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  1. Article: Phylogenetic origins for severe acetaminophen toxicity in snake species compared to other vertebrate taxa.

    van den Hurk, Peter / Kerkkamp, Harald M I

    Comparative biochemistry and physiology. Toxicology & pharmacology : CBP

    2018  Volume 215, Page(s) 18–24

    Abstract: While it has been known for a while that some snake species are extremely sensitive to acetaminophen, the underlying mechanism for this toxicity has not been reported. To investigate if essential detoxification enzymes are missing in snake species that ... ...

    Abstract While it has been known for a while that some snake species are extremely sensitive to acetaminophen, the underlying mechanism for this toxicity has not been reported. To investigate if essential detoxification enzymes are missing in snake species that are responsible for biotransformation of acetaminophen in other vertebrate species, livers were collected from a variety of snake species, together with samples from alligator, snapping turtle, cat, rat, and cattle. Subcellular fractions were analyzed for enzymatic activities of phenol-type sulfotransferase and UDP‑glucuronosyltransferase, total glutathione S‑transferase, and N‑acetyltransferase. The results showed that none of the snake species, together with the cat samples, had any phenol-type glucuronidation activity, and that this activity was much lower in alligator and turtle samples than in the mammalian species. Combined with the lack of N‑acetyltransferase activity in snakes and cats, this would explain the accumulation of the aminophenol metabolite, which induces methemoglobinemia and subsequent suffocation of snakes and cats after acetaminophen exposure. While previous investigations have concluded that in cats the gene for the phenol-type glucuronosyltransferase isoform has turned into a pseudogene because of several point mutations, evaluation of genomic information for snake species revealed that they have only 2 genes that may code for glucuronosyltransferase isoforms. Similarity of these genes with mammalian genes is <50%, and suggests that the expressed enzymes may act on other types of substrates than aromatic amines. This indicates that the extreme sensitivity for acetaminophen in snakes is based on a different phylogenetic origin than the sensitivity observed in cats.
    MeSH term(s) Acetaminophen/adverse effects ; Acetaminophen/metabolism ; Acetaminophen/toxicity ; Acetyltransferases/genetics ; Acetyltransferases/metabolism ; Agkistrodon/genetics ; Agkistrodon/physiology ; Analgesics, Non-Narcotic/adverse effects ; Analgesics, Non-Narcotic/metabolism ; Animals ; Biotransformation ; Boidae/genetics ; Boidae/physiology ; Colubridae/genetics ; Colubridae/physiology ; Crotalus/genetics ; Crotalus/physiology ; Databases, Genetic ; Drug Resistance ; Environmental Pollutants/metabolism ; Environmental Pollutants/toxicity ; Glucuronosyltransferase/genetics ; Glucuronosyltransferase/metabolism ; Glutathione Transferase/genetics ; Glutathione Transferase/metabolism ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Liver/enzymology ; Phylogeny ; Reptilian Proteins/genetics ; Reptilian Proteins/metabolism ; Snakes/genetics ; Snakes/physiology ; Species Specificity ; Sulfotransferases/genetics ; Sulfotransferases/metabolism ; Toxicokinetics
    Chemical Substances Analgesics, Non-Narcotic ; Environmental Pollutants ; Isoenzymes ; Reptilian Proteins ; Acetaminophen (362O9ITL9D) ; Acetyltransferases (EC 2.3.1.-) ; Glucuronosyltransferase (EC 2.4.1.17) ; Glutathione Transferase (EC 2.5.1.18) ; Sulfotransferases (EC 2.8.2.-)
    Language English
    Publishing date 2018-09-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 189285-x
    ISSN 1532-0456 ; 0306-4492 ; 0742-8413
    ISSN 1532-0456 ; 0306-4492 ; 0742-8413
    DOI 10.1016/j.cbpc.2018.09.003
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  2. Article ; Online: A non-lethal method for studying scorpion venom gland transcriptomes, with a review of potentially suitable taxa to which it can be applied.

    Vonk, Freek J / Bittenbinder, Mátyás A / Kerkkamp, Harald M I / Grashof, Dwin G B / Archer, John P / Afonso, Sandra / Richardson, Michael K / Kool, Jeroen / van der Meijden, Arie

    PloS one

    2021  Volume 16, Issue 11, Page(s) e0258712

    Abstract: Scorpion venoms are mixtures of proteins, peptides and small molecular compounds with high specificity for ion channels and are therefore considered to be promising candidates in the venoms-to-drugs pipeline. Transcriptomes are important tools for ... ...

