Target-derived neurotrophic factors regulate the death of developing forebrain neurons after a change in their trophic requirements

Many neurons die as the normal brain develops. How this is regulated and whether the mechanism involves neurotrophic molecules from target cells are unknown. We found that cultured neurons from a key forebrain structure, the dorsal thalamus, develop a need for survival factors including brain-derived neurotrophic factor (BDNF) from their major target, the cerebral cortex, at the age at which they innervate it. Experiments in vivo have shown that rates of dorsal thalamic cell death are reduced by increasing cortical levels of BDNF and are increased in mutant mice lacking functional BDNF receptors or thalamocortical projections; these experiments have also shown that an increase in the rates of dorsal thalamic cell death can be achieved by blocking BDNF in the cortex. We suggest that the onset of a requirement for cortex-derived neurotrophic factors initiates a competitive mechanism regulating programmed cell death among dorsal thalamic neurons

Parental investment and child health in a Yanomamö village suffering short-term food stress

The 1998 El Niño significantly reduced garden productivity in the Upper Orinoco region in Venezuela. Consequently, parents were forced to allocate food carefully to their children. Nutrition data collected from village children combined with genealogical data allowed the determination of which children suffered most, and whether the patterns of food distribution accorded with predictions from parental investment theory. For boys, three social variables accounted for over 70% of the variance in subcutaneous fat after controlling for age: number of siblings, age of the mother’s youngest child, and whether the mother was the senior or junior co-wife, or was married monogamously. These results accord well with parental investment theory. Parents experiencing food stress faced a trade-off between quantity and quality, and between investing in younger versus older offspring. In addition, boys with access to more paternal investment (i.e. no stepmother) were better nourished. These variables did not account for any of the variance in female nutrition. Girls’ nutrition was associated with the size of their patrilineage and the number of non-relatives in the village, suggesting that lineage politics may have played a role. An apparent lack of relationship between orphan status and nutrition is also interesting, given that orphans suffered high rates of skin flea infections. The large number of orphans being cared for by only two grandparents suggests that grooming time may have been the resource in short supply. Introductio

SUCI02 inhibits the erbB-2 tyrosine kinase receptor signaling pathway and arrests the cell cycle in G 1 phase in breast cancer cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73321/1/j.1349-7006.2006.00143.x.pd

Exploring 4D Quantum Hall Physics with a 2D Topological Charge Pump

The discovery of topological states of matter has profoundly augmented our understanding of phase transitions in physical systems. Instead of local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example thereof is the two-dimensional integer quantum Hall effect. It is characterized by the first Chern number which manifests in the quantized Hall response induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional systems leads to the appearance of a novel non-linear Hall response that is quantized as well, but described by a 4D topological invariant - the second Chern number. Here, we report on the first observation of a bulk response with intrinsic 4D topology and the measurement of the associated second Chern number. By implementing a 2D topological charge pump with ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small atom cloud as a local probe, we fully characterize the non-linear response of the system by in-situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probe higher-dimensional quantum Hall systems, where new topological phases with exotic excitations are predicted

p70 S6 kinase and actin dynamics: A perspective

p70 S6 kinase (p70S6K), a member of the AGC serine/threonine kinase family, was initially identified as a key player, together with its downstream effector S6, in the regulation of cellular growth and survival. The p70S6K protein has emerged in recent years as a multifunctional protein which also regulates the actin cytoskeleton and thus plays a role in cell migration. This new function is through two important activities of p70S6K, namely actin cross-linking and Rac1 and Cdc42 activation. The testis is critically dependent on an intricate balance of fundamental cellular processes such as adhesion, migration, and differentiation. It is increasingly evident that Rho GTPases and actin binding proteins play fundamental roles in regulating spermatogenesis within the testis. In this review, we will discuss current findings of p70S6K in the control of actin cytoskeleton dynamics. In addition, the potential role of p70S6K in spermatogenesis and testicular function will be highlighted

Surface structure and frictional properties of the skin of the Amazon tree boa Corallus hortulanus (Squamata, Boidae)

The legless locomotion of snakes requires specific adaptations of their ventral scales to maintain friction force in different directions. The skin microornamentation of the snake Corallus hortulanus was studied by means of scanning electron microscopy and the friction properties of the skin were tested on substrates of different roughness. Skin samples from various parts of the body (dorsal, lateral, ventral) were compared. Dorsal and lateral scales showed similar, net-like microornamentation and similar friction coefficients. Average friction coefficients for dorsal and lateral scales on the epoxy resin surfaces were 0.331 and 0.323, respectively. In contrast, ventral scales possess ridges running parallel to the longitudinal body axis. They demonstrated a significantly lower friction coefficient compared to both dorsal and lateral scales (0.191 on average). In addition, ventral scales showed frictional anisotropy comparing longitudinal and perpendicular direction of the ridges. This study clearly demonstrates that different skin microstructure is responsible for different frictional properties in different body regions

A Bayesian Framework to Account for Complex Non-Genetic Factors in Gene Expression Levels Greatly Increases Power in eQTL Studies

Gene expression measurements are influenced by a wide range of factors, such as the state of the cell, experimental conditions and variants in the sequence of regulatory regions. To understand the effect of a variable of interest, such as the genotype of a locus, it is important to account for variation that is due to confounding causes. Here, we present VBQTL, a probabilistic approach for mapping expression quantitative trait loci (eQTLs) that jointly models contributions from genotype as well as known and hidden confounding factors. VBQTL is implemented within an efficient and flexible inference framework, making it fast and tractable on large-scale problems. We compare the performance of VBQTL with alternative methods for dealing with confounding variability on eQTL mapping datasets from simulations, yeast, mouse, and human. Employing Bayesian complexity control and joint modelling is shown to result in more precise estimates of the contribution of different confounding factors resulting in additional associations to measured transcript levels compared to alternative approaches. We present a threefold larger collection of cis eQTLs than previously found in a whole-genome eQTL scan of an outbred human population. Altogether, 27% of the tested probes show a significant genetic association in cis, and we validate that the additional eQTLs are likely to be real by replicating them in different sets of individuals. Our method is the next step in the analysis of high-dimensional phenotype data, and its application has revealed insights into genetic regulation of gene expression by demonstrating more abundant cis-acting eQTLs in human than previously shown. Our software is freely available online at http://www.sanger.ac.uk/resources/software/peer/

Why I tense up when you watch me: inferior parietal cortex mediates an audience’s influence on motor performance

The presence of an evaluative audience can alter skilled motor performance through changes in force output. To investigate how this is mediated within the brain, we emulated real-time social monitoring of participants’ performance of a fine grip task during functional magnetic resonance neuroimaging. We observed an increase in force output during social evaluation that was accompanied by focal reductions in activity within bilateral inferior parietal cortex. Moreover, deactivation of the left inferior parietal cortex predicted both inter- and intra-individual differences in socially-induced change in grip force. Social evaluation also enhanced activation within the posterior superior temporal sulcus, which conveys visual information about others’ actions to the inferior parietal cortex. Interestingly, functional connectivity between these two regions was attenuated by social evaluation. Our data suggest that social evaluation can vary force output through the altered engagement of inferior parietal cortex; a region implicated in sensorimotor integration necessary for object manipulation, and a component of the action-observation network which integrates and facilitates performance of observed actions. Social-evaluative situations may induce high-level representational incoherence between one’s own intentioned action and the perceived intention of others which, by uncoupling the dynamics of sensorimotor facilitation, could ultimately perturbe motor output