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Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-c
We introduce a family of boundary confinements for Coulomb gas ensembles, and study them in the two-dimensional determinantal case of random normal matrices. The family interpolates between the free boundary and hard edge cases, which have been well studied in various random matrix theories. The confinement can also be relaxed beyond the free boundary to produce ensembles with fuzzier boundaries,
Duplicative horizontal gene transfer may bring two previously separated homologous genes together, which may raise questions about the interplay between the gene products. One such gene pair is the “native” PgiC1 and “foreign” PgiC2 in the perennial grass Festuca ovina. Both PgiC1 and PgiC2 encode cytosolic phosphoglucose isomerase, a dimeric enzyme whose proper binding is functionally essential.
Background: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis,
The sexes may have different optima in cognitive traits due to differences in life history strategies and the expense of investing in metabolically costly brain tissue. However, given genetic correlations, each sex could be constrained from reaching its cognitive optimum due to intralocus sexual conflict. We compared learning performance of two male alternative reproductive tactics and females fro
The article analyzes the varied meanings historically associated with concepts of voluntarism in relation to social relief as they were articulated by changing moral elites in Denmark from the late nineteenth century until the present. Concepts of voluntarism have historically constituted “normative counterconcepts” that link voluntary practices to desired futures in opposition to alternative mode
Walking is a simple form of exercise, widely promoted for its health benefits. Self-reported walking pace has been associated with a range of cardiorespiratory and cancer outcomes, and is a strong predictor of mortality. Here we perform a genome-wide association study of self-reported walking pace in 450,967 European ancestry UK Biobank participants. We identify 70 independent associated loci (P <
The under-representation of several ethnic groups in existing genetic databases and studies have undermined our understanding of the genetic variations and associated traits or diseases in many populations. Cost and technology limitations remain the challenges in performing large-scale genome sequencing projects in many developing countries, including Vietnam. As one of the most rapidly adopted ge
BACKGROUND: We explored the association of N-terminal probrain natriuretic peptide (NT-proBNP) with metabolic traits in a bi-ethnic African-Caucasian cohort.METHODS: Baseline examinations of the Sympathetic activity and Ambulatory Blood Pressure in African (SABPA) prospective cohort study were performed between 2008 and 2009, and re-examination after a three-year follow up in South African teacher
Background: Wide implementation of mammography screening has resulted in increased numbers of women diagnosed with breast carcinoma in situ. We aimed to determine the risk of invasive breast cancer in relatives of patients with breast carcinoma in situ in comparison to the risk in relatives of patients with invasive breast cancer. Methods: We analyzed the occurrence of cancer in a nationwide cohor
Background: Evidence is lacking on the differences between hospitalisation of people with dementia living in nursing homes and those living in the community. The objectives of this study were: 1) to describe the frequency of hospital admission among people with dementia in eight European countries living in nursing homes or in the community, 2) to examine the factors associated with hospitalisatio
In many ferroelectrics, large electromechanical strains are observed near regions of composition- or temperature- driven phase coexistence. Phenomenologically, this is attributed to easy re-orientation of the polarization vector and/or phase transition, although their effects are highly convoluted and difficult to distinguish experimentally. Here, we used synchrotron X-ray scattering and digital i
The real-world impact of psychosis prevention is reliant on effective strategies for identifying individuals at risk. A transdiagnostic, individualized, clinically-based risk calculator to improve this has been developed and externally validated twice in two different UK healthcare trusts with convincing results. The prognostic performance of this risk calculator outside the UK is unknown. All ind
Background: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild. Objectives: This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non–flow-limiting vulnerable plaques. Methods: Three-vessel imaging was performed with a combination intravascular ultraso
Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast
The mechanisms by which lime and/or phosphate addition impacts the preservation of soil organic matter (OM) are poorly understood. We explored the changes in quantity and chemistry of water-extractable organic matter (WEOM) in the bulk soil and its heavy density fraction (>1.6 g/cm3) of an unmanaged C-rich volcanic soil caused by lime and/or phosphate application. The addition of lime or phosphate
BACKGROUND: The comparative efficacy and safety of ticagrelor versus clopidogrel in older patients with myocardial infarction (MI) has received limited study. METHODS: We performed an observational analysis of all patients ≥80 years (n=14 005) who were discharged alive with aspirin combined with either clopidogrel (60.2%) or ticagrelor (39.8%) after a MI between 2010 and 2017 registered in the nat
Neuroblastoma is a childhood tumor of the sympathetic nervous system and the most common tumor form diagnosed in infants. Patients with aggressive tumors are treated intensely with multi-modal therapy including chemotherapy, surgery, radiotherapy and immunotherapy. Despite this, many children suffer from incurable relapses and long-term side effects are common. Novel treatments are thus necessary
Madsen et al. show substantial long term (26 years) population demography and genetic benefits of genetic rescue of an initially inbred adder (Vipera berus) population. A post-rescue genetic bottleneck did not affect population genetic diversity. To be successful large numbers of novel alleles should be introduced into the focal population.
