issue":"6","key":"ppat.1012692.ref064","doi-asserted-by":"crossref","first-page":"e17144","DOI":"10.15252\/emmm.202217144","article-title":"The under-appreciated world of the serpin family of serine proteinase inhibitors","volume":"15","author":"MC Bouton","year":"2023","journal-title":"EMBO Mol Med"},{"key":"ppat.1012692.ref065","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1146\/annurev-ento-010814-020834","article-title":"Adenotrophic viviparity in tsetse flies: potential for population control and as an insect model for lactation","volume":"60","author":"JB Benoit","year":"2015","journal-title":"Annual review of entomology"},{"key":"ppat.1012692.ref066","doi-asserted-by":"crossref","first-page":"949409","DOI":"10.3389\/fcimb.2022.949409","article-title":"Fatty acid uptake in Trypanosoma brucei: Host resources and possible mechanisms.","volume":"12","author":"NR Poudyal","year":"2022","journal-title":"Frontiers in cellular and infection microbiology"},{"issue":"51","key":"ppat.1012692.ref067","first-page":"49921","article-title":"Epithelial innate immunity. A novel antimicrobial peptide with antiparasitic activity in the blood-sucking insect Stomoxys calcitrans","volume":"277","author":"N Boulanger","year":"2002","journal-title":"The Journal of biological chemistry"},{"issue":"5","key":"ppat.1012692.ref068","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1128\/AAC.05180-14","article-title":"Antimicrobial peptides expressed in medicinal maggots of the blow fly Lucilia sericata show combinatorial activity against bacteria","volume":"59","author":"AK P\u00f6ppel","year":"2015","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"1","key":"ppat.1012692.ref069","doi-asserted-by":"crossref","first-page":"e0169582","DOI":"10.1371\/journal.pone.0169582","article-title":"Screening, Expression, Purification and Functional Characterization of Novel Antimicrobial Peptide Genes from Hermetia illucens (L.).","volume":"12","author":"O Elhag","year":"2017","journal-title":"PloS one."},{"issue":"D1","key":"ppat.1012692.ref070","doi-asserted-by":"crossref","first-page":"D67","DOI":"10.1093\/nar\/gkv1276","article-title":"GenBank.","volume":"44","author":"K Clark","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"ppat.1012692.ref071","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12915-020-00944-8","article-title":"Beyond Drosophila: resolving the rapid radiation of schizophoran flies with phylotranscriptomics.","volume":"19","author":"KM Bayless","year":"2021","journal-title":"BMC Biol.PubMed Central PMCID"},{"issue":"2","key":"ppat.1012692.ref072","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/bip.20370","article-title":"Solution structures of stomoxyn and spinigerin, two insect antimicrobial peptides with an alpha-helical conformation","volume":"81","author":"C Landon","year":"2006","journal-title":"Biopolymers"},{"issue":"1","key":"ppat.1012692.ref073","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1186\/s13071-017-2569-7","article-title":"Tsetse fly (Glossina pallidipes) midgut responses to Trypanosoma brucei challenge.","volume":"10","author":"R Bateta","year":"2017","journal-title":"Parasites & vectors."},{"issue":"7","key":"ppat.1012692.ref074","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nbt.1883","article-title":"Full-length transcriptome assembly from RNA-Seq data without a reference genome","volume":"29","author":"MG Grabherr","year":"2011","journal-title":"Nature biotechnology"},{"issue":"4","key":"ppat.1012692.ref075","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1089\/153036603322662165","article-title":"Cationic antimicrobial peptide killing of African trypanosomes and Sodalis glossinidius, a bacterial symbiont of the insect vector of sleeping sickness.","volume":"3","author":"LR Haines","year":"2003","journal-title":"Vector Borne Zoonotic Dis"},{"issue":"Pt 3","key":"ppat.1012692.ref076","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1017\/S0031182000057966","article-title":"Comparative study on the infection rates of different Glossina species for East and West African Trypanosoma vivax stocks","volume":"95","author":"SK Moloo","year":"1987","journal-title":"Parasitology"},{"key":"ppat.1012692.ref077","first-page":"2","article-title":"Trypanosoma cruzi Affects Rhodnius prolixus Lipid Metabolism During Acute Infection","author":"G Sousa","year":"2021","journal-title":"Frontiers in Tropical Diseases"},{"issue":"11","key":"ppat.1012692.ref078","doi-asserted-by":"crossref","first-page":"262","DOI":"10.15698\/mic2021.11.764","article-title":"Lipid and fatty acid metabolism in trypanosomatids","volume":"8","author":"G Parreira de Aquino","year":"2021","journal-title":"Microb Cell"},{"key":"ppat.1012692.ref079","doi-asserted-by":"crossref","DOI":"10.1007\/5584_2024_805","article-title":"Insect Lipids: Structure, Classification, and Function","author":"A Kaczmarek","year":"2024","journal-title":"Advances in experimental medicine and biology"},{"key":"ppat.1012692.ref080","doi-asserted-by":"crossref","first-page":"1119577","DOI":"10.3389\/finsc.2022.1119577","article-title":"Editorial: Insights into lipid biology and function in insect systems","volume":"2","author":"GM Attardo","year":"2022","journal-title":"Front Insect Sci"},{"issue":"2","key":"ppat.1012692.ref081","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.molbiopara.2010.04.001","article-title":"Lipid metabolism in Trypanosoma brucei","volume":"172","author":"TK Smith","year":"2010","journal-title":"Mol Biochem Parasitol"},{"issue":"4","key":"ppat.1012692.ref082","doi-asserted-by":"crossref","first-page":"e2649","DOI":"10.1371\/journal.pntd.0002649","article-title":"Insights into the trypanosome-host interactions revealed through transcriptomic analysis of parasitized tsetse fly salivary glands.","volume":"8","author":"EL Telleria","year":"2014","journal-title":"PLoS neglected tropical diseases."