66 research outputs found

    Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

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    Background: Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings: We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genomewide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79 % and 56–66 % of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions: We identified novel candidate genes associated with variation in resistance to oxidative stress that hav

    Population genomics reveals that an anthropophilic population of Aedes aegypti\textit{Aedes aegypti} mosquitoes in West Africa recently gave rise to American and Asian populations of this major disease vector

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    BACKGROUND\textbf{BACKGROUND}: The mosquito Aedes aegypti\textit{Aedes aegypti} is the main vector of dengue, Zika, chikungunya and yellow fever viruses. This major disease vector is thought to have arisen when the African subspecies Ae. aegypti\textit{Ae. aegypti} formosus evolved from being zoophilic and living in forest habitats into a form that specialises on humans and resides near human population centres. The resulting domestic subspecies, Ae. aegypti aegypti\textit{Ae. aegypti aegypti}, is found throughout the tropics and largely blood-feeds on humans. RESULTS\textbf{RESULTS}: To understand this transition, we have sequenced the exomes of mosquitoes collected from five populations from around the world. We found that Ae. aegypti\textit{Ae. aegypti} specimens from an urban population in Senegal in West Africa were more closely related to populations in Mexico and Sri Lanka than they were to a nearby forest population. We estimate that the populations in Senegal and Mexico split just a few hundred years ago, and we found no evidence of Ae. aegypti aegypti\textit{Ae. aegypti aegypti} mosquitoes migrating back to Africa from elsewhere in the tropics. The out-of-Africa migration was accompanied by a dramatic reduction in effective population size, resulting in a loss of genetic diversity and rare genetic variants. CONCLUSIONS\textbf{CONCLUSIONS}: We conclude that a domestic population of Ae. aegypti\textit{Ae. aegypti} in Senegal and domestic populations on other continents are more closely related to each other than to other African populations. This suggests that an ancestral population of Ae. aegypti \textit{Ae. aegypti }evolved to become a human specialist in Africa, giving rise to the subspecies Ae. aegypti aegypti\textit{Ae. aegypti aegypti}. The descendants of this population are still found in West Africa today, and the rest of the world was colonised when mosquitoes from this population migrated out of Africa. This is the first report of an African population of Ae. aegypti aegypti mosquitoes that is closely related to Asian and American populations. As the two subspecies differ in their ability to vector disease, their existence side by side in West Africa may have important implications for disease transmission.This work was funded by European Research Council grant Drosophila Infection 281668 to FMJ, a KAUST AEA award to FMJ and AP, a Medical Research Council Centenary Award to WJP and a National Institutes of Health Ruth L. Kirschstein National Research Service Award to JC

    New Unstructured Mesh Water Quality Model for Cooling Water Biocide Discharges

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    A new unstructured mesh coastal water and air quality model has been developed that includes species transport, nonlinear decay, by-product formation, and mass-exchange between sea and atmosphere. The model has been programmed with a graphical user interface and is applicable to coastal seawater, lakes, and rivers. Focused on species conversion and interaction with the atmosphere, the water and air quality model follows a modular approach. It is a compatible module which simulates distributions based on fluid dynamic field data of underlying existing hydrodynamic and atmospheric simulations. Nonlinear and spline approximations of decay and growth kinetics, by-product formation, and joint sea-atmosphere simulation have been embedded. The Windows application software includes functions allowing error analysis concerning mesh and finite volume approximation. In this work, a submerged residual chlorine cooling water discharge and halogenated matter by-product formation has been simulated. An error analysis has been carried out by varying vertical meshing, time-steps and comparing results based on explicit and implicit finite volume approximation. The new model has been named 3D Simulation for Marine and Atmospheric Reactive Transport, in short 3D SMART. © 2013 Springer Science+Business Media Dordrecht

    Use of magnetic resonance imaging in rectal cancer patients: Society of Abdominal Radiology (SAR) rectal cancer disease-focused panel (DFP) recommendations 2017

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    International audiencePURPOSE:To propose guidelines based on an expert-panel-derived unified approach to the technical performance, interpretation, and reporting of MRI for baseline and post-treatment staging of rectal carcinoma.METHODS:A consensus-based questionnaire adopted with permission and modified from the European Society of Gastrointestinal and Abdominal Radiologists was sent to a 17-member expert panel from the Rectal Cancer Disease-Focused Panel of the Society of Abdominal Radiology containing 268 question parts. Consensus on an answer was defined as ≥ 70% agreement. Answers not reaching consensus (< 70%) were noted.RESULTS:Consensus was reached for 87% of items from which recommendations regarding patient preparation, technical performance, pulse sequence acquisition, and criteria for MRI assessment at initial staging and restaging exams and for MRI reporting were constructed.CONCLUSION:These expert consensus recommendations can be used as guidelines for primary and post-treatment staging of rectal cancer using MRI
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