Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Membrane glycoprotein p150,95 of human cytotoxic T cell clones is involved in conjugate formation with target cells

Contains fulltext : 27218___.PDF (publisher's version ) (Open Access

Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95

Contains fulltext : 27226___.PDF (publisher's version ) (Open Access

Computational methods for debonding in composites

This contribution starts with a discussion of various phenomena in laminated composite structures that can lead to failure: matrix cracking, delamination between plies, and debonding and subsequent pull-out between fibres and the matrix material. The different scales are discussed at which the effect of these nonlinearities can be analysed. From these scales – the macro, meso and micro-levels – the meso-level is normally used for the analysis of delamination, which is the focus of this contribution. At this level, the plies are modelled as continua and interface elements between them conventionally serve as the framework to model delamination and debonding. After a a derivation of interface elements and a brief discussion of the cohesive–zone concept and its importance for the analysis of delamination, a particular finite element model for the plies is elaborated: the solid–like shell. Next, a more recent method to numerically model delamination is discussed, which exploits the partition–of–unity property of finite element shape functions. This approach offers advantages over interface elements, as will be discussed in detail

Activation of LFA-1 through a Ca2+-dependent epitope stimulates lymphocyte adhesion

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Both LFA-1 positive and -deficient T cell clones require the CD2/LFA-3 interaction for specific cytolytic activation

Contains fulltext : 27175___.PDF (publisher's version ) (Open Access

Synaptic Gain-of-Function Effects of Mutant Ca(v)2.1 Channels in a Mouse Model of Familial Hemiplegic Migraine Are Due to Increased Basal [Ca2+](i)

Mechanisms of disease, diagnostics and therap

Synaptic gain-of-function effects of mutant Cav2.1 channels in a mouse model of familial hemiplegic migraine are due to increased basal [Ca2+]i

Specific missense mutations in the CACNA1A gene, which encodes a subunit of voltage-gated CaV2.1 channels, are associated with familial hemiplegic migraine type 1 (FHM1), a rare monogenic subtype of common migraine with aura. We used transgenic knock-in (KI) mice harboring the human pathogenic FHM1 mutation S218L to study presynaptic Ca 2 currents, EPSCs, and in vivo activity at the calyx of Held synapse. Whole-cell patch-clamp recordings of presynaptic terminal