Toxicon: X最新文献

{"title":"Venom system variation and the division of labor in the colonial hydrozoan Hydractinia symbiolongicarpus","authors":"Anna M.L. Klompen ,&nbsp;Steven M. Sanders ,&nbsp;Paulyn Cartwright","doi":"10.1016/j.toxcx.2022.100113","DOIUrl":"https://doi.org/10.1016/j.toxcx.2022.100113","url":null,"abstract":"<div><p>Cnidarians (jellyfish, hydroids, sea anemones, and corals) possess a unique method for venom production, maintenance, and deployment through a decentralized system composed of different types of venom-filled stinging structures called nematocysts. In many species, nematocyst types are distributed heterogeneously across functionally distinct tissues. This has led to a prediction that different nematocyst types contain specific venom components. The colonial hydrozoan, <em>Hydractinia symbiolongicarpus,</em> is an ideal system to study the functional distribution of nematocyst types and their venoms, given that they display a division of labor through functionally distinct polyps within the colony. Here, we characterized the composition and distribution of nematocysts (cnidome) in the different polyp types and show that the feeding polyp (gastrozooid) has a distinct cnidome compared to the reproductive (gonozooid) and predatory polyp (dactylozooid). We generated a nematocyst-specific reporter line to track nematocyst development (nematogenesis) in <em>H. symbiolongicarpus</em>, and were able to confirm that nematogenesis primarily occurs in the mid-region of the gastrozooid and throughout stolons (tubes of epithelia that connect the polyps in the colony). This reporter line enabled us to isolate a nematocyst-specific lineage of cells for <em>de novo</em> transcriptome assembly, annotate venom-like genes (VLGs) and determine differential expression (DE) across polyp types. We show that a majority of VLGs are upregulated in gastrozooids, consistent with it being the primary site of active nematogenesis. However, despite gastrozooids producing more nematocysts, we found a number of VLGs significantly upregulated in dactylozooids, suggesting that these VLGs may be important for prey-capture. Our transgenic <em>Hydractinia</em> reporter line provides an opportunity to explore the complex interplay between venom composition, nematocyst diversity, and ecological partitioning in a colonial hydrozoan that displays a division of labor.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"14 ","pages":"Article 100113"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000236/pdfft?md5=f2cfbd2fe7402ca88a0403a0132ad428&pid=1-s2.0-S2590171022000236-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92095877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-compartmental toxicokinetic studies of the Nigerian Naja nigricollis venom","authors":"Auwal A. Bala ,&nbsp;Sani Malami ,&nbsp;Yusuf Abubakar Muhammad ,&nbsp;Binta Kurfi ,&nbsp;Ismaila Raji ,&nbsp;Sanusi Muhammad Salisu ,&nbsp;Mustapha Mohammed ,&nbsp;George Oche Ambrose ,&nbsp;Murtala Jibril ,&nbsp;Jacob A. Galan ,&nbsp;Elda E. Sanchez ,&nbsp;Basheer A.Z. Chedi","doi":"10.1016/j.toxcx.2022.100122","DOIUrl":"https://doi.org/10.1016/j.toxcx.2022.100122","url":null,"abstract":"<div><p>Snakebite envenoming (SBE) is a neglected public health problem, especially in Asia, Latin America and Africa. There is inadequate knowledge of venom toxicokinetics especially from African snakes. To mimic a likely scenario of a snakebite envenoming, we used an enzyme-linked immunosorbent assay (ELISA) approach to study the toxicokinetic parameters in rabbits, following a single intramuscular (IM) administration of Northern Nigeria <em>Naja nigricollis</em> venom. We used a developed and validated non-compartmental approach in the R package PK to determine the toxicokinetic parameters of the venom and subsequently used pharmacometrics modelling to predict the movement of the toxin within biological systems. We found that <em>N. nigricollis</em> venom contained sixteen venom protein families following a mass spectrometric analysis of the whole venom. Most of these proteins belong to the three-finger toxins family (3FTx) and venom phospholipase A₂ (PLA₂) with molecular weight ranging from 3 to 16 kDa. Other venom protein families were in small proportions with higher molecular weights. The <em>N. nigricollis</em> venom was rapidly absorbed at 0.5 h, increased after 1 h and continued to decrease until the 16th hour (T<em>max</em>), where maximum concentration (C<em>max</em>) was observed. This was followed by a decrease in concentration at the 32nd hour. The venom of <em>N. nigricollis</em> was found to have high volume of distribution (1250 ± 245 mL) and low clearance (29.0 ± 2.5 mL/h) with an elimination half-life of 29 h. The area under the curve (AUC) showed that the venom remaining in the plasma over 32 h was 0.0392 ± 0.0025 mg h.L⁻¹, and the mean residence time was 43.17 ± 8.04 h. The pharmacometrics simulation suggests that the venom toxins were instantly and rapidly absorbed into the extravascular compartment and slowly moved into the central compartment. Our study demonstrates that Nigerian <em>N. nigricollis</em> venom contains low molecular weight toxins that are well absorbed into the blood and deep tissues. The venom could be detected in rabbit blood 48 h after intramuscular envenoming.