3,134 publications from this institution
Summary: We have implemented a High Performance Computing (HPC) version of ProtTest (Abascal et al., 2007) that can be executed in parallel in multi-core desktops and clusters. This version, called ProtTest 3, includes new features and extended capabilities. Availability: ProtTest 3 source code and binaries are freely available under GNU license for download from
Polycyclic aromatic hydrocarbons (PAHs), at least those with high molecular mass, are classified as probable human carcinogens by the US Environmental Protection Agency. The importance of the material used to generate smoke is indicated by the attention that the European Union is paying to list the wood that can be used to produce smoking flavour agents. The paper examines the dependence on the nature of the wood used for smoking on the formation of eight PAHs (selected as markers of PAHs) and transfer of these PAHs into traditional Spanish smoked chorizo sausages with collagen and tripe casings. The results showed that the kind of combustion performed on different materials seriously affected the PAH levels in the smoke generated. Ignition and firing of the material with a flame compared with heating produced more PAHs in the smoke. The levels of PAHs found in the meat and in the collagen and tripe casings of the smoked chorizo samples suggest that the collagen-based casings behave as a better barrier to PAHs.
It has frequently been assumed that the persistence of a deleterious mutation (the average number of generations before its loss) and its pervasiveness (the average number of individuals carrying the gene before its loss) are equal. This is true for a particular simple, widely used infinite model, but this agreement is not general. If hs ≫ 1/(4Ne), where hs is the selective disadvantage of mutant heterozygotes and Ne is the effective population number, the contribution of homozygous mutants can be neglected and the simple approximate formula 1/hs gives the mean pervasiveness. But the expected persistence is usually much smaller, 2(loge(1/2hs) 1 − γ) where γ = 0.5772. For neutral mutations, the total number of heterozygotes until fixation or loss is often the quantity of interest, and its expected value is 2Ne, with remarkable generality for various population structures. In contrast, the number of generations until fixation or loss, 2(Ne/N)(1 loge2N), is much smaller than the total number of heterozygotes. In general the number of generations is less than the number of individuals.
Abstract A model of mutation-selection-drift balance incorporating pleiotropic and dominance effects of new mutations on quantitative traits and fitness is investigated and used to predict the amount and nature of genetic variation maintained in segregating populations. The model is based on recent information on the joint distribution of mutant effects on bristle traits and fitness in Drosophila melanogaster from experiments on the accumulation of spontaneous and P element-induced mutations. These experiments suggest a leptokurtic distribution of effects with an intermediate correlation between effects on the trait and fitness. Mutants of large effect tend to be partially recessive while those with smaller effect are on average additive, but apparently with very variable gene action. The model is parameterized with two different sets of information derived from P element insertion and spontaneous mutation data, though the latter are not fully known. They differ in the number of mutations per generation which is assumed to affect the trait. Predictions of the variance maintained for bristle number assuming parameters derived from effects of P element insertions, in which the proportion of mutations with an effect on the trait is small, fit reasonably well with experimental observations. The equilibrium genetic variance is nearly independent of the degree of dominance of new mutations. Heritabilities of between 0.4 and 0.6 are predicted with population sizes from 10(4) to 10(6), and most of the variance for the metric trait in segregating population is due to a small proportion of mutations (about 1% of the total number) with neutral or nearly neutral effects on fitness and intermediate effects on the trait (0.1-0.5 sigma P).(ABSTRACT TRUNCATED AT 250 WORDS)
Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p < .001), resulting in significantly higher prevalence of non-dipping in these two treatment-time regimen groups (80.5% and 77.3%, respectively) than in the bedtime regimen (54.4%; p < .001 between groups). Additionally, the prevalence of the riser BP pattern, associated with highest CVD risk, was much greater, 31.0% and 29.8%, respectively, among patients of the upon-awakening and BID-treatment regimens, compared with the bedtime regimen (17.6%; p < .001 between groups). Patients of the bedtime regimen also showed significantly higher prevalence of properly controlled ambulatory BP (p < .001) as a result of a greater proportion of them showing complete control of asleep SBP and DBP means. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of blunted nighttime BP decline, i.e., lower prevalence of CVD risk markers, in RH patients ingesting the full daily dose of ≥1 hypertension medications at bedtime than in those ingesting all of them upon awakening or ≥1 of them as split doses BID. In RH, ingesting the same medications BID neither improves ambulatory BP control nor reduces the prevalence of non-dipping, and cannot be considered chronotherapy. Collectively, findings of this study indicate that a bedtime hypertension medication regimen, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of true RH and avoid treatment-induced nocturnal hypotension, should be the therapeutic scheme of choice for patients who, by conventional cuff methods (and in the absence of ABPM) and the morning-treatment regimen, have been mistakenly judged to be resistant to therapy.
