Early growth response gene-2 (Egr-2) regulates the development of B and T cells

The study was supported by Arthritis Research UK. Copyright @ 2011 Li et al.BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2+ lymphocytes resulted in a severe reduction of CD4+CD8+ (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.This article is provided by the Brunel Open Access publishing fund

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

SINE indel polymorphism of AGL gene and association with growth and carcass traits in Landrace × Jeju black pig F2 population

Genetic polymorphisms in the glycogen debrancher enzyme (AGL) gene were assessed with regard to their association with growth and carcass traits in the F2 population crossbred Landrace and Jeju (Korea) Black pig. Three genotypes representing the insertion and/or deletion (indel) polymorphisms of short interspersed nuclear element were detected at frequencies of 0.278 (L/L), 0.479 (L/S), and 0.243 (S/S), respectively. The AGL S allele-containing pigs evidenced significantly heavier body weights at birth, the 3rd week, 10th week, and 20th week during developmental stages and higher average daily gains during the late period than were noted in the L/L homozygous pigs (P < 0.05), respectively. However, average daily gains during the early period were not significantly associated with genotype distribution (P > 0.05). With regard to the carcass traits, the S allele pigs (S/-) evidenced significantly heavier carcass weights and thicker backfat than was measured in L/L homozygous pigs (P < 0.05). However, body lengths, meat color, and marbling scores were all found not to be statistically significant (P > 0.05). Consequently, the faster growth rate during the late period and backfat deposition rather than intramuscular fat deposition cause differences in pig productivity according to genotypes of the AGL gene. These findings indicate that the AGL genotypes may prove to be useful genetic markers for the improvement of Jeju Black pig-related crossbreeding systems

The changing association between socioeconomic circumstances and the incidence of colorectal cancer: a population-based study

Background:There is emerging evidence to suggest that the association between socioeconomic circumstances and colorectal cancer incidence has changed over recent decades.Methods:We conducted a descriptive population-based study to describe the relationship between socioeconomic circumstances and the incidence of colorectal cancer in a pre-screened population. Incident cases of colorectal cancer from the West of Scotland were identified from the Scottish Cancer Registry and European age-standardised incidence rates (EASR) were calculated. Socioeconomic circumstances were measured using the area-based Scottish Index of Multiple Deprivation (SIMD).Results:In total, 14?051 incident cases of colorectal cancer were recorded from 1999 to 2007. Incidence of colorectal cancer was associated with increased deprivation in men but not among women; an association that became evident from 2005 onwards. From 2005 to 2007, the deprivation gap in incidence among men was 13.3 per 100?000 (95% confidence interval 3.2-23.4), with rates 19.5% lower among the least deprived compared with the most deprived. This deprivation gap now accounts for an estimated 75 excess cases per year of male colorectal cancer in the West of Scotland.Conclusion:Deprivation was associated with higher incidence rates of male, but not female, colorectal cancer before the implementation of a national bowel screening programme

The acceptability of waiting times for elective general surgery and the appropriateness of prioritising patients

BACKGROUND: Problematic waiting lists in public health care threaten the equity and timeliness of care provision in several countries. This study assesses different stakeholders' views on the acceptability of waiting lists in health care, their preferences for priority care of patients, and their judgements on acceptable waiting times for surgical patients. METHODS: A questionnaire survey was conducted among 257 former patients (82 with varicose veins, 86 with inguinal hernia, and 89 with gallstones), 101 surgeons, 95 occupational physicians, and 65 GPs. Judgements on acceptable waiting times were assessed using vignettes of patients with varicose veins, inguinal hernia, and gallstones. RESULTS: Participants endorsed the prioritisation of patients based on clinical need, but not on ability to benefit. The groups had significantly different opinions (p < 0.05) on the use of non-clinical priority criteria and on the need for uniformity in the prioritisation process. Acceptable waiting times ranged between 2 and 25 weeks depending on the type of disorder (p < 0.001) and the severity of physical and psychosocial problems of patients (p < 0.001). Judgements were similar between the survey groups (p = 0.3) but responses varied considerably within each group depending on the individual's attitude towards waiting lists in health care (p < 0.001). CONCLUSION: The explicit prioritisation of patients seems an accepted means for reducing the overall burden from waiting lists. The disagreement about appropriate prioritisation criteria and the need for uniformity, however, raises concern about equity when implementing prioritisation in daily practice. Single factor waiting time thresholds seem insufficient for securing timely care provision in the presence of long waiting lists as they do not account for the different consequences of waiting between patients

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV