Limb development, evolution, and regeneration and repair:Part two

International audienc

A career in sport does not eliminate risk of cardiovascular disease; A systematic review and meta-analysis of the cardiovascular health of field-based athletes

Objectives: To determine the prevalence of cardiovascular disease (CVD) risk factors in current field-based athletes. Design: Meta-analysis. Methods: This review was conducted and reported in accordance with PRISMA and pre-registered with PROSPERO. Articles were retrieved via online database search engines, with no date or language restriction. Studies investigating current field-based athletes (>18years) for CVD risk factors according to the European Society of Cardiology and American Heart Association were screened. Full texts were screened using Covidence and Cochrane criteria. Eligible articles were critically appraised using the AXIS tool. Individual study estimates were assessed by random-effect meta-analyses to examine the overall effect. Results: This study was ascribed a 1b evidence level, according to the Oxford Centre for Evidence-based Medicine. 41 studies were identified, including 5,546 athletes from four sports; American football; soccer; rugby and baseball (mean ages:18-28). Despite participation in sport, increased body mass was associated with increased total cholesterol, low-density lipoprotein, triglycerides, hypertension, systolic blood pressure, and decreased high-density lipoprotein. Linemen had increased prevalence of hypertension compared to non-athletes. Conflicting findings on fasting glucose were prevalent. There were inconsistencies in screening and reporting of CVD risk factors. Sport specific anthropometric demands were associated with elevated prevalence of CVD risk factors, most notably: elevated body mass; dyslipidemia; elevated systolic blood pressure and; glucose Conclusions: There are elevated levels of risk for CVD in some athletes, primarily football players. Lifestyle behaviours associated with elite athleticism, particularly football linemen potentially expose players to greater metabolic and CVD risk, which is not completely offset by sport participation

RNA polymerase II-associated proteins reveal pathways affected in VCP-related amyotrophic lateral sclerosis

Valosin-containing protein (VCP) is a hexameric ATPase associated with diverse cellular activities. Genetic mutations in VCP are associated with several forms of muscular and neuronal degeneration, including amyotrophic lateral sclerosis (ALS). Moreover, VCP mediates UV-induced proteolysis of RNA polymerase II (RNAPII), but little is known about the effects of VCP mutations on the transcriptional machinery. Here, we used silica particle-assisted chromatin enrichment and mass spectrometry to study proteins co-localized with RNAPII in precursor neurons differentiated from VCP-mutant or control induced pluripotent stem cells. Remarkably, we observed diminished RNAPII binding of proteins involved in transcription elongation and mRNA splicing in mutant cells. One of these is SART3, a recycling factor of the splicing machinery, whose knockdown leads to perturbed intron retention in several ALS-associated genes. Additional reduced proteins are RBM45, EIF5A and RNF220, mutations in which are associated with various neurodegenerative disorders and are linked to TDP-43 aggregation. Conversely, we observed increased RNAPII binding of heat shock proteins such as HSPB1. Together, these findings shed light on how transcription and splicing machinery are impaired by VCP mutations, which might contribute to aberrant alternative splicing and proteinopathy in neurodegeneration.journal articl

RNA polymerase II-associated proteins reveal pathways affected in VCP-related amyotrophic lateral sclerosis

Valosin-containing protein (VCP) is a hexameric ATPase associated with diverse cellular activities. Genetic mutations in VCP are associated with several forms of muscular and neuronal degeneration, including amyotrophic lateral sclerosis (ALS). Moreover, VCP mediates UV-induced proteolysis of RNA polymerase II (RNAPII), but little is known about the effects of VCP mutations on the transcriptional machinery. Here, we used silica particle-assisted chromatin enrichment and mass spectrometry to study proteins co-localized with RNAPII in precursor neurons differentiated from VCP-mutant or control induced pluripotent stem cells. Remarkably, we observed diminished RNAPII binding of proteins involved in transcription elongation and mRNA splicing in mutant cells. One of these is SART3, a recycling factor of the splicing machinery, whose knockdown leads to perturbed intron retention in several ALS-associated genes. Additional reduced proteins are RBM45, EIF5A and RNF220, mutations in which are associated with various neurodegenerative disorders and are linked to TDP-43 aggregation. Conversely, we observed increased RNAPII binding of heat shock proteins such as HSPB1. Together, these findings shed light on how transcription and splicing machinery are impaired by VCP mutations, which might contribute to aberrant alternative splicing and proteinopathy in neurodegeneration

The Role of Monitoring Interpretive Rates, Concordance Between Cytotechnologist and Pathologist Interpretations Before Sign-Out, and Turnaround Time in Gynecologic Cytology Quality Assurance Findings From the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference Working Group 1

Context.-The College of American Pathologists (CAP) conducted a national survey of gynecologic cytology quality assurance (QA) practices. Experts in gynecologic cytology were asked to join 5 working groups that studied the survey data on different aspects of QA. Evaluating the survey data and follow-up questions online, together with a review of pertinent literature, the working groups developed a series of preliminary statements on good laboratory practices in cytology QA. These were presented at a consensus conference and electronic voting occurred. Objective.-To evaluate a set of QA monitors in gynecologic cytology. Working group 1 evaluated (1) monitoring interpretive rate categories for Papanicolaou tests (Pap tests), (2) concordance of cytotechnologist and pathologist interpretations before sign-out, and (3) turnaround time for Pap tests. Data Sources.-The statements are based on a survey of gynecologic cytology QA practice patterns and of opinions from working group members and consensus conference attendees. Conclusions.-The outcomes of this process demonstrate the current state of practice patterns in gynecologic cytology QA. Monitoring interpretive rates for all Bethesda System categories is potentially useful, and it is most useful to monitor interpretive rates for cytotechnologists individually and in comparison to the entire laboratory. Laboratories need to determine what level of discrepancy between cytotechnologist and pathologist interpretations of Pap tests is important to track. Laboratories should consider formalizing procedures and policies to adjudicate such discrepant interpretations. Turnaround time should be monitored in gynecologic cytology, but individual laboratories should determine how to measure and use turnaround time internally

