Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Benthic macroinvertebrates assemblages and macrohabitat connectivity in Mediterranean-climate streams of northern California

Abstract. Drought leads to a loss of longitudinal and lateral hydrologic connectivity, which causes direct or indirect changes in stream ecosystem properties. Changes in macrohabitat availability from a rifflepool sequence to isolated pools are among the most conspicuous consequences of connectivity loss. Macroinvertebrate assemblages were compared among 3 distinct stream macrohabitats (riffles [R], pools connected to riffles [Pc], disconnected pools [Pd]) of 19 Mediterranean-climate sites in northern California to examine the influence of loss of habitat resulting from drought disturbance. At the time of sampling, 10 sites were perennial and included R and Pc macrohabitats, whereas 9 sites were intermittent and included only Pd macrohabitats. Taxa richness was more variable in Pd, and taxa richness was significantly lower in Pd than in Pc but not R. These results suggested a decline in richness between Pc and Pd that might be associated with loss of connectivity. Lower Ephemeroptera, Plecoptera, and Trichoptera (EPT) richness relative to Odonata, Coleoptera, and Heteroptera (OCH) richness was observed for Pd than R and Pc macrohabitats. Family composition was more similar between R and Pc than between R or Pc and Pd macrohabitats. This similarity may be associated with greater connectivity between R and Pc macrohabitats. Correspondence analysis indicated that macroinvertebrate composition changed along a gradient from R to Pc and Pd that was related to a perennialintermittent gradient across sites. High variability among macroinvertebrate assemblages in Pd could have been related to variability in the duration of intermittency. In cluster analysis, macroinvertebrate assemblages were grouped by macrohabitat first and then by site, suggesting that the macrohabitat filter had a greater influence on macroinvertebrate assemblages than did local site characteristics. Few taxa were found exclusively in Pc, and this macrohabitat shared numerous taxa with R and Pd, indicating that Pc may act as a bridge between R and Pd during drought. Drought is regarded as a ramp disturbance, but our results suggest that the response of macroinvertebrate assemblages to the loss of hydrological connectivity among macrohabitats is gradual, at least in Mediterranean-climate streams where drying is gradual. However, the changes may be more dramatic in arid and semiarid streams or in Mediterranean-climate streams if drying is rapid.

Copy number variation of KIR genes influences HIV-1 control.

A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3DS1 count associates with a lower viral set point if its putative ligand is present (p = 0.00028), as does an increase in KIR3DL1 count in the presence of KIR3DS1 and appropriate ligands for both receptors (p = 0.0015). We further provide functional data that demonstrate that NK cells from individuals with multiple copies of KIR3DL1, in the presence of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly, and associated with a significant expansion in the frequency of KIR3DS1+, but not KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the relative amounts of these activating and inhibitory KIR play a role in regulating the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may determine differences in HIV-1 control following infection.

Power variation of some integral fractional processes

We consider the asymptotic behaviour of the realized power variation of processes of the form ¿t0usdBHs, where BH is a fractional Brownian motion with Hurst parameter H E(0,1), and u is a process with finite q-variation, q<1/(1¿H). We establish the stable convergence of the corresponding fluctuations. These results provide new statistical tools to study and detect the long-memory effect and the Hurst parameter.

Etude de la variation interlaboratoire du test de dépistage prénatal des défauts de fermeture du tube neural [Interlaboratory variation in the prenatal screening test for neural tube closing defects].

Early detection of neural-tude defects is possible by determining Alpha-fetoprotein (AFP) in maternal serum. 16'685 pregnant women were observed. Three methods for the determination of the "normal" range are compared. The first one, already used in similar studies, makes use of a constant multiple of the median. The other two ones make use of robust estimates of location and scale. Their comparison shows the interest of the robust methods to reduce the interlaboratory variability.

Variation in thermal performance and reaction norms among populations of Drosophila melanogaster.

The major goal of evolutionary thermal biology is to understand how variation in temperature shapes phenotypic evolution. Comparing thermal reaction norms among populations from different thermal environments allows us to gain insights into the evolutionary mechanisms underlying thermal adaptation. Here, we have examined thermal adaptation in six wild populations of the fruit fly (Drosophila melanogaster) from markedly different natural environments by analyzing thermal reaction norms for fecundity, thorax length, wing area, and ovariole number under ecologically realistic fluctuating temperature regimes in the laboratory. Contrary to expectation, we found only minor differences in the thermal optima for fecundity among populations. Differentiation among populations was mainly due to differences in absolute (and partly also relative) thermal fecundity performance. Despite significant variation among populations in the absolute values of morphological traits, we observed only minor differentiation in their reaction norms. Overall, the thermal reaction norms for all traits examined were remarkably similar among different populations. Our results therefore suggest that thermal adaptation in D. melanogaster predominantly involves evolutionary changes in absolute trait values rather than in aspects of thermal reaction norms.

Scale-specific sex-biased dispersal in the Valais shrew unveiled by genetic variation on the Y chromosome, autosomes, and mitochondrial DNA.