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"14 ","pages":"Article 100122"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000327/pdfft?md5=558e8835902f5b4803e46d06b28b5a3c&pid=1-s2.0-S2590171022000327-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92095874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo preclinical venom inhibition assays identify metalloproteinase inhibiting drugs as potential future treatments for snakebite envenoming by Dispholidus typus","authors":"Stefanie K. Menzies ,&nbsp;Rachel H. Clare ,&nbsp;Chunfang Xie ,&nbsp;Adam Westhorpe ,&nbsp;Steven R. Hall ,&nbsp;Rebecca J. Edge ,&nbsp;Jaffer Alsolaiss ,&nbsp;Edouard Crittenden ,&nbsp;Amy E. Marriott ,&nbsp;Robert A. Harrison ,&nbsp;Jeroen Kool ,&nbsp;Nicholas R. Casewell","doi":"10.1016/j.toxcx.2022.100118","DOIUrl":"https://doi.org/10.1016/j.toxcx.2022.100118","url":null,"abstract":"<div><p>Snakebite envenoming affects more than 250,000 people annually in sub-Saharan Africa. Envenoming by <em>Dispholidus typus</em> (boomslang) results in venom-induced consumption coagulopathy (VICC), whereby highly abundant prothrombin-activating snake venom metalloproteinases (SVMPs) consume clotting factors and deplete fibrinogen. The only available treatment for <em>D. typus</em> envenoming is the monovalent SAIMR Boomslang antivenom. Treatment options are urgently required because this antivenom is often difficult to source and, at US$6000/vial, typically unaffordable for most snakebite patients. We therefore investigated the <em>in vitro</em> and <em>in vivo</em> preclinical efficacy of four SVMP inhibitors to neutralise the effects of <em>D. typus</em> venom; the matrix metalloproteinase inhibitors marimastat and prinomastat, and the metal chelators dimercaprol and DMPS<em>.</em> The venom of <em>D. typus</em> exhibited an SVMP-driven procoagulant phenotype <em>in vitro</em>. Marimastat and prinomastat demonstrated equipotent inhibition of the SVMP-mediated procoagulant activity of the venom <em>in vitro</em>, whereas dimercaprol and DMPS showed considerably lower potency. However, when tested in preclinical murine models of envenoming using mixed sex CD1 mice, DMPS and marimastat demonstrated partial protection against venom lethality, demonstrated by prolonged survival times of experimental animals, whereas dimercaprol and prinomastat failed to confer any protection at the doses tested. The preclinical results presented here demonstrate that DMPS and marimastat show potential as novel small molecule-based therapeutics for <em>D. typus</em> snakebite envenoming. These two drugs have been previously shown to be effective against <em>Echis ocellatus</em> VICC in preclinical models, and thus we conclude that marimastat and DMPS should be further explored as potentially valuable early intervention therapeutics to broadly treat VICC following snakebite envenoming in sub-Saharan Africa.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"14 ","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000285/pdfft?md5=208c541ca8bd1a7377592109b6e10d09&pid=1-s2.0-S2590171022000285-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92095876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling hymenopteran venom toxins: Protein families, structural landscape, biological activities, and pharmacological benefits","authors":"Juan Carlos Guido-Patiño ,&nbsp;Fabien Plisson","doi":"10.1016/j.toxcx.2022.100119","DOIUrl":"10.1016/j.toxcx.2022.100119","url":null,"abstract":"<div><p>Hymenopterans are an untapped source of venom secretions. Their recent proteo-transcriptomic studies have revealed an extraordinary pool of toxins that participate in various biological processes, including pain, paralysis, allergic reactions, and antimicrobial activities. Comprehensive and clade-specific campaigns to collect hymenopteran venoms are therefore needed. We consider that data-driven bioprospecting may help prioritise sampling and alleviate associated costs. This work established the current protein landscape from hymenopteran venoms to evaluate possible sample bias by studying their origins, sequence diversity, known structures, and biological functions. We collected all 282 reported hymenopteran toxins (peptides and proteins) from the UniProt database that we clustered into 21 protein families from the three studied clades - wasps, bees, and ants. We identified 119 biological targets of hymenopteran toxins ranging from pathogen membranes to eukaryotic proteases, ion channels and protein receptors. Our systematic study further extended to hymenopteran toxins' therapeutic and biotechnological values, where we revealed promising applications in crop pests, human infections, autoimmune diseases, and neurodegenerative disorders.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"14 ","pages":"Article 100119"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000297/pdfft?md5=02a7ddd19385c79beb148abded09d3a6&pid=1-s2.0-S2590171022000297-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45369393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An investigation into the toxicity of tissue extracts from two distinct marine Polychaeta","authors":"Mariaelena D'Ambrosio ,&nbsp;Íris Ramos ,&nbsp;Carla Martins ,&nbsp;Pedro M. Costa","doi":"10.1016/j.toxcx.2022.100116","DOIUrl":"10.1016/j.toxcx.2022.100116","url":null,"abstract":"<div><p>The present study investigated the potential toxicity of venomous secretions of two polychaetes, <em>Hediste diversicolor</em> and <em>Glycera alba</em> (Annelida: Phyllodocida). Toxic activity of putative toxins, measured on mussel gills through the Comet assay, revealed higher effects caused by extracts from <em>H. diversicolor</em> skin and <em>G. alba</em> specialised, jawed proboscis, when compared to control. The results suggest that <em>H</em>. <em>diversicolor</em> secretes toxins via skin for protection against predators, contrarily to <em>G. alba</em>, who secretes toxins for predation.