{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T02:15:23Z","timestamp":1774059323973,"version":"3.50.1"},"reference-count":97,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2020-06130"],"award-info":[{"award-number":["RGPIN-2020-06130"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ontario Ministry of Research Innovation Early Researcher Award","award":["ER17-13-113"],"award-info":[{"award-number":["ER17-13-113"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Neuropeptide Y-related signaling, consisting of various neuropeptides and their receptors including, for example, the mammalian neuropeptide Y (NPY), pancreatic polypeptide (PP), and peptide YY (PYY) families, along with neuropeptide Y-like peptides in insects, is evolutionarily conserved across vertebrates and invertebrate organisms. Vertebrate NPY is known as an important regulator of energy homeostasis and feeding behaviour, while studies on one NPY-associated signaling system in arthropods, known as RYamide, have mainly focused on functions regulating feeding-related behaviours. The current study aimed to begin exploring an additional functional role of RYamide signaling related to excretory physiology in\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    given that a candidate RYamide receptor, RYaR2, is enriched in the hindgut of adult mosquitoes based on publicly available RNA-seq databases. Herein, we report that the\n                    <jats:italic>RYamide<\/jats:italic>\n                    transcript is expressed in all post-embryonic stages with greatest abundance in adult male mosquitoes. Specifically, the central nervous system and the ventral nerve cord were demonstrated as the major sources of RYamide, as supported by RT-qPCR and intense RYamide immunoreactivity observed in the protocerebral posterior dorsomedial neurons and protocerebral anterolateral neurons in the mushroom body region, along with an intensively stained pair of neurons in the terminal abdominal ganglion (TAG). The pair of immunoreactive neurons in the TAG contain elaborate processes extending onto the hindgut, with a branch extending posteriorly over the rectum where fine processes are in close proximity to the rectal papillae (pads) while an anterior branch extends over the ileum terminating at the midgut-hindgut junction forming a fine circular plexus over the pyloric valve. Importantly, two orphan GPCRs, previously referred to as NPYLRs, were functionally deorphanized as\n                    <jats:italic>bona fide<\/jats:italic>\n                    RYamide receptors. Their responses to diverse peptidergic ligands were assessed, revealing that RYamides elicited the strongest receptor activation, with half maximal effective concentrations in the pico- to nanomolar range. Notably, our phylogenetic analysis revealed that while only a single RYaR is commonly found across most arthropods, culicine mosquito species including\n                    <jats:italic>A. aegypti<\/jats:italic>\n                    possess two RYaRs. The characterization of RYamide signaling with respect to excretory physiology involving the hindgut, particularly in species having two receptor isoforms such as culicine mosquitos, may provide valuable insights for development of novel, species-specific pest control strategies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0342341","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T18:49:45Z","timestamp":1771872585000},"page":"e0342341","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization and deorphanization of RYamide signaling in Aedes aegypti: A potential regulator of hindgut-associated physiology"],"prefix":"10.1371","volume":"21","author":[{"given":"Jinghan","family":"Tan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Luong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-0590","authenticated-orcid":true,"given":"Jean-Paul V.","family":"Paluzzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"issue":"3","key":"pone.0342341.ref001","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s13744-017-0520-4","article-title":"Why is Aedes aegypti linnaeus so successful as a species?","volume":"46","author":"FD Carvalho","year":"2017","journal-title":"Neotrop 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Dis"},{"issue":"1","key":"pone.0342341.ref005","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/nyas.13950","article-title":"Impact of recent and future climate change on vector-borne diseases","volume":"1436","author":"C Caminade","year":"2019","journal-title":"Ann N Y Acad