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Vitamin D and its analogues are fat-soluble vitamins that carry out important functions in human and animal organisms. Many studies have pointed out the relationship between the deficiency of these substances and the development of both skeletal-and extra-skeletal diseases. Although vitamin D is fundamentally derived from the bio-transformation of its precursor, 7-dehydrocholesterol, through the a
As institutional forms of political engagement continue to decline, participation in protests steadily become more common. These trends are particularly strong among younger citizens. Previous research indicates that social factors can explain participation in political protests, and that younger citizens’ participation in protests is more affected by social ties than older people’s participation.
The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified
Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of human gene inactivation that complements knockout studies in cells and model organisms. Here we report three key findings regarding the assessment of candidate drug targets using human loss-of-function variants. First, even essential genes, in which loss-of-function variants
Public procurement is widely used in order to incorporate competition into public services. Competition in procurement often leads to efficiency but the process can also raise some problems. While providing the procurement documents you do not know who will be your upcoming partner. Another aspect is how flexibility can be managed in contract design while maintaining a high service quality. The ai
This article examines the role of national parliaments in policy processes related to the realization of the 2030 Agenda for sustainable development, adopted in the UN General Assembly in 2015. We outline three main roles of parliaments in the case of national policy-making based on intergovernmental agreements: legislative and policy approval, citizen representation, and accountability. The cases
This article investigates whether the choice experiment approach can be used to assess people's preferences and the determinants of these preferences in order to estimate the costs and benefits of different configurations of the transport of hazardous materials by rail. Changes in the exposure to hazardous materials that people are subjected to are used rather than changes in accident risk. To the
MOTIVATION: Depletion of loss-of-function (LoF) mutations may provide a rank of genic functional intolerance and consequently susceptibility to disease.RESULTS: Here we have studied LoF mutations in 60 706 unrelated individuals and show that the most intolerant quartile of ranked genes is enriched in rare and early onset diseases and explains 87% of de novo haploinsufficient OMIM mutations, 17% mo
Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are two frequent causes of dementia that share both clinical and neuropathological features. Common to both disorders are the neurofibrillary tangles consisting of aggregations of hyperphosphorylated tau protein. Recently, a number of different pathogenic mutations in the tau gene have been identified in families with FTD and parkinsonism
The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located
Tumours displaying differentiation towards normal fat constitute the most common subgroup of soft tissue neoplasms. A series of such tumours was investigated by whole-exome sequencing followed by targeted ultra-deep sequencing. Eighty percent of angiolipomas, but not any other tumour type, displayed mutations in the protein kinase D2 (PRKD2) gene, typically in the part encoding the catalytic domai
