Exome array analysis of ischaemic stroke: results from a southern Swedish study.

BACKGROUND AND PURPOSE: Genome-wide association (GWA) studies have identified a few risk loci for ischaemic stroke, but these variants explain only a small part of the genetic contribution to the disease. Coding variants associated with amino acid substitutions or premature termination of protein synthesis could have a large effect on disease risk. We performed an exome array analysis for ischaemic stroke. METHODS: Patients with ischaemic stroke (n = 2385) and control subjects (n = 6077) from three Swedish studies were genotyped with the Illumina HumanOmniExpressExome BeadChip. Single-variant association analysis and gene-based tests were performed of exome variants with minor allele frequency of < 5%. A separate GWA analysis was also performed, based on 700 000 genotyped common markers and subsequent imputation. RESULTS: No exome variant or gene was significantly associated with all ischaemic stroke after Bonferroni correction (all P > 1.8 × 10-6 for single-variant and >4.15 × 10-6 for gene-based analysis). The strongest association in single-variant analysis was found for a missense variant in the DNAH11 gene (rs143362381; P = 5.01 × 10-6 ). In gene-based tests, the strongest association was for the ZBTB20 gene (P = 7.9 × 10-5 ). The GWA analysis showed that the sample was homogenous (median genomic inflation factor = 1.006). No genome-wide significant association with overall ischaemic stroke risk was found. However, previously reported associations for the PITX2 and ZFHX3 gene loci with cardioembolic stroke subtype were replicated (P = 7 × 10-15 and 6 × 10-3 ). CONCLUSIONS: This exome array analysis did not identify any single variants or genes reaching the pre-defined significance level for association with ischaemic stroke. Further studies on exome variants should be performed in even larger, well-defined and subtyped samples.

Optimization of confocal laser induced fluorescence in a plasma.

Laser Induced Fluorescence (LIF) provides measurements of flow speed, temperature, and density of ions or neutrals in a plasma. Traditionally, a LIF measurement requires two ports on a plasma device; one for laser injection and one for emission collection. Proper alignment of LIF optics is time consuming and sensitive to mechanical vibration. We describe a confocal configuration for LIF that requires a single port and requires no alignment. The measurement location is scanned radially by physically moving the entire optical structure. Confocal LIF measurements are compared to traditional LIF measurements over the same radial range.

Digital test assembly of truck parts with the IMMA-tool--an illustrative case.

Several digital human modelling (DHM) tools have been developed for simulation and visualisation of human postures and motions. In 2010 the DHM tool IMMA (Intelligently Moving Manikins) was introduced as a DHM tool that uses advanced path planning techniques to generate collision free and biomechanically acceptable motions for digital human models (as well as parts) in complex assembly situations. The aim of the paper is to illustrate how the IPS/IMMA tool is used at Scania CV AB in a digital test assembly process, and to compare the tool with other DHM tools on the market. The illustrated case of using the IMMA tool, here combined with the path planner tool IPS, indicates that the tool is promising. The major strengths of the tool are its user friendly interface, the motion generation algorithms, the batch simulation of manikins and the ergonomics assessment methods that consider time.

Complete genomic sequence of the lytic bacteriophage phiYeO3-12 of Yersinia enterocolitica serotype O:3.

phiYeO3-12 is a T3-related lytic bacteriophage of Yersinia enterocolitica serotype O:3. The nucleotide sequence of the 39,600-bp linear double-stranded DNA (dsDNA) genome was determined. The phage genome has direct terminal repeats of 232 bp, a GC content of 50.6%, and 54 putative genes, which are all transcribed from the same DNA strand. Functions were assigned to 30 genes based on the similarity of the predicted products to known proteins. A striking feature of the phiYeO3-12 genome is its extensive similarity to the coliphage T3 and T7 genomes; most of the predicted phiYeO3-12 gene products were >70% identical to those of T3, and the overall organizations of the genomes were similar. In addition to an identical promoter specificity, phiYeO3-12 shares several common features with T3, nonsubjectibility to F exclusion and growth on Shigella sonnei D(2)371-48 (M. Pajunen, S. Kiljunen, and M. Skurnik, J. Bacteriol. 182:5114-5120, 2000). These findings indicate that phiYeO3-12 is a T3-like phage that has adapted to Y. enterocolitica O:3 or vice versa. This is the first dsDNA yersiniophage genome sequence to be reported.

Mortality and cancer incidence among laboratory technicians in medical research and routine laboratories (Sweden).

OBJECTIVES: To investigate cancer incidence and mortality among laboratory employees. METHODS: Mortality and cancer incidence were investigated among 2553 female and male laboratory workers employed at the Karolinska Institute and Karolinska Hospital in Stockholm between 1950 and 1989. Mortality was followed from 1952-1993 and cancer incidence from 1958-1992. Expected numbers were based on the general population in Stockholm, standardizing for age, gender, and calendar period. RESULTS: The overall mortality and cancer incidence in the cohort was lower than expected. There were in all 10 cases of hemato-lymphatic malignancies (three acute myeloid leukemias, four non-Hodgkin lymphomas, two Hodgkin's lymphomas, and one multiple myeloma) in the cohort. The standardized incidence ratio (SIR) for hematolymphatic tumors was increased among workers who had ever been employed in laboratories with a high probability for chemical exposure, SIR 224 (95% CI 108-412). The risk of breast cancer among women was increased after more than 10 years of work in high-exposure laboratories, SIR 225 (128-365). The number of malignant melanomas exceeded those expected. CONCLUSIONS: The findings support earlier observations of an increased risk of hematolymphatic cancer among laboratory workers. The routine for handling chemicals and functionality of ventilatory equipment must be under continuous supervision.

Three-dimensional structure of renal Na,K-ATPase determined from two-dimensional membrane crystals of the p1 form.

Electron microscopy and image processing were used to reconstruct a three-dimensional model of membrane-bound monomeric renal Na,K-ATPase from negatively stained two-dimensional crystals of the p1 type. Correlation methods were applied to obtain projection averages which were aligned by a phase difference minimization procedure. The self-consistency of the reconstruction process was high as determined by correlation between experimental projections and projections of the calculated model. The three-dimensional model of the Na,K-ATPase promoter in the p1 crystal form contains three characteristic domains, a protein dense ellipsoid, a small globular stain deficient domain, and a connecting low-contrast region. The latter is thought to correspond to the lipid-penetrating part of the Na,K-ATPase promoter. The location of this domain gives the protein an asymmetric distribution in the bilayer so that it is exposed primarily on one side proposed to correspond to the intracellular face.

Assembly of two-dimensional membrane crystals of Na,K-ATPase.

The assembly of vanadate-induced two-dimensional membrane crystals of Na,K-ATPase was analyzed by electron microscopy and image processing. Electron micrographs of negatively stained linear arrays of protein molecules were recorded and processed by correlation averaging methods. The arrays were compared with fully developed p21 crystals of the enzyme. On the basis of similarity in protein form, symmetry, and packing arrangement it was concluded that the fully developed crystals are built of tightly packed ribbons. Assembly pathways for two-dimensional membrane crystals of Na,K-ATPase are proposed.