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L-type voltage-gated Ca2+ channels are expressed in the plasma membrane of muscles, neurons and endocrine cells where they serve as conductors of signals regulating cellular responses to changes in environment. Malfunctions of channels, as well as deregulations of their activity underlie numerous disorders and diseases commonly called channelopathies. In β-cells Ca2+ channels are central players f

Background: Excessive and inappropriate use of antibiotics is considered to be the most important reason for development of bacterial resistance to antibiotics. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious

Background: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. Design: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations o

Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that wou

Type 2 diabetes (T2D) and metabolic syndrome (MetS) are major health problems associated with cardiovascular disease. Both diseases are influenced by a combination of genetic and environmental factors. The aim of this thesis was to identify genetic risk factors for T2D, particularly T2D associated with obesity, and for MetS. To achieve this goal, we 1) followed-up a region linked to obese T2D in a

Obesity is increasing rapidly in all parts of the world and is now considered to be a global epidemic. Obesity is a major risk factor for several health issues such as type 2 diabetes (T2D) and cardiovascular disease. The adipose tissue is central in the maintenance of a normal energy homeostasis in the body for instance via regulating lipid storage and release. Besides being an important energy r

Tolerance is crucial for maintaining immunological balance and avoid autoimmune diseases like type 1 diabetes and the inflammatory bowel disease, ulcerative colitis (UC). In Study I, we have investigated the regulatory role of a class of noncoding RNAs, the miRNAs, during thymocyte development of the where central tolerance is established. We used the non-obese diabetic mouse (NOD) which is spon

Background: Early childhood environmental exposures, possibly infections, may be responsible for triggering islet autoimmunity and progression to type 1 diabetes (T1D). The Environmental Determinants of Diabetes in the Young (TEDDY) follows children with increased HLA-related genetic risk for future T1D. TEDDY asks parents to prospectively record the child's infections using a diary book. The pres

Background: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glut

På senare år har sjukdomspanoramat för hjärtsjukdomar förändrats, med sjunkande insjuknande och dödlighet i hjärtinfarkt men stigande insjuknande i förmaksflimmer och hjärtsvikt. Förmaksflimmer är den vanligaste hjärtrytmrubbningen och medför ökad risk för uppkomst av blodproppar i hjärtat som kan resultera i stroke, demens och förtida död. Symptom på förmaksflimmer är hjärtklappning, trötthet, anBackground: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and increases in prevalence. As AF confers increased risk of morbidity, stroke, dementia and mortality, a major objective of cardiovascular epidemiology today is the development of tools for prediction and prevention of AF and its consequences. Although AF has traditionally been considered a non-heritable disease,

Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors healthy weight, physical activity, non-smoking, limited

Diabetic patients suffer from macro- and microvascular complications causing increased morbidity and mortality. How hyperglycemia provokes vascular damage remains unclear, but glucose is believed to fuel a harmful low-grade chronic inflammation of the vessel wall. Previous work showed that glucose activates the transcription factor Nuclear Factor of Activated T cells (NFAT) in arteries ex vivo. NF

This thesis presents experimental results on the development and optimization of novel and highly compact sources of beams of fast ions, relativistic electrons and coherent x-rays, driven by intense laser-plasma interactions. The rapid development of high-power, short-pulse laser systems have made available peak powers reaching the petawatt regime and focused intensities reaching 10^21 W/cm2. Whe

The metabolic syndrome is a clustering of several risk factors associated with diabetes and cardiovascular disease. Diabetes is a global problem with 90% of patients suffering from type 2 diabetes (T2D), which is attributable to various factors including genetic predispositions and lifestyle. In T2D, there is a reduction in β cell mass and function, and impaired glucose homeostasis. It is often as