    Abstract Scorpion venoms are mixtures of proteins, peptides and small molecular compounds with high specificity for ion channels and are therefore considered to be promising candidates in the venoms-to-drugs pipeline. Transcriptomes are important tools for studying the composition and expression of scorpion venom. Unfortunately, studying the venom gland transcriptome traditionally requires sacrificing the animal and therefore is always a single snapshot in time. This paper describes a new way of generating a scorpion venom gland transcriptome without sacrificing the animal, thereby allowing the study of the transcriptome at various time points within a single individual. By comparing these venom-derived transcriptomes to the traditional whole-telson transcriptomes we show that the relative expression levels of the major toxin classes are similar. We further performed a multi-day extraction using our proposed method to show the possibility of doing a multiple time point transcriptome analysis. This allows for the study of patterns of toxin gene activation over time a single individual, and allows assessment of the effects of diet, season and other factors that are known or likely to influence intraindividual venom composition. We discuss the gland characteristics that may allow this method to be successful in scorpions and provide a review of other venomous taxa to which this method may potentially be successfully applied.
    MeSH term(s) Amino Acid Sequence/genetics ; Animals ; Gene Expression Profiling ; Peptides/classification ; Peptides/genetics ; Salivary Glands/metabolism ; Scorpion Venoms/genetics ; Scorpions/genetics ; Transcriptome/genetics
    Chemical Substances Peptides ; Scorpion Venoms
    Language English
    Publishing date 2021-11-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0258712
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  3. Article ; Online: Eye-Transcriptome and Genome-Wide Sequencing for Scolecophidia: Implications for Inferring the Visual System of the Ancestral Snake.

    Gower, David J / Fleming, James F / Pisani, Davide / Vonk, Freek J / Kerkkamp, Harald M I / Peichl, Leo / Meimann, Sonja / Casewell, Nicholas R / Henkel, Christiaan V / Richardson, Michael K / Sanders, Kate L / Simões, Bruno F

    Genome biology and evolution

    2021  Volume 13, Issue 12

    Abstract: Molecular genetic data have recently been incorporated in attempts to reconstruct the ecology of the ancestral snake, though this has been limited by a paucity of data for one of the two main extant snake taxa, the highly fossorial Scolecophidia. Here we ...

    Abstract Molecular genetic data have recently been incorporated in attempts to reconstruct the ecology of the ancestral snake, though this has been limited by a paucity of data for one of the two main extant snake taxa, the highly fossorial Scolecophidia. Here we present and analyze vision genes from the first eye-transcriptomic and genome-wide data for Scolecophidia, for Anilios bicolor, and A. bituberculatus, respectively. We also present immunohistochemistry data for retinal anatomy and visual opsin-gene expression in Anilios. Analyzed in the context of 19 lepidosaurian genomes and 12 eye transcriptomes, the new genome-wide and transcriptomic data provide evidence for a much more reduced visual system in Anilios than in non-scolecophidian (=alethinophidian) snakes and in lizards. In Anilios, there is no evidence of the presence of 7 of the 12 genes associated with alethinophidian photopic (cone) phototransduction. This indicates extensive gene loss and many of these candidate gene losses occur also in highly fossorial mammals with reduced vision. Although recent phylogenetic studies have found evidence for scolecophidian paraphyly, the loss in Anilios of visual genes that are present in alethinophidians implies that the ancestral snake had a better-developed visual system than is known for any extant scolecophidian.
    MeSH term(s) Animals ; Evolution, Molecular ; Lizards/genetics ; Mammals/genetics ; Opsins/genetics ; Phylogeny ; Snakes/genetics ; Transcriptome
    Chemical Substances Opsins
    Language English
    Publishing date 2021-11-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2495328-3
    ISSN 1759-6653 ; 1759-6653
    ISSN (online) 1759-6653
    ISSN 1759-6653
    DOI 10.1093/gbe/evab253
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Transcriptome annotation and characterization of novel toxins in six scorpion species.

    Grashof, Dwin G B / Kerkkamp, Harald M I / Afonso, Sandra / Archer, John / Harris, D James / Richardson, Michael K / Vonk, Freek J / van der Meijden, Arie

    BMC genomics

    2019  Volume 20, Issue 1, Page(s) 645

    Abstract: Background: Venom has evolved in parallel in multiple animals for the purpose of self-defense, prey capture or both. These venoms typically consist of highly complex mixtures of toxins: diverse bioactive peptides and/or proteins each with a specific ... ...