},{"issue":"10","key":"ppat.1012692.ref083","doi-asserted-by":"crossref","first-page":"R63","DOI":"10.1186\/gb-2003-4-10-r63","article-title":"Adult midgut expressed sequence tags from the tsetse fly Glossina morsitans morsitans and expression analysis of putative immune response genes","volume":"4","author":"MJ Lehane","year":"2003","journal-title":"Genome Biol"},{"issue":"1","key":"ppat.1012692.ref084","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1186\/s12864-016-3283-0","article-title":"Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland","volume":"17","author":"I Matetovici","year":"2016","journal-title":"BMC genomics"},{"issue":"4","key":"ppat.1012692.ref085","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/j.1365-2583.2006.00649.x","article-title":"Analysis of fat body transcriptome from the adult tsetse fly, Glossina morsitans morsitans","volume":"15","author":"GM Attardo","year":"2006","journal-title":"Insect molecular biology"},{"issue":"4","key":"ppat.1012692.ref086","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1093\/jmedent\/44.4.660","article-title":"Refractoriness in tsetse flies (Diptera: Glossinidae) may be a matter of timing.","volume":"44","author":"D Nayduch","year":"2007","journal-title":"Journal of medical entomology"},{"issue":"3","key":"ppat.1012692.ref087","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1006\/jipa.1996.4652","article-title":"Detection of phenoloxidase activity in the hemolymph of tsetse flies, refractory and susceptible to infection with Trypanosoma brucei rhodesiense","volume":"69","author":"Y Nigam","year":"1997","journal-title":"J Invertebr Pathol"},{"issue":"1","key":"ppat.1012692.ref088","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1365-2583.2003.00380.x","article-title":"Hidden from the host: Spiroplasma bacteria infecting Drosophila do not cause an immune response, but are suppressed by ectopic immune activation","volume":"12","author":"GD Hurst","year":"2003","journal-title":"Insect molecular biology"},{"issue":"4","key":"ppat.1012692.ref089","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"S Akira","year":"2006","journal-title":"Cell"},{"key":"ppat.1012692.ref090","doi-asserted-by":"crossref","first-page":"405310","DOI":"10.1155\/2011\/405310","article-title":"Innate immune recognition of Mycobacterium tuberculosis","volume":"2011","author":"J Kleinnijenhuis","year":"2011","journal-title":"Clinical & developmental immunology"},{"key":"ppat.1012692.ref091","doi-asserted-by":"crossref","first-page":"7344","DOI":"10.1038\/ncomms8344","article-title":"Lucilia cuprina genome unlocks parasitic fly biology to underpin future interventions","volume":"6","author":"CA Anstead","year":"2015","journal-title":"Nat Commun"},{"issue":"1","key":"ppat.1012692.ref092","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12915-021-00975-9","article-title":"The genome of the stable fly, Stomoxys calcitrans, reveals potential mechanisms underlying reproduction, host interactions, and novel targets for pest control","volume":"19","author":"PU Olafson","year":"2021","journal-title":"BMC Biol"},{"issue":"1","key":"ppat.1012692.ref093","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/jac\/dky386","article-title":"Profiling antimicrobial peptides from the medical maggot Lucilia sericata as potential antibiotics for MDR Gram-negative bacteria","volume":"74","author":"R Hirsch","year":"2019","journal-title":"J Antimicrob Chemother"},{"issue":"1","key":"ppat.1012692.ref094","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13071-021-05132-3","article-title":"Overview of paratransgenesis as a strategy to control pathogen transmission by insect vectors.","volume":"15","author":"NA Ratcliffe","year":"2022","journal-title":"Parasites & vectors."},{"issue":"Suppl 1","key":"ppat.1012692.ref095","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12866-018-1283-8","article-title":"Combining paratransgenesis with SIT: impact of ionizing radiation on the DNA copy number of Sodalis glossinidius in tsetse flies","volume":"18","author":"G Demirbas-Uzel","year":"2018","journal-title":"BMC microbiology"},{"issue":"3","key":"ppat.1012692.ref096","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1017\/S0031182000080021","article-title":"An artificial feeding technique for Glossina","volume":"63","author":"SK Moloo","year":"1971","journal-title":"Parasitology"},{"issue":"15","key":"ppat.1012692.ref097","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"AM Bolger","year":"2014","journal-title":"Bioinformatics"},{"issue":"Database issue","key":"ppat.1012692.ref098","doi-asserted-by":"crossref","first-page":"D707","DOI":"10.1093\/nar\/gku1117","article-title":"VectorBase: