De universiteitsbibliotheek in het databankenrecht

Universiteitsbibliotheken hebben vanouds te maken gehad met auteursrechten die rusten op de werken in hun collecties. Sinds 1999 kent het Nederlandse recht naast het auteursrecht het zogenaamde databankenrecht. Het databankenrecht beschermt de investeringen die producenten van databanken hebben gepleegd. Daartoe verschaft het databankenrecht de producenten - kort gezegd - een exclusief recht om hun databanken te exploiteren. Het databankenrecht (en het auteursrecht) raken het functioneren van bibliotheken in tweeërlei opzicht. Met de opkomst van gedigitaliseerde informatie is de bibliotheek enerzijds als afneemster van databanken in een afhankelijkere positie komen te verkeren. Anderzijds bestaat de toegevoegde waarde die bibliotheken realiseren voor een deel uit de voortbrenging van databanken, zoals bijvoorbeeld catalogi. Deze databanken zijn - met name als ze in digitale vorm verkeren - technisch gemakkelijk te exploiteren. Deze studie onderzoekt of het vanuit een juridisch perspectief noodzakelijk dan wel wenselijk is dat bibliotheken zich meer gaan profileren als producenten van informatie.

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Genetics of coronary artery disease: Genome-wide association studies and beyond

Genome-wide association (GWA) studies on coronary artery disease (CAD) have been very successful, identifying a total of 32 susceptibility loci so far. Although these loci have provided valuable insights into the etiology of CAD, their cumulative effect explains surprisingly little of the total CAD heritability. In this review, we first highlight and describe the type of genetic variants potentially underlying the missing heritability of CAD: single nucleotide polymorphisms (SNPs) or structural variants, each ofwhich may either be common or rare. Although finding missing heritability is important, we further argue in this review that it constitutes only a first step towards a fuller understanding of the etiology of CAD development. To close the gap between the genotype and phenotype, we propose a systems genetics approach in the post-GWA study era. This approach that integrates genetic, epigenetic, transcriptomic, proteomic, metabolic and intermediate outcome variables has potential to significantly aid the understanding of CAD etiology. (c) 2012 Elsevier Ireland Ltd. All rights reserved

LodGWAS: a software package for genome-wide association analysis of biomarkers with a limit of detection

Summary: Genome-wide association study (GWAS) of a biomarker is complicated when the assay procedure of the biomarker is restricted by a Limit of Detection (LOD). Those observations falling outside the LOD cannot be simply discarded, but should be included into the analysis by applying an appropriate statistical method. However, the problem of LOD in GWAS analysis of such biomarkers is usually overlooked. 'lodGWAS' is a flexible, easy-to-use R package that provides a simple and elegant way for GWAS analysis of such biomarkers while simultaneously accommodating the problem of LOD by applying a parametric survival analysis method. Availability and implementation: http://cran.r-project.org/web/packages/lodGWAS

In Silico Post Genome-Wide Association Studies Analysis of C-Reactive Protein Loci Suggests an Important Role for Interferons

Background - Genome-wide association studies (GWASs) have successfully identified several single nucleotide polymorphisms (SNPs) associated with serum levels of C-reactive protein (CRP). An important limitation of GWASs is that the identified variants merely flag the nearby genomic region and do not necessarily provide a direct link to the biological mechanisms underlying their corresponding phenotype. Here we apply a bioinformatics-based approach to uncover the functional characteristics of the 18 SNPs that had previously been associated with CRP at a genome-wide significant level. Methods and Results - In the first phase of in silico sequencing, we explore the vicinity of GWAS SNPs to identify all linked variants. In the second phase of expression quantitative trait loci analysis, we attempt to identify all nearby genes whose expression levels are associated with the corresponding GWAS SNPs. These 2 phases generate several relevant genes that serve as input to the next phase of functional network analysis. Our in silico sequencing analysis using 1000 Genomes Project data identified 7 nonsynonymous SNPs, which are in moderate to high linkage disequilibrium (r2>0.5) with the GWAS SNPs. Our expression quantitative trait loci analysis, which was based on one of the largest single data sets of genome-wide expression probes (n>5000) identified 23 significantly associated expression probes belonging to 15 genes (false discovery rate <0.01). The final phase of functional network analysis revealed 93 significantly enriched biological processes (false discovery rate <0.01). Conclusions - Our post-GWAS analysis of CRP GWAS SNPs confirmed the previously known overlap between CRP and lipids biology. Additionally, it suggested an important role for interferons in the metabolism of CRP