77 research outputs found
Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries
<p>Abstract</p> <p>Background</p> <p>Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome.</p> <p>Methods</p> <p>Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed.</p> <p>Results</p> <p>Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson).</p> <p>Conclusions</p> <p>The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.</p
The Hidden Sexuality of Alexandrium Minutum: An Example of Overlooked Sex in Dinoflagellates
Dinoflagellates are haploid eukaryotic microalgae in which rapid proliferation causes dense
blooms, with harmful health and economic effects to humans. The proliferation mode is
mainly asexual, as the sexual cycle is believed to be rare and restricted to stressful environmental
conditions. However, sexuality is key to explaining the recurrence of many dinoflagellate
blooms because in many species the fate of the planktonic zygotes (planozygotes)
is the formation of resistant cysts in the seabed (encystment). Nevertheless, recent
research has shown that individually isolated planozygotes in the lab can enter other routes
besides encystment, a behavior of which the relevance has not been explored at the population
level. In this study, using imaging flow cytometry, cell sorting, and Fluorescence In
Situ Hybridization (FISH), we followed DNA content and nuclear changes in a population of
the toxic dinoflagellate Alexandrium minutum that was induced to encystment. Our results
first show that planozygotes behave like a population with an “encystment-independent”
division cycle, which is light-controlled and follows the same Light:Dark (L:D) pattern as the
cycle governing the haploid mitosis. Resting cyst formation was the fate of just a small fraction
of the planozygotes formed and was restricted to a period of strongly limited nutrient
conditions. The diploid-haploid turnover between L:D cycles was consistent with two-step
meiosis. However, the diel and morphological division pattern of the planozygote division
also suggests mitosis, which would imply that this species is not haplontic, as previously
considered, but biphasic, because individuals could undergo mitotic divisions in both the
sexual (diploid) and the asexual (haploid) phases. We also report incomplete genome duplication
processes. Our work calls for a reconsideration of the dogma of rare sex in
dinoflagellates.Versión del edito
Le Darwinisme et les générations spontanées, ou, Réponse aux réfutations de MM. P. Flourens, de Quatrefages, Léon Simon, Chauvet, etc.
Correction: Insect netting: effect of mesh size and shape on exclusion of some fruit pests and natural enemies under laboratory and orchard conditions
Insect netting: effect of mesh size and shape on exclusion of some fruit pests and natural enemies under laboratory and orchard conditions
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