2-Axis Electric Off-Road Bucket Seat Bases

Off-road vehicle bucket seats are currently restricted to a single position relative to the floor of the vehicle. Drivers and riders desire the ability to adjust their seat position to increase comfort and allow for a greater size range of riders to fit safely within the cabin or roll cage. To develop a viable solution, the team has gone through an extensive design process and has constructed a functioning prototype. This Final Design Report encapsulates the entire design process and concludes with recommendations for changes we would make looking both back in review as well as moving forward with further iterations of the product

Cystatin C and Cardiovascular Disease

Background Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. Objectives The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. Methods We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. Results Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10−14). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10−211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10−5). A causal effect of cystatin C was not detected for any individual component of CVD. Conclusions Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

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Retention of functional variation despite extreme genomic erosion: MHC allelic repertoires in the Lynx genus

[Background] Demographic bottlenecks erode genetic diversity and may increase endangered species’ extinction risk via decreased fitness and adaptive potential. The genetic status of species is generally assessed using neutral markers, whose dynamic can differ from that of functional variation due to selection. The MHC is a multigene family described as the most important genetic component of the mammalian immune system, with broad implications in ecology and evolution. The genus Lynx includes four species differing immensely in demographic history and population size, which provides a suitable model to study the genetic consequences of demographic declines: the Iberian lynx being an extremely bottlenecked species and the three remaining ones representing common and widely distributed species. We compared variation in the most variable exon of the MHCI and MHCII-DRB loci among the four species of the Lynx genus.[Results] The Iberian lynx was characterised by lower number of MHC alleles than its sister species (the Eurasian lynx). However, it maintained most of the functional genetic variation at MHC loci present in the remaining and genetically healthier lynx species at all nucleotide, amino acid, and supertype levels.[Conclusions] Species-wide functional genetic diversity can be maintained even in the face of severe population bottlenecks, which caused devastating whole genome genetic erosion. This could be the consequence of divergent alleles being retained across paralogous loci, an outcome that, in the face of frequent gene conversion, may have been favoured by balancing selection.Funding for this project was provided by the Spanish Dirección General de Investigación Científica y Técnica (CGL2010–21540/BOS and CGL2013–47755-P), project "Adaptive variation in declining species: Survey of MHC variation in Eurasian lynx populations at the western edge of its range" funded by the internal EBD proposal call “Microproyectos” financed by the Spanish Ministry of Economy and Competitiveness, through the Severo Ochoa Program for Centres of Excellence in R + D + I (SEV-2012-0262), and project 2014/15/B/NZ8/00212 funded by the National Science Center, Poland. Elena Marmesat received a JAE predoctoral grant from CSIC (Spanish National Research Council). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe