The Accidental Terrorist: Okhrana Connections to the Extreme-Right and the Attempt to Assassinate Sergei Witte in 1907

This article represents a case study in the relationship between the tsarist secret police (commonly known as the Okhrana in the West and okhranka in Russia) and acts of political terror perpetrated by the extreme-right in late imperial Russia. This specific case concerns the tangled web of conspiracy, propaganda and controversy that surrounded the attempted assassination of former-Chairman of the Council of Ministers, Sergei Witte, in 1907

Resequencing three candidate genes for major depressive disorder in a Dutch cohort

Major depressive disorder (MDD) is a psychiatric disorder, characterized by periods of low mood of more than two weeks, loss of interest in normally enjoyable activities and behavioral changes. MDD is a complex disorder and does not have a single genetic cause. In 2009 a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. Many of the top signals of this GWAS mapped to a region spanning the gene PCLO, and the non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became genome wide significant after post-hoc analysis. We performed resequencing of PCLO, GRM7, and SLC6A4 in 50 control samples from the GAIN-MDD cohort, to detect new genomic variants. Subsequently, we genotyped these variants in the entire GAIN-MDD cohort and performed association analysis to investigate if rs2522833 is the causal variant or simply in linkage disequilibrium with a more associated variant. GRM7 and SLC6A4 are both candidate genes for MDD from literature. We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort. After next generation sequencing and association analysis we excluded the possibility of an undetected common variant to be more associated. For neither PCLO nor GRM7 we found a more associated variant. For SLC6A4, we found a new SNP that showed a lower P-value (P = 0.07) than in the GAIN-MDD GWAS (P = 0.09). However, no evidence for genome-wide significance was found. Although we did not take into account rare variants, we conclude that our results provide further support for the hypothesis that the non-synonymous coding SNP rs2522833 in the PCLO gene is indeed likely to be the causal variant in the GAIN-MDD cohort

4 Decades of Belgian Marine Monitoring: uplifting historical data to today’s needs - Final Report

Context : Long-term quality checked and integrated datasets for the Belgian Part of the North Sea (BPNS) are essential to detect changes in this complex ecosystem and support policy related decisions.Objectives: - Compile and safeguard quality checked, intercalibrated and integrated datasets and make them publicly accessible for further research and policy purposes.- Improve or develop methods and protocols to assess and interpret environmental change in the BPNS and compare trends with neighbouring areas.- Provide support and advice for policy related decisions and legal measures, like MSFD and OSPAR.Conclusions: A scheme with data management tools has been worked out for efficient data flow throughout the project. The scheme, including the mandatory metadata fields and standardization, can be used as a guideline for future projects. Inventories of datasources, projects and data-originators were compiled and the final datasets are available via the central dataportal. Even after compiling and quality checking the long-term datasets, the scientists had to consider some limitations, like changing methodologies and low data resolution, and incorporate these into their trend analyses procedures. Some remarkable environmental changes over time were observed. Model results of the contaminants showed decreasing trends for heavy metals and PCBs. Zn concentrations, however, were found increasing in marine sediments while As concentrations were found increasing in groyne mussels. Nearby the port of Zeebrugge and the mouth of the Scheldt, PCB concentrations were found slightly increasing again over the last decade. The study on eutrophication showed that nutrient (N, P) riverine concentrations and loads have decreased continuously from the end of the 1980‟s to now. However, this did not result in a comparable decrease of marine nutrient concentrations. No clear long-term trend effect was observed on in situ chlorophyll a concentrations following the nutrient decrease. However, a clear change in chlorophyll a phenology followed the increase in sea surface temperature in the period. Furthermore, biomass, seasonality and structure of diatom and dinoflagellate communities were compared between the 1970s and 2000s for the Belgian Part of the North Sea (BPNS), derived from the newly established Belgian Phytoplankton Database. Distinct changes were observed: changes in diatom and dinoflagellate biomass and shift of fulcrum; changes in community structure, with a trend towards seasonal homogenization in the diatom community; increased occurrence of harmful diatom (Pseudo-nitzschia) and dinoflagellate (e.g. Prorocentrum) genera. The observed changes correlate well with overall increases in temperature and changes in nutrient loads and ratios.And finally, for acidification, pH data reveal an increasing trend from the mid-70‟s to the mid-80‟s and a decrease of pH from the mid-80‟s onwards that seems consistent with changes in primary production patterns. The comparison of CH4 concentrations obtained in 1990 and 2016, showed a decreasing trend consistent with alleviation of eutrophication in the area.Based on the outcome of this successful project, the partners defined various recommendations regarding future monitoring strategies for policy makers

The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome

We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3′ end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 90° kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475,000 Individuals

Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results - Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10-8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant. Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up