Influence of climate on the presence of colour polymorphism in two montane reptile species.

The coloration of ectotherms plays an important role in thermoregulation processes. Dark individuals should heat up faster and be able to reach a higher body temperature than light individuals and should therefore have benefits in cool areas. In central Europe, montane local populations of adder (Vipera berus) and asp viper (Vipera aspis) exhibit a varying proportion of melanistic individuals. We tested whether the presence of melanistic V. aspis and V. berus could be explained by climatic conditions. We measured the climatic niche position and breadth of monomorphic (including strictly patterned individuals) and polymorphic local populations, calculated their niche overlap and tested for niche equivalency and similarity. In accordance with expectations, niche overlap between polymorphic local populations of both species is high, and even higher than that of polymorphic versus monomorphic montane local populations of V. aspis, suggesting a predominant role of melanism in determining the niche of ectothermic vertebrates. However, unexpectedly, the niche of polymorphic local populations of both species is narrower than that of monomorphic ones, indicating that colour polymorphism does not always enable the exploitation of a greater variability of resources, at least at the intraspecific level. Overall, our results suggest that melanism might be present only when the thermoregulatory benefit is higher than the cost of predation.

Large-scale imatinib dose-concentration-effect study in CML patients under routine care conditions.

This observational study analyzed imatinib pharmacokinetics and response in 2478 chronic myeloid leukemia (CML) patients. Data were obtained through centralized therapeutic drug monitoring (TDM) at median treatment duration of ≥2 years. First, individual initial trough concentrations under 400mg/day imatinib starting dose were estimated. Second, their correlation (C^min(400mg)) with reported treatment response was verified. Low imatinib levels were predicted in young male patients and those receiving P-gp/CYP3A4 inducers. These patients had also lower response rates (7% lower 18-months MMR in male, 17% lower 1-year CCyR in young patients, Kaplan-Meier estimates). Time-point independent multivariate regression confirmed a correlation of individual C^min(400mg) with response and adverse events. Possibly due to confounding factors (e.g. dose modifications, patient selection bias), the relationship seemed however flatter than previously reported from prospective controlled studies. Nonetheless, these observational results strongly suggest that a subgroup of patients could benefit from early dosage optimization assisted by TDM, because of lower imatinib concentrations and lower response rates.

Mass effects mediate coexistence in competing shrews.

Recent developments in metacommunity theory have raised awareness that processes occurring at regional scales might interfere with local dynamics and affect conditions for the local coexistence of competing species. Four main paradigms are recognized in this context (namely, neutral, patch-dynamics, species-sorting, and mass-effect), which differ according to the role assigned to ecological or life-history differences among competing species, as well as to the relative time scale of regional vs. local dynamics. We investigated the patterns of regional and local coexistence of two species of shrews (Crocidura russula and Sorex coronatus) sharing a similar diet (generalist insectivores) over four generations, in a spatially structured habitat at the altitudinal limit of their distributions. Local populations were small, and regional dynamics were strong, with high rates of extinction and recolonization. Niche analysis revealed significant habitat differentiation on a few important variables, including temperature and availability of winter resting sites. In sites suitable for both species, we found instances of local coexistence with no evidence of competitive exclusion. Patterns of temporal succession did not differ from random, with no suggestion of a colonization-competition trade-off. Altogether, our data provide support for the mass-effect paradigm, where regional coexistence is mediated by specialization on different habitat types, and local coexistence by rescue effects from source sites. The strong regional dynamics and demographic stochasticity, together with high dispersal rates, presumably contributed to mass effects by overriding local differences in specific competitive abilities.

The dynamics of yeast telomeres and silencing proteins through the cell cycle.