Sci"},{"issue":"4","key":"pone.0342341.ref006","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.micinf.2009.12.011","article-title":"The dengue vector Aedes aegypti: what comes next","volume":"12","author":"CC Jansen","year":"2010","journal-title":"Microbes Infect"},{"issue":"5","key":"pone.0342341.ref007","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/j.1461-0248.2005.00755.x","article-title":"Ecology of invasive mosquitoes: effects on resident species and on human health","volume":"8","author":"SA Juliano","year":"2005","journal-title":"Ecology Letters"},{"issue":"4","key":"pone.0342341.ref008","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3390\/insects9040158","article-title":"Effects of the environmental temperature on Aedes aegypti and Aedes albopictus mosquitoes: a review","volume":"9","author":"JM Reinhold","year":"2018","journal-title":"Insects"},{"issue":"3","key":"pone.0342341.ref009","first-page":"494","article-title":"The used tire trade: a mechanism for the worldwide dispersal of container breeding mosquitoes","volume":"3","author":"P Reiter","year":"1987","journal-title":"J Am Mosq Control Assoc"},{"issue":"5","key":"pone.0342341.ref010","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1093\/jme\/tjz051","article-title":"Localized control of Aedes aegypti (Diptera: Culicidae) in Miami, FL, via Inundative Releases of Wolbachia-Infected Male Mosquitoes","volume":"56","author":"JW Mains","year":"2019","journal-title":"J Med Entomol"},{"issue":"5","key":"pone.0342341.ref011","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1093\/jme\/tjad079","article-title":"Developing methods for chilling, compacting, and sterilizing adult Aedes aegypti (Diptera: Culicidae) and comparing mating competitiveness between males sterilized as adults versus pupae for sterile male release","volume":"60","author":"DA Tussey","year":"2023","journal-title":"J Med Entomol"},{"issue":"1","key":"pone.0342341.ref012","first-page":"10","article-title":"A Review of the Control of Aedes aegypti (Diptera: Culicidae) in the Continental United States","volume":"58","author":"BL McGregor","year":"2021","journal-title":"J Med Entomol"},{"issue":"4","key":"pone.0342341.ref013","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2018.12.004","article-title":"Small-molecule agonists of Ae. aegypti Neuropeptide Y receptor block mosquito biting","volume":"176","author":"LB Duvall","year":"2019","journal-title":"Cell"},{"issue":"1","key":"pone.0342341.ref014","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s13071-024-06347-w","article-title":"Next-generation neuropeptide Y receptor small-molecule agonists inhibit mosquito-biting behavior","volume":"17","author":"EV Zeledon","year":"2024","journal-title":"Parasit Vectors"},{"issue":"21","key":"pone.0342341.ref015","doi-asserted-by":"crossref","first-page":"8702","DOI":"10.1073\/pnas.1221833110","article-title":"Global view of the evolution and diversity of metazoan neuropeptide signaling","volume":"110","author":"G J\u00e9kely","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"22","key":"pone.0342341.ref016","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1219956110","article-title":"Molecular evolution of peptidergic signaling systems in bilaterians","volume":"110","author":"O Mirabeau","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0342341.ref017","doi-asserted-by":"crossref","first-page":"7220","DOI":"10.1038\/s41598-018-25606-2","article-title":"Discovery and functional characterisation of a luqin-type neuropeptide signalling system in a deuterostome","volume":"8","author":"LA Ya\u00f1ez-Guerra","year":"2018","journal-title":"Sci Rep"},{"issue":"10","key":"pone.0342341.ref018","doi-asserted-by":"crossref","first-page":"5296","DOI":"10.1021\/pr100570j","article-title":"Genomics and peptidomics of neuropeptides and protein hormones present in the parasitic wasp Nasonia vitripennis","volume":"9","author":"F Hauser","year":"2010","journal-title":"J Proteome Res"},{"issue":"4","key":"pone.0342341.ref019","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.bbrc.2011.06.081","article-title":"Identification of the novel bioactive peptides dRYamide-1 and dRYamide-2, ligands for a neuropeptide Y-like receptor in Drosophila","volume":"410","author":"T Ida","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0342341.ref020","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ibmb.2017.03.001","article-title":"Rudimentary expression of RYamide in Drosophila melanogaster relative to other Drosophila species points to a functional decline