{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:39:47Z","timestamp":1761676787858,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,17]],"date-time":"2019-11-17T00:00:00Z","timestamp":1573948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["8490","A557042"],"award-info":[{"award-number":["8490","A557042"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The European Association of Fish Pathologists Small Grant Scheme (EAFP SGS)","award":["01\/2018"],"award-info":[{"award-number":["01\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Excretory and secretory products are crucial for parasite infectivity and host immunomodulation, but the functioning and ultrastructure of the excretory gland cell (EC) that produces these products are still scarcely understood and described. In light of growing reports on anisakiasis cases in Europe, we aimed to characterise the EC of larval Anisakis pegreffii and adult Pseudoterranova azarasi. In the latter, EC starts 0.85 mm from the head tip, measuring 1.936 \u00d7 0.564 mm. Larval EC shows a long nucleus with thorn-like extravaginations toward the cytoplasm, numerous electron-dense and -lucent secretory granules spanning from the perinuclear to subplasmalemmal space, an elevated number of free ribosomes, small, spherical mitochondria with few cristae and a laminated matrix, small and few Golgi apparatuses, and few endoplasmic reticula, with wide cisternae complexes. Ultrastructure suggests that anaerobic glycolysis is the main metabolic pathway, obtained through nutrient endocytosis across the pseudocoelomic surface of the EC plasmalemma and its endocytic canaliculi. Thorn-like extravaginations of EC karyotheca likely mediate specific processes (Ca2+ signaling, gene expression, transport, nuclear lipid metabolism) into the extremely wide EC cytosol, enabling focal delivery of a signal to specific sites in a short time. These functional annotations of parasitic EC should help to clarify anisakiasis pathogenesis.<\/jats:p>","DOI":"10.3390\/cells8111451","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T04:31:10Z","timestamp":1574051470000},"page":"1451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional Ultrastructure of the Excretory Gland Cell in Zoonotic Anisakids (Anisakidae, Nematoda)"],"prefix":"10.3390","volume":"8","author":[{"given":"Ivona","family":"Mladineo","sequence":"first","affiliation":[{"name":"Institute of Oceanography and Fisheries, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7665-6319","authenticated-orcid":false,"given":"Jerko","family":"Hrabar","sequence":"additional","affiliation":[{"name":"Institute of Oceanography and Fisheries, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrvoje","family":"Smodlaka","sequence":"additional","affiliation":[{"name":"Western University of Health Sciences, College of Veterinary Medicine, Pomona, CA 91766, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Palmer","sequence":"additional","affiliation":[{"name":"Marine Mammal Care Center Los Angeles, San Pedro, CA 90731, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Sakamaki","sequence":"additional","affiliation":[{"name":"Pacific Marine Mammal Center, Laguna Beach, CA 92651, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kleoniki","family":"Keklikoglou","sequence":"additional","affiliation":[{"name":"Hellenic Centre for Marine Research, Heraklion, 71500 Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9905-5068","authenticated-orcid":false,"given":"Pantelis","family":"Katharios","sequence":"additional","affiliation":[{"name":"Hellenic Centre for Marine Research, Heraklion, 71500 Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1534\/genetics.106.066035","article-title":"Genes required for osmoregulation and apical secretion in Caenorhabditis elegans","volume":"175","author":"Benedetto","year":"2007","journal-title":"Genetics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/dneu.22408","article-title":"Gap junctions in C. elegans: Their roles in behavior and development","volume":"77","author":"Hall","year":"2017","journal-title":"Dev. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0022-5320(83)90050-3","article-title":"Fine structure of the Caenorhabditis elegans secretory\u2014Excretory system","volume":"82","author":"Nelson","year":"1983","journal-title":"J. Ultrastruct. Res."},{"key":"ref_4","unstructured":"Lee, D.L. (2002). General Organisation. Biol. Nematodes, Taylor & Francis. [1st ed.]."},{"key":"ref_5","unstructured":"Bird, A.F., and Bird, J. (1991). The Structure of Nematodes, Academic Press. [2nd ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kennedy, M.W., and Harnett, W. (2013). Parasitic Nematodes: Molecular Biology, Biochemistry and Immunology, CABI Publishing.","DOI":"10.1079\/9781845937591.0000"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.fsi.2013.06.007","article-title":"Effects of excretory\/secretory products from Anisakis simplex (Nematoda) on immune gene expression in rainbow trout (Oncorhynchus mykiss)","volume":"35","author":"Bahlool","year":"2013","journal-title":"Fish Shellfish. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.kjms.2017.08.002","article-title":"Excretory\/secretory proteases and mechanical movement of Anisakis pegreffii infective larvae in the penetration of BALB\/c mice gastrointestine","volume":"33","author":"Lee","year":"2017","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1365-2222.2004.01883.x","article-title":"Characterization of allergens secreted by Anisakis simplex parasite: Clinical relevance in comparison with somatic allergens","volume":"34","author":"Baeza","year":"2004","journal-title":"Clin. Exp. Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.euprot.2014.06.006","article-title":"Characterisation of potential novel allergens in the fish parasite Anisakis simplex","volume":"4","author":"Jonscher","year":"2014","journal-title":"EuPA Open Proteom."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ijpara.2012.11.011","article-title":"Immunomodulation by helminth parasites: Defining mechanisms and mediators","volume":"43","author":"McSorley","year":"2013","journal-title":"Int. J. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.molbiopara.2014.03.007","article-title":"Secretory products of helminth parasites as immunomodulators","volume":"195","author":"Harnett","year":"2014","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1139\/z68-125","article-title":"Molting in parasitic nematode, Phocanema decipiens. IV Ecdysis and its control","volume":"46","author":"Davey","year":"1968","journal-title":"Can. J. Zool."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3389\/fimmu.2012.00269","article-title":"Defense peptides secreted by helminth pathogens: Antimicrobial and\/or immunomodulator molecules?","volume":"3","author":"Cotton","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_15","first-page":"26","article-title":"Reciprocal Interactions between Nematodes and Their Microbial Environments","volume":"7","author":"Midha","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.3389\/fimmu.2018.02282","article-title":"Parasitic Nematodes Exert Antimicrobial Activity and Benefit from Microbiota-Driven Support for Host Immune Regulation","volume":"9","author":"Rausch","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Robinson, M.W., Donnelly, S., Hutchinson, A.T., To, J., Taylor, N.L., Norton, R.S., Perugini, M.A., and Dalton, J.P. (2011). A Family of Helminth Molecules that Modulate Innate Cell Responses via Molecular Mimicry of Host Antimicrobial Peptides. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002042"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Baird, F.J., Su, X., Aibinu, I., Nolan, M.J., Sugiyama, H., Otranto, D., Lopata, A.L., and Cantacessi, C. (2016). The Anisakis Transcriptome Provides a Resource for Fundamental and Applied Studies on Allergy-Causing Parasites. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004845"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"964350","DOI":"10.1155\/2014\/964350","article-title":"Harnessing the Helminth Secretome for Therapeutic Immunomodulators","volume":"2014","author":"Ditgen","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Moreno, Y., Gros, P.-P., Tam, M., Segura, M., Valanparambil, R., Geary, T.G., and Stevenson, M.M. (2011). Proteomic Analysis of Excretory-Secretory Products of Heligmosomoides polygyrus Assessed with Next-Generation Sequencing Transcriptomic Information. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001370"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41588-018-0262-1","article-title":"Comparative genomics of the major parasitic worms","volume":"51","author":"Coghlan","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13071-017-2585-7","article-title":"Tissue-specific transcriptomes of Anisakis simplex (sensu stricto) and Anisakis pegreffii reveal potential molecular mechanisms involved in pathogenicity","volume":"11","author":"Cavallero","year":"2018","journal-title":"Parasites Vectors"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1186\/s13071-016-1895-5","article-title":"Anisakis pegreffii (Nematoda: Anisakidae) products modulate oxidative stress and apoptosis-related biomarkers in human cell lines","volume":"9","author":"Messina","year":"2016","journal-title":"Parasites Vectors"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e12527","DOI":"10.1111\/pim.12527","article-title":"Anisakis pegreffii impacts differentiation and function of human dendritic cells","volume":"40","author":"Napoletano","year":"2018","journal-title":"Parasite Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1007\/s00436-018-6008-2","article-title":"Exploring tumourigenic potential of the parasite Anisakis: A pilot study","volume":"117","author":"Corcuera","year":"2018","journal-title":"Parasitol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2307\/3278820","article-title":"Ultrastructure of the Excretory System of Anisakis Larva (Nematoda: Anisakidae)","volume":"59","author":"Lee","year":"1973","journal-title":"J. Parasitol."},{"key":"ref_27","first-page":"S72","article-title":"Light and transmission electron microscopis studies of the third stage larvae of Anisakis simplex","volume":"64","author":"Roongruangchai","year":"2012","journal-title":"Siriraj Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.molbiopara.2017.01.003","article-title":"Population parameters and mito-nuclear mosaicism of Anisakis spp. in the Adriatic Sea","volume":"212","author":"Mladineo","year":"2017","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1645\/0022-3395(2000)086[0380:POTANA]2.0.CO;2","article-title":"Phylogeny of the Ascaridoidea (Nematoda: Ascaridida) based on three genes and morphology: Hypotheses of structural and sequence evolution","volume":"86","author":"Nadler","year":"2000","journal-title":"J. Parasitol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00916","DOI":"10.1128\/AAC.00916-18","article-title":"Efficiency of target larvicides is conditioned by ABC-mediated transport in the zoonotic nematode Anisakis pegreffii","volume":"62","author":"Mladineo","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Metscher, B.D. (2009). MicroCT for comparative morphology: Simple staining methods allow high-contrast 3D imaging of diverse non-mineralized animal tissues. BMC Physiol., 9.","DOI":"10.1186\/1472-6793-9-11"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"812","DOI":"10.2307\/3283072","article-title":"Morphology of the Excretory System of Hysterothylacium haze (Nematoda: Anisakidae: Raphidascaridinae)","volume":"75","author":"Yoshinaga","year":"1989","journal-title":"J. Parasitol."