Old-new ERP effects and remote memories : the late parietal effect is absent as recollection fails whereas the early mid-frontal effect persists as familiarity is retained

Acknowledgments Wael El-Deredy acknowledges the support from CONICYT Basal project FB0008, Chile.The authors would like to thank the two reviewers for their very useful suggestions and comments.Peer reviewedPublisher PD

Debating the use of Arc therapy and Tomotherapy

Debating the use of Arc Therapy and Tomotherapy Strong evidence base in support of these treatments. Advantages outweigh current standard practice. Widely accepted across the world. Progression is necessary

High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale

Chromosome conformation capture (3C) provides an adaptable tool for studying diverse biological questions. Current 3C methods generally provide either low-resolution interaction profiles across the entire genome, or high-resolution interaction profiles at limited numbers of loci. Due to technical limitations, generation of reproducible high-resolution interaction profiles has not been achieved at genome-wide scale. Here, to overcome this barrier, we systematically test each step of 3C and report two improvements over current methods. We show that up to 30% of reporter events generated using the popular in situ 3C method arise from ligations between two individual nuclei, but this noise can be almost entirely eliminated by isolating intact nuclei after ligation. Using Nuclear-Titrated Capture-C, we generate reproducible high-resolution genome-wide 3C interaction profiles by targeting 8055 gene promoters in erythroid cells. By pairing high-resolution 3C interaction calls with nascent gene expression we interrogate the role of promoter hubs and super-enhancers in gene regulation

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

Transcriptome Analysis of Arabidopsis Wild-Type and gl3–sst sim Trichomes Identifies Four Additional Genes Required for Trichome Development

Transcriptome analyses have been performed on mature trichomes isolated from wild-type Arabidopsis leaves and on leaf trichomes isolated from the gl3–sst sim double mutant, which exhibit many attributes of immature trichomes. The mature trichome profile contained many highly expressed genes involved in cell wall synthesis, protein turnover, and abiotic stress response. The most highly expressed genes in the gl3–sst sim profile encoded ribosomal proteins and other proteins involved in translation. Comparative analyses showed that all but one of the genes encoding transcription factors previously found to be important for trichome formation, and many other trichome-important genes, were preferentially expressed in gl3–sst sim trichomes. The analysis of genes preferentially expressed in gl3–sst sim led to the identification of four additional genes required for normal trichome development. One of these was the HDG2 gene, which is a member of the HD–ZIP IV transcription factor gene family. Mutations in this gene did not alter trichome expansion, but did alter mature trichome cell walls. Mutations in BLT resulted in a loss of trichome branch formation. The relationship between blt and the phenotypically identical mutant, sti, was explored. Mutations in PEL3, which was previously shown to be required for development of the leaf cuticle, resulted in the occasional tangling of expanding trichomes. Mutations in another gene encoding a protein with an unknown function altered trichome branch formation

Real-time and non-invasive measurements of cell mechanical behaviour with optical coherence phase microscopy

There is an unmet need in tissue engineering for non-invasive, label-free monitoring of cell mechanical behaviour in their physiological environment. Here, we describe a novel optical coherence phase microscopy (OCPM) set-up which can map relative cell mechanical behaviour in monolayers and 3D systems non-invasively, and in real-time. 3T3 and MCF-7 cells were investigated, with MCF-7 demonstrating an increased response to hydrostatic stimulus indicating MCF-7 being softer than 3T3, demonstrating the ability to provide qualitative data on cell mechanical behaviour. Quantitative measurements of 6% agarose beads have been taken with commercial Cell Scale Microsquisher® system demonstrating that their mechanical properties are in the same order of magnitude of cells, indicating that this is an appropriate test sample for the novel method desctibed

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Isotopic composition of carbon and nitrogen in ureilitic fragments of the Almahata Sitta meteorite

This study characterizes carbon and nitrogen abundances and isotopic compositions in ureilitic fragments of Almahata Sitta. Ureilites are carbon-rich (containing up to 7 wt% C) and were formed early in solar system history, thus the origin of carbon in ureilites has significance for the origin of solar system carbon. These samples were collected soon after they fell, so they are among the freshest ureilite samples available and were analyzed using stepped combustion mass spectrometry. They contained 1.2–2.3 wt% carbon; most showed the major carbon release at temperatures of 600–700 °C with peak values of δ13C from −7.3 to +0.4‰, similar to literature values for unbrecciated (“monomict”) ureilites. They also contained a minor low temperature (≤500 °C) component (δ13C = ca −25‰). Bulk nitrogen contents (9.4–27 ppm) resemble those of unbrecciated ureilites, with major releases mostly occurring at 600–750 °C. A significant lower temperature release of nitrogen occurred in all samples. Main release δ15N values of −53 to −94‰ fall within the range reported for diamond separates and acid residues from ureilites, and identify an isotopically primordial nitrogen component. However, they differ from common polymict ureilites which are more nitrogen-rich and isotopically heavier. Thus, although the parent asteroid 2008TC3 was undoubtedly a polymict ureilite breccia, this cannot be deduced from an isotopic study of individual ureilite fragments. The combined main release δ13C and δ15N values do not overlap the fields for carbonaceous or enstatite chondrites, suggesting that carbon in ureilites was not derived from these sources

Endogenous overexpression of Populus MYB186 increases trichome density, improves insect pest resistance, and impacts plant growth

Trichomes are specialized epidermal cells that generally play a role in reducing transpiration and act as a deterrent to herbivory. In a screen of activation-tagged Populus tremula  ×  Populus alba 717-1B4 trees, we identified a mutant line, fuzzy , with increased foliar trichome density. This mutant also had a 35% increase in growth rate and a 200% increase in the rate of photosynthesis as compared with wild-type poplar. The fuzzy mutant had significant resistance to feeding by larvae of the white-spotted tussock moth ( Orgyia leucostigma ), a generalist insect pest of poplar trees. The fuzzy trichome phenotype is attributable to activation tagging and increased expression of the gene encoding PtaMYB186 , which is related to Arabidopsis thaliana MYB106 , a known regulator of trichome initiation. The fuzzy phenotype can be recapitulated by overexpressing PtaMYB186 in poplar. PtaMYB186 overexpression results in reconfiguration of the poplar transcriptome, with changes in the transcript abundance of suites of genes that are related to trichome differentiation. It is notable that a plant with misexpression of a gene responsible for trichome development also had altered traits related to growth rate and pest resistance, suggesting that non-intuitive facets of plant development might be useful targets for plant improvement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79232/1/TPJ_4343_sm_FigsS1-S3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/79232/2/j.1365-313X.2010.04343.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/79232/3/TPJ_4343_sm_TableS5.pd