A cancer-associated, genome protective programme engaging PKCε.

Associated with their roles as targets for tumour promoters, there has been a long-standing interest in how members of the protein kinase C (PKC) family act to modulate cell growth and division. This has generated a great deal of observational data, but has for the most part not afforded clear mechanistic insights into the control mechanisms at play. Here, we review the roles of PKCε in protecting transformed cells from non-disjunction. In this particular cell cycle context, there is a growing understanding of the pathways involved, affording biomarker and interventional insights and opportunities

Consensus clustering in complex networks

The community structure of complex networks reveals both their organization and hidden relationships among their constituents. Most community detection methods currently available are not deterministic, and their results typically depend on the specific random seeds, initial conditions and tie-break rules adopted for their execution. Consensus clustering is used in data analysis to generate stable results out of a set of partitions delivered by stochastic methods. Here we show that consensus clustering can be combined with any existing method in a self-consistent way, enhancing considerably both the stability and the accuracy of the resulting partitions. This framework is also particularly suitable to monitor the evolution of community structure in temporal networks. An application of consensus clustering to a large citation network of physics papers demonstrates its capability to keep track of the birth, death and diversification of topics.Comment: 11 pages, 12 figures. Published in Scientific Report

A review of assessment methods for river hydromorphology

The work leading to this paper has received funding for the EU’s FP7 under Grant Agreement No. 282656 (REFORM

Guidelines for the use and interpretation of assays for monitoring autophagy (2nd edition)

In 2008 we published the first set of guidelines for standardiz- ing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new tech- nologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in differ- ent organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes..

A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog–Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog–Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2–Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal

Association between Type 2 Diabetes Loci and Measures of Fatness

Background: Type 2 diabetes (T2D) is a metabolic disorder characterized by disturbances of carbohydrate, fat and protein metabolism and insulin resistance. The majority of T2D patients are obese and obesity by itself may be a cause of insulin resistance. Our aim was to evaluate whether the recently identified T2D risk alleles are associated with human measures of fatness as characterized with Dual Energy X-ray Absorptiometry (DEXA). Methodology/Principal Findings: Genotypes and phenotypes of approximately 3,000 participants from cross-sectional ERF study were analyzed. Nine single nucleotide polymorphisms (SNPs) in CDKN2AB, CDKAL1, FTO, HHEX, IGF2BP2, KCNJ11, PPARG, SLC30A8 and TCF7L2 were genotyped. We used linear regression to study association between individual SNPs and the combined allelic risk score with body mass index (BMI), fat mass index (FMI), fat percentage (FAT), waist circumference (WC) and waist to hip ratio (WHR). Significant association was observed between rs8050136 (FTO) and BMI (p = 0.003), FMI (p = 0.007) and WC (p = 0.03); fat percentage was borderline significant (p = 0.053). No other SNPs alone or combined in a risk score demonstrated significant association to the measures of fatness. Conclusions/Significance: From the recently identified T2D risk variants only the risk variant of the FTO gene (rs8050136) showed statistically significant association with BMI, FMI, and WC

EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling

EROS (essential for reactive oxygen species) protein is indispensable for expression of gp91phox, the catalytic core of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of the severe immunodeficiency, chronic granulomatous disease, but its mechanism of action was unknown until now. We elucidate the role of EROS, showing it acts at the earliest stages of gp91phox maturation. It binds the immature 58 kDa gp91phox directly, preventing gp91phox degradation and allowing glycosylation via the oligosaccharyltransferase machinery and the incorporation of the heme prosthetic groups essential for catalysis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions, and P2X7 is almost absent in EROS-deficient mouse and human primary cells. Accordingly, lack of murine EROS results in markedly abnormal P2X7 signalling, inflammasome activation, and T cell responses. The loss of both ROS and P2X7 signalling leads to resistance to influenza infection in mice. Our work identifies EROS as a highly selective chaperone for key proteins in innate and adaptive immunity and a rheostat for immunity to infection. It has profound implications for our understanding of immune physiology, ROS dysregulation, and possibly gene therapy.</jats:p

Are Females More Responsive to Emotional Stimuli? A Neurophysiological Study Across Arousal and Valence Dimensions

Men and women seem to process emotions and react to them differently. Yet, few neurophysiological studies have systematically investigated gender differences in emotional processing. Here, we studied gender differences using Event Related Potentials (ERPs) and Skin Conductance Responses (SCR) recorded from participants who passively viewed emotional pictures selected from the International Affective Picture System (IAPS). The arousal and valence dimension of the stimuli were manipulated orthogonally. The peak amplitude and peak latency of ERP components and SCR were analyzed separately, and the scalp topographies of significant ERP differences were documented. Females responded with enhanced negative components (N100 and N200), in comparison to males, especially to the unpleasant visual stimuli, whereas both genders responded faster to high arousing or unpleasant stimuli. Scalp topographies revealed more pronounced gender differences on central and left hemisphere areas. Our results suggest a difference in the way emotional stimuli are processed by genders: unpleasant and high arousing stimuli evoke greater ERP amplitudes in women relatively to men. It also seems that unpleasant or high arousing stimuli are temporally prioritized during visual processing by both genders

New insights into the neolithisation process in southwest Europe according to spatial density analysis from calibrated radiocarbon dates

The agricultural way of life spreads throughout Europe via two main routes: the Danube corridor and the Mediterranean basin. Current archaeological literature describes the arrival to the Western Mediterranean as a rapid process which involves both demic and cultural models, and in this regard, the dispersal movement has been investigated using mathematical models, where the key factors are time and space. In this work, we have created a compilation of all available radiocarbon dates for the whole of Iberia, in order to draw a chronological series of maps to illustrate temporal and spatial patterns in the neolithisation process. The maps were prepared by calculating the calibrated 14C date probability density curves, as a proxy to show the spatial dynamics of the last hunter-gatherers and first farmers. Several scholars have pointed out problems linked with the variability of samples, such as the overrepresentation of some sites, the degree of regional research, the nature of the dated samples and above all the archaeological context, but we are confident that the selected dates, after applying some filters and statistical protocols, constitute a good way to approach settlement spatial patterns in Iberia at the time of the neolithisation process