{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:46:50Z","timestamp":1778741210450,"version":"3.51.4"},"reference-count":344,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T00:00:00Z","timestamp":1513728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The long-lasting interest in bioactive molecules (namely toxins) produced by (microalga) dinoflagellates has risen in recent years. Exhibiting wide diversity and complexity, said compounds are well-recognized for their biological features, with great potential for use as pharmaceutical therapies and biological research probes. Unfortunately, provision of those compounds is still far from sufficient, especially in view of an increasing demand for preclinical testing. Despite the difficulties to establish dinoflagellate cultures and obtain reasonable productivities of such compounds, intensive research has permitted a number of advances in the field. This paper accordingly reviews the characteristics of some of the most important biotoxins (and other bioactive substances) produced by dinoflagellates. It also presents and discusses (to some length) the main advances pertaining to dinoflagellate production, from bench to large scale\u2014with an emphasis on material published since the latest review available on the subject. Such advances encompass improvements in nutrient formulation and light supply as major operational conditions; they have permitted adaptation of classical designs, and aided the development of novel configurations for dinoflagellate growth\u2014even though shearing-related issues remain a major challenge.<\/jats:p>","DOI":"10.3390\/md15120393","type":"journal-article","created":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T11:34:14Z","timestamp":1513769654000},"page":"393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Biotechnological and Pharmacological Applications of Biotoxins and Other Bioactive Molecules from Dinoflagellates"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1379-6821","authenticated-orcid":false,"given":"Joana","family":"Assun\u00e7\u00e3o","sequence":"first","affiliation":[{"name":"LEPABE\u2014Laboratory of Process Engineering, Environment, Biotechnology and Energy, Rua Dr. Roberto Frias, s\/n, P-4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9181-512X","authenticated-orcid":false,"given":"A.","family":"Guedes","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, s\/n, P-4450-208 Matosinhos, Portugal"}]},{"given":"F.","family":"Malcata","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory of Process Engineering, Environment, Biotechnology and Energy, Rua Dr. Roberto Frias, s\/n, P-4200-465 Porto, Portugal"},{"name":"Department of Chemical Engineering, University of Porto, Rua Dr. Roberto Frias, s\/n, P-4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.bcp.2009.04.015","article-title":"A renaissance in marine pharmacology: From preclinical curiosity to clinical reality","volume":"78","author":"Glaser","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.3390\/md13052967","article-title":"Marine polysaccharides from algae with potential biomedical applications","volume":"13","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/j.biotechadv.2012.07.005","article-title":"Bioactives from microalgal dinoflagellates","volume":"30","author":"Chisti","year":"2012","journal-title":"Biotechnol. Adv."},{"key":"ref_4","unstructured":"Taylor, F.J.R. (1987). Dinoflagellates: An introduction. The Biology of Dinoflagellates, Blackwell Scientific Publications."},{"key":"ref_5","unstructured":"Taylor, F.J.R. (1987). Heterotrophic nutrition. The Biology of Dinoflagellates, Blackwell Scientific Publications."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3354\/meps117241","article-title":"Heterotrophic dinoflagellates in the ecosystem of the Gulf of Gdansk","volume":"117","author":"Bralewska","year":"1995","journal-title":"Mar. Ecol. Prog. Ser."},{"key":"ref_7","unstructured":"Hickman, C.P., Roberts, L.S., and Larson, A.L. (2008). Integrated Principles of Zoology, McGraw-Hill International Edition."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.protis.2005.02.004","article-title":"Genetic Diversity of Symbiotic Dinoflagellates in the Genus Symbiodinium","volume":"156","author":"Coffroth","year":"2005","journal-title":"Protist"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3390\/md6020349","article-title":"Neurotoxins from Marine Dinoflagellates: A Brief Review","volume":"6","author":"Wang","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"420","DOI":"10.2216\/i0031-8884-42-4-420.1","article-title":"Chemical ecology of eukaryotic microalgae in marine ecosystems","volume":"42","author":"Cembella","year":"2003","journal-title":"Phycologia"},{"key":"ref_11","unstructured":"Food and Agriculture Organization of the United Nations (2004). Marine Biotoxins. FAO Food and Nutritrion, Food and Agriculture Organization of the United Nations."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.4319\/lo.1997.42.5_part_2.1132","article-title":"What is a bloom? A commentary","volume":"42","author":"Smayda","year":"1997","journal-title":"Limnol. Oceanogr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"813","DOI":"10.3109\/15563658108990310","article-title":"Nonprotein Neurotoxins","volume":"18","author":"Bower","year":"1981","journal-title":"Clin. Toxicol."},{"key":"ref_14","unstructured":"Moestrup, \u00d8., Akselmann, R., Fraga, S., Hoppenrath, M., Iwataki, M., Kom\u00e1rek, J., Larsen, J., Lundholm, N., and Zingone, A. (2017, October 28). IOC-UNESCO Taxonomic Reference List of Harmful Micro Algae (HABs). Available online: http:\/\/www.marinespecies.org\/hab\/."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cimino, G., and Gavagnin, M. (2006). Bivalve Molluscs as Vectors of Marine Biotoxins Involved in Seafood Poisoning. Molluscs: Progress in Molecular and Subcellular Biology, Springer.","DOI":"10.1007\/978-3-540-30880-5"},{"key":"ref_16","unstructured":"Hallegraeff, G., Anderson, D., and Cembella, A. (2003). Chemical methods for lipophilic shellfish toxins. Manual on Harmful Marine Microalgae, Intergovernmental Oceanographic Comission (UNESCO)."},{"key":"ref_17","unstructured":"FAO (Food and Agriculture Organization)\/WHO (World Health Organization) (2016). Toxicity Equivalency Factors for Marine Biotoxins Associated with Bivalve Molluscs, Food and Agriculture Organization of the United Nations."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3390\/md8041011","article-title":"Biosynthesis and molecular genetics of polyketides in marine dinoflagellates","volume":"8","author":"Kellmann","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Senanayake, S.P.J.N., Ahmed, N., and Fichtali, J. (2010). Nutraceuticals and Bioactives from Marine Algae. Handbook of Seafood Quality, Safety and Health Applications, Wiley-Blackwell.","DOI":"10.1002\/9781444325546.ch37"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1271\/bbb.60597","article-title":"Induction of Apoptosis in DLD-1 Human Colon Cancer Cells by Peridinin Isolated from the Dinoflagellate, Heterocapsa triquetra","volume":"71","author":"Sugawara","year":"2007","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.3390\/md8072185","article-title":"Neurotoxic alkaloids: Saxitoxin and its analogs","volume":"8","author":"Wiese","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1039\/a901981b","article-title":"Natural guanidine derivatives","volume":"19","author":"Berlinck","year":"2002","journal-title":"Nat. Prod. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"991","DOI":"10.3390\/md11040991","article-title":"An overview on the marine neurotoxin, saxitoxin: Genetics, molecular targets, methods of detection and ecological functions","volume":"11","author":"Cusick","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_24","unstructured":"European Food Safety Authority (EFSA) (2009). Marine biotoxins in shellfish Marine biotoxins in shellfish\u2014Saxitoxin group. Scientific Opinion of the Panel on Contaminants in the Food chain. EFSA J., 1109, 1\u201347."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dur\u00e1n-Riveroll, L.M., Cembella, A.D., Band-Schmidt, C.J., Bustillos-Guzm\u00e1n, J.J., and Correa-Basurto, J. (2016). Docking Simulation of the Binding Interactions of Saxitoxin Analogs Produced by the Marine Dinoflagellate Gymnodinium catenatum to the Voltage-Gated Sodium Channel Nav1.4. Toxins, 8.","DOI":"10.3390\/toxins8050129"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.etap.2016.09.020","article-title":"Low dose extended exposure to saxitoxin and its potential neurodevelopmental effects: A review","volume":"48","author":"Musgrave","year":"2016","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.toxicon.2013.09.013","article-title":"Acute toxicities of saxitoxin, neosaxitoxin, decarbamoyl saxitoxin and gonyautoxins 1&4 and 2&3 to mice by various routes of administration","volume":"76","author":"Munday","year":"2013","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7125","DOI":"10.1073\/pnas.0900598106","article-title":"Prolonged duration local anesthesia with minimal toxicity","volume":"106","author":"Shichor","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/00115550-200001000-00010","article-title":"The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo","volume":"25","author":"Kohane","year":"2000","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/BF00003544","article-title":"Microalgae as sources of pharmaceuticals and other biologically active compounds","volume":"7","author":"Borowitzka","year":"1995","journal-title":"J. Appl. Phycol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s10350-004-0893-4","article-title":"Gonyautoxin: New treatment for healing acute and chronic anal fissures","volume":"48","author":"Garrido","year":"2005","journal-title":"Dis. Colon Rectum"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1179\/174313209X380829","article-title":"Local infiltration of gonyautoxin is safe and effective in treatment of chronic tension-type headache","volume":"31","author":"Lattes","year":"2009","journal-title":"Neurol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.toxicon.2012.11.026","article-title":"The molecular mystique of tetrodotoxin","volume":"63","author":"Moczydlowski","year":"2013","journal-title":"Toxicon"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/0041-0101(96)00117-1","article-title":"Occurrence of tetrodotoxin in Alexandrium tamarense, a causative dinoflagellate of paralytic shellfish poisoning","volume":"34","author":"Kodama","year":"1996","journal-title":"Toxicon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"693","DOI":"10.3390\/toxins6020693","article-title":"Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection","volume":"6","author":"Bane","year":"2014","journal-title":"Toxins"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.aquatox.2011.04.001","article-title":"On the origins and biosynthesis of tetrodotoxin","volume":"104","author":"Chau","year":"2011","journal-title":"Aquat. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18102","DOI":"10.1073\/pnas.1206952109","article-title":"Marked difference in saxitoxin and tetrodoxin affinity for the human nociceptive voltage-gated sodium","volume":"109","author":"Walker","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"407","DOI":"10.4161\/chan.2.6.7429","article-title":"Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxin","volume":"2","author":"Chong","year":"2008","journal-title":"Channels"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6384","DOI":"10.3390\/md13106384","article-title":"Tetrodotoxin, an extremely potent marine neurotoxin: Distribution, toxicity, origin and therapeutical uses","volume":"13","author":"Lago","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3390\/md10020281","article-title":"Tetrodotoxin (TTX) as a therapeutic agent for pain","volume":"10","author":"Nieto","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jpainsymman.2006.11.008","article-title":"An Open-Label, Multi-Dose Efficacy and Safety Study of Intramuscular Tetrodotoxin in Patients with Severe","volume":"34","author":"Hagen","year":"2007","journal-title":"J. Pain Symptom Manag."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jpainsymman.2007.05.011","article-title":"Tetrodotoxin for Moderate to Severe Cancer Pain: A Randomized, Double Blind, Parallel Design Multicenter Study","volume":"35","author":"Hagen","year":"2008","journal-title":"J. Pain Symptom Manag."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.3390\/md9122717","article-title":"Tetrodotoxin-bupivacaine-epinephrine combinations for prolonged local anesthesia","volume":"9","author":"Berde","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1440-1681.2011.05539.x","article-title":"Tetrodotoxin alleviates acute heroin withdrawal syndrome: A multicentre, randomized, double-blind, placebo-controlled study","volume":"38","author":"Song","year":"2011","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_45","first-page":"1","article-title":"Scientific Opinion of the Panel on Contaminants in the Food chain on a request from the European Commission on marine biotoxins in shellfish\u2014Okadaic acid and analogues","volume":"589","author":"Alexander","year":"2008","journal-title":"EFSA J."},{"key":"ref_46","first-page":"115","article-title":"Shellfish Poisoning and Toxins","volume":"6","author":"Cetinkaya","year":"2012","journal-title":"J. Biol. Environ. Sci."},{"key":"ref_47","unstructured":"Hallegraeff, G.F., Anderson, D.M., and Cembella, A.D. (2003). Harmful algal blooms: A global overview. Manual of Harmful Marine Microalgae, UNESCO Publishing."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1042\/bj3110017","article-title":"Serine\/threonine protein phosphatases","volume":"311","author":"Wera","year":"1995","journal-title":"Biochem. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.toxicon.2012.07.008","article-title":"Cytotoxicity of yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4","volume":"60","year":"2012","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.3390\/md11061866","article-title":"Self-association of okadaic acid: Structural and pharmacological significance","volume":"11","author":"Cruz","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4328","DOI":"10.3390\/md11114328","article-title":"Okadaic Acid: More than a diarrheic toxin","volume":"11","author":"Valdiglesias","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9363","DOI":"10.1016\/S0021-9258(18)92827-9","article-title":"Inhibition of protein phosphatases by okadaic acid induces AP1 in human T cells","volume":"266","author":"Kim","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neuro.2013.05.002","article-title":"Okadaic acid induced neurotoxicity: An emerging tool to study Alzheimer\u2019s disease pathology","volume":"37","author":"Kamat","year":"2013","journal-title":"Neurotoxicology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.lfs.2012.03.012","article-title":"A study on neuroinflammatory marker in brain areas of okadaic acid (ICV) induced memory impaired rats","volume":"90","author":"Kamat","year":"2012","journal-title":"Life Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/sj.npp.1300757","article-title":"Olanzapine attenuates the okadaic acid-induced spatial memory impairment and hippocampal cell death in rats","volume":"30","author":"He","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40478-016-0300-0","article-title":"A local insult of okadaic acid in wild-type mice induces tau phosphorylation and protein aggregation in anatomically distinct brain regions","volume":"4","author":"Baker","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1007\/s12035-015-9451-4","article-title":"Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by Activating the Nrf2\/HO-1 Antioxidant Pathway","volume":"53","author":"Dwivedi","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6859","DOI":"10.1128\/jvi.69.11.6859-6864.1995","article-title":"Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B","volume":"69","author":"Re","year":"1995","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10549-005-6942-4","article-title":"Anti-estrogenic effects of conjugated linoleic acid through modulation of estrogen receptor phosphorylation","volume":"94","author":"Liu","year":"2005","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"22222","DOI":"10.1038\/srep22222","article-title":"An extract of Urtica dioica L. mitigates obesity induced insulin resistance in mice skeletal muscle via protein phosphatase 2A (PP2A)","volume":"6","author":"Obanda","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.toxlet.2011.09.007","article-title":"Immunoregulatory potential of marine algal toxins yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4","volume":"207","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"15366","DOI":"10.1074\/jbc.272.24.15366","article-title":"Stimulation of interleukin-8 production by okadaic acid and vanadate in a human promyelocyte cell line, an HL-60 subline: Possible role of mitogen-activated protein kinase on the okadaic acid-induced NF-\u03baB activation","volume":"272","author":"Sonoda","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.canlet.2008.10.034","article-title":"Okadaic acid promotes angiogenesis via activation of hypoxia-inducible factor-1","volume":"276","author":"Kim","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/BF02180919","article-title":"Antimicrobial activities of polyether compounds of dinoflagellate origins","volume":"2","author":"Nagai","year":"1990","journal-title":"J. Appl. Phycol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"878","DOI":"10.3390\/toxins2040878","article-title":"Marine toxins: Chemistry, toxicity, occurrence and detection, with special reference to the dutch situation","volume":"2","author":"Gerssen","year":"2010","journal-title":"Toxins"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.toxicon.2004.05.021","article-title":"Production and release of yessotoxins by the dinoflagellates Protoceratium reticulatum and Lingulodinium polyedrum in culture","volume":"44","author":"Paz","year":"2004","journal-title":"Toxicon"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.hal.2005.06.008","article-title":"Yessotoxin production by Gonyaulax spinifera","volume":"5","author":"Rhodes","year":"2006","journal-title":"Harmful Algae"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.hal.2005.03.005","article-title":"Evidence for numerous analogs of yessotoxin in Protoceratium reticulatum","volume":"4","author":"Miles","year":"2005","journal-title":"Harmful Algae"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1016\/S0040-4039(01)81076-5","article-title":"Isolation and structure of yessotoxin, a novel polyether compound implicated in diarrhetic shellfish poisoning","volume":"28","author":"Murata","year":"1987","journal-title":"Tetrahedron Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3390\/md6020073","article-title":"Yessotoxins, a group of marine polyether toxins: An overview","volume":"6","author":"Paz","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.tiv.2014.04.013","article-title":"Yessotoxin triggers ribotoxic stress","volume":"28","author":"Korsnes","year":"2014","journal-title":"Toxicol. In Vitro"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.toxicon.2011.03.012","article-title":"Yessotoxin as an apoptotic inducer","volume":"57","author":"Espenes","year":"2011","journal-title":"Toxicon"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Alfonso, A., Vieytes, M., and Botana, L. (2016). Yessotoxin, a Promising Therapeutic Tool. Mar. Drugs, 14.","DOI":"10.3390\/md14020030"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tox.2015.01.004","article-title":"Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin","volume":"329","author":"Alfonso","year":"2015","journal-title":"Toxicology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0006-2952(02)01454-5","article-title":"Yessotoxin, a novel phycotoxin, activates phosphodiesterase activity: Effect of yessotoxin on cAMP levels in human lymphocytes","volume":"65","author":"Alfonso","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1007\/s00018-005-4533-5","article-title":"Phosphodiesterase: Overview of protein structures, potential therapeutic applications and recent progress in drug development","volume":"62","author":"Jeon","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S0006-2952(01)00549-4","article-title":"Modulation of cytosolic calcium levels of human lymphocytes by yessotoxin, a novel marine phycotoxin","volume":"61","author":"Alfonso","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.tiv.2006.01.022","article-title":"Apoptotic events induced by yessotoxin in myoblast cell lines from rat and mouse","volume":"20","author":"Korsnes","year":"2006","journal-title":"Toxicol. In Vitro"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.bbabio.2004.02.007","article-title":"Yessotoxin, a shellfish biotoxin, is a potent inducer of the permeability transition in isolated mitochondria and intact cells","volume":"1656","author":"Bianchi","year":"2004","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.toxicon.2009.07.033","article-title":"Yessotoxin inhibits phagocytic activity of macrophages","volume":"55","author":"Orsi","year":"2010","journal-title":"Toxicon"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.tiv.2006.07.012","article-title":"Cleavage of tensin during cytoskeleton disruption in YTX-induced apoptosis","volume":"21","author":"Korsnes","year":"2007","journal-title":"Toxicol. In Vitro"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1039\/b719215k","article-title":"Cadherins in development and cancer","volume":"4","author":"Stemmler","year":"2008","journal-title":"Mol. Biosyst."