Genetic and epigenetic catalysts in early-life programming of adult cardiometabolic disorders

Evidence has emerged across the past few decades that the lifetime risk of developing morbidities like type 2 diabetes, obesity, and cardiovascular disease may be influenced by exposures that occur in utero and in childhood. Developmental abnormalities are known to occur at various stages in fetal growth. Epidemiological and mechanistic studies have sought to delineate developmental processes and plausible risk factors influencing pregnancy outcomes and later health. Whether these observations reflect causal processes or are confounded by genetic and social factors remains unclear, although animal (and some human) studies suggest that epigenetic programming events may be involved. Regardless of the causal basis to observations of early-life risk factors and later disease risk, the fact that such associations exist and that they are of a fairly large magnitude justifies further research around this topic. Furthermore, additional information is needed to substantiate public health guidelines on lifestyle behaviors during pregnancy to improve infant health outcomes. Indeed, lifestyle intervention clinical trials in pregnancy are now coming online, where materials and data are being collected that should facilitate understanding of the causal nature of intrauterine exposures related with gestational weight gain, such as elevated maternal blood glucose concentrations. In this review, we provide an overview of these concepts

Genotype-based recall studies in complex cardiometabolic traits

In genotype-based recall (GBR) studies, people (or their biological samples) who carry genotypes of special interest for a given hypothesis test are recalled from a larger cohort (or biobank) for more detailed investigations. There are several GBR study designs that offer a range of powerful options to elucidate (1) genotype-phenotype associations (by increasing the efficiency of genetic association studies, thereby allowing bespoke phenotyping in relatively small cohorts), (2) the effects of environmental exposures (within the Mendelian randomization framework), and (3) gene-treatment interactions (within the setting of GBR interventional trials). In this review, we overview the literature on GBR studies as applied to cardiometabolic health outcomes. We also review the GBR approaches used to date and outline new methods and study designs that might enhance the utility of GBR-focused studies. Specifically, we highlight how GBR methods have the potential to augment randomized controlled trials, providing an alternative application for the now increasingly accepted Mendelian randomization methods usually applied to large-scale population-based data sets. Further to this, we consider how functional and basic science approaches alongside GBR designs offer intellectually intriguing and potentially powerful ways to explore the implications of alterations to specific (and potentially druggable) biological pathways

Molecular architecture of softwood revealed by solid-state NMR

Economically important softwood from conifers is mainly composed of the polysaccharides cellulose, galactoglucomannan and xylan, and the phenolic polymer, lignin. The interactions between these polymers lead to wood mechanical strength and must be overcome in biorefining. Here, we use 13C multidimensional solid-state NMR to analyse the polymer interactions in never-dried cell walls of the softwood, spruce. In contrast to some earlier softwood cell wall models, most of the xylan binds to cellulose in the two-fold screw conformation. Moreover, galactoglucomannan alters its conformation by intimately binding to the surface of cellulose microfibrils in a semi-crystalline fashion. Some galactoglucomannan and xylan bind to the same cellulose microfibrils, and lignin is associated with both of these cellulose-bound polysaccharides. We propose a model of softwood molecular architecture which explains the origin of the different cellulose environments observed in the NMR experiments. Our model will assist strategies for improving wood usage in a sustainable bioeconomy

Cross-Stratification, Dakota Sandstone (Cretaceous), Ottawa County, Kansas

Dip bearings of water-deposited cross-strata in sandstone of the Dakota Formation (Cretaceous) of central Kansas were measured at 79 localities in Ottawa County. Vector-resultant (average) dip bearings lie in nearly all compass directions, but average S 57° W, showing that transportation of Dakota sediments in Ottawa County was mainly from northeast to southwest and that the source, therefore, seemingly lay to the northeast. Computation of a regression line of standard deviation on consistency ratio indicates that, in Dakota sandstone, consistency ratio is a good predictor of standard deviation for ratio values between 0.65 and 0.95

Diel Vertical Movements of a Scalloped Hammerhead, \u3ci\u3eSphyrna lewini\u3c/i\u3e, in the Northern Gulf of Mexico

Despite the circumglobal distribution of scalloped hammerheads, Sphyrna lewini (Griffith and Smith, 1834), little information is available regarding fine-scale movement and habitat use patterns for this species. Over a 27-d period, data were collected on diel habitat use and environmental preferences of a 240 cm (total length) female S. lewini. The shark exhibited a consistent and repeated diel vertical movement pattern, making more than 76 deep nighttime dives; the maximum depth reached was 964 m, where the temperature was 5.8 degrees C. The purpose of the nightly oscillatory deep diving pattern is unknown but could possibly represent feeding behavior. These findings represent the first detailed account of S. lewini diel vertical behavior and habitat utilization in the western North Atlantic Ocean

Estimation of Free-Living Energy Expenditure by Heart Rate and Movement Sensing: A Doubly-Labelled Water Study.

BACKGROUND: Accurate assessment of energy expenditure (EE) is important for the study of energy balance and metabolic disorders. Combined heart rate (HR) and acceleration (ACC) sensing may increase precision of physical activity EE (PAEE) which is the most variable component of total EE (TEE). OBJECTIVE: To evaluate estimates of EE using ACC and HR data with or without individual calibration against doubly-labelled water (DLW) estimates of EE. DESIGN: 23 women and 23 men (22-55 yrs, 48-104 kg, 8-46%body fat) underwent 45-min resting EE (REE) measurement and completed a 20-min treadmill test, an 8-min step test, and a 3-min walk test for individual calibration. ACC and HR were monitored and TEE measured over 14 days using DLW. Diet-induced thermogenesis (DIT) was calculated from food-frequency questionnaire. PAEE (TEE ÷ REE ÷ DIT) and TEE were compared to estimates from ACC and HR using bias, root mean square error (RMSE), and correlation statistics. RESULTS: Mean(SD) measured PAEE and TEE were 66(25) kJ·day(-1)·kg(-1), and 12(2.6) MJ·day(-1), respectively. Estimated PAEE from ACC was 54(15) kJ·day(-1)·kg(-1) (p<0.001), with RMSE 24 kJ·day(-1)·kg(-1) and correlation r = 0.52. PAEE estimated from HR and ACC+HR with treadmill calibration were 67(42) and 69(25) kJ·day(-1)·kg(-1) (bias non-significant), with RMSE 34 and 20 kJ·day(-1)·kg(-1) and correlations r = 0.58 and r = 0.67, respectively. Similar results were obtained with step-calibrated and walk-calibrated models, whereas non-calibrated models were less precise (RMSE: 37 and 24 kJ·day(-1)·kg(-1), r = 0.40 and r = 0.55). TEE models also had high validity, with biases <5%, and correlations r = 0.71 (ACC), r = 0.66-0.76 (HR), and r = 0.76-0.83 (ACC+HR). CONCLUSIONS: Both accelerometry and heart rate may be used to estimate EE in adult European men and women, with improved precision if combined and if heart rate is individually calibrated.The study received financial support from Wellcome Trust, Unilever UK, and the Medical Research Council (MC_UU_12015/3).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.013720