Genes integrated near the telomeres of budding yeast have a variegated pattern of gene repression that is mediated by the silent information regulatory proteins Sir2p, Sir3p, and Sir4p. Immunolocalization and fluorescence in situ hybridization (FISH) reveal 6-10 perinuclear foci in which silencing proteins and subtelomeric sequences colocalize, suggesting that these are sites of Sir-mediated repression. Telomeres lacking subtelomeric repeat elements and the silent mating locus, HML, also localize to the periphery of the nucleus. Conditions that disrupt telomere proximal repression disrupt the focal staining pattern of Sir proteins, but not necessarily the localization of telomeric DNA. To monitor the telomere-associated pools of heterochromatin-binding proteins (Sir and Rap1 proteins) during mitotic cell division, we have performed immunofluorescence and telomeric FISH on populations of yeast cells synchronously traversing the cell cycle. We observe a partial release of Rap1p from telomeres in late G2/M, although telomeres appear to stay clustered during G2-phase and throughout mitosis. A partial release of Sir3p and Sir4p during mitosis also occurs. This is not observed upon HU arrest, although other types of DNA damage cause a dramatic relocalization of Sir and Rap1 proteins. The observed cell cycle dynamics were confirmed by direct epifluorescence of a GFP-Rap1p fusion. Using live GFP fluorescence we show that the diffuse mitotic distribution of GFP-Rap1p is restored to the interphase pattern of foci in early G1-phase.

Generating controlled image sets in cognitive neuroscience research.

The investigation of perceptual and cognitive functions with non-invasive brain imaging methods critically depends on the careful selection of stimuli for use in experiments. For example, it must be verified that any observed effects follow from the parameter of interest (e.g. semantic category) rather than other low-level physical features (e.g. luminance, or spectral properties). Otherwise, interpretation of results is confounded. Often, researchers circumvent this issue by including additional control conditions or tasks, both of which are flawed and also prolong experiments. Here, we present some new approaches for controlling classes of stimuli intended for use in cognitive neuroscience, however these methods can be readily extrapolated to other applications and stimulus modalities. Our approach is comprised of two levels. The first level aims at equalizing individual stimuli in terms of their mean luminance. Each data point in the stimulus is adjusted to a standardized value based on a standard value across the stimulus battery. The second level analyzes two populations of stimuli along their spectral properties (i.e. spatial frequency) using a dissimilarity metric that equals the root mean square of the distance between two populations of objects as a function of spatial frequency along x- and y-dimensions of the image. Randomized permutations are used to obtain a minimal value between the populations to minimize, in a completely data-driven manner, the spectral differences between image sets. While another paper in this issue applies these methods in the case of acoustic stimuli (Aeschlimann et al., Brain Topogr 2008), we illustrate this approach here in detail for complex visual stimuli.

Stochastic demography and the neutral substitution rate in class-structured populations.

The neutral rate of allelic substitution is analyzed for a class-structured population subject to a stationary stochastic demographic process. The substitution rate is shown to be generally equal to the effective mutation rate, and under overlapping generations it can be expressed as the effective mutation rate in newborns when measured in units of average generation time. With uniform mutation rate across classes the substitution rate reduces to the mutation rate.

Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.

BACKGROUND: Retinitis pigmentosa and other hereditary retinal degenerations (HRD) are rare genetic diseases leading to progressive blindness. Recessive HRD are caused by mutations in more than 100 different genes. Laws of population genetics predict that, on a purely theoretical ground, such a high number of genes should translate into an extremely elevated frequency of unaffected carriers of mutations. In this study we estimate the proportion of these individuals within the general population, via the analyses of data from whole-genome sequencing. METHODOLOGY/PRINCIPAL FINDINGS: We screened complete and high-quality genome sequences from 46 control individuals from various world populations for HRD mutations, using bioinformatic tools developed in-house. All mutations detected in silico were validated by Sanger sequencing. We identified clear-cut, null recessive HRD mutations in 10 out of the 46 unaffected individuals analyzed (∼22%). CONCLUSIONS/SIGNIFICANCE: Based on our data, approximately one in 4-5 individuals from the general population may be a carrier of null mutations that are responsible for HRD. This would be the highest mutation carrier frequency so far measured for a class of Mendelian disorders, especially considering that missenses and other forms of pathogenic changes were not included in our assessment. Among other things, our results indicate that the risk for a consanguineous couple of generating a child with a blinding disease is particularly high, compared to other genetic conditions.

Quantitative comparison of reconstruction methods for intra-voxel fiber recovery from diffusion MRI.