The performance of 14 different recombination detection methods was evaluated by analyzing several empirical data sets where the presence of recombination has been suggested or where recombination is assumed to be absent. In general, recombination methods seem to be more powerful with increasing levels of divergence, but different methods showed distinct performance. Substitution methods using summary statistics gave more accurate inferences than most phylogenetic methods. However, definitive conclusions about the presence of recombination should not be derived on the basis of a single method. Performance patterns observed from the analysis of real data sets coincided very well with previous computer simulation results. Previous recombination inferences from some of the data sets analyzed here should be reconsidered. In particular, recombination in HIV-1 seems to be much more widespread than previously thought. This finding might have serious implications on vaccine development and on the reliability of previous inferences of HIV-1 evolutionary history and dynamics.
Abstract.— Sexual selection (defined as the change in genotypic or phenotypic frequencies of mated versus total population frequencies) and sexual isolation (defined as the deviation from random mating in mated individuals) show different evolutionary consequences and partially confounded causes. Traditionally, the cross-product estimator has been used to quantify sexual selection, whereas a variety of indexes, such as Yule V, Yule Q, YA, joint I, and others have been used to quantify sexual isolation. Because the two types of estimators use different scales, the effects of both processes cannot be monitored simultaneously. We describe three new related statistics that quantify both sexual selection (PSS) and sexual isolation (PSI) effects for every mating pair combination in polymorphic traits, as well as measure their combined effects (PTI = PSI X PSS). The new statistics have the advantage of providing information on every mating pair combination, quantifying the effects of sexual selection and isolation in the same units, and detecting asymmetry in sexual isolation. The ability of the new statistics to ascertain the biological causes of sexual selection and sexual isolation are investigated under different models involving distinct marginal frequencies, mate propensity, and mate choice coefficients. We also studied the use of classical isolation indexes applied on PSI coefficients, instead of on raw data. The use of the classical indexes applied to PSI coefficients considerably reduces the statistical bias of the estimates, revealing the good estimation properties of the new statistics.
Little is known of the fate of polycyclic aromatic hydrocarbons (PAHs) in soils under burnt woodland. It is not clear what the behavior of the overlying wood ash layer will be along months. In this study, the levels of eight representative PAHs in the 1-5 cm layer of a periurban woodland soil that had undergone wildfire were compared with those measured in nearby and distant unburnt periurban woodland soils and in a distant unburnt rural woodland soil, and the levels at the burnt site were monitored during some 10 months. The analytical method optimized for the purpose afforded recoveries of 74-111% (depending on PAH) and repeatabilities (RSDs) better than 9%, with limits of detection ranging from 1 to 7 microg/kg. PAH levels in the 1-5 cm layer of the burnt periurban soil were very similar to those of distant unburnt periurban soil (188 vs 173 microg/kg), about seven times the 26 microg/kg measured in unburnt rural soil, which furthermore contained no detectable quantities of the highest molecular weight PAHs typical of traffic and other urban sources, as the periurban soils did. At the burnt site, PAH levels fell along the months (the total PAH level from 188 to 119 microg/kg), apparently as the result of rainfall and the prevention of further input from the atmosphere by the overlying layer of wood ash, which had a very high PAH adsorption capacity (1169 microg/kg) and did not itself appear to act as a source of PAHs. PAH transport may have been assisted by increased mobilization of PAHs associated with dissolvable organic matter due to an increase in soil pH due to alkaline ash components.