Non-specific LTD at parallel fibre - Purkinje cell synapses in cerebellar cortex provides robustness against local spatial noise during pattern recognition

© 2011 Safaryan et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedPoster presented at CNS 2011Peer reviewe

Distinct DNA methylation profiles in subtypes of orofacial cleft

Abstract Background Epigenetic data could help identify risk factors for orofacial clefts, either by revealing a causal role for epigenetic mechanisms in causing clefts or by capturing information about causal genetic or environmental factors. Given the evidence that different subtypes of orofacial cleft have distinct aetiologies, we explored whether children with different cleft subtypes showed distinct epigenetic profiles. Methods In whole-blood samples from 150 children from the Cleft Collective cohort study, we measured DNA methylation at over 450,000 sites on the genome. We then carried out epigenome-wide association studies (EWAS) to test the association between methylation at each site and cleft subtype (cleft lip only (CLO) n = 50; cleft palate only (CPO) n = 50; cleft lip and palate (CLP) n = 50). We also compared methylation in the blood to methylation in the lip or palate tissue using genome-wide data from the same 150 children and conducted an EWAS of CLO compared to CLP in lip tissue. Results We found four genomic regions in blood differentially methylated in CLO compared to CLP, 17 in CPO compared to CLP and 294 in CPO compared to CLO. Several regions mapped to genes that have previously been implicated in the development of orofacial clefts (for example, TBX1, COL11A2, HOXA2, PDGFRA), and over 250 associations were novel. Methylation in blood correlated with that in lip/palate at some regions. There were 14 regions differentially methylated in the lip tissue from children with CLO and CLP, with one region (near KIAA0415) showing up in both the blood and lip EWAS. Conclusions Our finding of distinct methylation profiles in different orofacial cleft (OFC) subtypes represents a promising first step in exploring the potential role of epigenetic modifications in the aetiology of OFCs and/or as clinically useful biomarkers of OFC subtypes

Advanced Processing of Food Waste Based Digestate for Mitigating Nitrogen Losses in a Winter Wheat Crop

The anaerobic digestion of food waste converts waste products into ‘green’ energy. Additionally, the secondary product from this process is a nutrient-rich digestate, which could provide a viable alternative to synthetically-produced fertilisers. However, like fertilisers, digestate applied to agricultural land can be susceptible to both ammonia (NH3) and nitrous oxide (N2O) losses, having negative environmental impacts, and reducing the amount of N available for crop uptake. Our main aim was to assess potential methods for mitigating N losses from digestate applied to a winter wheat crop and subsequent impact on yield. Plot trials were conducted at two UK sites, England (North Wyke-NW) and Wales (Henfaes-HF), to assess NH3 and N2O losses, yield and N offtake following a single band-spread digestate application. Treatments examined were digestate (D), acidified-digestate (AD), digestate with the nitrification inhibitor DMPP (D+NI), AD with DMPP (AD+NI), and a zero-N control (C). Determination of N losses was conducted using wind tunnels for NH3, and static manual and automatic chambers for N2O. The N offtake in both grain and straw was also measured. Ammonium nitrate (NH4NO3) fertiliser N response plots (from 75 to 300 kg N ha−1) were included to compare yields with the organic N source. Cumulative NH3-N losses were 27.6 % from D and D+NI plots and 1.5 % for AD and AD+NI of the total N applied, a significant reduction of 95 % with acidification. Cumulative N2O losses varied between 0.13 and 0.35 % of the total N applied and were reduced by 50 % with the use of DMPP. Grain yields for the digestate treatments were 7.52 – 9.21 and 7.23 – 9.23 t DM ha−1 at HF and NW, respectively. Yields were greater from the plots receiving acidified‐digestate relative to the non-acidified treatments but the differences were not significant. The yields (as a function of the N applied with each treatment) obtained for the digestate treatments ranged between 84.2 % (D+NI) and 103.6 % (D) of the yields produced by the same N rate from an inorganic source at HF. Advanced processing of digestate reduced N losses providing an environmentally sound option for N-management

Policies of personalisation in Norway and England: On the impact of political context

Within Europe the Norwegian and English welfare states represent two different welfare regimes. Due to common demographic challenges of an aging population as well as grassroots pressures, particularly from disabled people, significant changes in the delivery of longterm-care services for older and disabled people have taken place. This article focuses on the change towards personalisation policies encouraging people’s greater choice and control in regard to their care services and uses the case of ‘cash-for-care’, which gives people an allocation of funding to meet their needs, to discuss conditions and implications of personalisation policies within different contexts. Based on a theoretical framework exploring a democratic and a market discourse of personalisation policies the article provides a comparative analysis of the Norwegian and English cash-for-care schemes. While a crucial common change in the public sector’s role towards at arm’s length long-term-care services occurred, significant differences remain: while English residents are given greater choice and control from the beginning of the allocation of cash-for-care they also face more insecure circumstances due to the simultaneously stimulated care provider market. The Norwegian case, however, shows a possibility of increasing choice and control without a large diversity in a care provider market