We investigated sex specificities in the evolutionary processes shaping Y chromosome, autosomes, and mitochondrial DNA patterns of genetic structure in the Valais shrew (Sorex antinorii), a mountain dwelling species with a hierarchical distribution. Both hierarchical analyses of variance and isolation-by-distance analyses revealed patterns of population structure that were not consistent across maternal, paternal, and biparentally inherited markers. Differentiation on a Y microsatellite was lower than expected from the comparison with autosomal microsatellites and mtDNA, and it was mostly due to genetic variance among populations within valleys, whereas the opposite was observed on other markers. In addition, there was no pattern of isolation by distance for the Y, whereas there was strong isolation by distance on mtDNA and autosomes. We use a hierarchical island model of coancestry dynamics to discuss the relative roles of the microevolutionary forces that may induce such patterns. We conclude that sex-biased dispersal is the most important driver of the observed genetic structure, but with an intriguing twist: it seems that dispersal is strongly male biased at large spatial scale, whereas it is mildly biased in favor of females at local scale. These results add to recent reports of scale-specific sex-biased dispersal patterns, and emphasize the usefulness of the Y chromosome in conjunction with mtDNA and autosomes to infer sex specificities.

Photosynthesis and Rubisco kinetics in spring wheat and meadow fescue under conditions of simulated climate change with elevated CO[sub 2] and increased temperatures

Selostus: Kevätvehnän ja nurminadan fotosynteesi ja Rubisco-kinetiikka simuloidun ilmastonmuutoksen eli kohotetun hiilidioksidipitoisuuden ja kohotetun lämpötilan oloissa

Screening for gestational diabetes: variation in guidelines.

OBJECTIVE: To compare published guidelines concerning screening for gestational diabetes. STUDY DESIGN: Systematic search and comparative analysis of published guidelines. Appraisal of guidelines quality. Simulation analysis. RESULTS: Ten published guidelines proposed either universal screening (5), selective screening (3) or screening when clinically indicated (2). Variations of testing schedules and blood glucose thresholds were observed. The quality of the published guidelines was low, on average 22 (8-51) percentage points on the assessment scale. These differences would have led to large variations in the number of patients to be screened. CONCLUSIONS: Large variations between guidelines have been observed which would translate in large practice variations, if the guidelines were systematically applied. These variations are partially explained by the absence of definite evidence that universal or selective screening for gestational diabetes do more good than harm on infant and maternal health. The methodology of developing guidelines should be more evidence based, systematic and explicit.

Climate and vegetation history of western Portugal inferred from Albian near-shore deposits (Gale Formation, Lusitanian Basin)

The late Early Cretaceous greenhouse climate has been studied intensively based on proxy data derived essentially from open marine archives. In contrast, information on continental climatic conditions and on the accompanying response of vegetation is relatively scarce, most notably owing to the stratigraphic uncertainties associated with many Lower Cretaceous terrestrial deposits. Here, we present a palynological record from Albian near-shore deposits of the Lusitanian Basin of W Portugal, which have been independently dated using Sr-isotope signals derived from low-Mg oyster shell calcite. Sr-87/Sr-86 values fluctuate between 0.707373 +/- 0.00002 and 0.707456 +/- 0.00003; absolute values and the overall stratigraphic trend match well with the global open marine seawater signature during Albian times. Based on the new Sr-isotope data, existing biostratigraphic assignments of the succession are corroborated and partly revised. Spore-pollen data provide information on the vegetation community structure and are flanked by sedimentological and clay mineralogical data used to infer the overall climatic conditions prevailing on the adjacent continent. Variations in the distribution of climate-sensitive pollen and spores indicate distinct changes in moisture availability across the studied succession with a pronounced increase in hygrophilous spores in late Early Albian times. Comparison with time-equivalent palynofloras from the Algarve Basin of southern Portugal shows pronounced differences in the xerophyte/hygrophyte ratio, interpreted to reflect the effect of a broad arid climate belt covering southern and southeastern Iberia during Early Albian times.

Efficient total variation algorithm for fetal brain MRI reconstruction.

Fetal MRI reconstruction aims at finding a high-resolution image given a small set of low-resolution images. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has considered several regularization terms s.a. Dirichlet/Laplacian energy, Total Variation (TV)- based energies and more recently non-local means. Although TV energies are quite attractive because of their ability in edge preservation, standard explicit steepest gradient techniques have been applied to optimize fetal-based TV energies. The main contribution of this work lies in the introduction of a well-posed TV algorithm from the point of view of convex optimization. Specifically, our proposed TV optimization algorithm or fetal reconstruction is optimal w.r.t. the asymptotic and iterative convergence speeds O(1/n2) and O(1/√ε), while existing techniques are in O(1/n2) and O(1/√ε). We apply our algorithm to (1) clinical newborn data, considered as ground truth, and (2) clinical fetal acquisitions. Our algorithm compares favorably with the literature in terms of speed and accuracy.