Matthewskennedy4631

FUS is a nucleic acid binding protein that, when mutated, cause a subset of familial amyotrophic lateral sclerosis (ALS). Expression of FUS in yeast recapitulates several pathological features of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, formation of cytoplasmic inclusions, and cytotoxicity. Genetic screens using the yeast model of FUS have identified yeast genes and their corresponding human homologs suppressing FUS induced toxicity in yeast, neurons and animal models. To expand the search for human suppressor genes of FUS induced toxicity, we carried out a genome-scale genetic screen using a newly constructed library containing 13570 human genes cloned in an inducible yeast-expression vector. Through multiple rounds of verification, we found 37 human genes that, when overexpressed, suppress FUS induced toxicity in yeast. Human genes with DNA or RNA binding functions are overrepresented among the identified suppressor genes, supporting that perturbations of RNA metabolism is a key underlying mechanism of FUS toxicity. Copyright © The Author(s) 2020. Published by the Genetics Society of America.Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America. The fungus causing the disease invades skin tissues of hibernating bats, resulting in disruption of hibernation behavior, premature energy depletion, and subsequent death. We used whole-genome sequencing to investigate changes in allele frequencies within a population of Myotis lucifugus in eastern North America to search for genetic resistance to WNS. Our results show low FST values within the population across time, i.e. prior to WNS (Pre-WNS) compared to the population that has survived WNS (Post-WNS). However, when dividing the population with a geographical cut-off between the states of Pennsylvania and New York, a sharp increase in values on scaffold GL429776 is evident in the Post-WNS samples. Genes present in the diverged area are associated with thermoregulation and promotion of brown fat production. Thus, although WNS may not have subjected the entire M. lucifugus population to selective pressure, it may have selected for specific alleles in Pennsylvania through decreased gene flow within the population. However, the persistence of remnant sub-populations in the aftermath of WNS is likely due to multiple factors in bat life history. Copyright © The Author(s) 2020. Published by the Genetics Society of America.INTRODUCTION Hypertension is one of the most common medical conditions and represents a major risk factor for heart attack, stroke, kidney disease and mortality. The risk of progression to hypertension depends on several factors, and combining these risk factors into a multivariable model for risk stratification would help to identify high-risk individuals who should be targeted for healthy behavioural changes and/or medical treatment to prevent the development of hypertension. The risk prediction models can be further improved in terms of accuracy by using a metamodel updating technique where existing hypertension prediction models can be updated by combining information available in existing models with new data. A systematic review and meta-analysis will be performed of hypertension prediction models in order to identify known risk factors for high blood pressure and to summarise the magnitude of their association with hypertension. METHODS AND ANALYSIS MEDLINE, Embase, Web of Science, Scopus and grey literature will be systematically searched for studies predicting the risk of hypertension among the general population. The search will be based on two key concepts hypertension and risk prediction. The summary statistics from the individual studies will be the regression coefficients of the hypertension risk prediction models, and random-effect meta-analysis will be used to obtain pooled estimates. Heterogeneity and publication bias will be assessed, along with study quality, which will be assessed using the Prediction Model Risk of Bias Assessment Tool checklist. ETHICS AND DISSEMINATION Ethics approval is not required for this systematic review and meta-analysis. We plan to disseminate the results of our review through journal publications and presentations at applicable platforms. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To evaluate the association between socioeconomic status (SES) and referral to cardiac rehabilitation (CR) after incident acute coronary syndrome (ACS) by dividing the referral process into three phases (1) informed about CR, (2) willingness to participate in CR, (3) and assigned CR setting. DESIGN Cross-sectional study. SETTING Department of Cardiology at a Danish University Hospital from 1 January 2011 to 31 December 2014. PARTICIPANTS A total of 1229 patients assessed for CR during hospitalisation with ACS were prospectively registered in the Rehab-North Register from 2011 to 2014. SES was assessed using data from national registers, concerning personal income, occupational status, educational level and civil status. Patients were excluded if one of the following criteria was fulfilled (1) missing data on SES, or (2) acceptable reason for not informing patients about CR (treatment with coronary artery bypass grafting, transfer to another hospital, still under treatment or death). MAIN OUTCOME MEAs) (or their employer(s)) 2020. find more Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES Symptom Screening in Pediatrics Tool (SSPedi) is a validated approach to measuring bothersome symptoms for English-speaking and Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplantation (HSCT) recipients. Objectives were to translate SSPedi into French, and among French-speaking children receiving cancer treatments, to evaluate understandability and cultural relevance. METHODS We conducted a multiphase, descriptive study to translate SSPedi into French. Forward translation was performed by four medical translators. After confirming that back translation was satisfactory, we enrolled French-speaking children with cancer and paediatric HSCT recipients at four centres in France and Canada. PRIMARY AND SECONDARY OUTCOME MEASURES Understandability was evaluated by children themselves who self-reported degree of difficulty, and by two adjudicators who rated incorrectness. Assessment of cultural relevance was qualitative. Participants were enrolled in cohorts of 10. RESULTS There were 30 children enrolled.