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.toxicon.2009.07.038","article-title":"Yessotoxins: A toxicological overview","volume":"56","author":"Tubaro","year":"2010","journal-title":"Toxicon"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fcell.2017.00030","article-title":"Mitotic Catastrophe in BC3H1 Cells following Yessotoxin Exposure","volume":"5","author":"Korsnes","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Tob\u00edo, A., Alfonso, A., Madera-Salcedo, I., Botana, L.M., and Blank, U. (2016). Yessotoxin, a Marine Toxin, Exhibits Anti-Allergic and Anti-Tumoural Activities Inhibiting Melanoma Tumour Growth in a Preclinical Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167572"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-\u03b2 and Tau The Trigger and Bullet in Alzheimer Disease Pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/0041-0101(90)90148-Z","article-title":"Histopathological studies on experimental marine toxin poisoning\u20145. The effects in mice of yessotoxin isolated from Patinopecten yessoensis and of a desulfated derivative","volume":"28","author":"Terao","year":"1990","journal-title":"Toxicon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cellsig.2013.10.004","article-title":"Yessotoxin induces ER-stress followed by autophagic cell death in glioma cells mediated by mTOR and BNIP3","volume":"26","author":"Rubiolo","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.3390\/md13041666","article-title":"Occurrence of Lipophilic Marine Toxins in Shellfish from Galicia (NW of Spain) and Synergies among Them","volume":"13","author":"Paz","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1021\/tx9002337","article-title":"Impact of the pectenotoxin C-43 oxidation degree on its cytotoxic effect on rat hepatocytes","volume":"23","author":"Louzao","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.jmb.2007.05.056","article-title":"A Structural Basis for Regulation of Actin Polymerization by Pectenotoxins","volume":"371","author":"Allingham","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6082","DOI":"10.1111\/j.1742-4658.2008.06714.x","article-title":"Marine toxins and the cytoskeleton: Pectenotoxins, unusual macrolides that disrupt actin","volume":"275","author":"Rubiolo","year":"2008","journal-title":"FEBS J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000100647","article-title":"Lactone ring of pectenotoxins: A key factor for their activity on cytoskeletal dynamics","volume":"19","author":"Ares","year":"2007","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_94","first-page":"223","article-title":"Esculetin inhibits cell proliferation through the Ras\/ERK1\/2 pathway in human colon cancer cells","volume":"25","author":"Moon","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/np50125a012","article-title":"Cytotoxic compounds from a two-sponge association","volume":"58","author":"Jung","year":"1995","journal-title":"J. Nat. Prod."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.1038\/sj.onc.1208640","article-title":"Oocyte-based screening of cytokinesis inhibitors and identification of pectenotoxin-2 that induces Bim\/Bax-mediated apoptosis in p53-deficient tumors","volume":"24","author":"Chae","year":"2005","journal-title":"Oncogene"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.biotechadv.2006.11.008","article-title":"Biotechnological significance of toxic marine dinoflagellates","volume":"25","author":"Belarbi","year":"2007","journal-title":"Biotechnol. Adv."},{"key":"ref_98","first-page":"8","article-title":"The origin of ciguatera\u2014An update","volume":"2","author":"Holmes","year":"1992","journal-title":"Ciguatera Inf. Bull."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Friedman, M.A., Fernandez, M., Backer, L.C., Dickey, R.W., Bernstein, J., Schrank, K., Kibler, S., Stephan, W., Gribble, M.O., and Bienfang, P. (2017). An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management. Mar. Drugs, 15.","DOI":"10.3390\/md15030072"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0168-1605(00)00382-2","article-title":"Ciguatera: Recent advances but the risk remains","volume":"61","author":"Lehane","year":"2000","journal-title":"Int. J. Food Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1136\/pgmj.75.889.678","article-title":"Ciguatera fish poisoning","volume":"75","author":"Crump","year":"1999","journal-title":"Postgrad. Med. J."},{"key":"ref_102","first-page":"615","article-title":"Origin and transfer of toxins involved in ciguatera","volume":"106","author":"Lewis","year":"1993","journal-title":"Comp. Biochem. Physiol. C"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/S0041-0101(02)00146-0","article-title":"Multiple ciguatoxins present in Indian Ocean reef fish","volume":"40","author":"Hamilton","year":"2002","journal-title":"Toxicon"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1126\/science.155.3767.1267","article-title":"Ciguatoxin: Isolation and chemical nature","volume":"155","author":"Scheuer","year":"1967","journal-title":"Science"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3390\/md403082","article-title":"Ciguatoxins: Cyclic polyether modulators of voltage-gated ion channel function","volume":"4","author":"Nicholson","year":"2006","journal-title":"Mar. Drugs"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1046\/j.1460-9568.2002.02071.x","article-title":"Ciguatoxin-induced oscillations in membrane potential and action potential firing in rat parasympathetic neurons","volume":"16","author":"Hogg","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/0014-5793(87)80252-1","article-title":"Ciguatoxin and brevetoxins share a common receptor site on the neuronal voltage-dependent Na+ channel","volume":"219","author":"Lombet","year":"1987","journal-title":"FEBS Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.neuropharm.2014.06.001","article-title":"Involvement of both sodium influx and potassium efflux in ciguatoxin-induced nodal swelling of frog myelinated axons","volume":"85","author":"Mattei","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1002\/(SICI)1097-4547(19990315)55:6<666::AID-JNR2>3.0.CO;2-H","article-title":"Neurotoxins targeting receptor site 5 of voltage-dependent sodium channels increase the nodal volume of myelinated axons","volume":"55","author":"Mattei","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0022-510X(91)90021-X","article-title":"Effects of ciguatoxin on nerve excitability in rats (Part I)","volume":"101","author":"Cameron","year":"1991","journal-title":"J. Neurol. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0022-510X(91)90022-Y","article-title":"Electrophysiological studies on ciguatera poisoning in man (Part II)","volume":"101","author":"Cameron","year":"1991","journal-title":"J. Neurol. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1476-5381.1990.tb12991.x","article-title":"Ciguatoxin enhances quantal transmitter release from frog motor nerve terminals","volume":"99","author":"Comella","year":"1990","journal-title":"Br. J. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Mattei, C., Wen, P.J., Nguyen-Huu, T.D., Alvarez, M., Benoit, E., Bourdelais, A.J., Lewis, R.J., Baden, D.G., Molg\u00f3, J., and Meunier, F.A. (2008). Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003448"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"7597","DOI":"10.1074\/jbc.M806481200","article-title":"Synthetic ciguatoxins selectively activate Nav1.8-derived chimeric sodium channels expressed in HEK293 cells","volume":"284","author":"Yamaoka","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.1038\/emboj.2012.207","article-title":"Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling","volume":"31","author":"Vetter","year":"2012","journal-title":"EMBO J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.toxicon.2014.09.016","article-title":"The voltage-gated sodium channel: A major target of marine neurotoxins","volume":"91","author":"Mattei","year":"2014","journal-title":"Toxicon"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1093\/brain\/aws225","article-title":"Neurological perspectives on voltage-gated sodium channels","volume":"135","author":"Eijkelkamp","year":"2012","journal-title":"Brain"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/ijch.201100003","article-title":"Maitotoxin: An inspiration for synthesis","volume":"51","author":"Nicolaou","year":"2011","journal-title":"Isr. J. Chem."},{"key":"ref_119","unstructured":"Botana, L.M. (2014). Maitotoxin: An Enigmatic Toxic Molecule with Useful Applications in the Biomedical Sciences. Seafood and Freshwater Toxins Pharmacology, Physiology, and Detection, CRC Press."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/nt.2620020204","article-title":"Purification and characterisation of large and small maitotoxins from cultured Gambierdiscus toxicus","volume":"2","author":"Holmes","year":"1994","journal-title":"Nat. Toxins"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1093\/oxfordjournals.jbchem.a122438","article-title":"Some chemical properties of maitotoxin, a putative calcium channel agonist isolated from a marine dinoflagellate","volume":"104","author":"Yokoyama","year":"1988","journal-title":"J. Biochem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.hal.2014.07.018","article-title":"Production of ciguatoxin and maitotoxin by strains of Gambierdiscus australes, G. pacificus and G. polynesiensis (Dinophyceae) isolated from Rarotonga, Cook Islands","volume":"39","author":"Rhodes","year":"2014","journal-title":"Harmful Algae"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Pisapia, F., Sibat, M., Herrenknecht, C., Lhaute, K., Gaiani, G., Ferron, P.-J., Fessard, V., Fraga, S., Nascimento, S.M., and Litaker, R.W. (2017). Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus. Mar. Drugs, 15.","DOI":"10.3390\/md15070220"},{"key":"ref_124","unstructured":"Wexler, P. (2014). Algae. Encyclopedia of Toxicology, Academic Press."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1021\/tx990014m","article-title":"Maitotoxin-induced calcium influx in erythrocyte ghosts and rat glioma C6 cells, and blockade by gangliosides and other membrane lipids","volume":"12","author":"Konoki","year":"1999","journal-title":"Chem. Res. Toxicol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"25025","DOI":"10.1016\/S0021-9258(19)74000-9","article-title":"Maitotoxin induces a calcium-dependent membrane depolarization in GH4C1 pituitary cells via activation of type L voltage-dependent calcium channels","volume":"267","author":"Xi","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/S0022-3565(25)23098-1","article-title":"Stimulatory effects of maitotoxin on insulin release in insulinoma HIT cells: Role of calcium uptake and phosphoinositide breakdown","volume":"255","author":"Soergel","year":"1990","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/0006-8993(86)90088-0","article-title":"Maitotoxin and Bay-K-8644: Two putative calcium channel activators with different effects on endogenous dopamine release from tuberoinfundibular neurons","volume":"381","author":"Taglialatela","year":"1986","journal-title":"Brain Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"10944","DOI":"10.1016\/S0021-9258(17)44367-5","article-title":"Ca2+ channel activating function of maitotoxin, the most potent marine toxin known, in clonal rat pheochromocytoma cells","volume":"258","author":"Takahashi","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0014-5793(88)81371-1","article-title":"Differential effects of maitotoxin on ATP secretion and on phosphoinositide breakdown in rat pheochromocytoma cells","volume":"233","author":"Gusovsky","year":"1988","journal-title":"FEBS Lett."