of this neuropeptide gene","volume":"83","author":"JA Veenstra","year":"2017","journal-title":"Insect Biochem Mol Biol"},{"key":"pone.0342341.ref021","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.peptides.2016.02.003","article-title":"Expression of RYamide in the nervous and endocrine system of Bombyx mori","volume":"80","author":"L Roller","year":"2016","journal-title":"Peptides"},{"issue":"6","key":"pone.0342341.ref022","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.peptides.2011.03.013","article-title":"A comparative review of short and long neuropeptide F signaling in invertebrates: Any similarities to vertebrate neuropeptide Y signaling?","volume":"32","author":"DR N\u00e4ssel","year":"2011","journal-title":"Peptides"},{"issue":"2","key":"pone.0342341.ref023","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0166-2236(98)01292-2","article-title":"Feeding and body-weight regulation by hypothalamic neuropeptides--mediation of the actions of leptin","volume":"22","author":"A Inui","year":"1999","journal-title":"Trends Neurosci"},{"issue":"3","key":"pone.0342341.ref024","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.tem.2015.01.003","article-title":"Regulation of energy homeostasis by the NPY system","volume":"26","author":"K Loh","year":"2015","journal-title":"Trends Endocrinol Metab"},{"key":"pone.0342341.ref025","doi-asserted-by":"crossref","first-page":"101455","DOI":"10.1016\/j.molmet.2022.101455","article-title":"NPY derived from AGRP neurons controls feeding via Y1 and energy expenditure and food foraging behaviour via Y2 signalling","volume":"59","author":"Y Qi","year":"2022","journal-title":"Mol Metab"},{"key":"pone.0342341.ref026","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.peptides.2018.03.009","article-title":"Functional characterization of mosquito short neuropeptide F receptors","volume":"103","author":"P Christ","year":"2018","journal-title":"Peptides"},{"issue":"11","key":"pone.0342341.ref027","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0188243","article-title":"Feeding-induced changes in allatostatin-A and short neuropeptide F in the antennal lobes affect odor-mediated host seeking in the yellow fever mosquito, Aedes aegypti","volume":"12","author":"P Christ","year":"2017","journal-title":"PLoS One"},{"key":"pone.0342341.ref028","first-page":"145","article-title":"Mosquito peptide hormones: diversity, production, and function","volume":"51","author":"MR Strand","year":"2016","journal-title":"Adv In Insect 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B"},{"key":"pone.0342341.ref032","doi-asserted-by":"crossref","first-page":"7795","DOI":"10.1038\/srep07795","article-title":"Functional characterization of aquaporins and aquaglyceroporins of the yellow fever mosquito, Aedes aegypti","volume":"5","author":"LL Drake","year":"2015","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0342341.ref033","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1242\/jeb.27.2.145","article-title":"Osmotic regulation in mosquito larvae","volume":"27","author":"JA Ramsay","year":"1950","journal-title":"J Exp Biol"},{"key":"pone.0342341.ref034","doi-asserted-by":"crossref","first-page":"1365651","DOI":"10.3389\/finsc.2024.1365651","article-title":"Protein localization of aquaporins in the adult female disease vector mosquito, Aedes aegypti","volume":"4","author":"B Picinic","year":"2024","journal-title":"Front Insect Sci"},{"key":"pone.0342341.ref035","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1242\/jeb.01422","article-title":"Analysis of Na+, Cl-, K+, H+ and NH4+ concentration gradients adjacent to the surface of anal papillae of the mosquito Aedes aegypti: application of self-referencing ion-selective microelectrodes","volume":"208","author":"A Donini","year":"2005","journal-title":"J Exp Biol"},{"key":"pone.0342341.ref036","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0065-2806(08)60103-4","article-title":"Mechanisms and control of reabsorption in insect hindgut.","author":"JE Phillips","year":"1987","journal-title":"Advances in Insect Physiology. Elsevier"},{"issue":"9","key":"pone.0342341.ref037","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/0022-1910(91)90040-7","article-title":"The hindgut muscularis of the stable fly, Stomoxys calcitrans: Some of its structural, motile and pharmacological properties","volume":"37","author":"BJ Cook","year":"1991","journal-title":"Journal of Insect Physiology"},{"issue":"2","key":"pone.0342341.ref038","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0022-1910(95)00089-5","article-title":"Defecation