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Precise regulation of β-cell function is crucial for maintaining blood glucose homeostasis. Pax6 is an essential regulator of β-cell-specific factors like insulin and Glut2. Studies in the developing eye suggest that Pax6 interacts with Mitf to regulate pigment cell differentiation. Here, we show that Mitf, like Pax6, is expressed in all pancreatic endocrine cells during mouse postnatal developmen
It is still unclear whether carbohydrate consumption is associated with cardiovascular disease (CVD) risk. Genetic susceptibility might modify the associations between dietary intakes and disease risk.
Microglia, resident immune cells of the brain, react to the presence of pathogens/danger signals with a large repertoire of functional responses including morphological changes, proliferation, chemotaxis, production/release of cytokines, and phagocytosis. In vitro studies suggest that many of these effector functions are Ca2+-dependent, but our knowledge about in vivo Ca2+ signalling in microglia
Background: Allergy and asthma are closely linked. Inhalation of allergen induces an early allergic response (EAR) within the airways of allergic asthmatic subjects, which is followed by a late allergic response (LAR) in approximately 50% of the subjects. The LAR is defined as a drop in forced expiratory volume in 1 second (FEV1) from baseline usually occurring 4-8 hours after exposure and is beli
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
Objective. The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Methods. Bionaïve nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieve
BACKGROUND: Chromosome 9p21 variants are associated with cardiovascular disease (CVD) but not with any of its known risk markers. However, recent studies have suggested that the risk associated with 9p21 variation is modified by a prudent dietary pattern and smoking. We tested if the increased risk of CVD by the 9p21 single nucleotide polymorphism rs4977574 is modified by intakes of vegetables, fr
Background: Exposure to airborne particles has a major impact on global health. The probability of these particles to deposit in the respiratory tract during breathing is essential for their toxic effects. Observations have shown that there is a substantial variability in deposition between subjects, not only due to respiratory diseases, but also among individuals with healthy lungs. The factors d
The tremendous increases in production of plastic materials has led to an accumulation of plastic pollution worldwide. Many studies have addressed the physical effects of large-sized plastics on organisms, whereas few have focused on plastic nanoparticles, despite their distinct chemical, physical and mechanical properties. Hence our understanding of their effects on ecosystem function, behaviour
Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR
BACKGROUND The association between neighborhood deprivation and mortality is well established, but knowledge about whether deprivation is best assessed regionally or nationally is scarce. OBJECTIVE The present study aims to examine whether there is a difference in results when using national and county-specific neighborhood deprivation indices and whether the level of urbanization modifies the ass
A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from ge
A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdom
We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants’ data, better
Background: Although sugar consumption has been associated with several risk factors for cardiometabolic diseases, evidence for harmful long-term effects is lacking. In addition, most studies have focused on sugar-sweetened beverages (SSBs), not sugar per se. Objective: The aim of this study was to examine the associations between added and free sugar intake, intake of different sugar sources, a
Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation proc
We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Se
Endocrine disorders that lead to a state of chronic high blood glucose levels are collectively referred to as diabetes. This metabolic disease is mainly categorized into type 1 (T1D) and type 2 diabetes (T2D). These diabetic forms originate from distinct triggering environmental, genetic, and altered mechanisms. T2D is a consequence of metabolic load, peripheral insulin resistance, and failure of
BACKGROUND: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of melanoma families and whether performance improvements can be achieved.METHODS: 2,116 familial melanoma cases were ascertained by the inte