Validation is arguably the bottleneck in the diffusion magnetic resonance imaging (MRI) community. This paper evaluates and compares 20 algorithms for recovering the local intra-voxel fiber structure from diffusion MRI data and is based on the results of the "HARDI reconstruction challenge" organized in the context of the "ISBI 2012" conference. Evaluated methods encompass a mixture of classical techniques well known in the literature such as diffusion tensor, Q-Ball and diffusion spectrum imaging, algorithms inspired by the recent theory of compressed sensing and also brand new approaches proposed for the first time at this contest. To quantitatively compare the methods under controlled conditions, two datasets with known ground-truth were synthetically generated and two main criteria were used to evaluate the quality of the reconstructions in every voxel: correct assessment of the number of fiber populations and angular accuracy in their orientation. This comparative study investigates the behavior of every algorithm with varying experimental conditions and highlights strengths and weaknesses of each approach. This information can be useful not only for enhancing current algorithms and develop the next generation of reconstruction methods, but also to assist physicians in the choice of the most adequate technique for their studies.

Start-up conditions and the performance of women – and men- controlled businesses in manufacturating industries

Recent research on the economic performance of women-controlled firms suggests that their underperformance may not result from differences in the managerial ability of women as compared to men, but it can be the result of different levels of start-up resources. Using accounting data, this paper examines the effects that selected start-up conditions have on the economic performance observed in a sample of 4450 Spanish manufacturing firms. The results indicate significant differences regarding the initial conditions, showing lower levels of assets and number of employees what have implications on the economic performance of women-controlled firms.

Binding under Conflict Conditions: State-Space Analysis of Multivariate EEG Synchronization.

Real-world objects are often endowed with features that violate Gestalt principles. In our experiment, we examined the neural correlates of binding under conflict conditions in terms of the binding-by-synchronization hypothesis. We presented an ambiguous stimulus ("diamond illusion") to 12 observers. The display consisted of four oblique gratings drifting within circular apertures. Its interpretation fluctuates between bound ("diamond") and unbound (component gratings) percepts. To model a situation in which Gestalt-driven analysis contradicts the perceptually explicit bound interpretation, we modified the original diamond (OD) stimulus by speeding up one grating. Using OD and modified diamond (MD) stimuli, we managed to dissociate the neural correlates of Gestalt-related (OD vs. MD) and perception-related (bound vs. unbound) factors. Their interaction was expected to reveal the neural networks synchronized specifically in the conflict situation. The synchronization topography of EEG was analyzed with the multivariate S-estimator technique. We found that good Gestalt (OD vs. MD) was associated with a higher posterior synchronization in the beta-gamma band. The effect of perception manifested itself as reciprocal modulations over the posterior and anterior regions (theta/beta-gamma bands). Specifically, higher posterior and lower anterior synchronization supported the bound percept, and the opposite was true for the unbound percept. The interaction showed that binding under challenging perceptual conditions is sustained by enhanced parietal synchronization. We argue that this distributed pattern of synchronization relates to the processes of multistage integration ranging from early grouping operations in the visual areas to maintaining representations in the frontal networks of sensory memory.

Transitions in social complexity along elevational gradients reveal a combined impact of season length and development time on social evolution.

Eusociality is taxonomically rare, yet associated with great ecological success. Surprisingly, studies of environmental conditions favouring eusociality are often contradictory. Harsh conditions associated with increasing altitude and latitude seem to favour increased sociality in bumblebees and ants, but the reverse pattern is found in halictid bees and polistine wasps. Here, we compare the life histories and distributions of populations of 176 species of Hymenoptera from the Swiss Alps. We show that differences in altitudinal distributions and development times among social forms can explain these contrasting patterns: highly social taxa develop more quickly than intermediate social taxa, and are thus able to complete the reproductive cycle in shorter seasons at higher elevations. This dual impact of altitude and development time on sociality illustrates that ecological constraints can elicit dynamic shifts in behaviour, and helps explain the complex distribution of sociality across ecological gradients.