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Estacion, M., and Schilling, W.P. (2001). Maitotoxin-induced membrane blebbing and cell death in bovine aortic endothelial cells. BMC Physiol., 1.","DOI":"10.1186\/1472-6793-1-2"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/aja.2010.80","article-title":"The opening of maitotoxin-sensitive calcium channels induces the acrosome reaction in human spermatozoa: Differences from the zona pellucida","volume":"13","author":"Nishigaki","year":"2011","journal-title":"Asian J. Androl."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/jcp.20487","article-title":"Maitotoxin potently promotes Ca2+ influx in mouse spermatogenic cells and sperm, and induces the acrosome reaction","volume":"206","author":"Nishigaki","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1124\/mol.66.4.909","article-title":"Maitotoxin induces biphasic interleukin-1beta secretion and membrane blebbing in murine macrophages","volume":"66","author":"Verhoef","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Flores, P., Rodr\u00edguez, E., Zapata, E., Carb\u00f3, R., Far\u00edas, J., and Mart\u00ednez, M. (2017). Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes. Mar. Drugs, 15.","DOI":"10.3390\/md15070198"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Rossini, P. (2014). Pharmacological Actions of Palytoxin. Toxins and Biologically Active Compounds from Microalgae, Volume 2: Biological Effects and Risk Management, CRC Press\/Taylor and Francis.","DOI":"10.1201\/b16806"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1126\/science.172.3982.495","article-title":"Palytoxin: A new marine toxin from a coelenterate","volume":"172","author":"Moore","year":"1971","journal-title":"Science"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"658","DOI":"10.3390\/md8030658","article-title":"Targets and effects of yessotoxin, okadaic acid and palytoxin: A differential review","volume":"8","author":"Franchini","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.3390\/md8072021","article-title":"Palytoxin and analogs: Biological and ecological effects","volume":"8","author":"Ramos","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s11596-015-1506-3","article-title":"Toxic potential of palytoxin","volume":"35","author":"Patocka","year":"2015","journal-title":"J. Huazhong Univ. Sci. Technol.\u2014Med. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1039\/C6TX00084C","article-title":"Pro-inflammatory effects of palytoxin: An in vitro study on human keratinocytes and inflammatory cells","volume":"5","author":"Pelin","year":"2016","journal-title":"Toxicol. Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1111\/j.1742-4658.2008.06712.x","article-title":"Marine toxins and the cytoskeleton: A new view of palytoxin toxicity","volume":"275","author":"Louzao","year":"2008","journal-title":"FEBS J."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1021\/tx800273f","article-title":"Ostreocin-d Impact on Globular Actin of Intact Cells","volume":"22","author":"Ares","year":"2009","journal-title":"Chem. Res. Toxicol."},{"key":"ref_144","unstructured":"Botana, L.M., and Amparo, A. (2015). Pharmacology of palytoxins and ostreocins. Phycotoxins, John Wiley & Sons, Ltd."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.toxicon.2010.09.011","article-title":"Palytoxin action on the Na+, K+-ATPase and the disruption of ion equilibria in biological systems","volume":"57","author":"Bigiani","year":"2011","journal-title":"Toxicon"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1152\/ajpcell.00254.2006","article-title":"Palytoxin: Exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis","volume":"292","author":"Wattenberg","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1021\/ja00054a061","article-title":"Gambierol: A new toxic polyether compound isolated from the marine dinoflagellate Gambierdiscus toxicus","volume":"115","author":"Satake","year":"1993","journal-title":"J. Am. Chem. Soc."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fchem.2014.00116","article-title":"Concise synthesis of the A\/BCD-ring fragment of gambieric acid A","volume":"2","author":"Fuwa","year":"2015","journal-title":"Front. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0960-894X(03)00467-0","article-title":"Synthesis and biological evaluation of gambierol analogues","volume":"13","author":"Fuwa","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.toxicon.2003.09.011","article-title":"Pathological effects on mice by gambierol, possibly one of the ciguatera toxins","volume":"42","author":"Ito","year":"2003","journal-title":"Toxicon"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Botana, L.M., and Alfonso, A. (2015). Therapeutics of marine toxins. Phycotoxins: Chemistry and Biochemistry, John Wiley & Sons Ltd.","DOI":"10.1002\/9781118500354"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1124\/jpet.108.138230","article-title":"Influence of lipid-soluble gating modifier toxins on sodium influx in neocortical neurons","volume":"326","author":"Cao","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.toxicon.2008.01.004","article-title":"Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels","volume":"51","author":"Cuypers","year":"2008","journal-title":"Toxicon"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/toxsci\/kfi097","article-title":"Inhibition of voltage-gated potassium currents by gambierol in mouse taste cells","volume":"85","author":"Ghiaroni","year":"2005","journal-title":"Toxicol. Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1085\/jgp.201210890","article-title":"The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state","volume":"141","author":"Kopljar","year":"2013","journal-title":"J. Gen. Physiol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1124\/jpet.114.215319","article-title":"Gambierol inhibition of voltage-gated potassium channels augments spontaneous Ca2+ oscillations in cerebrocortical neurons","volume":"350","author":"Cao","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1021\/tx300242m","article-title":"Effect of Gambierol and Its Tetracyclic and Heptacyclic Analogues in Cultured Cerebellar Neurons: A Structure\u2013Activity Relationships Study","volume":"25","author":"Vale","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/jcb.22566","article-title":"Calcium oscillations induced by gambierol in cerebellar granule cells","volume":"110","author":"Alonso","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.3390\/toxins7051749","article-title":"Toxins Targeting the Kv1.3 Channel: Potential Immunomodulators for Autoimmune Diseases","volume":"7","author":"Zhao","year":"2015","journal-title":"Toxins"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s00204-014-1299-2","article-title":"Potassium currents inhibition by gambierol analogs prevents human T lymphocyte activation","volume":"89","author":"Rubiolo","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"17414","DOI":"10.1073\/pnas.0605136103","article-title":"Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases","volume":"103","author":"Beeton","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1124\/jpet.107.124271","article-title":"Gambierol acts as a functional antagonist of neurotoxin site 5 on voltage-gated sodium channels in cerebellar granule neurons","volume":"323","author":"LePage","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1096\/fasebj.3.7.2565840","article-title":"Brevetoxins: Unique polyether dinoflagellate toxins","volume":"3","author":"Baden","year":"1989","journal-title":"FASEB J."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.toxicon.2009.11.007","article-title":"Advances in monitoring and toxicity assessment of brevetoxins in molluscan shellfish","volume":"56","author":"Plakas","year":"2010","journal-title":"Toxicon"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.chemosphere.2010.03.051","article-title":"Toxicity comparison between Chattonella marina and Karenia brevis using marine medaka (Oryzias melastigma): Evidence against the suspected ichthyotoxins of Chattonella marina","volume":"80","author":"Shen","year":"2010","journal-title":"Chemosphere"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.hal.2009.02.001","article-title":"Haemolytic activity within the species Fibrocapsa japonica (Raphidophyceae)","volume":"8","author":"Tyl","year":"2009","journal-title":"Harmful Algae"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1365-2109.1997.tb01309.x","article-title":"Neurotoxins in a toxic red tide of Heterosigma akashiwo (Raphidophyceae) in Kagoshima Bay, Japan","volume":"28","author":"Khan","year":"1997","journal-title":"Aquac. Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1289\/ehp.7499","article-title":"Natural and derivative brevetoxins: Historical background, multiplicity, and effects","volume":"113","author":"Baden","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1002\/cbic.200700317","article-title":"Synthesis, modeling, and biological evaluation of analogues of the semisynthetic brevetoxin antagonist beta-naphthoyl-brevetoxin","volume":"8","author":"Michelliza","year":"2007","journal-title":"Chembiochem"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1080\/15287390490483809","article-title":"Inhalation toxicity of brevetoxin 3 in rats exposed for 5 days","volume":"67","author":"Benson","year":"2004","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0026-895X(25)10324-6","article-title":"Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes","volume":"30","author":"Poli","year":"1986","journal-title":"Mol. Pharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0041-0101(85)90034-0","article-title":"Interaction of brevetoxin A with a new receptor site on the sodium channel","volume":"23","author":"Catterall","year":"1985","journal-title":"Toxicon"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0006-8993(02)03737-X","article-title":"Brevetoxin derivatives act as partial agonists at neurotoxin site 5 on the voltage-gated Na+ channel","volume":"959","author":"LePage","year":"2003","journal-title":"Brain Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0300-9084(00)01174-3","article-title":"Molecular mechanisms of neurotoxin action on voltage-gated sodium channels","volume":"82","author":"Catterall","year":"2000","journal-title":"Biochimie"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S0022-3565(24)37263-5","article-title":"Brevetoxin-3 (PbTx-3) and its derivatives modulate single tetrodotoxin-sensitive sodium channels in rat sensory neurons","volume":"284","author":"Jeglitsch","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/1074-5521(95)90187-6","article-title":"The relationship of brevetoxin \u201clength\u201d and A-ring functionality to binding and activity in neuronal sodium channels","volume":"2","author":"Gawley","year":"1995","journal-title":"Chem. Biol."