A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

Simulations of extensional flow in microrheometric devices

We present a detailed numerical study of the flow of a Newtonian fluid through microrheometric devices featuring a sudden contraction–expansion. This flow configuration is typically used to generate extensional deformations and high strain rates. The excess pressure drop resulting from the converging and diverging flow is an important dynamic measure to quantify if the device is intended to be used as a microfluidic extensional rheometer. To explore this idea, we examine the effect of the contraction length, aspect ratio and Reynolds number on the flow kinematics and resulting pressure field. Analysis of the computed velocity and pressure fields show that, for typical experimental conditions used in microfluidic devices, the steady flow is highly three-dimensional with open spiraling vortical structures in the stagnant corner regions. The numerical simulations of the local kinematics and global pressure drop are in good agreement with experimental results. The device aspect ratio is shown to have a strong impact on the flow and consequently on the excess pressure drop, which is quantified in terms of the dimensionless Couette and Bagley correction factors. We suggest an approach for calculating the Bagley correction which may be especially appropriate for planar microchannels

Targeting the proteostasis network in Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion mutation in the huntingtin protein. Expansions above 40 polyglutamine repeats are invariably fatal, following a symptomatic period characterised by choreiform movements, behavioural abnormalities, and cognitive decline. While mutant huntingtin (mHtt) is widely expressed from early life, most patients with HD present in mid-adulthood, highlighting the role of ageing in disease pathogenesis. mHtt undergoes proteolytic cleavage, misfolding, accumulation, and aggregation into inclusion bodies. The emerging model of HD pathogenesis proposes that the chronic production of misfolded mHtt overwhelms the chaperone machinery, diverting other misfolded clients to the proteasome and the autophagy pathways, ultimately leading to a global collapse of the proteostasis network. Multiple converging hypotheses also implicate ageing and its impact in the dysfunction of organelles as additional contributing factors to the collapse of proteostasis in HD. In particular, mitochondrial function is required to sustain the activity of ATP-dependent chaperones and proteolytic machinery. Recent studies elucidating mitochondria-endoplasmic reticulum interactions and uncovering a dedicated proteostasis machinery in mitochondria, suggest that mitochondria play a more active role in the maintenance of cellular proteostasis than previously thought. The enhancement of cytosolic proteostasis pathways shows promise for HD treatment, protecting cells from the detrimental effects of mHtt accumulation. In this review, we consider how mHtt and its post translational modifications interfere with protein quality control pathways, and how the pharmacological and genetic modulation of components of the proteostasis network impact disease phenotypes in cellular and in vivo HD models

Pollen storage by stingless bees as an environmental marker for metal contamination : spatial and temporal distribution of metal elements.

Since the middle of the 20th century, human activities have led to overall ecosystem contamination and to major modifications in landscape structure and composition. Mining activities represent a major source of environmental contamination by metal residues. The objective of our study was to evaluate the presence of heavy metals and other elements on stingless bee pollen, and compare them to samples of Suspended Particulate Material (SPM) in five points a Mineral Province, in Brazil. More than 50 elements were identified by ICP-OES and ICP-MS, after microwave digestion. Overall, we found a strong relation among elements present on pollen and SPM. Samples from the four areas exhibited higher levels of minerals compared to the reference site. Mineral levels varied widely within the two seasonal periods. Some elements, like Pb, Cd, As, Cu, Zn, and Fe were found at levels considered potentially toxic to human health. Pollen stored by stingless bees was a successful bioindicator, and demonstrated the value of quantitative ecological information for detecting air pollution

An overview of the current status of CMB observations

In this paper we briefly review the current status of the Cosmic Microwave Background (CMB) observations, summarising the latest results obtained from CMB experiments, both in intensity and polarization, and the constraints imposed on the cosmological parameters. We also present a summary of current and future CMB experiments, with a special focus on the quest for the CMB B-mode polarization.Comment: Latest CMB results have been included. References added. To appear in "Highlights of Spanish Astrophysics V", Proceedings of the VIII Scientific Meeting of the Spanish Astronomical Society (SEA) held in Santander, 7-11 July, 200

Drought generates large, long-term changes in tree and liana regeneration in a monodominant Amazon forest

The long-term dynamics of regeneration in tropical forests dominated by single tree species remains largely undocumented, yet is key to understanding the mechanisms by which one species can gain dominance and resist environmental change. We report here on the long-term regeneration dynamics in a monodominant stand of Brosimum rubescens Taub. (Moraceae) at the southern border of the Amazon forest. Here the climate has warmed and dried since the mid-1990′s. Twenty-one years of tree and liana regeneration were evaluated in four censuses in 30 plots by assessing species abundance, dominance, and diversity in all regeneration classes up to 5 cm diameter. The density of B. rubescens seedlings declined markedly, from 85% in 1997 to 29% in 2018 after the most intense El Niño-driven drought. While the fraction contributed by other tree species changed little, the relative density of liana seedlings increased from just 1 to 54% and three-quarters of liana species underwent a ten-fold or greater increase in abundance. The regeneration community experienced a high rate of species turnover, with changes in the overall richness and species diversity determined principally by lianas, not trees. Long-term maintenance of monodominance in this tropical forest is threatened by a sharp decline in the regeneration of the monodominant species and the increase in liana density, suggesting that monodominance will prove to be a transitory condition. The close association of these rapid changes with drying indicates that monodominant B. rubescens forests are impacted by drought-driven changes in regeneration, and therefore are particularly sensitive to climatic change