    Abstract Background: Venom has evolved in parallel in multiple animals for the purpose of self-defense, prey capture or both. These venoms typically consist of highly complex mixtures of toxins: diverse bioactive peptides and/or proteins each with a specific pharmacological activity. Because of their specificity, they can be used as experimental tools to study cell mechanisms and develop novel medicines and drugs. It is therefore potentially valuable to explore the venoms of various animals to characterize their toxins and identify novel toxin-families. This study focuses on the annotation and exploration of the transcriptomes of six scorpion species from three different families. The transcriptomes were annotated with a custom-built automated pipeline, primarily consisting of Basic Local Alignment Search Tool searches against UniProt databases and filter steps based on transcript coverage.
    Results: We annotated the transcriptomes of four scorpions from the family Buthidae, one from Iuridae and one from Diplocentridae using our annotation pipeline. We found that the four buthid scorpions primarily produce disulfide-bridged ion-channel targeting toxins, while the non-buthid scorpions have a higher abundance of non-disulfide-bridged toxins. Furthermore, analysis of the "unidentified" transcripts resulted in the discovery of six novel putative toxin families containing a total of 37 novel putative toxins. Additionally, 33 novel toxins in existing toxin-families were found. Lastly, 19 novel putative secreted proteins without toxin-like disulfide bonds were found.
    Conclusions: We were able to assign most transcripts to a toxin family and classify the venom composition for all six scorpions. In addition to advancing our fundamental knowledge of scorpion venomics, this study may serve as a starting point for future research by facilitating the identification of the venom composition of scorpions and identifying novel putative toxin families.
    MeSH term(s) Animals ; Gene Expression Profiling ; Molecular Sequence Annotation ; Scorpions/genetics ; Toxins, Biological/genetics
    Chemical Substances Toxins, Biological
    Language English
    Publishing date 2019-08-13
    Publishing country England
    Document type Journal Article
    ISSN 1471-2164
    ISSN (online) 1471-2164
    DOI 10.1186/s12864-019-6013-6
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  5. Article ; Online: Snake Genome Sequencing: Results and Future Prospects.

    Kerkkamp, Harald M I / Kini, R Manjunatha / Pospelov, Alexey S / Vonk, Freek J / Henkel, Christiaan V / Richardson, Michael K

    Toxins

    2016  Volume 8, Issue 12

    Abstract: Snake genome sequencing is in its infancy-very much behind the progress made in sequencing the genomes of humans, model organisms and pathogens relevant to biomedical research, and agricultural species. We provide here an overview of some of the snake ... ...

    Abstract Snake genome sequencing is in its infancy-very much behind the progress made in sequencing the genomes of humans, model organisms and pathogens relevant to biomedical research, and agricultural species. We provide here an overview of some of the snake genome projects in progress, and discuss the biological findings, with special emphasis on toxinology, from the small number of draft snake genomes already published. We discuss the future of snake genomics, pointing out that new sequencing technologies will help overcome the problem of repetitive sequences in assembling snake genomes. Genome sequences are also likely to be valuable in examining the clustering of toxin genes on the chromosomes, in designing recombinant antivenoms and in studying the epigenetic regulation of toxin gene expression.
    MeSH term(s) Animals ; Genome ; Repetitive Sequences, Nucleic Acid ; Snakes/genetics ; Toxins, Biological/genetics
    Chemical Substances Toxins, Biological
    Language English
    Publishing date 2016-12-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins8120360
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: How the Cobra Got Its Flesh-Eating Venom: Cytotoxicity as a Defensive Innovation and Its Co-Evolution with Hooding, Aposematic Marking, and Spitting.

    Panagides, Nadya / Jackson, Timothy N W / Ikonomopoulou, Maria P / Arbuckle, Kevin / Pretzler, Rudolf / Yang, Daryl C / Ali, Syed A / Koludarov, Ivan / Dobson, James / Sanker, Brittany / Asselin, Angelique / Santana, Renan C / Hendrikx, Iwan / van der Ploeg, Harold / Tai-A-Pin, Jeremie / van den Bergh, Romilly / Kerkkamp, Harald M I / Vonk, Freek J / Naude, Arno /
    Strydom, Morné A / Jacobsz, Louis / Dunstan, Nathan / Jaeger, Marc / Hodgson, Wayne C / Miles, John / Fry, Bryan G

    Toxins

    2017  Volume 9, Issue 3

    Abstract: The cytotoxicity of the venom of 25 species of Old World elapid snake was tested and compared with the morphological and behavioural adaptations of hooding and spitting. We determined that, contrary to previous assumptions, the venoms of spitting species ...

    Abstract The cytotoxicity of the venom of 25 species of Old World elapid snake was tested and compared with the morphological and behavioural adaptations of hooding and spitting. We determined that, contrary to previous assumptions, the venoms of spitting species are not consistently more cytotoxic than those of closely related non-spitting species. While this correlation between spitting and non-spitting was found among African cobras, it was not present among Asian cobras. On the other hand, a consistent positive correlation was observed between cytotoxicity and utilisation of the defensive hooding display that cobras are famous for. Hooding and spitting are widely regarded as defensive adaptations, but it has hitherto been uncertain whether cytotoxicity serves a defensive purpose or is somehow useful in prey subjugation. The results of this study suggest that cytotoxicity evolved primarily as a defensive innovation and that it has co-evolved twice alongside hooding behavior: once in the
    MeSH term(s) Animals ; Behavior, Animal ; Biological Evolution ; Cell Line ; Cell Line, Tumor ; Cell Survival/drug effects ; Chickens ; Elapid Venoms/toxicity ; Elapidae/physiology ; Humans ; Muscle, Skeletal/innervation ; Neuromuscular Junction/drug effects ; Neurotoxins/toxicity ; Pigmentation
    Chemical Substances Elapid Venoms ; Neurotoxins
    Language English
    Publishing date 2017-03-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins9030103
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