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Joseph, A. (2016). Oceans: Abode of Nutraceuticals, Pharmaceuticals, and Biotoxins. Investigating Seafloors and Oceans, Candice Janco.","DOI":"10.1016\/B978-0-12-809357-3.00009-6"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1007\/s00204-009-0443-x","article-title":"Brevetoxins 2, 3, 6, and 9 show variability in potency and cause significant induction of DNA damage and apoptosis in Jurkat E6-1 cells","volume":"83","author":"Murrell","year":"2009","journal-title":"Arch. Toxicol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/0091-6749(88)90889-5","article-title":"In vitro red tide toxin effects on human bronchial smooth muscle","volume":"81","author":"Shimoda","year":"1988","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1164\/rccm.200406-735OC","article-title":"Airway responses to aerosolized brevetoxins in an animal model of asthma","volume":"171","author":"Abraham","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00204-010-0564-2","article-title":"Marine brevetoxin induces ige-independent mast cell activation","volume":"85","author":"Hilderbrand","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.ijheh.2010.06.007","article-title":"Brevetoxin-2 induces an inflammatory response in an alveolar macrophage cell line","volume":"213","author":"Sas","year":"2010","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3390\/md6020291","article-title":"Effects of in vitro brevetoxin exposure on apoptosis and cellular metabolism in a leukemic T cell line (Jurkat)","volume":"6","author":"Walsh","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"19840","DOI":"10.1073\/pnas.1212584109","article-title":"Bidirectional in fl uence of sodium channel activation on NMDA receptor\u2013dependent cerebrocortical neuron structural plasticity","volume":"109","author":"George","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.3390\/md11124698","article-title":"Shellfish Toxins Targeting Voltage-Gated Sodium Channels","volume":"11","author":"Zhang","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/09670260802578534","article-title":"Azadinium spinosum gen. et sp. nov. (Dinophyceae) identified as a primary producer of azaspiracid toxins","volume":"44","author":"Tillmann","year":"2009","journal-title":"Eur. J. Phycol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1111\/jpy.12104","article-title":"A new potentially toxic Azadinium species (Dinophyceae) from the Mediterranean Sea, A. dexteroporum sp. nov","volume":"49","author":"Percopo","year":"2013","journal-title":"J. Phycol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"6687","DOI":"10.3390\/md13116687","article-title":"Structure elucidation and in vitro toxicity of new azaspiracids isolated from the marine dinoflagellate Azadinium poporum","volume":"13","author":"Krock","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Botana, L.M. (2014). Azaspiracids: Chemistry, Biosynthesis, Metabolism, and Detection. Seafood and Freshwater Toxins, CRC Press.","DOI":"10.1201\/b16662"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.hal.2016.02.012","article-title":"Toxigenic algae and associated phycotoxins in two coastal embayments in the Ebro Delta (NW Mediterranean)","volume":"55","author":"Busch","year":"2016","journal-title":"Harmful Algae"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"9967","DOI":"10.1021\/ja981413r","article-title":"Azaspiracid, a New Marine Toxin Having Unique Spiro Ring Assemblies, Isolated from Irish Mussels, Mytilus edulis","volume":"120","author":"Satake","year":"1998","journal-title":"J. Am. Chem. Soc."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"6075","DOI":"10.1111\/j.1742-4658.2008.06713.x","article-title":"Marine toxins and the cytoskeleton: Azaspiracids","volume":"275","year":"2008","journal-title":"FEBS J."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.toxicon.2005.02.015","article-title":"Cytotoxic and cytoskeletal effects of azaspiracid-1 on mammalian cell lines","volume":"45","author":"Twiner","year":"2005","journal-title":"Toxicon"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.toxicon.2005.02.014","article-title":"Teratogenic effects of azaspiracid-1 identified by microinjection of Japanese medaka (Oryzias latipes) embryos","volume":"45","author":"Colman","year":"2005","journal-title":"Toxicon"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/toxsci\/kfp312","article-title":"Involvement of Caspase Activation in Azaspiracid-Induced Neurotoxicity in Neocortical Neurons","volume":"114","author":"Cao","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/toxsci\/kfp246","article-title":"Cell volume decrease as a link between azaspiracid-induced cytotoxicity and c-Jun-.-terminal kinase activation in cultured neurons","volume":"113","author":"Vale","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1021\/tx0341862","article-title":"Effects of Azaspiracids 2 and 3 on Intracellular cAMP, [Ca2+], and pH","volume":"17","author":"Alfonso","year":"2004","journal-title":"Chem. Res. Toxicol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1021\/tx3001785","article-title":"Induction of Apoptosis Pathways in Several Cell Lines following Exposure to the Marine Algal Toxin Azaspiracid","volume":"25","author":"Twiner","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ygeno.2007.10.015","article-title":"Transcriptional profiling and inhibition of cholesterol biosynthesis in human T lymphocyte cells by the marine toxin azaspiracid","volume":"91","author":"Twiner","year":"2008","journal-title":"Genomics"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1021\/tx300283t","article-title":"Marine Algal Toxin Azaspiracid Is an Open-State Blocker of hERG Potassium Channels","volume":"25","author":"Twiner","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"5829","DOI":"10.1016\/S0040-4039(02)01171-1","article-title":"Gymnocin-A, a cytotoxic polyether from the notorious red tide dinoflagellate, Gymnodinium mikimotoi","volume":"43","author":"Satake","year":"2002","journal-title":"Tetrahedron Lett."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"6803","DOI":"10.1016\/j.tetlet.2006.07.081","article-title":"Structure-activity relationship studies of gymnocin-A","volume":"47","author":"Tsukano","year":"2006","journal-title":"Tetrahedron Lett."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbamem.2004.09.002","article-title":"Membrane-permeabilizing activities of amphidinol 3, polyene-polyhydroxy antifungal from a marine dinoflagellate","volume":"1667","author":"Houdai","year":"2004","journal-title":"Biochim. Biophys. Acta-Biomembr."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.copbio.2010.09.013","article-title":"The expanding role of marine microbes in pharmaceutical","volume":"21","author":"Waters","year":"2011","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.hal.2015.07.006","article-title":"Ichthyotoxic Karlodinium veneficum (Ballantine) J Larsen in the Upper Swan River Estuary (Western Australia): Ecological conditions leading to a fish kill","volume":"48","author":"Adolf","year":"2015","journal-title":"Harmful Algae"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.hal.2007.10.003","article-title":"Characterization and quantification of karlotoxins by liquid chromatography-mass spectrometry","volume":"7","author":"Bachvaroff","year":"2008","journal-title":"Harmful Algae"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"15705","DOI":"10.1002\/anie.201507418","article-title":"Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical-Shift Analysis: Insights into their Mechanism of Action","volume":"54","author":"Waters","year":"2015","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1021\/np100158r","article-title":"Structure and relative potency of several karlotoxins from Karlodinium veneficum","volume":"73","author":"Deeds","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.hal.2016.08.001","article-title":"Two new karlotoxins found in Karlodinium veneficum (strain GM2) from the East China Sea","volume":"58","author":"Cai","year":"2016","journal-title":"Harmful Algae"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1021\/ja9091853","article-title":"Structure and absolute configuration of Karlotoxin-2, an ichthyotoxin from the marine dinoflagellate Karlodinium veneficum","volume":"132","author":"Peng","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"6457","DOI":"10.1016\/j.tetlet.2008.08.103","article-title":"Isolation and characterization of karlotoxin 1, a new amphipathic toxin from Karlodinium veneficum","volume":"49","author":"Deeds","year":"2008","journal-title":"Tetrahedron Lett."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1021\/ja983655x","article-title":"Absolute configuration of amphidinol 3, the first complete structure determination from amphidinol homologues: Application of a new configuration analysis based on carbon-hydrogen spin-coupling constants","volume":"121","author":"Murata","year":"1999","journal-title":"J. Am. Chem. Soc."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.hal.2011.10.021","article-title":"Karlodinium veneficum\u2014The little dinoflagellate with a big bite","volume":"14","author":"Place","year":"2012","journal-title":"Harmful Algae"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1577\/H05-027.1","article-title":"Histopathological Effects in Fish Exposed to the Toxins from Karlodinium micrum","volume":"18","author":"Deeds","year":"2006","journal-title":"J. Aquat. Anim. Health"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.aquatox.2014.11.028","article-title":"The cytotoxic mechanism of karlotoxin 2 (KmTx 2) from Karlodinium veneficum (Dinophyceae)","volume":"159","author":"Deeds","year":"2014","journal-title":"Aquat. Toxicol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/j.bmcl.2010.02.025","article-title":"Sterol effect on interaction between amphidinol 3 and liposomal membrane as evidenced by surface plasmon resonance","volume":"20","author":"Swasono","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2989\/18142320609504190","article-title":"Sterol-specific membrane interactions with the toxins from Karlodinium micrum (Dinophyceae)\u2014A strategy for self-protection?","volume":"28","author":"Deeds","year":"2006","journal-title":"Afr. J. Mar. Sci."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1039\/C0NP00051E","article-title":"Chemical ecology of the marine plankton","volume":"28","author":"Sieg","year":"2011","journal-title":"Nat. Prod. Rep."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2216\/i0031-8884-39-1-67.1","article-title":"The marine dinoflagellate Alexandrium ostenfeldii (Dinophyceae) as the causative organism of spirolide shellfish toxins","volume":"39","author":"Cembella","year":"2000","journal-title":"Phycologia"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.hal.2008.04.001","article-title":"Morphogenetic diversity and biotoxin composition of Alexandrium (Dinophyceae) in Irish coastal waters","volume":"7","author":"Touzet","year":"2008","journal-title":"Harmful Algae"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"4838","DOI":"10.1021\/jf030101r","article-title":"Gymnodimine C, an Isomer of Gymnodimine B, from Karenia selliformis","volume":"51","author":"Miles","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"7087","DOI":"10.3390\/md13127057","article-title":"Potential threats posed by new or emerging marine biotoxins in UK waters and examination of detection methodologies used for their Control: Cyclic imines","volume":"13","author":"Davidson","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"7671","DOI":"10.1016\/0040-4039(96)01721-2","article-title":"Characterization of biologically inactive spirolides E and F: Identification of the spirolide pharmacophore","volume":"37","author":"Hu","year":"1996","journal-title":"Tetrahedron Lett."