Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations

It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.     

Possible tropical lakes on Titan from observations of dark terrain

Titan has clouds, rain and lakes--like Earth--but composed of methane rather than water. Unlike Earth, most of the condensable methane (the equivalent of 5?m depth globally averaged) lies in the atmosphere. Liquid detected on the surface (about 2?m deep) has been found by radar images only poleward of 50° latitude, while dune fields pervade the tropics. General circulation models explain this dichotomy, predicting that methane efficiently migrates to the poles from these lower latitudes. Here we report an analysis of near-infrared spectral images of the region between 20°?N and 20°?S latitude. The data reveal that the lowest fluxes in seven wavelength bands that probe Titan's surface occur in an oval region of about 60?×?40?km(2), which has been observed repeatedly since 2004. Radiative transfer analyses demonstrate that the resulting spectrum is consistent with a black surface, indicative of liquid methane on the surface. Enduring low-latitude lakes are best explained as supplied by subterranean sources (within the last 10,000 years), which may be responsible for Titan's methane, the continual photochemical depletion of which furnishes Titan's organic chemistry.     

On Modeling Bio-Scaffolds: Structural and Fluid Transport Characterization Based on 3-D Imaging Data

Bio-scaffolds which are most commonly open celled porous structures are increasingly used for tissue engineering and regenerative medicine. A number of studies have shown that the bulk properties of such irregular structures are poorly modeled using idealized unit cell approaches. The paper therefore uses novel image based meshing techniques to explore both fluid flow and bulk structural properties of a bone scaffold, as accurate modeling of bio-scaffolds with non-uniform cellular structures is very important for the development of optimal scaffolds for tissue engineering application. In this study, a porous hydroxyapatite/tricalcium phosphate (HA/TCP) bone scaffold has been scanned in a Micro-CT scanner, and converted into a volumetric mesh using image processing software developed by the authors. The resulting mesh was then exported to commercial FEA and CFD solvers for analysis. Initial FEA and CFD studies have shown promising results and have highlighted the importance of accurate modeling to understand how microstructures influence the mechanical property of the scaffold, and to analyze flow regimes through the sample. The work highlights the potential use of image based meshing for the ad hoc characterization of scaffolds as well as for assisting in the design of scaffolds with tailored strength, stiffness, and transport properties.     

The in vitro effect of aprotinin upon spleen cells from normal and tumour-bearing mice exposed to PPD and tumour cells

Aprotinin (Trasylol) is shown to enhance the response of spleen cells from normal and tumour bearing mice to PPD nd tumour cells. This enhancement is greater in the tumour-bearing mice.     

The Italian-Hour Nocturnal

The general view is that there is one type of nocturnal, which is universal, first illustrated in a printed book in 1524. Recently, a number of quite differently constructed nocturnals has come to light. Six of these were made at the very beginning of the sixteenth century by Falcono of Bergamo in northern Italy. One of them, with the initials of the inventor, may well be the prototype. Five more are closely similar. Five further nocturnals of the same type have been identified, but they are unsigned, and are not by Falcono. This paper establishes the existence of a hitherto unrecognized Italian workshop, and of a variant type of nocturnal.     

Changes in Mule Deer Size in Utah

Trends in age-specific, eviscerated carcass weights were determined for hunter-harvested yearling and two-year-old buck mule deer. Carcass weights declined over an 11-year period from two areas of similar management, but with independenly collected data sets. Carcass weights also declined between the opening and second weekends of the hunt. Management implications are discussed.