56 research outputs found

    Molecular and life-history effects of a natural toxin on herbivorous and non-target soil arthropods

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    Natural toxins, such as isothiocyanate (ITC), are harmful secondary metabolites produced by plants. Many natural toxins occur in commercial crops, yet their possible negative repercussions on especially non-target soil organisms are largely unknown. This study examined life-history and gene transcriptional responses to 2-phenylethyl ITC on two soil arthropod species: Folsomia candida and Protaphorura fimata. To that end the standardized ISO guideline for ecotoxicological tests and a microarray for F. candida were used. The dissipation of 2-phenylethyl ITC in natural soil was investigated using GC-MS/MS for quantification. Half-lives, tested at four concentration levels in natural soil, were on average 16 h with biodegradation as the plausible main removal process. Regardless, toxic effects on reproduction were shown for F. candida and P. fimata, with EC50 values of around 11.5 nmol/g soil illustrating the toxic character of this compound. Gene expression profiles revealed the importance of fatty acid metabolism at low exposure concentrations (EC10), which is associated with the lipophilic nature of 2-phenylethyl ITC. At higher concentrations (EC50) gene expression became more ubiquitous with over-expression of especially stress-related genes and sugar metabolism. The regulation of a gene encoding a precursor of follistatin, furthermore, implied the inhibition of reproduction and may be an important molecular target that can be linked to the observed adverse effect of life-history traits

    Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities.

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    OBJECTIVES: The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognized. We aimed to investigate this paucity of diagnoses. METHODS: We undertook weighted burden analysis of whole-exome sequencing (WES) data from 138 individuals with unresolved generalized dystonia of suspected genetic etiology, followed by additional case-finding from international databases, first for the gene implicated by the burden analysis (VPS16), and then for other functionally related genes. Electron microscopy was performed on patient-derived cells. RESULTS: Analysis revealed a significant burden for VPS16 (Fisher's exact test p value, 6.9 × 109 ). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome-lysosome fusion. A total of 18 individuals harboring heterozygous loss-of-function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early onset progressive dystonia with predominant cervical, bulbar, orofacial, and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss-of-function variants in VPS41, another HOPS-complex encoding gene, in an individual with infantile-onset generalized dystonia. Electron microscopy of patient-derived lymphocytes and fibroblasts from both patients with VPS16 and VPS41 showed vacuolar abnormalities suggestive of impaired lysosomal function. INTERPRETATION: Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, although variants in different subunits display different phenotypic and inheritance characteristics. ANN NEUROL 2020;88:867-877

    Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms

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    Neurotoxic shellfish poisoning: Een literatuurstudie

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    This review contains information on the neurotoxic shellfish poisoning (NSP) syndrome and the provoking toxins called brevetoxins, produced by the dinoflagellate Gymnodinium breve. Data on chemical structures and detection methods for brevetoxins, sources for brevetoxins, marine organisms associated with NSP, toxicity of brevetoxins for animals and man, possible preventive measures for NSP, case reports/outbreaks of NSP and regulations and monitoring for NSP are included. Finally some recommendations are given for a better control of the NSP problem in the futureDit literatuuroverzicht bevat informatie betreffende het "neurotoxic shellfish poisoning" (NSP) syndroom en de veroorzakende toxines, nl.de brevetoxines, welke geproduceerd worden door de dinoflagellaat Gymnodinium breve. Chemische structuren en detectie-methodes van de brevetoxines, de bronnen voor brevetoxines, mariene organismen welke geassocieerd worden met brevetoxines, de toxiciteit van brevetoxines voor dier en mens, mogelijke preventieve maatregelen voor NSP, NSP gevallen en controle van en regelingen voor NSP toxines worden besproken. Tenslotte worden enkele aanbevelingen gedaan voor een betere controle van het NSP probleem in de toekomst

    Amnesic shellfish poisoning: een literatuurstudie

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    Deze literatuurstudie bevat informatie betreffende het 'amnesic shellfish poisoning' (ASP) syndroom en de veroorzakende ASP toxines, van welke "domoic acid" de belangrijkste component is. Chemische structuren en detectie-methodes van ASP toxines, de bronnen voor ASP toxines, mariene organismen welke geassocieerd worden met ASP toxines, de toxiciteit van ASP toxines voor dier en mens, mogelijke preventieve maatregelen voor ASP, ASP gevallen en controle van en regelingen voor ASP toxines worden besproken. Tenslotte worden enkele aanbevelingen gedaan voor een betere controle van het ASP probleem in de toekomst.This review reports information on the amnesic shellfish poisoning (ASP) syndrome and the ASP toxins causing this poisoning, of which domoic acid is the major component. Data includes chemical structures and detection methods of ASP toxins, sources of ASP toxins, marine organisms associated with ASP, toxicity of ASP toxins for animals and humans, possible preventive measures for ASP, case reports/outbreaks of ASP and regulations and monitoring of ASP toxins. The review ends with several recommendations for better control of the ASP problem in the future.VWS-HIG

    Neurotoxic shellfish poisoning: Een literatuurstudie

    No full text
    Dit literatuuroverzicht bevat informatie betreffende het "neurotoxic shellfish poisoning" (NSP) syndroom en de veroorzakende toxines, nl.de brevetoxines, welke geproduceerd worden door de dinoflagellaat Gymnodinium breve. Chemische structuren en detectie-methodes van de brevetoxines, de bronnen voor brevetoxines, mariene organismen welke geassocieerd worden met brevetoxines, de toxiciteit van brevetoxines voor dier en mens, mogelijke preventieve maatregelen voor NSP, NSP gevallen en controle van en regelingen voor NSP toxines worden besproken. Tenslotte worden enkele aanbevelingen gedaan voor een betere controle van het NSP probleem in de toekomst.This review contains information on the neurotoxic shellfish poisoning (NSP) syndrome and the provoking toxins called brevetoxins, produced by the dinoflagellate Gymnodinium breve. Data on chemical structures and detection methods for brevetoxins, sources for brevetoxins, marine organisms associated with NSP, toxicity of brevetoxins for animals and man, possible preventive measures for NSP, case reports/outbreaks of NSP and regulations and monitoring for NSP are included. Finally some recommendations are given for a better control of the NSP problem in the futureHIGB/VW
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