The genomic signature of trait-associated variants

BACKGROUND: Genome-wide association studies have identified thousands of SNP variants associated with hundreds of phenotypes. For most associations the causal variants and the molecular mechanisms underlying pathogenesis remain unknown. Exploration of the underlying functional annotations of trait-associated loci has thrown some light on their potential roles in pathogenesis. However, there are some shortcomings of the methods used to date, which may undermine efforts to prioritize variants for further analyses. Here, we introduce and apply novel methods to rigorously identify annotation classes showing enrichment or depletion of trait-associated variants taking into account the underlying associations due to co-location of different functional annotations and linkage disequilibrium. RESULTS: We assessed enrichment and depletion of variants in publicly available annotation classes such as genic regions, regulatory features, measures of conservation, and patterns of histone modifications. We used logistic regression to build a multivariate model that identified the most influential functional annotations for trait-association status of genome-wide significant variants. SNPs associated with all of the enriched annotations were 8 times more likely to be trait-associated variants than SNPs annotated with none of them. Annotations associated with chromatin state together with prior knowledge of the existence of a local expression QTL (eQTL) were the most important factors in the final logistic regression model. Surprisingly, despite the widespread use of evolutionary conservation to prioritize variants for study we find only modest enrichment of trait-associated SNPs in conserved regions. CONCLUSION: We established odds ratios of functional annotations that are more likely to contain significantly trait-associated SNPs, for the purpose of prioritizing GWAS hits for further studies. Additionally, we estimated the relative and combined influence of the different genomic annotations, which may facilitate future prioritization methods by adding substantial information

Radiation Testing of Electronics for the CMS Endcap Muon System

The electronics used in the data readout and triggering system for the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC) particle accelerator at CERN are exposed to high radiation levels. This radiation can cause permanent damage to the electronic circuitry, as well as temporary effects such as data corruption induced by Single Event Upsets. Once the High Luminosity LHC (HL-LHC) accelerator upgrades are completed it will have five times higher instantaneous luminosity than LHC, allowing for detection of rare physics processes, new particles and interactions. Tests have been performed to determine the effects of radiation on the electronic components to be used for the Endcap Muon electronics project currently being designed for installation in the CMS experiment in 2013. During these tests the digital components on the test boards were operating with active data readout while being irradiated with 55 MeV protons. In reactor tests, components were exposed to 30 years equivalent levels of neutron radiation expected at the HL-LHC. The highest total ionizing dose (TID) for the muon system is expected at the inner-most portion of the CMS detector, with 8900 rad over ten years. Our results show that Commercial Off-The-Shelf (COTS) components selected for the new electronics will operate reliably in the CMS radiation environment

Turbulent drag on a low-frequency vibrating grid in superfluid He-4 at very low temperatures

We present measurements of the dissipative turbulent drag on a vibrating grid in superfluid He-4 over a wide range of (low) frequencies. At high velocities, the dissipative drag is independent of frequency and is approximately the same as that measured in normal liquid He-4. We present measurements on a similar grid in superfluid He-3-B at low temperatures which shows an almost identical turbulent drag coefficient at low frequencies. However, the turbulent drag in He-3-B is substantially higher at higher frequencies. We also present measurements of the inertial drag coefficient for grid turbulence in He-4. The inertial drag coefficient is significantly reduced by turbulence in both superfluid and normal liquid He-4

Effect of transport and rest stop duration on the welfare of conditioned cattle transported by road

The effects of providing rest on physiological and behavioural indicators of welfare of cattle being transported by road has not been well studied in North America. New revisions to Canada’s Health of Animals Regulations Part XII: Transportation of Animals indicate un-weaned and weaned calves can be transported a maximum of 12 and 36 h, respectively, before an 8 h rest is required. Therefore, the aim of this study was to assess the effects of rest duration, after 12 and 36 h of transport, on physiological and behavioural indicators of welfare in 7–8 mo-old beef calves. Three hundred and twenty conditioned calves (258 ± 23.9 kg BW) were randomly assigned to a 2 × 4 factorial design where the main factors included transport duration: 12 h (12; n = 160) and 36 h (36; n = 160) and rest stop duration: 0 h (R0; n = 80), 4 h (R4; n = 80), 8 h (R8; n = 80) and 12 h (R12; n = 80). After the resting period, animals were transported for an additional 4 h. Blood and hair samples were taken from 12 animals per treatment prior to and after the first and the 4 h transport; and then 7 h, 2 d and 28 d after the 4 h transport. The concentrations of haptoglobin, creatine kinase, non-esterified fatty acids (NEFA), lactate, and serum and hair cortisol were determined. Standing and lying behaviour was assessed for 14 d after transport, while feeding behaviour of calves in one pen per treatment were assessed for 28 d after transportation using an electronic feed bunk monitoring system. Body weight (BW), average daily gain (ADG) and shrink (%) was assessed for all calves. The data was modeled using generalized linear mixed methods (SAS PROC GLIMMIX), where transport and time (nested in rest) were considered fixed effects and animal and pen were considered random effects. Statistically significant (p < 0.05) effects of transport were observed on BW and shrink, where 36 h-transported calves had lower (p < 0.01) BW and greater (p < 0.01) shrink than 12 h-transported calves. A transport × time (nested in rest) interaction (p < 0.01) was observed for lying percentage where, 36-R8 calves had greater (p < 0.01) lying percentage than 12-R8 calves on d 1 after transportation. The area under the curve (AUC) for NEFA was greater (p < 0.01) for 36-R0 calves than 12-R0, 36-R4, and 36-R8 calves, and greater (p < 0.01) in 36-R12 calves than 12-R12 calves. Haptoglobin AUC was greater (p = 0.05) in 36-R12 than 12-R12 calves. Overall, physiological indicators of reduced welfare were greater in calves transported for 36 than 12 h, while no clear differences were observed between rest stop groups with the exception of NEFA. Based on these results, conditioned calves benefit from shorter transport durations but there was no clear evidence that calves rested 4, 8, and 12 h following transportation experienced reduced transport related stress compared to those that were not rested (0h).info:eu-repo/semantics/publishedVersio

Tick Ecdysteroid Hormone, Global Microbiota/\u3ci\u3eRickettsia\u3c/i\u3e Signaling in the Ovary Versus Carcass During Vitellogenesis in Part-Fed (Virgin) American Dog Ticks, \u3ci\u3eDermacentor variabilis\u3c/i\u3e

The transovarial transmission of tick-borne bacterial pathogens is an important mechanism for their maintenance in natural populations and transmission, causing disease in humans and animals. The mechanism for this transmission and the possible role of tick hormones facilitating this process have never been studied. Injections of physiological levels of the tick hormone, 20-hydroxyecdysone (20E), into part-fed (virgin) adult females of the American dog tick, Dermacentor variabilis, attached to the host caused a reduction in density of Rickettsia montanensis in the carcass and an increase in the ovaries compared to buffer-injected controls. This injection initiates yolk protein synthesis and uptake by the eggs but has no effect on blood feeding. Francisella sp. and R. montanensis were the predominant bacteria based on the proportionality in the carcass and ovary. The total bacteria load increased in the carcass and ovaries, and bacteria in the genus Pseudomonas increased in the carcass after the 20E injection. The mechanism of how the Rickettsia species respond to changes in tick hormonal regulation needs further investigation. Multiple possible mechanisms for the proliferation of R. montanensis in the ovaries are proposed