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"14 ","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000261/pdfft?md5=77b86e2b571fa5bdd143efb9a1697f05&pid=1-s2.0-S2590171022000261-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42337875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicon and Toxicon: X – 2022 and beyond","authors":"Raymond S. Norton ,&nbsp;Denise V. Tambourgi","doi":"10.1016/j.toxcx.2022.100098","DOIUrl":"10.1016/j.toxcx.2022.100098","url":null,"abstract":"","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/5d/main.PMC8844711.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39948819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verified envenomations by crevice weaver spiders (genus Kukulcania): Bites are of minor expression but the spiders are commonly misidentified as medically important brown recluses (genus Loxosceles) in North America","authors":"Richard S. Vetter","doi":"10.1016/j.toxcx.2022.100091","DOIUrl":"10.1016/j.toxcx.2022.100091","url":null,"abstract":"<div><p>From southern North America, five verified bites by crevice weaver spiders, <em>Kukulcania</em> spp. (Filistatidae), are presented here, three of which are pediatric cases. Although the envenomation manifestations were of minimal expression, the salient aspect of this report is that <em>Kukulcania</em> spiders are frequently misidentified as brown recluse spiders (genus <em>Loxosceles</em>) which are infamous for causing serious dermonecrosis and rarely, life-threatening systemic effects. Misidentification of this relatively harmless spider as a medically important recluse when presented to a physician in an envenomation episode could lead to unwarranted and overzealous treatment such as contraindicated debridement of the affected area.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39879613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A transdisciplinary approach to snakebite envenoming","authors":"Rafael Ruiz de Castañeda ,&nbsp;Isabelle Bolon ,&nbsp;José María Gutiérrez","doi":"10.1016/j.toxcx.2021.100088","DOIUrl":"10.1016/j.toxcx.2021.100088","url":null,"abstract":"","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behaviour of the Sydney funnel-web spider Atrax robustus over different contexts, time, and stimuli","authors":"Linda Hernández Duran ,&nbsp;David Thomas Wilson ,&nbsp;Tasmin Lee Rymer","doi":"10.1016/j.toxcx.2022.100093","DOIUrl":"https://doi.org/10.1016/j.toxcx.2022.100093","url":null,"abstract":"<div><p><em>Atrax robustus</em> is an iconic Australian spider because the venom can be lethal to humans. Moreover, some of the venom biomolecules have promise as therapeutic and bioinsecticidal leads. Nonetheless, aspects related to the life history and behaviour of this species, which might influence changes in venom components, have been overlooked. We assessed different behavioural traits (antipredator behaviour, defensiveness and activity) of juveniles and adult females across different contexts (predation, conspecific tolerance and exploration of a new territory) and stimuli (puff of air versus prod) over time. Adults responded to a puff of air faster than juveniles, but in response to a prod, both juveniles and adults become more defensive over time. No differences were observed between adults and juveniles for conspecific tolerance and exploration. Understanding behaviour of venomous species is important because behaviours may affect physiological traits, such as venom, and the ability of spiders to adapt to different conditions.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000030/pdfft?md5=1eccf8013ff220686ada70e83b6a3dfc&pid=1-s2.0-S2590171022000030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92167674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of bleaching on cnidarian venom ecology","authors":"K.L. Kaposi ,&nbsp;R.L. Courtney ,&nbsp;J.E. Seymour","doi":"10.1016/j.toxcx.2022.100094","DOIUrl":"10.1016/j.toxcx.2022.100094","url":null,"abstract":"<div><p>Cnidarian bleaching research often focuses on the effects on a cnidarian's physiological health and fitness, whilst little focus has been towards the impacts of these events on their venom ecology. Given the importance of a cnidarian's venom to their survival and the increasing threat of bleaching events, it is important to understand the effects that this threat may have on this important aspect of their ecology as it may have unforeseen impacts on their ability to catch prey and defend themselves. This review aims to explore evidence that suggests that bleaching may impact on each of the key aspects of a cnidarians' venom ecology: cnidae, venom composition, and venom toxicity. Additionally, the resulting energy deficit, compensatory heterotrophic feeding, and increased defensive measures have been highlighted as possible ecological factors driving these changes. Suggestions are also made to guide the success of research in this field into the future, specifically in regards to selecting a study organism, the importance of accurate symbiont and cnidae identification, use of appropriate bleaching methods, determination of bleaching, and animal handling. Ultimately, this review highlights a significant and important gap in our knowledge into how cnidarians are, and will, continue to be impacted by bleaching stress.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"13 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/e1/main.PMC8819380.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39614364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}