Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

The Development of Functional Overreaching Is Associated with a Faster Heart Rate Recovery in Endurance Athletes

Purpose The aim of the study was to investigate whether heart rate recovery (HRR) may represent an effective marker of functional overreaching (f-OR) in endurance athletes. Methods and Results Thirty-one experienced male triathletes were tested (10 control and 21 overload subjects) before (Pre), and immediately after an overload training period (Mid) and after a 2-week taper (Post). Physiological responses were assessed during an incremental cycling protocol to exhaustion, including heart rate, catecholamine release and blood lactate concentration. Ten participants from the overload group developed signs of f-OR at Mid (i.e. -2.1 ± 0.8% change in performance associated with concomitant high perceived fatigue). Additionally, only the f-OR group demonstrated a 99% chance of increase in HRR during the overload period (+8 ± 5 bpm, large effect size). Concomitantly, this group also revealed a >80% chance of decreasing blood lactate (-11 ± 14%, large), plasma norepinephrine (-12 ± 37%, small) and plasma epinephrine peak concentrations (-51 ± 22%, moderate). These blood measures returned to baseline levels at Post. HRR change was negatively correlated to changes in performance, peak HR and peak blood metabolites concentrations. Conclusion These findings suggest that i) a faster HRR is not systematically associated with improved physical performance, ii) changes in HRR should be interpreted in the context of the specific training phase, the athletes perceived level of fatigue and the performance response; and, iii) the faster HRR associated with f-OR may be induced by a decreased central commandand by a lower chemoreflex activity

An Introduction to Temporal Graphs: An Algorithmic Perspective

A \emph{temporal graph} is, informally speaking, a graph that changes with time. When time is discrete and only the relationships between the participating entities may change and not the entities themselves, a temporal graph may be viewed as a sequence $G_1,G_2\ldots,G_l$ of static graphs over the same (static) set of nodes $V$. Though static graphs have been extensively studied, for their temporal generalization we are still far from having a concrete set of structural and algorithmic principles. Recent research shows that many graph properties and problems become radically different and usually substantially more difficult when an extra time dimension in added to them. Moreover, there is already a rich and rapidly growing set of modern systems and applications that can be naturally modeled and studied via temporal graphs. This, further motivates the need for the development of a temporal extension of graph theory. We survey here recent results on temporal graphs and temporal graph problems that have appeared in the Computer Science community

Acquisition of a Unique Onshore/Offshore Geophysical and Geochemical Dataset in the Northern Malawi (Nyasa) Rift

The Study of Extension and maGmatism in Malawi aNd Tanzania (SEGMeNT) project acquired a comprehensive suite of geophysical and geochemical datasets across the northern Malawi (Nyasa) rift in the East Africa rift system. Onshore/offshore active and passive seismic data, long‐period and wideband magnetotelluric data, continuous Global Positioning System data, and geochemical samples were acquired between 2012 and 2016. This combination of data is intended to elucidate the sedimentary, crustal, and upper‐mantle architecture of the rift, patterns of active deformation, and the origin and age of rift‐related magmatism. A unique component of our program was the acquisition of seismic data in Lake Malawi, including seismic reflection, onshore/offshore wide‐angle seismic reflection/refraction, and broadband seismic data from lake‐bottom seismometers, a towed streamer, and a large towed air‐gun source

A New Direction to Athletic Performance: Understanding the Acute and Longitudinal Responses to Backward Running

Backward running (BR) is a form of locomotion that occurs in short bursts during many overground field and court sports. It has also traditionally been used in clinical settings as a method to rehabilitate lower body injuries. Comparisons between BR and forward running (FR) have led to the discovery that both may be generated by the same neural circuitry. Comparisons of the acute responses to FR reveal that BR is characterised by a smaller ratio of braking to propulsive forces, increased step frequency, decreased step length, increased muscle activity and reliance on isometric and concentric muscle actions. These biomechanical differences have been critical in informing recent scientific explorations which have discovered that BR can be used as a method for reducing injury and improving a variety of physical attributes deemed advantageous to sports performance. This includes improved lower body strength and power, decreased injury prevalence and improvements in change of direction performance following BR training. The current findings from research help improve our understanding of BR biomechanics and provide evidence which supports BR as a useful method to improve athlete performance. However, further acute and longitudinal research is needed to better understand the utility of BR in athletic performance programs

The perceptions of social responsibility for community resilience to flooding: the impact of past experience, age, gender and ethnicity

Community resilience to flooding depends, to a large extent, on the participation of community members to take more responsibility for enhancing their own resilience. The perception of social responsibility (SR) which is argued to be one of the antecedents influencing individual’s willingness to undertake resilient behaviours can significantly contribute to community resilience through individual and collective actions. Understanding of factors influencing the perceptions of SR of individuals within community might help with developing strategies to increase the perceptions of SR. This research explores perceptions of SR in relation to flooding for householders and local businesses and establishes their relationships with experience of flooding and demographic factors of age, gender and ethnicity. The data were obtained via a questionnaire survey of three communities in Birmingham and one community in South East London, UK, three with experience of flooding and one without. A total of 414 responses were received and used in the multiple regression analysis. The analysis identified ‘experience of flooding’, ‘age’ and ‘South Asian’ ethnic group as significant variables, suggesting that older individuals from South Asian ethnic groups with previous experience of flooding are likely to be more socially responsible than others without these attributes

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Measuring perinatal complications: methodologic issues related to gestational age

<p>Abstract</p> <p>Background</p> <p>Perinatal outcomes differ by week of gestational age. However, it appears that how measures to examine these outcomes vary among various studies. The current paper explores how perinatal complications are reported and how they might differ when different denominators, numerators, and comparison groups are utilized.</p> <p>Conclusion</p> <p>One issue that can clearly affect absolute rates and trends is how groups of women are categorized by their gestational age. Since most perinatal outcomes can only occur in women and neonates who have delivered, using the number of pregnancies delivered (PD) as the denominator of outcomes is appropriate. However, for an outcome such as antepartum stillbirth, all women who are pregnant at a particular gestational age are at risk. Thus, the denominator should include all ongoing pregnancies (OP). When gestational age is used by week this means using both deliveries during a particular week plus those women who deliver beyond the particular week of gestation in the denominator. Researchers should be careful to make sure they are utilizing the appropriate measure of perinatal complications so they do not report findings that would be misleading to clinicians, patients, and policy makers.</p