A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants

Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.     

Kepler detected gravity-mode period spacings in a red giant star

Stellar interiors are inaccessible through direct observations. For this reason, helioseismologists made use of the Sun's acoustic oscillation modes to tune models of its structure. The quest to detect modes that probe the solar core has been ongoing for decades. We report the detection of mixed modes penetrating all the way to the core of an evolved star from 320 days of observations with the Kepler satellite. The period spacings of these mixed modes are directly dependent on the density gradient between the core region and the convective envelope.     

Genome sequence of Theileria parva, a bovine pathogen that transforms lymphocytes

We report the genome sequence of Theileria parva, an apicomplexan pathogen causing economic losses to smallholder farmers in Africa. The parasite chromosomes exhibit limited conservation of gene synteny with Plasmodium falciparum, and its plastid-like genome represents the first example where all apicoplast genes are encoded on one DNA strand. We tentatively identify proteins that facilitate parasite segregation during host cell cytokinesis and contribute to persistent infection of transformed host cells. Several biosynthetic pathways are incomplete or absent, suggesting substantial metabolic dependence on the host cell. One protein family that may generate parasite antigenic diversity is not telomere-associated.     

Crystal structure of cobra-venom phospholipase A2 in a complex with a transition-state analogue

The crystal structure of a complex between a phosphonate transition-state analogue and the phospholipase A2 (PLA2) from Naja naja atra venom has been solved and refined to a resolution of 2.0 angstroms. The identical stereochemistry of the two complexes that comprise the crystal's asymmetric unit indicates both the manner in which the transition state is stabilized and how the hydrophobic fatty acyl chains of the substrate are accommodated by the enzyme during interfacial catalysis. The critical features that suggest the chemistry of binding and catalysis are the same as those seen in the crystal structure of a similar complex formed with the evolutionarily distant bee-venom PLA2.     

Characterization of integron mediated antimicrobial resistance in Salmonella isolated from diseased swine

Forty-two Salmonella isolates obtained from diseased swine were genetically characterized for the presence of specific antimicrobial resistance mechanisms. Twenty of these isolates were characterized as S. Typhimurium DT104 strains. Pulsed-field gel electrophoresis was used to determine genetic relatedness and revealed 20 distinct genetic patterns among the 42 isolates. However, all DT104 isolates fell within 2 closely related genetic clusters. Other Salmonella isolates were genetically grouped together according to serotype. All DT104 isolates displayed the penta-resistance phenotype to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline. Resistance to sulfamethoxazole, tetracycline, streptomycin, kanamycin, and ampicillin was most common among the non-DT104 Salmonella isolates. All DT104 strains contained 2 chromosomal integrons of 1000 and 1200 base pairs. The DNA sequencing revealed that the 2 integrons contained genes encoding a resistance to streptomycin and ampicillin, respectively. None of the non-DT104 strains showed the same pattern, although several strains possessed integrons of 1000 base pairs or larger. However, the majority of non-DT104 Salmonella strains did not possess any integrons. Two Salmonella isolates displayed tolerance to the organic solvent cyclohexane, indicating the possibility that they are overexpressing chromosomal regulatory genes marA or soxS or the associated multidrug efflux pump, acrAB. This research suggests that integrons contribute to antimicrobial resistance among specific swine Salmonella serotypes; however, they are not as widely disseminated among non-Typhimurium swine Salmonella serotypes as previously thought.     

The effect of speed of wheeling on soil stresses, rut depth and soil physical properties in an ameliorated transitional red-brown earth

Soil stress measurements were made in an ameliorated transitional red-brown earth (Natric Palexeralf) during one pass of a heavily loaded (4 t) wheel. Different speeds (up to about 8 km h⁻¹ and soil water contents (close to the lower plastic limit) were used for measurements of total stress, final bulk density, air permeability and rut depth. Effective stresses appeared to decrease with speed. Increases of total stress caused by extra fluid pressure (i.e. pore-water pressure) at 20-cm depth were associated with fast deformation rates of the soil (up to about 3 m s⁻¹) just behind the leading edge of the tyre contact area. Shear stress changed very little with speed. Equations relating speed and water content to rut depth and resultant bulk density were also found. These predicted approximately 10% less mean rut depth or bulk density at 20-cm depth by increasing speed from 0.5 to 10 km h⁻¹ over this soil at water contents near the lower plastic limit.     

Associations between the distance traveled from sale barns to commercial feedlots in the United States and overall performance, risk of respiratory disease, and cumulative mortality in feeder cattle during 1997 to 2009

Most beef cattle are transported at least once during their lives, and this potentially stressful practice may affect subsequent health and performance. Limited research is available quantifying the effects of transport on feedlot performance and health, and particularly the risk of bovine respiratory disease complex (BRD), which is the most common disease of weaned calves after arrival to the feedlot. The objective of this retrospective study was to determine potential associations between distance traveled (DTV) during transportation with health (cumulative BRD morbidity and mortality of all causes) and performance (ADG and HCW) parameters in cattle cohorts (n = 14,601) that arrived to 21 U.S. commercial feedlots from 1997 to 2009. Multivariable mixed-effects negative binomial and linear regression models were employed to determine associations between health and performance outcomes with DTV and other cohort-level demographic variables. Cattle were transported a median of 552 km from origin to feedlot with a mean (± SEM) of 698 ± 4.4 km. The mean (±SEM) cumulative BRD morbidity was 4.9% ± 0.01% (median = 1.1%; range: 0 to 100%) whereas the mean (±SEM) cumulative mortality due to all causes was 1.3% ± 0.01% (median = 0.8%; range: 0 to 28.7%). Distance traveled was significantly associated (P < 0.05) with BRD morbidity, overall mortality, HCW and ADG, and its effects were modified by demographic characteristics (i.e., cohort region of origin, mean arrival BW, gender, and the season of the year) of the cohort. Knowledge of the distance traveled during transportation could allow a more precise prediction of cattle feedlot health and performance.