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1039\/c005400n","article-title":"Spiroimine shellfish poisoning (SSP) and the spirolide family of shellfish toxins: Isolation, structure, biological activity and synthesis","volume":"27","author":"Brimble","year":"2010","journal-title":"Nat. Prod. Rep."},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Couesnon, A., Ar\u00e1oz, R., Iorga, B.I., Benoit, E., Reynaud, M., Servent, D., and Molg\u00f3, J. (2016). The Dinoflagellate Toxin 20-Methyl Spirolide-G Potently Blocks Skeletal Muscle and Neuronal Nicotinic Acetylcholine Receptors. Toxins, 8.","DOI":"10.3390\/toxins8090249"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1021\/np800795q","article-title":"Characterization of a Dispiroketal Spirolide Subclass from Alexandrium ostenfeldii","volume":"72","author":"Roach","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0161-813X(03)00014-7","article-title":"Neural injury biomarkers of novel shellfish toxins, spirolides: A pilot study using immunochemical and transcriptional analysis","volume":"24","author":"Gill","year":"2003","journal-title":"Neurotoxicology"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"7093","DOI":"10.1016\/0040-4039(95)01434-J","article-title":"Gymnodimine, a new marine toxin of unprecedented structure isolated from New Zealand oysters and the dinoflagellate, Gymnodinium sp.","volume":"36","author":"Seki","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1016\/j.tetlet.2011.05.137","article-title":"Occurrence of 12-methylgymnodimine in a spirolide-producing dinoflagellate Alexandrium peruvianum and the biogenetic implications","volume":"52","author":"Misner","year":"2011","journal-title":"Tetrahedron Lett."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.toxicon.2016.01.064","article-title":"Identification of gymnodimine D and presence of gymnodimine variants in the dinoflagellate Alexandrium ostenfeldii from the Baltic Sea","volume":"112","author":"Harju","year":"2016","journal-title":"Toxicon"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1111\/j.1471-4159.2008.05677.x","article-title":"The marine phycotoxin gymnodimine targets muscular and neuronal nicotinic acetylcholine receptor subtypes with high affinity","volume":"107","author":"Kharrat","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1016\/j.neuropharm.2012.01.009","article-title":"Comparison of acetylcholine receptor interactions of the marine toxins, 13-desmethylspirolide C and gymnodimine","volume":"62","author":"Hauser","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.etap.2005.02.008","article-title":"Investigations into the cellular actions of the shellfish toxin gymnodimine and analogues","volume":"20","author":"Dragunow","year":"2005","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1159\/000330086","article-title":"The Cholinergic Antagonist Gymnodimine Improves A\u03b2 and Tau Neuropathology in an in Vitro Model of Alzheimer Disease","volume":"27","author":"Alonso","year":"2011","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.hal.2012.04.004","article-title":"Prevalence and persistence of gymnodimines in clams from the Gulf of Gabes (Tunisia) studied by mouse bioassay and LC\u2013MS\/MS","volume":"18","author":"Naila","year":"2012","journal-title":"Harmful Algae"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"5448","DOI":"10.1021\/jo00046a029","article-title":"Gambieric acids, new potent antifungal substances with unprecedented polyether structures from a marine dinoflagellate Gambierdiscus toxicus","volume":"57","author":"Nagai","year":"1992","journal-title":"J. Org. Chem."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"8995","DOI":"10.1016\/S0040-4020(00)00753-5","article-title":"The Absolute Configuration of Gambieric Acids A\u2013D, Potent Antifungal Polyethers, Isolated from the Marine Dinoflagellate Gambierdiscus toxicus","volume":"56","author":"Morohashi","year":"2000","journal-title":"Tetrahedron"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"520","DOI":"10.7164\/antibiotics.46.520","article-title":"Biological activities of novel polyether antifungals, gamberic acids A and B from a marine dinogflagellate Gambierdiscus toxicus","volume":"46","author":"Nagai","year":"1993","journal-title":"J. Antibiot."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1002\/tcr.201402052","article-title":"Total synthesis and complete structural assignment of gambieric acid A, a large polycyclic ether marine natural product","volume":"14","author":"Sasaki","year":"2014","journal-title":"Chem. Rec."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0041-0101(02)00369-0","article-title":"Inhibition of brevetoxin binding to the voltage-gated sodium channel by gambierol and gambieric acid-A","volume":"41","author":"Inoue","year":"2003","journal-title":"Toxicon"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0040-4039(00)86674-5","article-title":"Goniodomin a, a novel polyether macrolide from the dinoflagellate goniodoma pseudogoniaulax","volume":"29","author":"Murakami","year":"1988","journal-title":"Tetrahedron Lett."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.hal.2005.08.004","article-title":"Production of goniodomin A by the planktonic, chain-forming dinoflagellate Alexandrium monilatum (Howell) Balech isolated from the Gulf Coast of the United States","volume":"5","author":"Hsia","year":"2006","journal-title":"Harmful Algae"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.toxicon.2015.12.018","article-title":"First report of goniodomin A production by the dinoflagellate Alexandrium pseudogonyaulax developing in southern Mediterranean (Bizerte Lagoon, Tunisia)","volume":"111","author":"Triki","year":"2016","journal-title":"Toxicon"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1021\/ol8000377","article-title":"Assignment of the Absolute Configuration of Goniodomin A by NMR Spectroscopy and Synthesis of Model Compounds","volume":"10","author":"Takeda","year":"2008","journal-title":"Org. Lett."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/jcp.10040","article-title":"Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells","volume":"190","author":"Abe","year":"2002","journal-title":"J. Cell. Physiol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.2042-7158.1998.tb06899.x","article-title":"Goniodomin A, an antifungal polyether macrolide, increases the filamentous actin content of 1321N1 human astrocytoma cells","volume":"50","author":"Mizuno","year":"1998","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_247","first-page":"10","article-title":"Cytotoxicity of goniodomin A and B in non contractile cells","volume":"250\u2013251","author":"Cagide","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1039\/b310427n","article-title":"Amphidinolides, bioactive macrolides from symbiotic marine dinoflagellates","volume":"21","author":"Kobayashi","year":"2004","journal-title":"Nat. Prod. Rep."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1248\/cpb.c16-00281","article-title":"Search for New Bioactive Marine Natural Products","volume":"64","author":"Kobayashi","year":"2016","journal-title":"Chem. Pharm. Bull."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/1568011013354660","article-title":"Chemistry of Potent Anti-Cancer Compounds, Amphidinolides","volume":"1","author":"Chakraborty","year":"2001","journal-title":"Curr. Med. Chem. Anticancer Agents"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/ja.2008.39","article-title":"Amphidinolides and its related macrolides from marine dinoflagellates","volume":"61","author":"Kobayashi","year":"2008","journal-title":"J. Antibiot."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.chembiol.2004.07.014","article-title":"Amphidinolide H, a Potent Cytotoxic Macrolide, Covalently Binds on Actin Subdomain 4 and Stabilizes Actin Filament","volume":"11","author":"Usui","year":"2004","journal-title":"Chem. Biol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.hal.2004.07.004","article-title":"The structures of five new antifungal and hemolytic amphidinol analogs from Amphidinium carterae collected in New Zealand","volume":"4","author":"Echigoya","year":"2005","journal-title":"Harmful Algae"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1021\/np500275x","article-title":"Antifungal amphidinol 18 and its 7-sulfate derivative from the marine dinoflagellate Amphidinium carterae","volume":"77","author":"Nuzzo","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Cutignano, A., Nuzzo, G., Sardo, A., and Fontana, A. (2017). The missing piece in biosynthesis of amphidinols: First evidence of glycolate as a starter unit in New polyketides from Amphidinium carterae. Mar. Drugs, 15.","DOI":"10.3390\/md15060157"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1021\/acs.jnatprod.7b00345","article-title":"Structures of the Largest Amphidinol Homologues from the Dinoflagellate Amphidinium carterae and Structure\u2013Activity Relationships","volume":"80","author":"Satake","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"9859","DOI":"10.1021\/ja00026a027","article-title":"Amphidinol, a polyhydroxy-polyene antifungal agent with an unprecedented structure, from a marine dinoflagellate, Amphidinium klebsii","volume":"113","author":"Satake","year":"1991","journal-title":"J. Am. Chem. Soc."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1021\/np300604w","article-title":"Confirmation of the Absolute Configuration at C45 of Amphidinol 3","volume":"75","author":"Manabe","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1016\/j.tet.2005.01.069","article-title":"Hairpin conformation of amphidinols possibly accounting for potent membrane permeabilizing activities","volume":"61","author":"Houdai","year":"2005","journal-title":"Tetrahedron"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1021\/bi5002932","article-title":"Direct and stereospecific interaction of amphidinol 3 with sterol in lipid bilayers","volume":"53","author":"Espiritu","year":"2014","journal-title":"Biochemistry"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1016\/j.tetlet.2014.04.086","article-title":"Amphirionin-5, a novel linear polyketide from a cultured marine dinoflagellate Amphidinium species with a potent cell proliferation-promoting activity","volume":"55","author":"Akakabe","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.1021\/ol5023504","article-title":"Amphirionin-4 with potent proliferation-promoting activity on bone marrow stromal cells from a marine dinoflagellate Amphidinium species","volume":"16","author":"Minamida","year":"2014","journal-title":"Org. Lett."