A screen for RNA-binding proteins in yeast indicates dual functions for many enzymes.

Hundreds of RNA-binding proteins (RBPs) control diverse aspects of post-transcriptional gene regulation. To identify novel and unconventional RBPs, we probed high-density protein microarrays with fluorescently labeled RNA and selected 200 proteins that reproducibly interacted with different types of RNA from budding yeast Saccharomyces cerevisiae. Surprisingly, more than half of these proteins represent previously known enzymes, many of them acting in metabolism, providing opportunities to directly connect intermediary metabolism with posttranscriptional gene regulation. We mapped the RNA targets for 13 proteins identified in this screen and found that they were associated with distinct groups of mRNAs, some of them coding for functionally related proteins. We also found that overexpression of the enzyme Map1 negatively affects the expression of experimentally defined mRNA targets. Our results suggest that many proteins may associate with mRNAs and possibly control their fates, providing dense connections between different layers of cellular regulation

Euro-Atlantic weather regimes in the PRIMAVERA coupled climate simulations: impact of resolution and mean state biases on model performance

Recently, much attention has been devoted to better understand the internal modes of variability of the climate system. This is particularly important in mid-latitude regions like the North-Atlantic, which is characterized by a large natural variability and is intrinsically difficult to predict. A suitable framework for studying the modes of variability of the atmospheric circulation is to look for recurrent patterns, commonly referred to as Weather Regimes. Each regime is characterized by a specific large-scale atmospheric circulation pattern, thus influencing regional weather and extremes over Europe. The focus of the present paper is the study of the Euro-Atlantic wintertime Weather Regimes in the climate models participating to the PRIMAVERA project. We analyse here the set of coupled historical simulations (hist-1950), which have been performed both at standard and increased resolution, following the HighresMIP protocol. The models’ performance in reproducing the observed Weather Regimes is assessed in terms of different metrics, focussing on systematic biases and on the impact of resolution. We also analyse the connection of the Weather Regimes with the Jet Stream latitude and blocking frequency over the North-Atlantic sector. We find that—for most models—the regime patterns are better represented in the higher resolution version, for all regimes but the NAO-. On the other side, no clear impact of resolution is seen on the regime frequency of occurrence and persistence. Also, for most models, the regimes tend to be more tightly clustered in the increased resolution simulations, more closely resembling the observed ones. However, the horizontal resolution is not the only factor determining the model performance, and we find some evidence that biases in the SSTs and mean geopotential field might also play a role

Reviewing the integration of patient data: how systems are evolving in practice to meet patient needs

<p>Abstract</p> <p>Background</p> <p>The integration of Information Systems (IS) is essential to support shared care and to provide consistent care to individuals – patient-centred care. This paper identifies, appraises and summarises studies examining different approaches to integrate patient data from heterogeneous IS.</p> <p>Methods</p> <p>The literature was systematically reviewed between 1995–2005 to identify articles mentioning patient records, computers and data integration or sharing.</p> <p>Results</p> <p>Of 3124 articles, 84 were included describing 56 distinct projects. Most of the projects were on a regional scale. Integration was most commonly accomplished by messaging with pre-defined templates and middleware solutions. HL7 was the most widely used messaging standard. Direct database access and web services were the most common communication methods. The user interface for most systems was a Web browser. Regarding the type of medical data shared, 77% of projects integrated diagnosis and problems, 67% medical images and 65% lab results. More recently significantly more IS are extending to primary care and integrating referral letters.</p> <p>Conclusion</p> <p>It is clear that Information Systems are evolving to meet people's needs by implementing regional networks, allowing patient access and integration of ever more items of patient data. Many distinct technological solutions coexist to integrate patient data, using differing standards and data architectures which may difficult further interoperability.</p

Mer receptor tyrosine kinase mediates both tethering and phagocytosis of apoptotic cells

