Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.Molecular Epidemiolog

The 'road to health' card in tuberculous meningitis

Failure to gain mass adequately prior to the development of TBM is documented on the 'Road to Health' cards of 18 children. The period of failure to gain mass varied from 4 to 25 months (median 9 months) and this could be looked upon as an extension of the normally accepted prodromal period. This failure to gain adequately in mass is a sensitive sign of the presence of TBM and should assist peripheral health workers in the early initiation of anti-tuberculous therapy. BCG vaccination did not prevent the development of TBM in our patients nor did it appear to promote a milder course or more rapid recovery.Articl

Tactical treatment with copper oxide wire particles and symptomatic levamisole treatment using the FAMACHA© system in indigenous goats in South Africa

Haemonchosis is considered to be the most economically important gastrointestinal disease of small ruminants in the tropics and subtropics. However, chemical anthelmintics, which were the mainstay of control, have been compromised by a high prevalence of resistance worldwide. Copper oxide wire particles (COWP) have been shown to have anthelmintic effects, but few studies have examined their use under field conditions. The use of COWP was therefore evaluated as a tactical anthelmintic treatment in indigenous goats raised under communal farming conditions in Bergville, KwaZulu-Natal Province, South Africa. At the beginning of the summer rainfall season (October 2007), the faecal egg counts of 172 female goats belonging to 15 farmers were determined and this sampling continued every four weeks until the second week of January 2008. The goats within each of the 15 herds were ranked according to their faecal egg counts for this week. The goats were sequentially paired off within each ranking starting with those goats with the highest counts. One goat from each pair was randomly allocated to a treated or control group. Two weeks later, a 4 g COWP bolus was randomly administered to each goat in the treated group. Faecal egg counts were carried out on the goats two weeks following treatment, and the sampling of the goats then proceeded every four weeks until October 2008. Except for the six-week period prior to the administration of the COWP, the goats were examined according to the FAMACHA© system and symptomatically treated with 12 mg/kg levamisole when anaemic. The percentage reduction in faecal egg count due to the COWP treatment was 89.0%. Mean pre- and post-treatment faecal egg counts for the COWP-treated group (n = 73) were 2347 eggs per gram of faeces (epg) and 264 epg, respectively. The corresponding values for the untreated controls (n = 66) were 2652 epg and 2709 epg. The prevalence of Haemonchus spp. larvae in pre- and post-treatment faecal cultures was 72% and 46%, respectively. Symptomatic anthelmintic treatments in combination with mid-summer tactical treatments with COWP appear to be useful strategies for the control of Haemonchus contortus in indigenous goats in this farming system and this approach could have application in other similar agro-ecological zones

The T2K experiment

The T2K experiment is a long baseline neutrino oscillation experiment. Its main goal is to measure the last unknown lepton sector mixing angle θ13 by observing νe appearance in a νμ beam. It also aims to make a precision measurement of the known oscillation parameters, and sin22θ23, via νμ disappearance studies. Other goals of the experiment include various neutrino cross-section measurements and sterile neutrino searches. The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC. This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem