Evidence of reduced individual heterogeneity in adult survival of long‐lived species

The canalization hypothesis postulates that the rate at which trait variation generates variation in the average individual fitness in a population determines how buffered traits are against environmental and genetic factors. The ranking of a species on the slow‐fast continuum – the covariation among life‐history traits describing species‐specific life cycles along a gradient going from a long life, slow maturity, and low annual reproductive output, to a short life, fast maturity, and high annual reproductive output – strongly correlates with the relative fitness impact of a given amount of variation in adult survival. Under the canalization hypothesis, long‐lived species are thus expected to display less individual heterogeneity in survival at the onset of adulthood, when reproductive values peak, than short‐lived species. We tested this life‐history prediction by analysing long‐term time series of individual‐based data in nine species of birds and mammals using capture‐recapture models. We found that individual heterogeneity in survival was higher in species with short‐generation time (< 3 years) than in species with long generation time (> 4 years). Our findings provide the first piece of empirical evidence for the canalization hypothesis at the individual level from the wild.     

Effects of endurance training on hyperammonaemia during a 45-min constant exercise intensity

Eleven laboratory-pretrained subjects (initial VO2max = 54 ml.kg-1.min-1) took part in a study to evaluate the effect of a short endurance training programme [8-12 sessions, 1 h per session, with an intensity varying from 60% to 90% maximal oxygen consumption (VO2max)] on the responses of blood ammonia (b[NH+4]) and lactate (b[la]) concentrations during progressive and constant exercise intensities. After training, during which VO2max did not increase, significant decreases in b[NH+4], b[la] and muscle proton concentration were observed at the end of the 80% VO2max constant exercise intensity, although b[NH+4] and b[la] during progressive exercise were unchanged. On the other hand, no correlations were found between muscle fibre composition and b[NH+4] in any of the exercise procedures. This study demonstrated that a constant exercise intensity was necessary to reveal the effect of training on muscle metabolic changes inducing the decrease in b[NH+4] and b[la]. At a relative power of exercise of 80% VO2max, there was no effect of muscle fibre composition on b[NH+4] accumulation.     

Dynamin‐Actin Cross Talk Contributes to Phagosome Formation and Closure

Phagocytosis is a mechanism used by macrophages to internalize and eliminate microorganisms or cellular debris. It relies on profound rearrangements of the actin cytoskeleton that is the driving force allowing plasma membrane extension around the particle. The closure step of phagocytosis, however, remains poorly defined. We used a dedicated experimental setup with Total Internal Reflection Fluorescence Microscopy (TIRFM) to monitor phagosome formation and closure in three dimensions in living cells. We show that dynamin‐2, which mediates the scission of endocytic vesicles, was recruited early and concomitantly with actin during phagosome formation. Dynamin‐2 accumulated at the site of phagosome closure in living macrophages. Inhibition of its activity with dominant negative mutants or drugs demonstrated that dynamin‐2 is implicated in actin dynamics and pseudopod extension. Depolymerization of actin led to impaired dynamin‐2 recruitment or activity. Finally, we show that dynamin‐2 plays a critical role in the effective scission of the phagosome from the plasma membrane. Thus, we establish that a cross talk between actin and dynamin takes place for phagosome formation and closure before dynamin functions for scission.      

A Mycobacterium Strain with Extended Capacities for Degradation of Gasoline Hydrocarbons

A bacterial strain (strain IFP 2173) was selected from a gasoline-polluted aquifer on the basis of its capacity to use 2,2,4-trimethylpentane (isooctane) as a sole carbon and energy source. This isolate, the first isolate with this capacity to be characterized, was identified by 16S ribosomal DNA analysis, and 100% sequence identity with a reference strain of Mycobacterium austroafricanum was found. Mycobacterium sp. strain IFP 2173 used an unusually wide spectrum of hydrocarbons as growth substrates, including n-alkanes and multimethyl-substituted isoalkanes with chains ranging from 5 to 16 carbon atoms long, as well as substituted monoaromatic hydrocarbons. It also attacked ethers, such as methyl t-butyl ether. During growth on gasoline, it degraded 86% of the substrate. Our results indicated that strain IFP 2173 was capable of degrading 3-methyl groups, possibly by a carboxylation and deacetylation mechanism. Evidence that it attacked the quaternary carbon atom structure by an as-yet-undefined mechanism during growth on 2,2,4-trimethylpentane and 2,2-dimethylpentane was also obtained.     

Quick, "Imputation-free" meta-analysis with proxy-SNPs

ABSTRACT: BACKGROUND: Meta-analysis (MA) is widely used to pool genome-wide association studies (GWASes) in order to a) increasethe power to detect strong or weak genotype effects or b) as a result verification method. As a consequence ofdiffering SNP panels among genotyping chips, imputation is the method of choice within GWAS consortia toavoid losing too many SNPs in a MA. YAMAS (Yet Another Meta Analysis Software), however, enablescross-GWAS conclusions prior to finished and polished imputation runs, which eventually are time-consuming. RESULTS: Here we present a fast method to avoid forfeiting SNPs present in only a subset of studies, without relying onimputation. This is accomplished by using reference linkage disequilibrium data from 1,000Genomes/HapMap projects to find proxy-SNPs together with in-phase alleles for SNPs missing in at least onestudy. MA is conducted by combining association effect estimates of a SNP and those of its proxy-SNPs. Ouralgorithm is implemented in the MA software YAMAS. Association results from GWAS analysis applicationscan be used as input files for MA, tremendously speeding up MA compared to the conventional imputationapproach. We show that our proxy algorithm is well-powered and yields valuable ad hoc results, possiblyproviding an incentive for follow-up studies. We propose our method as a quick screening step prior toimputation-based MA, as well as an additional main approach for studies without available reference datamatching the ethnicities of study participants. As a proof of principle, we analyzed six dbGaP Type II DiabetesGWAS and found that the proxy algorithm clearly outperforms naive MA on the P-value level: for 17 out of23 we observe an improvement on the p-value level by a factor of more than two, and a maximumimprovement by a factor of 2127. CONCLUSIONS: YAMAS is an efficient and fast meta-analysis program which offers various methods, including conventionalMA as well as inserting proxy-SNPs for missing markers to avoid unnecessary power loss. MA with YAMAScan be readily conducted as YAMAS provides a generic parser for heterogeneous tabulated file formats withinthe GWAS field and avoids cumbersome setups. In this way, it supplements the meta-analysis process.     

A systems model of training responses and its relationship to hormonal responses in elite weight-lifters

A systems model, providing an estimation of fatigue and fitness levels was applied to a 1-year training period of six elite weight-lifters. The model parameters were individually determined by fitting the predicted performance (calculated as the difference between fitness and fatigue) to the actual one. The purpose of this study was to validate the systems model by comparing the estimated levels of fatigue and fitness with biological parameters external to the model calculation. The predicted and the actual performances were significantly correlated in each subject. The calculated fitness and fatigue levels were related to serum testosterone concentration, testosterone: cortisol and testosterone: sex hormone binding globulin ratios. The best results were obtained by the comparison between fitness and testosterone levels, which varied in parallel in each subject. In two subjects this correlation was significant (r = 0.91, P less than 0.05, and r = 0.92, P less than 0.01). The fitness changes calculated in each subject between the 15th and the 51st weeks of training were significantly correlated with the changes in serum testosterone concentration measured in the same period (r = 0.99, P less than 0.001). For the whole group testosterone and fitness variations were also significantly intercorrelated (r = 0.73, P less than 0.001). Correlations, less homogeneous and less significant, were calculated also for other hormones and ratios. These results suggest that (1) the relationships between training and performance can be described by the systems model, (2) the estimated index of fitness has a physiological meaning. The fatigue index remains to be clarified.     

