Epigenome-wide association study of objectively measured physical activity in peripheral blood leukocytes.

Background: Few studies have explored the association between DNA methylation and physical activity. The aim of this study was to evaluate the association of objectively measured hours of sedentary behavior (SB) and moderate physical activity (MPA) with DNA methylation. We further aimed to explore the association between SB or MPA related CpG sites and cardiometabolic traits, gene expression, and genetic variation.

Exploring barriers to accessing treatment for Lymphatic Filariasis through a socio-ecological lens in Buvuma and Napak districts, Uganda.

Background: The World Health Organization launched the Global Programme to Eliminate Lymphatic Filariasis in 2000, which aimed at eradicating the disease by 2030. This goal depends on community mass drug administration and essential care. Despite these efforts, many rural communities still face untreated lymphatic filariasis and lack access to treatment and self-management.

A Research Roadmap to Address the Heterogeneity of Diabetes and Advance Precision Medicine.

The current classification of diabetes had its genesis over 85 years ago, when individuals with diabetes were first subclassified into insulin sensitive and insulin insensitive states based on the response to an oral glucose tolerance test. About 35 years later, the contemporary classifications of type 1 and type 2 diabetes were coined. Today's evidence, however, suggests that multiple etiologic and pathogenic processes lead to both type 1 and type 2 diabetes, reflecting significant heterogeneity in factors associated with initiation, progression, and clinical presentation of each disorder of glucose homeostasis.

DNA methylation in cord blood partially mediates the effects of prepregnancy BMI on early childhood offspring BMI.

Objective: We investigated whether prepregnancy BMI (prePregBMI) in women with obesity was associated with differential DNA methylation (DNAm) in cord blood (CB) and whether DNAm may mediate the association of prePregBMI and early childhood BMI z score (BMIz).

Methods: From the Treatment of Obese Pregnant Women (TOP) study, 232 mother-child pairs were included. We conducted an epigenome-wide association study on prePregBMI and CB DNAm (450k array), followed by causal mediation analyses to test whether DNAm may mediate effects of prePregBMI on  BMIz at age 36 months (BMIz36).

Diabetes and obesity: leveraging heterogeneity for precision medicine.

The increasing prevalence of diabetes, obesity, and their cardiometabolic sequelae present major global health challenges and highlight shortfalls of current approaches to the prevention and treatment of these conditions. Representing the largest global burden of morbidity and mortality, the pathobiological processes underlying cardiometabolic diseases are in principle preventable and, even when disease is manifest, sometimes reversable. Nevertheless, with current clinical and public health strategies, goals of widespread prevention and remission remain largely aspirational.

Subclassification of obesity for precision prediction of cardiometabolic diseases.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000).

Warming triggers stomatal opening by enhancement of photosynthesis and ensuing guard cell CO sensing, whereas higher temperatures induce a photosynthesis-uncoupled response.

Plants integrate environmental stimuli to optimize photosynthesis vs water loss by controlling stomatal apertures. However, stomatal responses to temperature elevation and the underlying molecular genetic mechanisms remain less studied. We developed an approach for clamping leaf-to-air vapor pressure difference (VPD) to fixed values, and recorded robust reversible warming-induced stomatal opening in intact plants.

presence relative to the vertical and temporal variability of oceanographic conditions in the Southern California Bight.

The oceanographic conditions of the Southern California Bight (SCB) dictate the distribution and abundance of prey resources and therefore the presence of mobile predators, such as goose-beaked whales (). Goose-beaked whales are deep-diving odontocetes that spend a majority of their time foraging at depth. Due to their cryptic behavior, little is known about how they respond to seasonal and interannual changes in their environment.

Variability of polygenic prediction for body mass index in Africa.

Background: Polygenic prediction studies in continental Africans are scarce. Africa's genetic and environmental diversity pose a challenge that limits the generalizability of polygenic risk scores (PRS) for body mass index (BMI) within the continent. Studies to understand the factors that affect PRS variability within Africa are required.

Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.

Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the association of T2D pPS with diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin, or placebo arms.

The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study.

Context: The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood.

Objective: We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.

Methods: We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D.

Land surface conductance linked to precipitation: Co-evolution of vegetation and climate in Earth system models.

Vegetation and precipitation are known to fundamentally influence each other. However, this interdependence is not fully represented in climate models because the characteristics of land surface (canopy) conductance to water vapor and CO are determined independently of precipitation. Working within a coupled atmosphere and land modelling framework (CAM6/CLM5; coupled Community Atmosphere Model v6/Community Land Model v5), we have developed a new theoretical approach to characterizing land surface conductance by explicitly linking its dynamic properties to local precipitation, a robust proxy for moisture available to vegetation.

Factors associated with cellulitis in lymphoedema of the arm - an international cross-sectional study (LIMPRINT).

Background: Lymphoedema is a globally neglected health care problem and a common complication following breast cancer treatment. Lymphoedema is a well-known predisposing factor for cellulitis, but few have investigated the risk factors for cellulitis in this patient cohort on an international level. The aim of this study was to identify the frequency of cellulitis in patients with lymphoedema of the arm, including potential risk factors for cellulitis.

Human Genetic Variation at rs10071329 Correlates With Adiposity-Related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function.

Human genetic variation in PPARGC1B has been associated with adiposity, but the genetic variants that affect PPARGC1B expression have not been experimentally determined. Here, guided by previous observational data, we used clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) to scarlessly edit the alleles of the candidate causal genetic variant rs10071329 in a human brown adipocyte cell line. Switching the rs10071329 genotype from A/A to G/G enhanced PPARGC1B expression throughout the adipogenic differentiation, identifying rs10071329 as a cis-expression quantitative trait loci (eQTL).