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1016\/j.tet.2014.03.025","article-title":"Iriomoteolide-13a, a cytotoxic 22-membered macrolide from a marine dinoflagellate Amphidinium species","volume":"70","author":"Akakabe","year":"2014","journal-title":"Tetrahedron"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1039\/c3np70062c","article-title":"Isolation, structural determination and synthetic approaches toward amphidinol 3","volume":"31","author":"Bensoussan","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4236\/pp.2013.43A003","article-title":"The Success of Natural Products in Drug Discovery","volume":"4","author":"Lahlou","year":"2013","journal-title":"Pharmacol. Pharm."},{"key":"ref_266","doi-asserted-by":"crossref","unstructured":"Fusetani, N. (2000). Microalgae as a Drug Source. Drugs from the Sea, Karger Medical and Scientific Publishers.","DOI":"10.1159\/isbn.978-3-318-00599-8"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10811-008-9351-3","article-title":"Crypthecodinium cohnii with emphasis on DHA production: A review","volume":"21","author":"Mendes","year":"2009","journal-title":"J. Appl. Phycol."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s10811-011-9726-8","article-title":"Optimization of growth and production of toxins by three dinoflagellates in photobioreactor cultures","volume":"24","author":"Beuzenberg","year":"2012","journal-title":"J. Appl. Phycol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/btpr.161","article-title":"Causes of shear sensitivity of the toxic dinoflagellate Protoceratium reticulatum","volume":"25","author":"Belarbi","year":"2009","journal-title":"Biotechnol. Prog."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.procbio.2009.12.018","article-title":"Culture of dinoflagellates in a fed-batch and continuous stirred-tank photobioreactors: Growth, oxidative stress and toxin production","volume":"45","author":"Belarbi","year":"2010","journal-title":"Process Biochem."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1046\/j.1365-313X.1998.00040.x","article-title":"Genetic transformation of dinoflagellates (Amphidinium and Symbiodinium): Expression of GUS in microalgae using heterologous promoter constructs","volume":"13","author":"Miller","year":"1998","journal-title":"Plant J."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1128\/EC.00364-09","article-title":"Genetic engineering of algae for enhanced biofuel production","volume":"9","author":"Radakovits","year":"2010","journal-title":"Eukaryot. Cell"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.copbio.2009.06.002","article-title":"Engineering algae for biohydrogen and biofuel production","volume":"20","author":"Beer","year":"2009","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1550-7408.2008.00357.x","article-title":"Nuclear Genome Sequence Survey of the Dinoflagellate Heterocapsa triquetra","volume":"55","author":"McEwan","year":"2008","journal-title":"J. Eukaryot. Microbiol."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev-micro-090110-102841","article-title":"Dinoflagellate Genome Evolution","volume":"65","author":"Wisecaver","year":"2011","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_276","doi-asserted-by":"crossref","unstructured":"Jaeckisch, N., Yang, I., Wohlrab, S., Gl\u00f6ckner, G., Kroymann, J., Vogel, H., Cembella, A., and John, U. (2011). Comparative Genomic and Transcriptomic Characterization of the Toxigenic Marine Dinoflagellate Alexandrium ostenfeldii. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028012"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.resmic.2011.04.006","article-title":"Genomic understanding of dinoflagellates","volume":"162","author":"Lin","year":"2011","journal-title":"Res. Microbiol."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jprot.2015.08.008","article-title":"Paralytic shellfish toxin biosynthesis in cyanobacteria and dinoflagellates: A molecular overview","volume":"135","author":"Wang","year":"2016","journal-title":"J. Proteom."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"10252","DOI":"10.1021\/ja00146a010","article-title":"Total Synthesis of Brevetoxin B. 3. Final Strategy and Completion","volume":"117","author":"Nicolaou","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/(SICI)1521-3765(19990201)5:2<646::AID-CHEM646>3.0.CO;2-E","article-title":"Total Synthesis of Brevetoxin A: Part 4: Final Stages and Completion","volume":"5","author":"Nicolaou","year":"1999","journal-title":"Chem. Eur. J."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"14983","DOI":"10.1021\/ja028167a","article-title":"Total Synthesis of (\u2212)-Gambierol","volume":"124","author":"Fuwa","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"4326","DOI":"10.1021\/ja042686r","article-title":"Convergent Total Synthesis of Gymnocin-A and Evaluation of Synthetic Analogues","volume":"127","author":"Tsukano","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1021\/ja0547477","article-title":"Total Synthesis and Structural Elucidation of Azaspiracid-1. Final Assignment and Total Synthesis of the Correct Structure of Azaspiracid-1","volume":"128","author":"Nicolaou","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"11984","DOI":"10.1021\/ja305864z","article-title":"Total Synthesis and Complete Stereostructure of Gambieric Acid A","volume":"134","author":"Fuwa","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/ja.2016.18","article-title":"Synthesis of the ABCDEF and FGHI ring system of yessotoxin and adriatoxin","volume":"69","author":"Zhang","year":"2016","journal-title":"J. Antibiot."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.procbio.2007.08.001","article-title":"Determination of shear stress thresholds in toxic dinoflagellates cultured in shaken flasks. Implications in bioprocess engineering","volume":"42","author":"Belarbi","year":"2007","journal-title":"Process Biochem."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.biortech.2016.06.027","article-title":"Pilot-scale bubble column photobioreactor culture of a marine dinoflagellate microalga illuminated with light emission diodes","volume":"216","author":"Beato","year":"2016","journal-title":"Bioresour. Technol."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.biortech.2015.08.087","article-title":"An optimisation approach for culturing shear-sensitive dinoflagellate microalgae in bench-scale bubble column photobioreactors","volume":"197","year":"2015","journal-title":"Bioresour. Technol."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.biortech.2016.06.128","article-title":"Long-term dinoflagellate culture performance in a commercial photobioreactor: Amphidinium carterae case","volume":"218","author":"Bayliss","year":"2016","journal-title":"Bioresour. Technol."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.procbio.2011.01.005","article-title":"Photobioreactor scale-up for a shear-sensitive dinoflagellate microalga","volume":"46","author":"Belarbi","year":"2011","journal-title":"Process Biochem."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.biotechadv.2012.04.007","article-title":"Flow cytometry for the development of biotechnological processes with microalgae","volume":"31","author":"Hyka","year":"2013","journal-title":"Biotechnol. Adv."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0734-9750(02)00050-2","article-title":"Recovery of microalgal biomass and metabolites: Process options and economics","volume":"20","author":"Grima","year":"2003","journal-title":"Biotechnol. Adv."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0168-1656(01)00353-4","article-title":"Tubular photobioreactor design for algal cultures","volume":"92","author":"Grima","year":"2001","journal-title":"J. Biotechnol."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1016\/S0009-2509(00)00521-2","article-title":"Airlift-driven external-loop tubular photobioreactors for outdoor production of microalgae: Assessment of design and performance","volume":"56","author":"Molina","year":"2001","journal-title":"Chem. Eng. Sci."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/bies.20250","article-title":"Proliferation of dinoflagellates: Blooming or bleaching","volume":"27","author":"Wong","year":"2005","journal-title":"BioEssays"},{"key":"ref_296","first-page":"1","article-title":"Dinoflagellate evolution and diversity through time","volume":"4","author":"Fensome","year":"1995","journal-title":"Mar. Micropaleontol."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.hal.2006.02.002","article-title":"Vertical migration of the toxic dinoflagellate Gymnodinium catenatum under different concentrations of nutrients and humic substances in culture","volume":"5","author":"Doblin","year":"2006","journal-title":"Harmful Algae"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"758","DOI":"10.4319\/lo.2001.46.4.0758","article-title":"Effect of fluid shear and irradiance on population growth and cellular toxin content of the dinoflagellate Alexandrium fundyense","volume":"46","author":"Juhl","year":"2001","journal-title":"Limnol. Oceanogr."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.3390\/md11051583","article-title":"Influence of environmental factors on the paralytic shellfish toxin content and profile of Alexandrium catenella (Dinophyceae) isolated from the Mediterranean Sea","volume":"11","author":"Laabir","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.hal.2006.04.001","article-title":"Temperature as a factor regulating growth and toxin content in the dinoflagellate Alexandrium catenella","volume":"5","author":"Navarro","year":"2006","journal-title":"Harmful Algae"},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.hal.2012.02.008","article-title":"Growth and toxicity responses of Mediterranean Ostreopsis cf. ovata to seasonal irradiance and temperature conditions","volume":"17","author":"Scalco","year":"2012","journal-title":"Harmful Algae"},{"key":"ref_302","first-page":"229","article-title":"Simultaneous effect of temperature and irradiance on growth and okadaic acid production from the marine dinoflagellate Prorocentrum belizeanum","volume":"6","author":"Belarbi","year":"2013","journal-title":"Toxins"},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"234","DOI":"10.2216\/i0031-8884-32-3-234.1","article-title":"Stichochrysis immobilis is a diatom, not a chrysophyte","volume":"32","author":"Guillard","year":"1993","journal-title":"Phycologia"},{"key":"ref_304","unstructured":"Chanley, M.H., and Smith, W.L. (1975). Culture of Phytoplankton for Feeding Marine Invertebrates. Culture of Marine Invertebrate Animals, Springer."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1139\/m62-029","article-title":"Studies of marine planktonic diatoms. I. Cyclotella nana Hustedt, and Detonula confervacea (cleve) Gran","volume":"8","author":"Guillard","year":"1962","journal-title":"Can. J. Microbiol."},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1529-8817.1987.tb04217.x","article-title":"Media for the culture of oceanic ultraphytoplankton","volume":"23","author":"Keller","year":"1987","journal-title":"J. Phycol."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.hal.2008.06.002","article-title":"Macronutrients requirements of the dinoflagellate Protoceratium reticulatum","volume":"8","author":"Belarbi","year":"2009","journal-title":"Harmful Algae"},{"key":"ref_308","doi-asserted-by":"crossref","unstructured":"Hardison, D.R., Sunda, W.G., Shea, D., and Litaker, R.W. (2013). Increased toxicity of Karenia brevis during phosphate limited growth: Ecological and evolutionary implications. