Accessible and Generalizable in Vitro Luminescence Assay for Detecting GPCR Activation.

G protein-coupled receptors (GPCRs) serve critical physiological roles as the most abundant family of receptors. Here, we describe the design of a generalizable and cell lysate-based method that leverages the interaction between an agonist-activated GPCR and a conformation-specific binder to reconstitute split nanoluciferase (NanoLuc) in vitro. This tool, n vitro PCR split anoLuc lgand riggered eporter (IGNiTR), has broad applications.

The Relationship Between Trimethylamine-N-Oxide and Prevalent Cardiovascular Disease in a Multiethnic Population Living in Canada.

Background: Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular disease (CVD) risk, but these associations have not been examined in ethnically diverse populations. In a multiethnic population-based study of adults in Canada, we assessed the stability of TMAO and L-carnitine in stored serum samples and their association with intimal medial thickness, prevalent risk factors, and clinical events.

Methods: In a randomly sampled cross-sectional study of 1286 Canadians, fasting serum samples were collected and stored.

Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.

Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear.

Maternal and newborn health profile in a first nations community in Canada.

Objectives: We sought to characterize maternal health profiles and birth outcomes among First Nations people living in Southern Ontario.

Methods: We performed a retrospective chart review of all 453 women from the Six Nations Reserve, Ontario, who were pregnant between 2005 and 2010. Maternal health behaviours, past medical history, physical measurements, birth outcomes, and newborn characteristics were abstracted.

Causal relationship between adiponectin and metabolic traits: a Mendelian randomization study in a multiethnic population.

Background: Adiponectin, a secretagogue exclusively produced by adipocytes, has been associated with metabolic features, but its role in the development of the metabolic syndrome remains unclear.

Objectives: We investigated the association between serum adiponectin level and metabolic traits, using both observational and genetic epidemiologic approaches in a multiethnic population assembled in Canada.

Methods: Clinical data and serum adiponectin level were collected in 1,157 participants of the SHARE/SHARE-AP studies.

Aboriginal birth cohort (ABC): a prospective cohort study of early life determinants of adiposity and associated risk factors among Aboriginal people in Canada.

Background: Aboriginal people living in Canada have a high prevalence of obesity, type 2 diabetes, and cardiovascular disease (CVD). To better understand the pre and postnatal influences on the development of adiposity and related cardio-metabolic factors in adult Aboriginal people, we will recruit and follow prospectively Aboriginal pregnant mothers and their children - the Aboriginal Birth Cohort (ABC) study.

Methods/design: We aim to recruit 300 Aboriginal pregnant mothers and their newborns from the Six Nations Reserve, and follow them prospectively to age 3 years.

Computationally estimated apolipoproteins B and A1 in predicting cardiovascular risk.

Objective: Apolipoproteins B (apoB) and A1 (apoA1) may be better markers of atherosclerosis than serum lipids. We used computational methods to estimate apoB and apoA1 from serum total cholesterol, HDL-cholesterol and triglycerides and tested their clinical value in comparison to measured apoB and apoA1 values.

Methods: ApoB and apoA1 were measured with standard methods and estimated based on neural network regression models in 2166 young adult with data on carotid artery intima-media thickness (cIMT).

Contextual determinants of health behaviours in an aboriginal community in Canada: pilot project.

Background: Rapid change in food intake, physical activity, and tobacco use in recent decades have contributed to the soaring rates of obesity, type 2 diabetes and cardiovascular disease (CVD) in Aboriginal populations living in Canada. The nature and influence of contextual factors on Aboriginal health behaviours are not well characterized.

Methods: To describe the contextual determinants of health behaviours associated with cardiovascular risk factors on the Six Nations reserve, including the built environment, access and affordability of healthy foods, and the use of tobacco.

BRCA2 variants and cardiovascular disease in a multi-ethnic study.

Background: Germline mutations of BRCA1/2 are associated with hereditary breast and ovarian cancer. Recent data suggests excess mortality in mutation carriers beyond that conferred by neoplasia, and recent in vivo and in vitro studies suggest a modulatory role for BRCA proteins in endothelial and cardiomyocyte function. We therefore tested the association of BRCA2 variants with clinical cardiovascular disease (CVD).

Genetic variation in hyaluronan metabolism loci is associated with plasma plasminogen activator inhibitor-1 concentration.

Elevated plasma plasminogen activator inhibitor-1 (PAI-1) concentration is associated with cardiovascular disease risk. PAI-1 is the primary inhibitor of fibrinolysis within both the circulation and the arterial wall, playing roles in both atherosclerosis and thrombosis. To define the heritable component, subjects within the population-based SHARE (Study of Health Assessment and Risk in Ethnic groups) and SHARE-AP (Study of Health Assessment and Risk Evaluation in Aboriginal Peoples) studies, composed of Canadians of South Asian (n = 298), Chinese (n = 284), European (n = 227), and Aboriginal (n = 284) descent, were genotyped using the gene-centric Illumina HumanCVD BeadChip.

Ethnic variation in adiponectin and leptin levels and their association with adiposity and insulin resistance.

Objective: To investigate ethnic differences in adiponectin and leptin concentration and to determine whether these adipokines and a high-glycemic index diet account for ethnic variation in insulin resistance.

Research Design And Methods: In 1,176 South Asian, Chinese, Aboriginal, and European Canadians, fasting blood samples were drawn, and clinical history and dietary habits including glycemic index/glycemic load were recorded using standardized questionnaires. Insulin resistance was defined using homeostasis model assessment-insulin resistance (HOMA-IR).