{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:02:28Z","timestamp":1784289748682,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013406","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000}}],"reference-count":148,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/T002727\/1"],"award-info":[{"award-number":["BB\/T002727\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016337","name":"Department for the Economy, Northern Ireland","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100016337","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000277","name":"Department for Environment, Food and Rural Affairs, UK Government","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100000277","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Fasciola<\/jats:italic>\n                    sp. (liver fluke) are parasitic flatworms that impose a significant burden on the agri-food industry and human health. Immature worms can cause severe damage to the liver as they migrate towards the bile ducts, and yet there is only a single drug to treat this pathogenic life stage, driving the need to identify targets for novel flukicides. Given their crucial role in the growth\/development of immature\n                    <jats:italic>Fasciola hepatica<\/jats:italic>\n                    , neoblast-like stem cells are an attractive source of new flukicide targets. Kinases are a hugely diverse group of phosphorylating enzymes with key roles in almost all cellular processes. Kinase dysregulation can result in the development of cancerous cells\/tissues, linking many to cell cycle-associated proliferation and growth. Here, we annotate the\n                    <jats:italic>F. hepatica<\/jats:italic>\n                    kinome, identifying 271 putative protein kinases, representing around 1.6% of predicted\n                    <jats:italic>F. hepatica<\/jats:italic>\n                    protein-coding genes with family proportions similar to those of other parasitic flatworms. Many of these kinases, such as polo-like kinase 1 (\n                    <jats:italic>fhplk1<\/jats:italic>\n                    ), are upregulated in immature worms undergoing rapid growth and development, a process underpinned by the proliferation of neoblast-like stem cells. RNA interference (RNAi)-mediated silencing of\n                    <jats:italic>fhplk1<\/jats:italic>\n                    in juvenile liver fluke reduced growth and cell proliferation, suggesting a conserved role within the cell-cycle; the cessation of stem cell proliferation persisted for at least a week following\n                    <jats:italic>fhplk1-<\/jats:italic>\n                    RNAi. A PLK inhibitor (BI 2536) was shown to phenocopy the\n                    <jats:italic>fhplk1<\/jats:italic>\n                    -RNAi phenotype in a dose-dependent manner, supporting the feasibility of targeting\n                    <jats:italic>F. hepatica<\/jats:italic>\n                    neoblast-like cells through kinase inhibitors. Transcriptomic analysis of\n                    <jats:italic>fhplk1<\/jats:italic>\n                    -RNAi juveniles revealed 946 downregulated genes, principally associated with the cell cycle or ribosomes. Over 80 of these downregulated genes were also downregulated following juvenile\n                    <jats:italic>F. hepatica<\/jats:italic>\n                    irradiation, supporting roles for these kinases in neoblast-like stem cells, and marking them as putative targets for control. Among the 1244 upregulated genes in\n                    <jats:italic>fhplk1-<\/jats:italic>\n                    RNAi juvenile worms were many neurotransmitters, receptors and ion channels, exposing the apparent upregulation of diverse inter-cellular signalling systems. While many neurotransmitter pathways promote proliferation in mammalian systems the interaction between neoblast-like stem cells and neuronal signalling in parasitic flatworms remains elusive. Here, the transcriptomic response of\n                    <jats:italic>fhplk1-<\/jats:italic>\n                    RNAi juveniles supports a link between neoblast-like stem cell driven growth\/development and neuronal signalling.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013406","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:50:45Z","timestamp":1764701445000},"page":"e1013406","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Polo-like kinase 1 regulates growth in juvenile Fasciola hepatica"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0030-1594","authenticated-orcid":true,"given":"Paul","family":"McCusker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan G.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Robb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"McVeigh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Krasky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Selzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki J.","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron G.","family":"Maule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ppat.1013406.ref001","volume-title":"Diseases in domestic animals caused by flukes","author":"FAO","year":"1994"},{"key":"ppat.1013406.ref002","author":"WHO","year":"2017"},{"issue":"6","key":"ppat.1013406.ref003","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.pt.2016.03.002","article-title":"Current Threat of Triclabendazole Resistance in Fasciola hepatica","volume":"32","author":"JM Kelley","year":"2016","journal-title":"Trends 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