The perilous state of seagrass in the British Isles

Seagrass ecosystems face widespread threat from reduced water quality, coastal development and poor land use. In recent decades, their distribution has declined rapidly, and in the British Isles, this loss is thought to have been extensive. Given increasing knowledge of how these ecosystems support fisheries production, the understanding of their potential rapid loss, and the difficulty in restoring them, it is vital we develop an understanding of the risks they are under, so that management actions can be developed accordingly. Developing an understanding of their environmental status and condition is therefore critical to their long-term management. This study provided, to our knowledge, the first examination of the environmental health of seagrass meadows around the British Isles. This study used a bioindicator approach and involved collecting data on seagrass density and morphology alongside analysis of leaf biochemistry. Our study provides, to the best of our knowledge, the first strong quantitative evidence that seagrass meadows of the British Isles are mostly in poor condition in comparison with global averages, with tissue nitrogen levels 75% higher than global values. Such poor status places their long-term resilience in doubt. Elemental nutrient concentrations and morphological change suggest conditions of excess nitrogen and probable low light, placing many of the meadows sampled in a perilous state, although others, situated away from human populations were perceived to be healthy. Although some sites were of a high environmental health, all sites were considered at risk from anthropogenic impacts, particularly poor water quality and boating-based disturbances. The findings of this study provide a warning of the need to take action, with respect to water quality and disturbance, to prevent the further loss and degradation of these systems across the British Isles

Implementation of electroweak corrections in the POWHEG BOX: single W production

We present a fully consistent implementation of electroweak and strong radiative corrections to single W hadroproduction in the POWHEG BOX framework, treating soft and collinear photon emissions on the same ground as coloured parton emissions. This framework can be easily extended to more complex electroweak processes. We describe how next-to-leading order (NLO) electroweak corrections are combined with the NLO QCD calculation, and show how they are interfaced to QCD and QED shower Monte Carlo. The resulting tool fills a gap in the literature and allows to study comprehensively the interplay of QCD and electroweak effects to W production using a single computational framework. Numerical comparisons with the predictions of the electroweak generator HORACE, as well as with existing results on the combination of electroweak and QCD corrections to W production, are shown for the LHC energies, to validate the reliability and accuracy of the approachComment: 31 pages, 7 figures. Minor corrections, references added and updated. Final version to appear in JHE

Colored Resonant Signals at the LHC: Largest Rate and Simplest Topology

We study the colored resonance production at the LHC in a most general approach. We classify the possible colored resonances based on group theory decomposition, and construct their effective interactions with light partons. The production cross section from annihilation of valence quarks or gluons may be on the order of 400 - 1000 pb at LHC energies for a mass of 1 TeV with nominal couplings, leading to the largest production rates for new physics at the TeV scale, and simplest event topology with dijet final states. We apply the new dijet data from the LHC experiments to put bounds on various possible colored resonant states. The current bounds range from 0.9 to 2.7 TeV. The formulation is readily applicable for future searches including other decay modes.Comment: 29 pages, 9 figures. References updated and additional K-factors include

A systematic review of strategies to recruit and retain primary care doctors

Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

Functionally Orthologous Viral and Cellular MicroRNAs Studied by a Novel Dual-Fluorescent Reporter System