by the mosquito, Aedes aegypti, is controlled by the terminal abdominal ganglion","volume":"42","author":"E Van Handel","year":"1996","journal-title":"Journal of Insect Physiology"},{"key":"pone.0342341.ref039","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/jcb.29874","article-title":"Activation of Bombyx mori neuropeptide G protein-coupled receptor A19 by neuropeptide RYamides couples to Gq protein-dependent signaling pathways","volume":"122","author":"Z Guo","year":"2021","journal-title":"J Cell Biochem"},{"key":"pone.0342341.ref040","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkx976","article-title":"FlyAtlas 2: a new version of the Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data","volume":"46","author":"DP Leader","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0342341.ref041","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1086\/342002","article-title":"The characterization of ion regulation in Amazonian mosquito larvae: evidence of phenotypic plasticity, population-based disparity, and novel mechanisms of ion uptake","volume":"75","author":"ML Patrick","year":"2002","journal-title":"Physiol Biochem Zool"},{"key":"pone.0342341.ref042","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1242\/jeb.02551","article-title":"P-type Na+\/K+-ATPase and V-type H+-ATPase expression patterns in the osmoregulatory organs of larval and adult mosquito Aedes aegypti","volume":"209","author":"ML Patrick","year":"2006","journal-title":"J Exp Biol"},{"key":"pone.0342341.ref043","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev.en.32.010187.002255","article-title":"Physiology of osmoregulation in mosquitoes","volume":"32","author":"TJ Bradley","year":"1987","journal-title":"Annu Rev Entomol"},{"key":"pone.0342341.ref044","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1242\/jeb.106.1.71","article-title":"Cellular mechanisms and control of KCl absorption in insect hindgut","volume":"106","author":"JW Hanrahan","year":"1983","journal-title":"J Exp Biol"},{"issue":"3","key":"pone.0342341.ref045","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1365-2818.1967.tb00585.x","article-title":"The fine-structural changes observed in the rectal papillae of the mosquito Aedes aegypti, L. and their relation to epithelial transport of water and inorganic ions","volume":"86","author":"CR Hopkins","year":"1967","journal-title":"J R Microsc Soc"},{"issue":"10","key":"pone.0342341.ref046","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0002486","article-title":"Functional and genetic characterization of neuropeptide Y-like receptors in Aedes aegypti","volume":"7","author":"J Liesch","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"pone.0342341.ref047","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40851-015-0034-z","article-title":"Suppressive effects of dRYamides on feeding behavior of the blowfly, Phormia regina","volume":"1","author":"T Maeda","year":"2015","journal-title":"Zoological Lett"},{"issue":"7","key":"pone.0342341.ref048","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0219050","article-title":"Enteroendocrine peptides regulate feeding behavior via controlling intestinal contraction of the silkworm Bombyx mori","volume":"14","author":"S Matsumoto","year":"2019","journal-title":"PLoS One"},{"issue":"3","key":"pone.0342341.ref049","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0040-8166(86)90061-3","article-title":"FMRFamide- and pancreatic polypeptide-like immunoreactivity of endocrine cells in the midgut of a mosquito","volume":"18","author":"MR Brown","year":"1986","journal-title":"Tissue Cell"},{"issue":"3","key":"pone.0342341.ref050","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00441-021-03462-3","article-title":"FMRF-related peptides in Aedes aegypti midgut: neuromuscular connections and enteric nervous system","volume":"385","author":"RSM Godoy","year":"2021","journal-title":"Cell Tissue Res"},{"issue":"9","key":"pone.0342341.ref051","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/S0196-9781(99)00097-2","article-title":"Identification of a Drosophila brain-gut peptide related to the neuropeptide Y family","volume":"20","author":"MR Brown","year":"1999","journal-title":"Peptides"},{"issue":"8","key":"pone.0342341.ref052","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0196-9781(02)00074-8","article-title":"Neuropeptide F and its expression in the yellow fever mosquito, Aedes aegypti","volume":"23","author":"DM