Billions of inflammatory leukocytes die and are phagocytically cleared each day. This regular renewal facilitates the normal termination of inflammatory responses, suppressing pro-inflammatory mediators and inducing their anti-inflammatory counterparts. Here we investigate the role of the receptor tyrosine kinase (RTK) Mer and its ligands Protein S and Gas6 in the initial recognition and capture of apoptotic cells (ACs) by macrophages. We demonstrate extremely rapid binding kinetics of both ligands to phosphatidylserine (PtdSer)-displaying ACs, and show that ACs can be co-opsonized with multiple PtdSer opsonins. We further show that macrophage phagocytosis of ACs opsonized with Mer ligands can occur independently of a requirement for αV integrins. Finally, we demonstrate a novel role for Mer in the tethering of ACs to the macrophage surface, and show that Mer-mediated tethering and subsequent AC engulfment can be distinguished by their requirement for Mer kinase activity. Our results identify Mer as a receptor uniquely capable of both tethering ACs to the macrophage surface and driving their subsequent internalization

Anthropogenic intensification of short-duration rainfall extremes

Short- duration (1-3 h) rainfall extremes can cause serious damage to societies through rapidly developing (flash) flooding and are determined by complex, multifaceted processes that are altering as Earth's climate warms. In this Review, we examine evidence from observational, theoretical and modelling studies for the intensification of these rainfall extremes, the drivers and the impact on flash flooding. Both short- duration and long- duration (\textgreater1 day) rainfall extremes are intensifying with warming at a rate consistent with the increase in atmospheric moisture (~7% K-1), while in some regions, increases in short- duration extreme rainfall intensities are stronger than expected from moisture increases alone. These stronger local increases are related to feedbacks in convective clouds, but their exact role is uncertain because of the very small scales involved. Future extreme rainfall intensification is also modulated by changes to temperature stratification and large- scale atmospheric circulation. The latter remains a major source of uncertainty. Intensification of short- duration extremes has likely increased the incidence of flash flooding at local scales and this can further compound with an increase in storm spatial footprint to considerably increase total event rainfall. These findings call for urgent climate change adaptation measures to manage increasing flood risks

Beyond equilibrium climate sensitivity

ISSN:1752-0908ISSN:1752-089

Interplay between posttranscriptional and posttranslational interactions of RNA-binding proteins

RNA-bindingproteins (RBPs) play important roles in the posttranscriptional control of gene expression. However, our understanding of how RBPs interact with each other at different regulatory levels to coordinate the RNA metabolism of the cell is rather limited. Here, we construct the posttranscriptional regulatory network among 69 experimentally studied RBPs in yeast to show that more than one-third of the RBPs autoregulate their expression at the posttranscriptional level and demonstrate that autoregulatory RBPs show reduced protein noise with a tendency to encode for hubs in this network. We note that in- and outdegrees in the posttranscriptional RBP–RBP regulatory network exhibit gaussian and scale-free distributions, respectively. This network was also densely interconnected with extensive cross-talk between RBPs belonging to different posttranscriptional steps, regulating varying numbers of cellular RNA targets. We show that feed-forward loops and superposed feed-forward/feedback loops are the most significant three-node subgraphs in this network. Analysis of the corresponding protein–proteininteraction (posttranslational) network revealed that it is more modular than the posttranscriptional regulatory network. There is significant overlap between the regulatory and protein–proteininteraction networks, with RBPs that potentially control each other at the posttranscriptional level tending to physically interact and being part of the same ribonucleoprotein (RNP) complex. Our observations put forward a model wherein RBPs could be classified into those that can stably interact with a limited number of protein partners, forming stable RNP complexes, and others that form transient hubs, having the ability to interact with multiple RBPs forming many RNPs in the cell

Genome-wide association studies of hypertension: have they been fruitful?

Over the last two decades candidate gene association studies and genome-wide linkage scans have met with little success in characterizing risk variants for hypertension. Several factors could be responsible for the relative lack of success, although our understanding of the genetics has evolved to support the belief that there are multiple common risk variants, which are associated with hypertension with modest effect sizes. Genome-wide association studies (GWAS) have successfully identified risk loci for several complex polygenic disease states. Until recently, the productivity of GWAS with respect to identifying risk loci for hypertension was limited. In this paper we describe the recent success of GWAS of hypertension in identifying over a dozen loci associated with essential hypertension. We will review these findings, and place these results in the context of the future potential of pharmocogenetics of hypertension