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Intracellular C3 protects β-cells from IL-1β-driven cytotoxicity via interaction with Fyn-related kinase

One of the hallmarks of type 1 but also type 2 diabetes is pancreatic islet inflammation, associated with altered pancreatic islet function and structure, if unresolved. IL-1β is a proinflammatory cytokine which detrimentally affects β-cell function. In the course of diabetes, complement components, including the central complement protein C3, are deregulated. Previously, we reported high C3 expre

Smoking induces overexpression of immediate early genes in active Graves' ophthalmopathy.

Background: Cigarette smoking is a risk factor for the development of Graves' ophthalmopathy (GO). In a previous study of gene expression in intraorbital fat, adipocyte-related immediate early genes (IEGs) were overexpressed in patients with GO compared to controls. We investigated whether IEGs are upregulated by smoking and examined other pathways that may be affected by smoking. Methods: Gene ex

ACTH following overnight dexamethasone suppression can be used in the verification of autonomous cortisol secretion in patients with adrenal incidentalomas

Objective: During the investigation of adrenal incidentalomas, it is important to accurately diagnose autonomous cortisol secretion (ACS) but the specificity of cortisol ≥50 nmol/L after overnight dexamethasone suppression (cortisolONDST) is low. Therefore, ACTH following overnight dexamethasone suppression (ACTHONDST) and cortisol following a 2-day dexamethasone suppression test (cortisol2-DAYDST

Leveraging cross-species transcription factor binding site patterns: from diabetes risk Loci to disease mechanisms.

Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation w

Indigenous Peoples – A Hinder to Development?: The Right to Prior Consultation in Colombia and Peru

The thesis deals with the following question: Do the national legislation initiatives of Colombia and Peru, aiming at protecting the Indigenous Peoples’ right to land through their right to be consulted prior to any measures that may affect their lives and lands, reach the internationally set standards that these countries have committed to? The thesis concludes that the term Indigenous Peoples

Eukaryotic translation initiation factor 3 subunit e controls intracellular calcium homeostasis by regulation of cav1.2 surface expression.

Inappropriate surface expression of voltage-gated Ca(2+)channels (CaV) in pancreatic ß-cells may contribute to the development of type 2 diabetes. First, failure to increase intracellular Ca(2+) concentrations at the sites of exocytosis impedes insulin release. Furthermore, excessive Ca(2+) influx may trigger cytotoxic effects. The regulation of surface expression of CaV channels in the pancreatic

Adaptive Immunity in Cardiovascular Disease

Atherosclerosis, thickening of the major arteries, is a chronic disease leading to cardiovascular disease (CVD) such as myocardial infarction (MI) and stroke, both affecting millions worldwide. T-cells and antibodies have been implicated in atherosclerosis. This thesis contains studies on CD4+ helper subsets and studies on antibodies against methylglyoxal-modified apolipoprotein B100 (MGO-ApoB100)

Regulation of glucagon secretion from pancreatic alpha cells

Glucagon secreted by pancreatic α-cells plays an important role in the regulation of blood glucose. In this thesis, different techniques such as electrophysiology, immunohistochemistry and hormone secretion assay were combined to explore the mechanisms by which glucagon secretion is regulated. Like pancreatic β-cells, which produce insulin, α-cells are electrically excitable and equipped with dif

Gene Therapy for Neurological Disorders

Popular Abstract in Danish Genterapi er en attraktiv terapiform mod neurologiske lidelser som Parkinsons sygdom og epilepsi af flere grunde. Gener med en terapeutisk effekt kan introduceres lokalt ved præcise injektioner i det syge væv, hvor genproduktet kan frigives fra nerveceller i respons til aktivitet i det omgivende væv. Ved genterapi omgås den forhindring som blod-hjernebarrieren udgør, ligGene therapy is an attractive strategy for neurological disorders, such as Parkinson’s disease and epilepsy, for several reasons. Introduction of genes with a therapeutic potential can be achieved locally, by accurate injections in the compromised tissue, and release of a transgene therapeutic substance can be regulated by the surrounding host neural circuitry. The gene therapy approach circumvent

Study on administration of 1,5-anhydro-D-fructose in C57BL/6J mice challenged with high-fat diet

1,5-Anhydro-D-fructose (AF) is a mono-saccharide directly formed from starch and glycogen by the action of alpha-1,4-glucan lyase (EC 4.2.2.13). Our previous study has indicated that AF increases glucose tolerance and insulin secretion in NMRI mice after administration through a gastric gavage in a single dose at 150 mg per mouse. In this study, we used high-fat feeding of C57BL/6J mice to examine

Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans

A major concern in common disease epigenomics is distinguishing causal from consequential epigenetic variation. One means of addressing this issue is to identify the temporal origins of epigenetic variants via longitudinal analyses. However, prospective birth-cohort studies are expensive and time consuming. Here, we report DNA methylomics of archived Guthrie cards for the retrospective longitudina

Syndecan-4 signaling via NFAT regulates extracellular matrix production and cardiac myofibroblast differentiation in response to mechanical stress

Pressure overload activates cardiac fibroblasts leading to excessive production of extracellular matrix which may contribute to compromised heart function. The activated fibroblast acquires smooth muscle-like features such as expression of smooth muscle alpha-actin (SMA) and SM22 and is therefore referred to as myofibroblast. The molecular mechanisms underlying mechanical stress-induced myofibrobl

Detecting microRNA activity from gene expression data

Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA

Serum cytokine pattern in young children with screening detected celiac disease.

Celiac disease is an autoimmune disease characterized by inflammation localized to the small bowel, but less is known about systemic signs of inflammation. The aim was to measure cytokines of the T helper 1 (Th1) and T helper 2 (Th2) cell patterns in children with screening detected celiac disease before and after treatment with a gluten free diet.

Characterization of the Lipid Droplet Proteome of a Clonal Insulin-producing β-Cell Line (INS-1 832/13).

Lipids are known to play a crucial role both in the normal control of insulin release and in the deterioration of β-cell function, as observed in type 2 diabetes. Despite this established dual role of lipids, little is known about lipid storage and handling in β-cells. Here, we isolated lipid droplets from oleate-incubated INS-1 832/13 cells and characterized the lipid droplet proteome. In a total

Maternal Autoimmune Thyroid Disease and the Fetal Immune System.

OBJECTIVE: Several studies indicate that in utero exposure to maternal autoimmune diseases and transplacental passage of autoantibodies affect the risk of autoimmunity in the offspring, e. g., maternally derived GAD65 autoantibody correlates with decreased risk of type 1 diabetes, whereas thyroid peroxidase autoantibody (TPOAb) positivity at birth is associated with increased incidence of autoimmu