an updated bioinformatics resource for invertebrate vectors and other organisms related with human diseases","volume":"43","author":"GI Giraldo-Calderon","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"ppat.1012692.ref099","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"2","key":"ppat.1012692.ref100","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014a Python framework to work with high-throughput sequencing data","volume":"31","author":"S Anders","year":"2015","journal-title":"Bioinformatics"},{"issue":"12","key":"ppat.1012692.ref101","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"ppat.1012692.ref102","first-page":"57","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing.","author":"Y Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B."},{"issue":"10","key":"ppat.1012692.ref103","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1093\/nar\/gkn176","article-title":"High-throughput functional annotation and data mining with the Blast2GO suite","volume":"36","author":"S Gotz","year":"2008","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"ppat.1012692.ref104","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"SF Altschul","year":"1990","journal-title":"Journal of molecular biology"},{"key":"ppat.1012692.ref105","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.19535","article-title":"Symbiont-induced odorant binding proteins mediate insect host hematopoiesis","volume":"6","author":"JB Benoit","year":"2017","journal-title":"eLife"},{"issue":"2","key":"ppat.1012692.ref106","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqz040","article-title":"MicroRNA miR-7 Regulates Secretion of Insulin-Like Peptides","volume":"161","author":"P Agbu","year":"2020","journal-title":"Endocrinology"},{"issue":"10","key":"ppat.1012692.ref107","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1186\/s13059-014-0466-3","article-title":"Genome of the house fly, Musca domestica L., a global vector of diseases with adaptations to a septic environment","volume":"15","author":"JG Scott","year":"2014","journal-title":"Genome Biol"},{"issue":"22","key":"ppat.1012692.ref108","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice","volume":"22","author":"JD Thompson","year":"1994","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"ppat.1012692.ref109","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1093\/bioinformatics\/btu031","article-title":"InterProScan 5: genome-scale protein function classification","volume":"30","author":"P Jones","year":"2014","journal-title":"Bioinformatics"},{"issue":"21","key":"ppat.1012692.ref110","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.1093\/bioinformatics\/btz305","article-title":"RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference","volume":"35","author":"AM Kozlov","year":"2019","journal-title":"Bioinformatics"},{"key":"ppat.1012692.ref111","first-page":"30","article-title":"MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform","author":"K. Katoh","year":"2002","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"ppat.1012692.ref112","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1128\/AEM.03959-12","article-title":"Characterization of the achromobactin iron acquisition operon in Sodalis glossinidius","volume":"79","author":"CL Smith","year":"2013","journal-title":"Applied and environmental microbiology"},{"issue":"2","key":"ppat.1012692.ref113","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0001-706X(97)00079-X","article-title":"The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro.","volume":"68","author":"B R\u00e4z","year":"1997","journal-title":"Acta tropica"},{"issue":"5","key":"ppat.1012692.ref114","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/j.1460-2075.1985.tb03772.x","article-title":"Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense","volume":"4","author":"T Baltz","year":"1985","journal-title":"The EMBO journal"},{"issue":"5","key":"ppat.1012692.ref115","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1177\/1087057111398295","article-title":"A high-throughput fluorescence resonance energy transfer-based assay for DNA ligase","volume":"16","author":"AB Shapiro","year":"2011","journal-title":"Journal of biomolecular screening"},{"issue":"3","key":"ppat.1012692.ref116","first-page":"289","article-title":"Sch\u00f6nenberger. Cultivation and in vitro cloning or procyclic culture forms of Trypanosoma brucei in a semi-defined medium. Short communication","volume":"36","author":"R Brun","year":"1979","journal-title":"Acta tropica"},{"issue":"9","key":"ppat.1012692.ref117","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"MW Pfaffl","year":"2002","journal-title":"Nucleic Acids Res"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012692","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012692","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:50:15Z","timestamp":1739386215000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012692"}},"subtitle":[],"editor":[{"given":"Christine","family":"Clayton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":117,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012692","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1012692","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}