Developing reduced SNP assays from whole-genome sequence data to estimate C-lineage introgression in the Iberian honeybee (Apis mellifera iberiensis)

The honeybee has been subject to a growing number of threats. In Western Europe one such threat is large-scale introductions of commercial strains (C-lineage), which is leading to introgressive hybridization and even the local extinction of native populations (M-lineage). Here, we developed reduced assays of highly informative SNPs from 176 whole genomes to estimate C-lineage introgression in ;M-lineage subspecies Apis mellifera iberiensis. We started by evaluating the effects of sample size and sampling a geographically restricted area on the number of highly informative SNPs. We demonstrated that a bias in the number of fixed SNPs (FST=1) is introduced when the sample size is small (N≤10) and when sampling only captures a small fraction of a population’s genetic diversity. These results underscore the importance of having a representative sample when developing reliable reduced SNP assays for organisms with complex genetic patterns. We used a training dataset to design four independent SNP assays selected from pairwise FST between the Iberian and C-lineage honeybees. The designed assays, which were validated in holdout and simulated hybrid datasets, proved to be highly accurate and can be readily used for monitoring populations not only in the native range of A. m. iberiensis in Iberia but also in the introduced range in the Balearic islands, Macaronesia, and South America, in a time- and cost-effective manner. While our approach used the Iberian honeybee as model system, it has a high value in a wide range of scenarios for the monitoring and conservation of potentially hybridized domestic and wildlife populations.info:eu-repo/semantics/publishedVersio

Synaptic Vesicles Position Complexin to Block Spontaneous Fusion

SummarySynapses continually replenish their synaptic vesicle (SV) pools while suppressing spontaneous fusion events, thus maintaining a high dynamic range in response to physiological stimuli. The presynaptic protein complexin can both promote and inhibit fusion through interactions between its α-helical domain and the SNARE complex. In addition, complexin’s C-terminal half is required for the inhibition of spontaneous fusion in worm, fly, and mouse, although the molecular mechanism remains unexplained. We show here that complexin’s C-terminal domain binds lipids through a novel protein motif, permitting complexin to inhibit spontaneous exocytosis in vivo by targeting complexin to SVs. We propose that the SV pool serves as a platform to sequester and position complexin where it can intercept the rapidly assembling SNAREs and control the rate of spontaneous fusion

The link between soil geochemistry in South-West England and human exposure to soil arsenic

The aim of this research is to use the whole soil geochemistry and selected bioaccessibility measurements, using the BioAcessibility Research Group of Europe (BARGE) method, on the same soils to identify the geochemical controls on arsenic (As) bioaccessibility and to gain an understanding of its spatial distribution in south-west England. The total element concentrations of 1154 soils were measured with As concentrations ranging from 4.7–1948 mg·kg−1, with the bioaccessible As of 50 selected soils ranging from 0.6–237 mg·kg−1. A Self Modelling Mixture Resolution approach was applied to the total soil element chemistry to identify the intrinsic soil constituents (ISCs). The ISCs were used as predictor variables and As bioaccessibility as the dependant variables in a regression model for the prediction of As bioaccessibility at all soil locations to examine its regional spatial distribution. This study has shown that bioaccessibility measurements can be directly linked to the geochemical properties of soils. In summary, it seems the primary source of bioaccessible As comes from soils developed directly over the mineralised areas surrounding the granite intrusions. Secondary sources of bioaccessible As are derived from As that has been mobilised from the primary mineralised source and then re-absorbed onto clay material, Fe oxides and carbonate coatings. This information can be of direct use for land development, since land contamination can affect the health of people living, working, visiting or otherwise present on a sit

