Effect of concrete slats, three mat types and out-wintering pads on performance and welfare of finishing beef steers

peer-reviewedBackground The objective was to investigate the effect of placing mats on concrete slatted floors on performance, behaviour, hoof condition, dirt scores, physiological and immunological variables of beef steers, and to compare responses with animals on out-wintering pads. Continental crossbred beef steers [n = 360; mean (±SD) initial live weight 539 kg (42.2)] were blocked by breed and live weight and randomly assigned to one of five treatments; (1) Concrete slats alone, (2) Mat 1 (Natural Rubber structure) (Durapak Rubber Products), (3) Mat 2 (Natural rubber structure) (EasyFix), (4) Mat 3 (modified ethylene vinyl acetate (EVA) foam structure) and (5) Out-wintering pads (OWP’s). Results Animals on the OWPs had a greater (P  0.05) as the other treatments. Animals on the OWPs had reduced lying percentage time compared with all the other treatments. Dry matter (DM) intake was greater for animals on the OWPs compared with all the other treatments. Carcass weight, kill out proportion, carcass fat score, carcass composition score, FCR and physiological responses were similar (P > 0.05) among treatments. No incidence of laminitis was observed among treatments. The number of hoof lesions was greater on all mat types (P < 0.05) compared with concrete slats and OWP treatments. Dirt scores were greater (P < 0.05) for animals on OWPs when measured on days 42, 84, 105, 126 and 150 compared with animals on slats. Conclusions Under the conditions adopted for the present study, there was no evidence to suggest that animals housed on bare concrete slats were disadvantaged in respect of animal welfare compared with animals housed on other floor types. It is concluded that the welfare of steers was not adversely affected by slats compared with different mat types or OWPs

Is primary care a neglected piece of the jigsaw in ensuring optimal stroke care? Results of a national study

<p>Abstract</p> <p>Background</p> <p>Stroke is a major cause of mortality and morbidity with potential for improved care and prevention through general practice. A national survey was undertaken to determine current resources and needs for optimal stroke prevention and care.</p> <p>Methods</p> <p>Postal survey of random sample of general practitioners undertaken (N = 204; 46% response). Topics included practice organisation, primary prevention, acute management, secondary prevention, long-term care and rehabilitation.</p> <p>Results</p> <p>Service organisation for both primary and secondary prevention was poor. Home management of acute stroke patients was used at some stage by 50% of responders, accounting for 7.3% of all stroke patients. Being in a structured cardiovascular management scheme, a training practice, a larger practice, or a practice employing a practice nurse were associated with structures and processes likely to support stroke prevention and care.</p> <p>Conclusion</p> <p>General practices were not fulfilling their potential to provide stroke prevention and long-term management. Systems of structured stroke management in general practice are essential to comprehensive national programmes of stroke care.</p

Critical Roles for LIGHT and Its Receptors in Generating T Cell-Mediated Immunity during Leishmania donovani Infection

LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTβR). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNγ- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTβR interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4+ T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Enhancing GTEx by bridging the gaps between genotype, gene expression, and disease

Academi

Dynamic landscape and regulation of RNA editing in mammals

Adenosine-to-inosine (A-to-I) RNA editing is a conserved post-transcriptional mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering selected nucleotides in RNA molecules1. Although many editing sites have recently been discovered2,3,4,5,6,7, the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood8,9,10. Here we report dynamic spatiotemporal patterns and new regulators of RNA editing, discovered through an extensive profiling of A-to-I RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples. We show that editing levels in non-repetitive coding regions vary more between tissues than editing levels in repetitive regions. Globally, ADAR1 is the primary editor of repetitive sites and ADAR2 is the primary editor of non-repetitive coding sites, whereas the catalytically inactive ADAR3 predominantly acts as an inhibitor of editing. Cross-species analysis of RNA editing in several tissues revealed that species, rather than tissue type, is the primary determinant of editing levels, suggesting stronger cis-directed regulation of RNA editing for most sites, although the small set of conserved coding sites is under stronger trans-regulation. In addition, we curated an extensive set of ADAR1 and ADAR2 targets and showed that many editing sites display distinct tissue-specific regulation by the ADAR enzymes in vivo. Further analysis of the GTEx data revealed several potential regulators of editing, such as AIMP2, which reduces editing in muscles by enhancing the degradation of the ADAR proteins. Collectively, our work provides insights into the complex cis- and trans-regulation of A-to-I editing

Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics

Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease genes are enriched among significant associations for related traits, suggesting that smaller alterations of these genes may cause a spectrum of milder phenotypes