Stanek","year":"2002","journal-title":"Peptides"},{"issue":"4","key":"pone.0342341.ref053","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.aspen.2020.09.004","article-title":"Sulfakinin inhibits activity of digestive enzymes in the brown planthopper, Nilaparvata lugens","volume":"23","author":"D Guo","year":"2020","journal-title":"Journal of Asia-Pacific Entomology"},{"issue":"9","key":"pone.0342341.ref054","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/S0022-1910(00)00046-9","article-title":"Sulfakinins reduce food intake in the desert locust, Schistocerca gregaria","volume":"46","author":"Z Wei","year":"2000","journal-title":"J Insect Physiol"},{"issue":"2","key":"pone.0342341.ref055","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/cne.903380210","article-title":"Spatial and temporal expression identify dromyosuppressin as a brain-gut peptide in Drosophila melanogaster","volume":"338","author":"J McCormick","year":"1993","journal-title":"J Comp Neurol"},{"issue":"2","key":"pone.0342341.ref056","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.peptides.2012.05.002","article-title":"Structure-activity and immunochemical data provide evidence of developmental- and tissue-specific myosuppressin signaling","volume":"36","author":"M Dickerson","year":"2012","journal-title":"Peptides"},{"issue":"4","key":"pone.0342341.ref057","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.bbrc.2011.07.131","article-title":"Identification of the Drosophila and Tribolium receptors for the recently discovered insect RYamide neuropeptides","volume":"412","author":"C Collin","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0342341.ref058","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1038\/s41598-018-20517-8","article-title":"Molecular identification, transcript expression, and functional deorphanization of the adipokinetic hormone\/corazonin-related peptide receptor in the disease vector, Aedes aegypti","volume":"8","author":"A Wahedi","year":"2018","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0342341.ref059","article-title":"The heterodimeric glycoprotein hormone, GPA2\/GPB5, regulates ion transport across the hindgut of the adult mosquito, Aedes aegypti","volume":"9","author":"J-P Paluzzi","year":"2014","journal-title":"PLoS One"},{"key":"pone.0342341.ref060","doi-asserted-by":"crossref","first-page":"114618","DOI":"10.1016\/j.ygcen.2024.114618","article-title":"Functional characterization of CCHamides and deorphanization of their receptors in the yellow fever mosquito, Aedes aegypti","volume":"359","author":"J Tan","year":"2024","journal-title":"Gen Comp Endocrinol"},{"issue":"2","key":"pone.0342341.ref061","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0092-8674(86)90762-2","article-title":"Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes","volume":"44","author":"M Kozak","year":"1986","journal-title":"Cell"},{"key":"pone.0342341.ref062","unstructured":"Luong TDN. Characterization of RYamide neuropeptides and their Receptor in the Disease Vector Mosquito, Aedes aegypti. York University. 2023. https:\/\/yorkspace.library.yorku.ca\/items\/0d0e566b-7a57-49d5-8a7b-4bf619445dca"},{"issue":"1","key":"pone.0342341.ref063","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.peptides.2011.10.025","article-title":"Investigation of the potential involvement of eicosanoid metabolites in anti-diuretic hormone signaling in Rhodnius prolixus","volume":"34","author":"J-PV Paluzzi","year":"2012","journal-title":"Peptides"},{"issue":"4","key":"pone.0342341.ref064","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1111\/j.1476-5381.1993.tb13960.x","article-title":"Increases in intracellular calcium via activation of an endogenous P2-purinoceptor in cultured CHO-K1 cells","volume":"110","author":"PA Iredale","year":"1993","journal-title":"Br J Pharmacol"},{"issue":"21","key":"pone.0342341.ref065","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"MA Larkin","year":"2007","journal-title":"Bioinformatics"},{"issue":"6","key":"pone.0342341.ref066","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"S Kumar","year":"2018","journal-title":"Mol Biol Evol"},{"issue":"3","key":"pone.0342341.ref067","first-page":"275","article-title":"The rapid generation of mutation data matrices from protein sequences","volume":"8","author":"DT Jones","year":"1992","journal-title":"Comput Appl Biosci"},{"key":"pone.0342341.ref068","doi-asserted-by":"crossref","first-page":"490","DOI":"10.3389\/fphys.2020.00490","article-title":"Receptor characterization and functional activity of pyrokinins on the hindgut in the adult mosquito, Aedes aegypti","volume":"11","author":"A