Diversity in Xanthophyll Cycle Pigments Content and Related Nonphotochemical Quenching (NPQ) Among Microalgae: Implications for Growth Strategy and Ecology

Xanthophyll cycle-related nonphotochemical quenching (NPQ), which is present in most photoautotrophs, allows dissipation of excess light energy. Xanthophyll cycle-related NPQ depends principally on xanthophyll cycle pigments composition and their effective involvement in NPQ. Xanthophyll cycle-related NPQ is tightly controlled by environmental conditions in a species-/strain-specific manner. These features are especially relevant in microalgae living in a complex and highly variable environment. The goal of this study was to perform a comparative assessment of NPQ ecophysiologies across microalgal taxa in order to underline the specific involvement of NPQ in growth adaptations and strategies. We used both published results and data acquired in our laboratory to understand the relationships between growth conditions (irradiance, temperature, and nutrient availability), xanthophyll cycle composition, and xanthophyll cycle pigments quenching efficiency in microalgae from various taxa. We found that in diadinoxanthin-containing species, the xanthophyll cycle pigment pool is controlled by energy pressure in all species. At any given energy pressure, however, the diatoxanthin content is higher in diatoms than in other diadinoxanthin-containing species. XC pigments quenching efficiency is species-specific and decreases with acclimation to higher irradiances. We found a clear link between the natural light environment of species/ecotypes and quenching efficiency amplitude. The presence of diatoxanthin or zeaxanthin at steady state in all species examined at moderate and high irradiances suggests that cells maintain a light-harvesting capacity in excess to cope with potential decrease in light intensity.     

Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model

Lipoprotein components are crucial factors for hepatitis C virus (HCV) assembly and entry. As hepatoma cells producing cell culture-derived HCV (HCVcc) particles are impaired in some aspects of lipoprotein metabolism, it is of upmost interest to biochemically and functionally characterize the in vivo produced viral particles, particularly regarding how lipoprotein components modulate HCV entry by lipid transfer receptors such as scavenger receptor BI (SR-BI). Sera from HCVcc-infected liver humanized FRG mice were separated by density gradients. Viral subpopulations, termed HCVfrg particles, were characterized for their physical properties, apolipoprotein association, and infectivity. We demonstrate that, in contrast to the widely spread distribution of apolipoproteins across the different HCVcc subpopulations, the most infectious HCVfrg particles are highly enriched in apoE, suggesting that such apolipoprotein enrichment plays a role for entry of in vivo derived infectious particles likely via usage of apolipoprotein receptors. Consistent with this salient feature, we further reveal previously undefined functionalities of SR-BI in promoting entry of in vivo produced HCV. First, unlike HCVcc, SR-BI is a particularly limiting factor for entry of HCVfrg subpopulations of very low density. Second, HCVfrg entry involves SR-BI lipid transfer activity but not its capacity to bind to the viral glycoprotein E2. In conclusion, we demonstrate that composition and biophysical properties of the different subpopulations of in vivo produced HCVfrg particles modulate their levels of infectivity and receptor usage, hereby featuring divergences with in vitro produced HCVcc particles and highlighting the powerfulness of this in vivo model for the functional study of the interplay between HCV and liver components.     

Social instability in laying quail: consequences on yolk steroids and offspring's phenotype

Individual phenotypic characteristics of many species are influenced by non-genetic maternal effects. Female birds can influence the development of their offspring before birth via the yolk steroid content of their eggs. We investigated this prenatal maternal effect by analysing the influence of laying females' social environment on their eggs' hormonal content and on their offspring's development. Social instability was applied to groups of laying Japanese quail females. We evaluated the impact of this procedure on laying females, on yolk steroid levels and on the general development of chicks. Agonistic interactions were more frequent between females kept in an unstable social environment (unstable females) than between females kept in a stable social environment (stable females). Testosterone concentrations were higher in unstable females' eggs than in those of stable females. Unstable females' chicks hatched later and developed more slowly during their first weeks of life than those of stable females. The emotional reactivity of unstable females' chicks was higher than that of stable females' chicks. In conclusion, our study showed that social instability applied to laying females affected, in a non-genetic way, their offspring's development, thus stressing the fact that females' living conditions during laying can have transgenerational effects.