Recent research raised the possibility that some viral microRNAs (miRNAs) may function as orthologs of cellular miRNAs. In the present work, to study the functional orthologous relationships of viral and cellular miRNAs, we first constructed a dual-fluorescent protein reporter vector system for the easy determination of miRNA function. By expressing the miRNAs and the indicator and internal control fluorescent proteins individually from a single vector, this simple reporter system can be used for miRNA functional assays that include visualizing miRNA activity in live cells. Sequence alignments indicated that the simian virus 40 (SV40) encoded miRNA sv40-mir-S1-5p contains a seed region identical to that of the human miRNA hsa-miR423-5p. Using the new reporter system, it was found that sv40-mir-S1-5p and hsa-miR423-5p downregulate the expression of common artificial target mRNAs and some predicted biological targets of hsa-miR423-5p, demonstrating that they are functional orthologs. The human immunodeficiency virus 1 (HIV-1) encoded hiv1-miR-N367 also contains a seed sequence identical to that of the human miRNA hsa-miR192. Functional assays showed that hiv1-miR-N367 and hsa-miR192 could downregulate common artificial and predicted biological targets, suggesting that these miRNAs may also act as functional orthologs. Thus, this study presents a simple and universal system for testing miRNA function and identifies two new pairs of functional orthologs, sv40-mir-S1-5p and hsa-miR423-5p as well as hiv-1-miR-N367 and hsa-miR192. These findings also expand upon our current knowledge of functional homology and imply that a more general phenomenon of orthologous relationships exists between viral and cellular miRNAs

Synchronized turbo apoptosis induced by cold-shock

In our research on the role of apoptosis in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE), we aim to evaluate the effects of early and late apoptotic cells and blebs on antigen presenting cells. This requires the in vitro generation of sufficiently large and homogeneous populations of early and late apoptotic cells. Here, we present a quick method encountered by serendipity that results in highly reproducible synchronized homogeneous apoptotic cell populations. In brief, granulocytic 32Dcl3 cells are incubated on ice for 2 h and subsequently rewarmed at 37°C. After 30–90 min at 37°C more than 80–90% of the cells become early apoptotic (Annexin V positive/propidium iodide negative). After 24 h of rewarming at 37°C 98% of the cells were late apoptotic (secondary necrotic; Annexin V positive/propidium iodide positive). Cells already formed apoptotic blebs at their cell surface after approximately 20 min at 37°C. Inter-nucleosomal chromatin cleavage and caspase activation were other characteristics of this cold-shock-induced process of apoptosis. Consequently, apoptosis could be inhibited by a caspase inhibitor. Finally, SLE-derived anti-chromatin autoantibodies showed a high affinity for apoptotic blebs generated by cold-shock. Overall, cold-shock induced apoptosis is achieved without the addition of toxic compounds or antibodies, and quickly leads to synchronized homogeneous apoptotic cell populations, which can be applied for various research questions addressing apoptosis

Identification of Combinatorial Patterns of Post-Translational Modifications on Individual Histones in the Mouse Brain

Post-translational modifications (PTMs) of proteins are biochemical processes required for cellular functions and signalling that occur in every sub-cellular compartment. Multiple protein PTMs exist, and are established by specific enzymes that can act in basal conditions and upon cellular activity. In the nucleus, histone proteins are subjected to numerous PTMs that together form a histone code that contributes to regulate transcriptional activity and gene expression. Despite their importance however, histone PTMs have remained poorly characterised in most tissues, in particular the brain where they are thought to be required for complex functions such as learning and memory formation. Here, we report the comprehensive identification of histone PTMs, of their combinatorial patterns, and of the rules that govern these patterns in the adult mouse brain. Based on liquid chromatography, electron transfer, and collision-induced dissociation mass spectrometry, we generated a dataset containing a total of 10,646 peptides from H1, H2A, H2B, H3, H4, and variants in the adult brain. 1475 of these peptides carried one or more PTMs, including 141 unique sites and a total of 58 novel sites not described before. We observed that these PTMs are not only classical modifications such as serine/threonine (Ser/Thr) phosphorylation, lysine (Lys) acetylation, and Lys/arginine (Arg) methylation, but also include several atypical modifications such as Ser/Thr acetylation, and Lys butyrylation, crotonylation, and propionylation. Using synthetic peptides, we validated the presence of these atypical novel PTMs in the mouse brain. The application of data-mining algorithms further revealed that histone PTMs occur in specific combinations with different ratios. Overall, the present data newly identify a specific histone code in the mouse brain and reveal its level of complexity, suggesting its potential relevance for higher-order brain functions