Heart failure (HF) is associated with impaired L-arginine transport. In the present study, we tested the hypothesis that augmented L-arginine transport prevents the loss of kidney function in HF. Renal function was assessed in wild-type mice (WT), transgenic mice with HF (DCM) and double transgenic mice (HFCAT-1) with HF and endothelial specific overexpression of the predominant L-arginine tran...

Switzerland: Springer International Publishing

Energy waveform (ew) ECG uses continuous wavelet transforms (CWT) to create time-frequency energy characterizations. Although ewECG changes reflect myocardial disease, optimal features for prediction of subclinical left ventricular dysfunction (Stage B heart failure [SBHF]) are unclear. Using machine learning (ML), we investigated whether ewECG could predict SBHF in at-risk community subjects t...

Single-cell transcriptomics enables inference of context-dependent phenotypes of individual cells and determination of cellular diversity of complex tissues. Cardiac fibrosis is a leading factor in the development of heart failure and a major cause of morbidity and mortality worldwide with no effective treatment. Single-cell RNA-sequencing (scRNA-seq) offers a promising new platform to identify...

While antibodies are becoming an increasingly important therapeutic class, especially in personalized medicine, their development and optimization has been largely through experimental exploration. While there have been many efforts to develop computational tools to guide rational antibody engineering, most approaches are of limited accuracy when applied to antibody design, and have largely bee...

Significant efforts have been invested into understanding and predicting the molecular consequences of mutations in protein coding regions, however nearly all approaches have been developed using globular, soluble proteins. These methods have been shown to poorly translate to studying the effects of mutations in membrane proteins. To fill this gap, here we report, mCSM-membrane, a user-friendly...

High blood cholesterol is typically considered a feature of wealthy western countries. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which h...

Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a p...

Lipid rafts are distinct liquid-ordered domains of plasma membranes of most eukaryotic cells providing platform for signaling pathways. Lipid composition of rafts is critical for their structural integrity and for regulation of signaling pathways originating from rafts. Here we provide a protocol to isolate lipid rafts from cultured human and animal cells and comprehensively analyse their lipid...

COVID-19 is a global pandemic currently in an acute phase of rapid expansion. While public health measures remain the most effective protection strategy at this stage, when the peak passes, it will leave in its wake important health problems. Historically, very few viruses have ever been eradicated. Instead, the virus may persist in communities causing recurrent local outbreaks of the acute inf...

Several circulating markers, including autoantibodies to erythropoietin receptor (anti-EPOR antibodies), have been identified as useful biomarkers in predicting diabetic kidney disease progression. However, a direct comparison of their utility is lacking. We aimed to validate and to compare the prognostic value of anti-EPOR antibodies with that of other known biomarkers, using the ADVANCE trial...

Type 2 diabetes (T2D) is a complex polygenic disease with unclear mechanisms. Clinical studies on the association of vitamin A with T2D in humans are still controversial. Herein, we aimed to investigate the plasma levels of vitamin A, predictor factors, and its correlations with clinical phenotypes in Emirati population. The effect of glucose-and lipid-lowering medications on vitamin A levels w...

Endothelial dysfunction is a major risk factor for several of the vascular complications of diabetes, including ischemic stroke. Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO•), is resistant to scavenging by superoxide, but the role of HNO in diabetes mellitus associated endothelial dysfunction in the carotid artery remains unknown. To assess how diabetes aff...

Microbes transform aqueous mercury (Hg) into methylmercury (MeHg), a potent neurotoxin that accumulates in terrestrial and marine food webs, with potential impacts on human health. This process requires the gene pair hgcAB, which encodes for proteins that actuate Hg methylation, and has been well described for anoxic environments. However, recent studies report potential MeHg formation in subox...

DNA methylation (DNAm) is an epigenetic modification that acts to regulate gene transcription, is essential for cellular processes and plays an important role in complex traits and disease. Variation in DNAm levels is influenced by both genetic and environmental factors. Several studies have examined the extent to which common genetic variation influences DNAm (i.e. mQTLs), however, an improved...

We examined the effect of power training on habitual, intervention and total physical activity (PA) levels in older adults with type 2 diabetes and their relationship to metabolic control.103 adults with type 2 diabetes were randomized to receive supervised power training or sham exercise three times/week for 12 months. Habitual, intervention, and total PA, as well as insulin resistance (HOMA2-...

GPR37L1 is a family A orphan G protein-coupled receptor (GPCR) with a putative role in blood pressure regulation and cardioprotection. In mice, genetic ablation of causes sex-dependent effects; female mice lacking (GPR37L1) have a modest but significant elevation in blood pressure, while male GPR37L1 mice are more susceptible to cardiovascular dysfunction following angiotensin II-induced hype...

Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer's disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer's and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype refle...

Frequent use of screen-based devices could be a modifiable risk factor for adolescent depression, but findings have been inconsistent and mostly from cross-sectional studies. We examined prospective associations of video gaming, social media, and internet use with depressive symptoms in adolescents.A total of 11 341 adolescents from the Millennium Cohort Study, a representative, UK population-b...