Preoperative heart rate and myocardial injury after non-cardiac surgery: results of a predefined secondary analysis of the VISION study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Funding for this study comes from more than 50 grants for VISION and its sub-studies: Canadian Institutes of Health Research (six grants); Heart and Stroke Foundation of Ontario (two grants); Academic Health Science Centres Alternative Funding Plan Innovation Fund Grant; Population Health Research Institute Grant; Clarity Research Group Grant; McMaster University, Department of Surgery, Surgical Associates Research Grant; Hamilton Health Science New Investigator Fund Grant; Hamilton Health Sciences Grant; Ontario Ministry of Resource and Innovation Grant; Stryker Canada, McMaster University, Department of Anesthesiology (two grants); Saint Joseph′s Healthcare, Department of Medicine (two grants); Father Sean O′Sullivan Research Centre (two grants); McMaster University, Department of Medicine (two grants); Hamilton Health Sciences Summer Studentships (six grants); McMaster University, Department of Clinical Epidemiology and Biostatistics Grant; McMaster University, Division of Cardiology Grant, and Canadian Network and Centre for Trials International Grant; Winnipeg Health Sciences Foundation Operating Grant; Diagnostic Services of Manitoba Research Grant; University of Manitoba, Faculty of Dentistry Operational Fund; Projeto Hospitais de Excelencia a Serviço do SUS grant from the Brazilian Ministry of Health in Partnership with Hcor (Cardiac Hospital Sao Paulo-SP); School of Nursing, Universidad Industrial de Santander; Grupo de Cardiología Preventiva, Universidad Autónoma de Bucaramanga; Fundación Cardioinfantil Instituto de Cardiología; Alianza Diagnóstica SA; University of Malaya Research Grant; and University of Malaya, Penyelidikan Jangka Pendek Grant. Roche Diagnostics provided the troponin T assays and some financial support for the VISION Study. Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1 to T.E.F.A.); National Institute for Health Research professorship (to R.P.); British Journal of Anaesthesia and Royal College of Anaesthetists basic science fellowship (to G.A.); National Research Foundation of South Africa (to R.N.R.); Heart and Stroke Foundation of Ontario Career Investigator Award (to P.J.D.); Yusuf Chair in Cardiology (P.J.D.).Funding for this study comes from more than 50 grants for VISION and its sub-studies: Canadian Institutes of Health Research (six grants); Heart and Stroke Foundation of Ontario (two grants); Academic Health Science Centres Alternative Funding Plan Innovation Fund Grant; Population Health Research Institute Grant; Clarity Research Group Grant; McMaster University, Department of Surgery, Surgical Associates Research Grant; Hamilton Health Science New Investigator Fund Grant; Hamilton Health Sciences Grant; Ontario Ministry of Resource and Innovation Grant; Stryker Canada, McMaster University, Department of Anesthesiology (two grants); Saint Joseph′s Healthcare, Department of Medicine (two grants); Father Sean O′Sullivan Research Centre (two grants); McMaster University, Department of Medicine (two grants); Hamilton Health Sciences Summer Studentships (six grants); McMaster University, Department of Clinical Epidemiology and Biostatistics Grant; McMaster University, Division of Cardiology Grant, and Canadian Network and Centre for Trials International Grant;Winnipeg Health Sciences Foundation Operating Grant; Diagnostic Services of Manitoba Research Grant; University of Manitoba, Faculty of Dentistry Operational Fund; Projeto Hospitais de Excelencia a Serviço do SUS grant from the Brazilian Ministry of Health in Partnership with Hcor (Cardiac Hospital Sao Paulo-SP); School of Nursing, Universidad Industrial de Santander; Grupo de Cardiología Preventiva, Universidad Autónoma de Bucaramanga; Fundación Cardioinfantil Instituto de Cardiología; Alianza Diagnóstica SA; University of Malaya Research Grant; and University of Malaya, Penyelidikan Jangka Pendek Grant. Roche Diagnostics provided the troponin T assays and some financial support for the VISION Study. Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1 to T.E.F.A.); National Institute for Health Research professorship (to R.P.); British Journal of Anaesthesia and Royal College of Anaesthetists basic science fellowship (to G.A.); National Research Foundation of South Africa (to R.N.R.); Heart and Stroke Foundation of Ontario Career Investigator Award (to P.J.D.); Yusuf Chair in Cardiology (P.J.D.)

MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide:a comprehensive meta-analysis based on a Cochrane Review

BACKGROUND: The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) causes resistance of tumor cells to alkylating agents. It is a predictive biomarker in high-grade gliomas treated with temozolomide, however, there is no consensus on which test method, methylation sites, and cutoff values to use. METHODS: We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included (i) adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; (ii) where MGMT status was determined in tumor tissue, and assessed by 1 or more technique; and (iii) where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios (HRs). Two or more methods were compared in 32 independent cohorts with 3474 patients. RESULTS: Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP. CONCLUSIONS: We cannot draw strong conclusions about use of frozen tissue vs formalin-fixed paraffin-embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and PSQ at CpG sites ranging from 72 to 95. A cutoff threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in 2 of the 3 good-quality studies. About 190 studies were identified presenting HRs from survival analysis in patients in which MGMT methylation was measured by 1 technique only

To what extent is behaviour a problem in English schools?:Exploring the scale and prevalence of deficits in classroom climate

The working atmosphere in the classroom is an important variable in the process of education in schools, with several studies suggesting that classroom climate is an important influence on pupil attainment. There are wide differences in the extent to which classroom climate is considered to be a problem in English schools. Some ‘official’ reports suggest that behaviour in schools is ‘satisfactory or better’ in the vast majority of schools; other sources have pointed to behaviour being a serious and widespread problem. The paper details four studies conducted over the past decade which aimed to explore these disparities. The aim of the research was to gain a more accurate insight into the extent to which deficits in classroom climate limit educational attainment and equality of educational opportunity in English schools. The findings question the suggestion that behaviour is satisfactory or better in 99.7% of English schools and the concluding section suggests ways in which deficits in classroom climate might be addressed. Although the study is limited to classrooms in England, OECD studies suggest that deficits in the working atmosphere in classrooms occur in many countries. The study therefore has potential relevance for education systems in other countries

Successful Recanalization of Chronic Total Occlusions Is Associated With Improved Long-Term Survival

ObjectivesThis study investigated the impact of procedural success on mortality following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in a large cohort of patients in the drug-eluting stent era.BackgroundDespite advances in expertise and technologies, many patients with CTO are not offered PCI.MethodsA total of 6,996 patients underwent elective PCI for stable angina at a single center (2003 to 2010), 836 (11.9%) for CTO. All-cause mortality was obtained to 5 years (median: 3.8 years; interquartile range: 2.0 to 5.4 years) and stratified according to successful chronic total occlusion (sCTO) or unsuccessful chronic total occlusion (uCTO) recanalization. Major adverse cardiac events (MACE) included myocardial infarction (MI), urgent revascularization, stroke, or death.ResultsA total of 582 (69.6%) procedures were successful. Stents were implanted in 97.0% of successful procedures (mean: 2.3 ± 0.1 stents per patient, 73% drug-eluting). Prior revascularization was more frequent among uCTO patients: coronary artery bypass grafting (CABG) (16.5% vs. 7.4%; p < 0.0001), PCI (36.0% vs. 21.2%; p < 0.0001). Baseline characteristics were otherwise similar. Intraprocedural complications, including coronary dissection, were more frequent in unsuccessful cases (20.5% vs. 4.9%; p < 0.0001), but did not affect in-hospital MACE (3% vs. 2.1%; p = NS). All-cause mortality was 17.2% for uCTO and 4.5% for sCTO at 5 years (p < 0.0001). The need for CABG was reduced following sCTO (3.1% vs. 22.1%; p < 0.0001). Multivariate analysis demonstrated that procedural success was independently predictive of mortality (hazard ratio [HR]: 0.32 [95% confidence interval (CI): 0.18 to 0.58]), which persisted when incorporating a propensity score (HR: 0.28 [95% CI: 0.15 to 0.52]).ConclusionsSuccessful CTO PCI is associated with improved survival out to 5 years. Adoption of techniques and technologies to improve procedural success may have an impact on prognosis