NEW AND LITTLE-KNOWN NEUROPTERA FROM THE DUTCH EAST INDIES.

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Methylmercury Exposure and Adverse Cardiovascular Effects in Faroese Whaling Men

Background: Methylmercury (MeHg), a worldwide contaminant found in fish and seafood, has been linked to an increased risk of cardiovascular mortality. Objective: We examined 42 Faroese whaling men (30–70 years of age) to assess possible adverse effects within a wide range of MeHg exposures from consumption of pilot whale meat. Methods: We assessed exposure levels from mercury analysis of toenails and whole blood (obtained at the time of clinical examination), and a hair sample collected 7 years previously. Outcome measures included heart rate variability (HRV), blood pressure (BP), common carotid intima-media thickness (IMT), and brainstem auditory evoked potentials (BAEP). We carried out multiple regression and structural equation model (SEM) analyses to determine the confounder-adjusted effect of mercury exposure. Taking into account correlations among related measures, we categorized exposure and outcomes in groups to derive latent exposure and response variables in SEMs. We used multiple regression analysis to compare the predictive validity of individual exposure biomarkers and the latent exposure variable on individual and latent outcomes. Results: The toenail mercury concentrations varied widely and had a geometric mean of 2.0 μg/g; hair concentrations averaged about 3-fold higher. Mercury exposure was significantly associated with increased BP and IMT. This effect was reflected by SEMs, but mercury in toenails tended to be the best effect predictor. Conclusions: The results support the notion that increased MeHg exposure promotes the development of cardiovascular disease

Re-evaluation of the LHC potential for the measurement of Mw

We present a study of the LHC sensitivity to the W boson mass based on simulation studies. We find that both experimental and phenomenological sources of systematic uncertainties can be strongly constrained with Z measurements: the lineshape is robustly predicted, and its analysis provides an accurate measurement of the detector resolution and absolute scale, while the differential cross-section analysis absorbs most of the strong interaction uncertainties. A sensitivity \delta Mw \sim 7 \MeV for each decay channel (W --> e nu, W --> mu nu), and for an integrated luminosity of 10 fb-1, appears as a reasonable goal

European birth cohorts for environmental health research

Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning

Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity

Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots

Myrmeleontiden aus S\ufcd-Indien

Volume: 38Start Page: 445End Page: 44