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058545"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S1568-9883(03)00061-1","article-title":"Toxin production and competitive abilities under phosphorus limitation of Alexandrium species","volume":"3","author":"Guisande","year":"2004","journal-title":"Harmful Algae"},{"key":"ref_310","first-page":"11","article-title":"Growth dynamics and toxicity of Alexandrium fundyense (Dinophyceae): The effect of changing N:P supply ratios on internal toxin and nutrient levels","volume":"35","author":"John","year":"2000","journal-title":"Eur. J. Phycol."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.hal.2011.12.003","article-title":"Nitrogen and phosphorus limitation effects on cell growth, biovolume, and toxin production in Ostreopsis cf. ovata","volume":"15","author":"Vanucci","year":"2012","journal-title":"Harmful Algae"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jembe.2004.08.014","article-title":"Effects of selenium, iron and cobalt addition to growth and yessotoxin production of the toxic marine dinoflagellate Protoceratium reticulatum in culture","volume":"313","author":"Mitrovic","year":"2004","journal-title":"J. Exp. Mar. Biol. Ecol."},{"key":"ref_313","first-page":"560","article-title":"The vitamin B1 and B12 required by the marine dinoflagellate Lingulodinium polyedrum can be provided by its associated bacterial community in culture","volume":"7","author":"Maske","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.algal.2016.01.002","article-title":"Artificial neural network modeling for predicting the growth of the microalga Karlodinium veneficum","volume":"14","author":"Belarbi","year":"2016","journal-title":"Algal Res."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.biortech.2013.07.141","article-title":"Modelling of multi-nutrient interactions in growth of the dinoflagellate microalga Protoceratium reticulatum using artificial neural networks","volume":"146","year":"2013","journal-title":"Bioresour. Technol."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S1389-1723(01)80027-X","article-title":"Experimental design for fermentation media development: Statistical design or global random search?","volume":"90","year":"2000","journal-title":"J. Biosci. Bioeng."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.hal.2011.05.005","article-title":"Genetic algorithm-based medium optimization for a toxic dinoflagellate microalga","volume":"10","author":"Chisti","year":"2011","journal-title":"Harmful Algae"},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.algal.2015.05.006","article-title":"An optimal culture medium for growing Karlodinium veneficum: Progress towards a microalgal dinoflagellate-based bioprocess","volume":"10","author":"Chisti","year":"2015","journal-title":"Algal Res."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.tibtech.2014.06.001","article-title":"Light emitting diodes (LEDs) applied to microalgal production","volume":"32","author":"Schulze","year":"2014","journal-title":"Trends Biotechnol."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"417","DOI":"10.5109\/27374","article-title":"Laboratory Study for the Phytoremediation of Eutrophic Coastal Sediment Using Benthic Microalgae and Light Emitting Diode (LED)","volume":"58","author":"Kwon","year":"2013","journal-title":"J. Fac. Agric. Kyushu Univ."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.biortech.2014.12.019","article-title":"Cultivation of the benthic microalga Prorocentrum lima for the production of diarrhetic shellfish poisoning toxins in a vertical flat photobioreactor","volume":"179","author":"Wang","year":"2015","journal-title":"Bioresour. Technol."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.biortech.2015.12.057","article-title":"Flashing light in microalgae biotechnology","volume":"203","author":"Fixler","year":"2016","journal-title":"Bioresour. Technol."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.hal.2014.06.011","article-title":"Evaluation of the effects of light intensity on growth of the benthic dinoflagellate Ostreopsis sp. 1 using a newly developed photoirradiation-culture system and a novel regression analytical method","volume":"39","author":"Yamaguchi","year":"2014","journal-title":"Harmful Algae"},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1016\/j.dsr2.2005.06.026","article-title":"Effects of temperature, irradiance, and salinity on photosynthesis, growth rates, total toxicity, and toxin composition for Alexandrium fundyense isolates from the Gulf of Maine and Bay of Fundy","volume":"52","author":"Etheridge","year":"2005","journal-title":"Deep Sea Res. Part II Top. Stud. Oceanogr."},{"key":"ref_325","doi-asserted-by":"crossref","unstructured":"Lee, T.C.H., Fong, F.L.Y., Ho, K.C., and Lee, F.W.F. (2016). The mechanism of diarrhetic shellfish poisoning toxin production in Prorocentrum spp.: Physiological and molecular perspectives. Toxins, 8.","DOI":"10.3390\/toxins8100272"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s002270050569","article-title":"Cell cycle and toxin production in the benthic dinoflagellate Prorocentrum lima","volume":"134","author":"Pan","year":"1999","journal-title":"Mar. Biol."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.4319\/lo.1997.42.5_part_2.1178","article-title":"Toxin variability during the cell cycle of the dinoflagellate Alexandrium fundyense","volume":"42","author":"Kulis","year":"1997","journal-title":"Limnol. Oceanogr."},{"key":"ref_328","unstructured":"Hallegraeff, G.M., Blackburn, S.I., Bolch, C.J., and Lewis, R.J. (2001). Spirolide production and photoperiod-dependent growth of the marine dinoflagellate Alexandrium ostenfeldii. Harmful Algal Blooms 2000, International Oceanographic Commission (UNESCO)."},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"11093","DOI":"10.1021\/jf072704z","article-title":"Convenient Large-Scale Purification of Yessotoxin from Protoceratium reticulatum Culture and Isolation of a Novel Furanoyessotoxin","volume":"55","author":"Loader","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_330","unstructured":"Jauffrais, T., Sechet, V., Herrenknecht, C., Krock, B., Amzil, Z., and Hess, P. (2010, January 1\u20135). Growth and toxin production of Azadinium spinosum in batch and continuous culture. Proceedings of the 14th International Conference on Harmful Algae, Hersonissos, Crete, Greece."},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.3390\/md10061360","article-title":"Production and isolation of azaspiracid-1 and -2 from Azadinium spinosum culture in pilot scale photobioreactors","volume":"10","author":"Jauffrais","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_332","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10811-006-9081-3","article-title":"Improvement in growth and toxin production of Alexandrium tamarense by two-step culture method","volume":"18","author":"Hu","year":"2006","journal-title":"J. Appl. Phycol."},{"key":"ref_333","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1023\/A:1022326103191","article-title":"Production of C2 toxin by Alexandrium tamarense CI01 using different culture methods","volume":"14","author":"Wang","year":"2002","journal-title":"J. Appl. Phycol."},{"key":"ref_334","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/S0041-0101(01)00125-8","article-title":"Dynamics of C2 toxin and chlorophyll-a formation in the dinoflagellate Alexandrium tamarense during large scale cultivation","volume":"39","author":"Wang","year":"2001","journal-title":"Toxicon"},{"key":"ref_335","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1021\/bp060221u","article-title":"New culture approaches for yessotoxin production from the dinoflagellate Protoceratium reticulatum","volume":"23","author":"Belarbi","year":"2007","journal-title":"Biotechnol. Prog."},{"key":"ref_336","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1023\/A:1022170330857","article-title":"Growth of the toxic dinoflagellate Alexandrium minutum (Dinophyceae) using high biomass culture systems","volume":"14","author":"Parker","year":"2002","journal-title":"J. Appl. Phycol."},{"key":"ref_337","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.hal.2011.06.012","article-title":"Alexandrium ostenfeldii growth and spirolide production in batch culture and photobioreactor","volume":"10","author":"Medhioub","year":"2011","journal-title":"Harmful Algae"},{"key":"ref_338","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.marpolbul.2016.01.057","article-title":"Paralytic shellfish toxin production by the dinoflagellate Alexandrium pacificum (Chinhae Bay, Korea) in axenic, nutrient-limited chemostat cultures and nutrient-enriched batch cultures","volume":"104","author":"Han","year":"2016","journal-title":"Mar. Pollut. Bull."},{"key":"ref_339","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4490\/algae.2013.28.1.111","article-title":"In vitro studies of anti-inflammatory and anticancer activities of organic solvent extracts from cultured marine microalgae","volume":"28","author":"Samarakoon","year":"2013","journal-title":"Algae"},{"key":"ref_340","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10126-012-9450-7","article-title":"Biomass and Lipid Production of Dinoflagellates and Raphidophytes in Indoor and Outdoor Photobioreactors","volume":"15","author":"Alacid","year":"2013","journal-title":"Mar. Biotechnol."},{"key":"ref_341","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s10126-014-9581-0","article-title":"Immobilized Growth of the Peridinin-Producing Marine Dinoflagellate Symbiodinium in a Simple Biofilm Photobioreactor","volume":"16","author":"Benstein","year":"2014","journal-title":"Mar. Biotechnol."},{"key":"ref_342","first-page":"268","article-title":"Growth Characteristics of Three Benthic Dinoflagellates in Mass Culture and Their Antioxidant Properties","volume":"11","author":"Samarakoon","year":"2016","journal-title":"J. Fish. Aquat. Sci."},{"key":"ref_343","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jphotobiol.2014.12.023","article-title":"Comparing the diel vertical migration of Karlodinium veneficum (dinophyceae) and Chattonella subsalsa (Raphidophyceae): PSII photochemistry, circadian control, and carbon assimilation","volume":"143","author":"Tilney","year":"2015","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_344","doi-asserted-by":"crossref","unstructured":"Borowitzka, M.A., and Moheimani, N. (2013). Photobioreactors for Microalgal Biofuel Production. Algae for Biofuels and Energy, Springer.","DOI":"10.1007\/978-94-007-5479-9"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/15\/12\/393\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:54:48Z","timestamp":1760208888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/15\/12\/393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,20]]},"references-count":344,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["md15120393"],"URL":"https:\/\/doi.org\/10.3390\/md15120393","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,20]]}}}