Lajevardi","year":"2020","journal-title":"Front 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Neurosci"},{"issue":"7383","key":"pone.0342341.ref078","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature10776","article-title":"Conditional modulation of spike-timing-dependent plasticity for olfactory learning","volume":"482","author":"S Cassenaer","year":"2012","journal-title":"Nature"},{"issue":"4","key":"pone.0342341.ref079","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/(SICI)1096-9861(19981228)402:4<520::AID-CNE6>3.0.CO;2-K","article-title":"Mushroom bodies of the cockroach: Their participation in place memory","volume":"402","author":"M Mizunami","year":"1998","journal-title":"J Comp Neurol"},{"issue":"6","key":"pone.0342341.ref080","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/S0959-4388(00)00147-1","article-title":"Behavioral functions of the insect mushroom bodies","volume":"10","author":"T Zars","year":"2000","journal-title":"Curr Opin 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Physiol"},{"issue":"33","key":"pone.0342341.ref084","doi-asserted-by":"crossref","first-page":"14833","DOI":"10.1073\/pnas.1009318107","article-title":"Limited taste discrimination in Drosophila","volume":"107","author":"P Masek","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pone.0342341.ref085","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.asd.2008.05.005","article-title":"Tritocerebral tract input to the insect mushroom bodies","volume":"37","author":"SM Farris","year":"2008","journal-title":"Arthropod Struct Dev"},{"issue":"3","key":"pone.0342341.ref086","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/sleep\/34.3.273","article-title":"Go signaling in mushroom bodies regulates sleep in Drosophila","volume":"34","author":"F Guo","year":"2011","journal-title":"Sleep"},{"issue":"33","key":"pone.0342341.ref087","doi-asserted-by":"crossref","first-page":"10495","DOI":"10.1523\/JNEUROSCI.23-33-10495.2003","article-title":"Dopamine and octopamine differentiate between aversive and appetitive olfactory memories in Drosophila","volume":"23","author":"M Schwaerzel","year":"2003","journal-title":"J Neurosci"},{"issue":"17","key":"pone.0342341.ref088","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/j.cub.2006.07.023","article-title":"Light-induced activation of distinct modulatory neurons triggers appetitive or aversive learning in Drosophila larvae","volume":"16","author":"C Schroll","year":"2006","journal-title":"Curr Biol"},{"issue":"28","key":"pone.0342341.ref089","article-title":"Reciprocal interactions between neuropeptide F and RYamide regulate host attraction in the mosquito Aedes aegypti","volume":"121","author":"X Dou","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pone.0342341.ref090","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0022-1910(72)90126-6","article-title":"Neuro-hormonal regulation of sexual receptivity in female Aedes aegypti","volume":"18","author":"RW Gwadz","year":"1972","journal-title":"J Insect Physiol"},{"issue":"1","key":"pone.0342341.ref091","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/0006-2944(75)90099-X","article-title":"Direct determination of uric acid in fecal material","volume":"12","author":"E Van Handel","year":"1975","journal-title":"Biochem Med"},{"issue":"4","key":"pone.0342341.ref092","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/0022-1910(66)90006-0","article-title":"Ultrastructural variations in the anal papillae of Aedes aegypti (L.) at different environment salinities","volume":"12","author":"RS Sohal","year":"1966","journal-title":"J Insect Physiol"},{"key":"pone.0342341.ref093","article-title":"Cold tolerance of Drosophilaspecies is tightly linked to epithelial K+ transport capacity of the Malpighian tubules and rectal pads","author":"MK Andersen","year":"2017","journal-title":"Journal of Experimental Biology"},{"key":"pone.0342341.ref094","article-title":"A Signaling hub in the mosquito rectum coordinates reproductive investment after blood feeding","author":"C Greppi","year":"2025","journal-title":"bioRxiv"},{"key":"pone.0342341.ref095","doi-asserted-by":"crossref","DOI":"10.1385\/0896032418","volume-title":"The Biology of Neuropeptide Y and Related Peptides","author":"WF Colmers","year":"1993"},{"issue":"5","key":"pone.0342341.ref096","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0092-8674(00)81609-8","article-title":"Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans","volume":"94","author":"M de 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