9 research outputs found

    Aggregation dynamics and identification of aggregation-prone mutants of the von Hippel-Lindau tumor suppressor protein

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    International audienceQuality control mechanisms promote aggregation and degradation of misfolded proteins. In budding yeast, the human von Hippel-Lindau protein (pVHL, officially known as VHL) is misfolded and forms aggregates. Here, we investigated the aggregation of three pVHL isoforms (pVHL213, pVHL160, pVHL172) in fission yeast. The full-length pVHL213 isoform aggregates in highly dynamic small puncta and in large spherical inclusions, either close to the nucleus or to the cell ends. The large inclusions contain the yeast Hsp104 chaperone. Aggregate clearance is regulated by proteasomal degradation. The pVHL160 isoform forms dense foci and large irregularly shaped aggregates. In silico, prediction of pVHL aggregation propensity identified a key aggregation-promoting region within exon 2. Consistently, the pVHL172 isoform, which lacks exon 2, formed rare reduced inclusions. We studied the aggregation propensity of pVHL variants harbouring missense mutations found in kidney carcinomas. We show that the P86L mutation stimulated small aggregate formation, the P146A mutation increased large inclusion formation, whereas the I151S mutant destabilized pVHL. The prefoldin subunit Pac10 (the human homolog VBP-1 binds to pVHL) is required for pVHL stability. Reduction of soluble functional pVHL might be crucial in VHL-related diseases

    Evaluation of Carabus hungaricus (Coleoptera: Carabidae) populations distribution in Romania

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    International audienceCarabus hungaricus, a species protected by Council Directive 92/43 / EEC and the Berne Convention, is very localized in Romania and has a distribution that seems to have changed compared to the last century and for which recent discoveries show that there are still gaps in knowledge. Over time, there have been reports of the presence of the species in localities where the species is no longer confirmed but the paper presents new locations and reconfirmations of the present species. In Romania, being a species with isolated populations on small areas, there is a real danger of extinction by natural and anthropogenic causes. Carabus hungaricus is a Natura 2000 species present in only 6 of the Community European countries. In each country it has a very limited distribution and an unfavourable state of conservation except for Hungary where it has a wide spread and favourable state of conservation. If it is unanimously accepted that the declining of the distribution area is due to the development of agriculture, the distribution in the field and the limiting factors that determine the isolation of the species in islands at the geographical level are insufficiently known and was never explained by the verifiable indices of the limiting factors. The paper proposes updating the distribution data of the species in Romania, the spatial analysis of the areas where the species was identified and the characterization of the habitats but also the identification of the main pressures and threats. In 2019 we rediscovered the species in South-West of Romania and in July 2020 we discovered two new places in North-West. The discovery of new locations and the absence in others known from historical data show that knowledge of distribution at the national level may

    Study of Carabus (MORPHOCARABUS) ROTHI COMPTUS Dejean 1831

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    International audienceC. (Morphocarabus) rothi comptus Dejean 1831, is a endemic species of the Romania, appearing localized to some mountainous massifs of Romanian Banat and their piedmont areas (Poiana Rusca Mountains, Čšarcu Mountains). Its presence in the Apuseni Mountains is doubtful, due to the lack of recent captures and to the confusion with C. (Morphocarabus) hampei diffinis Csiki 1905, morphologically like. In Banat the species occurs in two forms: szorenyensis Csiki 1908 at higher altitude (1300-2000 m) and ulrichhoffmanni Lie 1982 in hilly areas, which is distinguished by a larger size. Whatever the altitude and the ecological conditions, the period of activity is brief, spread over a month with a maximum of over two weeks. Molecular biology studies: confirm the belonging of comptus to rothi as a subspecies of her (28SRNA5 marker); suggest (concatenation COI I / cyt b) a low infra-specific variability between provenances of the szorenyensis (Rusca, Muntele Mic) and between the origins of the ulrichhoffmanni

    Genetic structure of Spartina hybrids between native Spartina maritima and invasive Spartina densiflora in Southwest Europe

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    International audienceInterspecific hybridization represents an evolutionary force resulting in novel genotypes. The genomic changes that occur as a result of hybridization affect both genome structure and gene expression and consequently determine hybrid phenotypes and ecology. This study provides new data on the dynamics of hybrid invasions, integrating effects of the genetic, phenotypic, geographical and environmental scenarios with hybridization following invasion of a halophyte community by an exotic plant species. We analyzed the spatial genetic structure of sterile Spartina F1 hybrid populations established at the Gulf of Cadiz (Southwest Iberian Peninsula) and that of their parental species native S. maritima and invasive S. densiflora using nuclear DNA (Simple Sequence Repeats) and chloroplast DNA sequences. We also analyzed the relationships between the spatial genetic structure of the hybrids, their phenotypic variability and their marsh environment. The studied populations of Spartina hybrids were establishing hybrid zones with a spatial genetic structure inherited from both parental species. The hybrids were genetically more similar to the native than to the invasive species. The hybrid populations with greater genetic differentiation were those more spatially separated from each other and that were present in more contrasted sedimentary environments, revealing respective isolation processes by distance and by environment. The hybrids in the Guadiana Estuary were the most genetically differentiated and with the highest transgressive behavior in terms of tiller height

    Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

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    International audienceSpontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways
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