Age-targeted chemotherapy for control of urinary schistosomiais in endemic populations

Severity of urinary tract morbidity increases with intensity and duration of Schistosoma haematobium infection. We assessed the ability of yearly drug therapy to control infection intensity and reduce S. haematobium-associated disease in children 5-21 years old in an endemic area of Kenya. In year I, therapy resulted in reduced prevalence (66% to 22%, P < 0.001) and intensity of S. haematobium infection (20 to 2 eggs/10 mL, urine), with corresponding reductions in the prevalence of hematuria (52% to 19%, P < 0.001). There was not, however, a significant first-year effect on prevalence of urinary tract abnormalities detected by ultrasound. Repeat therapy in years 2 and 3 resulted in significant regression of hydronephrosis and bladder abnormalities (41% to 6% prevalence, P< 0.001), and further reductions in proteinuria. Repeat age-targeted therapy was associated with decreased prevalence of infection among young children (< 5yr) entering into the target age group. Two years after discontinuation of therapy, intensity of S. haematobium infection and ultrasound abnormalities remained suppressed, but hematuria prevalence began to increase (to 33% in 1989). Reinstitution of annual therapy in 1989 and 1990 reversed this trends. We conclude that annual oral therapy provides an effective strategy for control of morbidity due to S. haematobium on population basis, both through regression of disease in treated individuals, and prevention of infection in untreated subjects.

Interleukin-28B polymorphisms, IP-10, viral load and age predict the outcome of therapy in genotype 1 hepatitis C virus under real-life conditions

Background and Aims: IL28B polymorphisms, interferon (IFN)-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score have been reported to predict rapid (RVR) and sustained (SVR) virological response in chronic hepatitis C (CHC), but it is not known whether these factors represent independent, clinically useful predictors. The aim of the study was to assess factors (including IL28B polymorphisms, IP-10 levels and HOMA-IR score) independently predicting response to therapy in CHC under real life conditions.Methods: Multivariate analysis of factors predicting RVR and SVR in 280 consecutive, treatment-naive CHC patients treated with pegylated IFN alpha and ribavirin in a prospective multicenter study.Results: Independent predictors of RVR were HCV RNA < 400,000 IU/ml (OR11.37; 95% CI 3.03-42.6), rs12980275 AA (vs. AG/GG) (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline γ-glutamyl-transferase levels (OR = 0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age < 40 yrs (OR = 4.79; 1.50-15.34) and HCV RNA < 400,000 IU/ml (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR = 6.26; 1.98-19.74) and age < 40 yrs (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (32 of 33, 97%; OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99; p=0.009) or 3 patients (OR 7.8, 1.43-42.67; p=0.01).Conclusions: In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pretreatment prediction of SVR. HOMA-IR score is not associated with viral response.

Prevalence of antibodies to Hepatitis C virus in populations at low and high risk for sexually transmited diseases in Rio de Janeiro

In order to investigate the sexual transmission of the Hepatitis C Virus (HCV), the prevalence of specific antibodies in populations at high and low risk for sexually transmitted diseases (STDs) was evaluated. The population at low risk for STDs was composed of persons who voluntarity donated blood at the Hospital Universitário Clementino Fraga Filho (HUCFF) between July and November, 1990 (n = 2494). The population at high risk for STDs was drawn from an ongoing study on the natural history of Human Immunodeficiency Virus (HIV) infection (n = 210, 187 with sexual risk factors for HIV infection). All samples were screened using a first generation ELISA. Repeat reactive samples were then tested in a second generation RIBA. For all ELISA positive samples, two sex and age-matched ELISA negative controls were selected. Data pertaining to the presence of antibodies to the Hepatitis B core antigen (anti-HBC antibodies) and to Treponema pallidum were abstracted from the medical records. The prevalence of RIBA 2 confirmed HCV infection among the blood donors was 2.08%, which is well above the reported prevalence in similar populations from developed western countries. Among the HIV infected homosexuals, the encountered prevalence was 7.96% (p < 0.0005). For the whole group with sexually acquired HIV infection, the prevalence was 8.02% (p < 0.000005). Anti-HBc antibodies were more frequently present in anti-HCV RIBA-2 confirmed positive blood donors than in controls (p < 0.001). 33.3% of the HCV-positive blood donors and 11.04% controls were found to be anti-HBc positive (p < 0.0005). As for the FTA-ABs, 17.6% HCV-positive donors and 4,9% controls were positive (p < 0.01). 5.9% samples from blood donors were both anti-HBc and FTA-ABS positive, whereas none of the controls reacted in both tests (p < 0.05). The association between HCV, Hepatitis B infection and syphilis in individuals at low risk for parenterally transmitted diseases suggests that sexual transmission contributes to the maintenance of the endemicity of HCV in the local population.