},{"key":"ref_33","first-page":"495","article-title":"The excretory system of Anisakis simplex","volume":"5","author":"Mueller","year":"1927","journal-title":"Cell Tissue Res."},{"key":"ref_34","first-page":"81","article-title":"Comparative histochemical observations on the excretory system of helminth parasites","volume":"52","author":"Parshad","year":"1977","journal-title":"Parasitol. Res."},{"key":"ref_35","first-page":"285","article-title":"Ultrastructure of the excretory-secretory system in Toxocara canis (Nematoda, Ascarididae) infective larvae","volume":"56","author":"Dallai","year":"1989","journal-title":"Ital. J. Zool."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1017\/S0031182000069675","article-title":"The excretory system of the kidney worm Stephanurus dentatus (Nematoda)","volume":"58","author":"Waddell","year":"1968","journal-title":"Parasitology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3750\/AIP1976.06.1.08","article-title":"Studies on the life cycle and morphogenesis of Anisakis simplex (Rudolphi, 1809) (Nematoda: Anisakidae) cultured in vitro","volume":"6","author":"Grabda","year":"1976","journal-title":"Acta Ichtyol. Piscat."},{"key":"ref_38","unstructured":"Pavelka, M., and Roth, J. (2005). Functional Ultrastructure: An Atlas of Tissue Biology and Pathology, Springer."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"jcs186254","DOI":"10.1242\/jcs.186254","article-title":"The actin cortex at a glance","volume":"131","author":"Chugh","year":"2018","journal-title":"J. Cell. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1126\/science.175.4026.1128","article-title":"Pancreatic Beta-Cell Web: Its Possible Role in Insulin Secretion","volume":"175","author":"Orci","year":"1972","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1186\/s13071-019-3636-z","article-title":"Microbiota and gut ultrastructure of Anisakis pegreffii isolated from stranded cetaceans in the Adriatic Sea","volume":"12","author":"Mladineo","year":"2019","journal-title":"Parasites Vectors"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1152\/physrev.00031.2002","article-title":"Secretory granule exocytosis","volume":"83","author":"Burgoyne","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00436-004-1228-z","article-title":"Comparative studies on intestine ultrastructure of third-stage larvae and adults of Cystidicoloides ephemeridarum (Nematoda, Cystidicolidae)","volume":"94","author":"Moravec","year":"2004","journal-title":"Parasitol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0968-0004(00)01609-1","article-title":"The internal structure of mitochondria","volume":"25","author":"Frey","year":"2000","journal-title":"Trends Biochem. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S0959-4388(97)80058-X","article-title":"Ca2+ and the regulation of neurotransmitter secretion","volume":"7","author":"Bennett","year":"1997","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.15252\/embr.201744261","article-title":"Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo-tomography","volume":"18","author":"Gold","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/BF02191712","article-title":"Characterization of the let-653 gene in Caenorhabditis elegans","volume":"248","author":"Jones","year":"1995","journal-title":"Mol. Genet. Genom."},{"key":"ref_48","unstructured":"Chitwood, B.G., and Chitwood, M.B. (1950). General Structure of Nematodes. Introduction to Nematology, University Park Press."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.tcb.2011.03.008","article-title":"The nucleoplasmic reticulum: Form and function","volume":"21","author":"Malhas","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_50","first-page":"545","article-title":"XXI. On the anatomy and physiology of the nematoids, parasitic and free; with observations on their zoological position and affinities to the echinoderms","volume":"156","author":"Bastian","year":"1866","journal-title":"Philos. Trans. R. Soc. Lond."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nrm1172","article-title":"Nuclear speckles: A model for nuclear organelles","volume":"4","author":"Lamond","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1091\/mbc.e04-03-0253","article-title":"Proteomic analysis of interchromartin granule clusters","volume":"15","author":"Saitoh","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0962-8924(03)00054-0","article-title":"Pre-ribosomes on the road from the nucleolus to the cytoplasm","volume":"13","author":"Tschochner","year":"2003","journal-title":"Trends Cell Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/11\/1451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:35:15Z","timestamp":1760189715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/11\/1451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,17]]},"references-count":53,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["cells8111451"],"URL":"https:\/\/doi.org\/10.3390\/cells8111451","relation":{},"ISSN":["2073-4409"],"issn-type":[{"type":"electronic","value":"2073-4409"}],"subject":[],"published":{"date-parts":[[2019,11,17]]}}}