The CLEAR (Considering Leading Experts’ Antithrombotic Regimes around peripheral angioplasty) survey:an international perspective on antiplatelet and anticoagulant practice for peripheral arterial endovascular intervention

BACKGROUND: Antiplatelet and anticoagulant therapy are commonly used before, during and after peripheral arterial endovascular intervention. This survey aimed to establish antiplatelet and anticoagulant choice for peripheral arterial endovascular intervention in contemporary clinical practice. METHODS: Pilot-tested questionnaire distributed via collaborative research networks. RESULTS: One hundred and sixty-two complete responses were collected from responders in 22 countries, predominantly the UK (48%) and the rest of the European Union (44%). Antiplatelet monotherapy was the most common choice pre-procedurally (62%). In the UK, there was no difference between dual and single antiplatelet therapy use post procedure (50% vs. 37% p = 0.107). However, a significant majority of EU respondents used dual therapy (68% vs. 20% p < 0.001). There was variation in choice of antiplatelet therapy by the device used and the anatomical location of the intervention artery. The majority (82%) of respondents believed there was insufficient evidence to guide antithrombotic therapy after peripheral endovascular intervention and most (92%) would support a randomised trial. CONCLUSIONS: There is widespread variation in the use of antiplatelet therapy, especially post peripheral arterial endovascular intervention. Clinicians would support the development of a randomised trial comparing dual antiplatelet therapy with monotherapy

Remodelers organize cellular chromatin by counteracting intrinsic histone-DNA sequence preferences in a class-specific manner

The nucleosome is the fundamental repeating unit of eukaryotic chromatin. Here, we assessed the interplay between DNA sequence and ATP-dependent chromatin-remodeling factors (remodelers) in the nucleosomal organization of a eukaryotic genome. We compared the genome-wide distribution of Drosophila NURD, (P)BAP, INO80, and ISWI, representing the four major remodeler families. Each remodeler has a unique set of genomic targets and generates distinct chromatin signatures. Remodeler loci have characteristic DNA sequence features, predicted to influence nucleosome formation. Strikingly, remodelers counteract DNA sequence-driven nucleosome distribution in two distinct ways. NURD, (P)BAP, and INO80 increase histone density at their target sequences, which intrinsically disfavor positioned nucleosome formation. In contrast, ISWI promotes open chromatin at sites that are propitious for precise nucleosome placement. Remodelers influe

Evaluating changes in marine communities that provide ecosystem services through comparative assessments of community indicators

Fisheries provide critical provisioning services, especially given increasing human population. Understanding where marine communities are declining provides an indication of ecosystems of concern and highlights potential conflicts between seafood provisioning from wild fisheries and other ecosystem services. Here we use the nonparametric statistic, Kendall's tau, to assess trends in biomass of exploited marine species across a range of ecosystems. The proportion of 'Non-Declining Exploited Species' (NDES) is compared among ecosystems and to three community-level indicators that provide a gauge of the ability of a marine ecosystem to function both in provisioning and as a regulating service: survey-based mean trophic level, proportion of predatory fish, and mean life span. In some ecosystems, NDES corresponds to states and temporal trajectories of the community indicators, indicating deteriorating conditions in both the exploited community and in the overall community. However differences illustrate the necessity of using multiple ecological indicators to reflect the state of the ecosystem. For each ecosystem, we discuss patterns in NDES with respect to the community-level indicators and present results in the context of ecosystem-specific drivers. We conclude that using NDES requires context-specific supporting information in order to provide guidance within a management framework

Ecological indicators to capture the effects of fishing on biodiversity and conservation status of marine ecosystems

IndiSeas ("Indicators for the Seas") is a collaborative international working group that was established in 2005 to evaluate the status of exploited marine ecosystems using a suite of indicators in a comparative framework. An initial shortlist of seven ecological indicators was selected to quantify the effects of fishing on the broader ecosystem using several criteria (i.e., ecological meaning, sensitivity to fishing, data availability, management objectives and public awareness). The suite comprised: (i) the inverse coefficient of variation of total biomass of surveyed species, (ii) mean fish length in the surveyed community, (iii) mean maximum life span of surveyed fish species, (iv) proportion of predatory fish in the surveyed community, (v) proportion of under and moderately exploited stocks, (vi) total biomass of surveyed species, and (vii) mean trophic level of the landed catch. In line with the Nagoya Strategic Plan of the Convention on Biological Diversity (2011-2020), we extended this suite to emphasize the broader biodiversity and conservation risks in exploited marine ecosystems. We selected a subset of indicators from a list of empirically based candidate biodiversity indicators initially established based on ecological significance to complement the original IndiSeas indicators. The additional selected indicators were: (viii) mean intrinsic vulnerability index of the fish landed catch, (ix) proportion of non-declining exploited species in the surveyed community, (x) catch-based marine trophic index, and (xi) mean trophic level of the surveyed community. Despite the lack of data in some ecosystems, we also selected (xii) mean trophic level of the modelled community, and (xiii) proportion of discards in the fishery as extra indicators. These additional indicators were examined, along with the initial set of IndiSeas ecological indicators, to evaluate whether adding new biodiversity indicators provided useful additional information to refine our understanding of the status evaluation of 29 exploited marine ecosystems. We used state and trend analyses, and we performed correlation, redundancy and multivariate tests. Existing developments in ecosystem-based fisheries management have largely focused on exploited species. Our study, using mostly fisheries independent survey-based indicators, highlights that biodiversity and conservation-based indicators are complementary to ecological indicators of fishing pressure. Thus, they should be used to provide additional information to evaluate the overall impact of fishing on exploited marine ecosystems

Yeast Genes Controlling Responses to Topogenic Signals in a Model Transmembrane Protein

Yeast protein insertion orientation (PIO) mutants were isolated by selecting for growth on sucrose in cells in which the only source of invertase is a C-terminal fusion to a transmembrane protein. Only the fraction with an exocellular C terminus can be processed to secreted invertase and this fraction is constrained to 2–3% by a strong charge difference signal. Identified pio mutants increased this to 9–12%. PIO1 is SPF1, encoding a P-type ATPase located in the endoplasmic reticulum (ER) or Golgi. spf1-null mutants are modestly sensitive to EGTA. Sensitivity is considerably greater in an spf1 pmr1 double mutant, although PIO is not further disturbed. Pmr1p is the Golgi Ca(2+) ATPase and Spf1p may be the equivalent ER pump. PIO2 is STE24, a metalloprotease anchored in the ER membrane. Like Spf1p, Ste24p is expressed in all yeast cell types and belongs to a highly conserved protein family. The effects of ste24- and spf1-null mutations on invertase secretion are additive, cell generation time is increased 60%, and cells become sensitive to cold and to heat shock. Ste24p and Rce1p cleave the C-AAX bond of farnesylated CAAX box proteins. The closest paralog of SPF1 is YOR291w. Neither rce1-null nor yor291w-null mutations affected PIO or the phenotype of spf1- or ste24-null mutants. Mutations in PIO3 (unidentified) cause a weaker Pio phenotype, enhanced by a null mutation in BMH1, one of two yeast 14-3-3 proteins