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Eleven Amino Acids of HLA-DRB1 and Fifteen Amino Acids of HLA-DRB3, 4 and 5 Include Potentially "Causal Residues" Responsible for the Risk of Childhood Type 1 Diabetes

Next generation targeted sequencing of HLA-DRB1, -DRB3, -DRB4 and -DRB5 (abbreviated as DRB345) provides high resolution of functional variant positions to investigate their associations with type 1 diabetes risk and with autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A) or ZnT8 (ZnT8A). To overcome exceptional DR sequence complexity due to high polymorphisms and extended linkage-di

Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report

OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progre

Using metabolite profiling to construct and validate a metabolite risk score for predicting future weight gain

Background Excess weight gain throughout adulthood can lead to adverse clinical outcomes and are influenced by complex factors that are difficult to measure in free-living individuals. Metabolite profiling offers an opportunity to systematically discover new predictors for weight gain that are relatively easy to measure compared to traditional approaches. Methods and results Using baseline metabol

Expression levels of enzymes generating NO and CO in islets of murine and human diabetes

The possible implication of the gasotransmitters NO and CO for the development of diabetes remains unresolved. Our previous investigations in rodents suggested NO being inhibitory, and CO stimulatory, to glucose-stimulated insulin secretion (GSIS). Here we studied the possible role of these gasotransmitters in both murine and human type 2 diabetes (T2D) by mapping the expression pattern of neural

Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes

Type 1 (T1D) and type 2 (T2D) diabetes share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, whereas beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell frag

Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort

OBJECTIVES: There are significant geographical differences in the prevalence and incidence of celiac disease that cannot be explained by HLA alone. More than 40 loci outside of the HLA region have been associated with celiac disease. We investigated the roles of these non-HLA genes in the development of tissue transglutaminase autoantibodies (tTGA) and celiac disease in a large international prosp

Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk : Results from the EPIC cohort study

Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee an

Optical Studies of Single Quantum Dots

Popular Abstract in Swedish En halvledare är en kristall vars egenskaper till stor del bestäms av dess bandgap, som i någon mening kan ses som lägesenergin hos fria elektroner i kristallen. En kvantprick är en liten volym halvledarmaterial som är inbäddad i ett annat material med större bandgap. Det gör att volymen attraherar laddning eftersom elektroner (precis som allt annat) helst minimerar sinThis thesis presents spectroscopic studies of single self-assembled InP quantum dots (QDs). The electronic properties of these QDs have been studied by photoluminescence (PL) and scanning tunnelling luminescence (STL). The QDs were grown in the Stranski-Krastanow mode and were embedded in GaInP. This material is slightly n-type, giving a Fermi-level close to the conduction band edge at low temper

Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS-We have conducted a meta-analysis of genome-wide as

Updated Genetic Score Based on 34 Confirmed Type 2 Diabetes Loci Is Associated With Diabetes Incidence and Regression to Normoglycemia in the Diabetes Prevention Program

OBJECTIVE Over 30 loci have been associated with risk of type 2 diabetes at genome-wide statistical significance. Genetic risk scores (GRSs) developed from these loci predict diabetes in the general population. We tested if a GRS based on an updated list of 34 type 2 diabetes-associated loci predicted progression to diabetes or regression toward normal glucose regulation (NGR) in the Diabetes Prev

From association to function : MTNR1B

The discovery that variants in the melatonin receptor 2 (MTNR1B) gene were associated with glucose levels, insulin secretion, and risk for type 2 diabetes (T2D) in genome-wide association studies (GWAS) reinforced the previously suggested link between glucose homeostasis and circadian rhythmicity. Diurnal secretion of melatonin has reported to be altered in people with diabetes and rodent models o

Genetics of type 2 diabetes : It matters from which parent we inherit the risk

Type 2 diabetes (T2D) results from a co-occurrence of genes and environmental factors. There are more than 120 genetic loci suggested to be associated with T2D, or with glucose and insulin levels in European and multi-ethnic populations. Risk of T2D is higher in the offspring if the mother rather than the father has T2D. Genetically, this can be associated with a unique parent-of-origin (PoO) tran

A Case Study Evaluation of the Guideline-Supported QUPER Model for Elicitation of Quality Requirements

[Context & motivation] For market-driven software product developing organizations operating on a competitive open market, it is important to plan the product’s releases so that they can reach the market as early as possible with a competitive level of quality compared to its competitors' products. Hence, quality requirements can be seen as a key competitive advantage. The QUPER model was deve

GPR40 protein levels are crucial to the regulation of stimulated hormone secretion in pancreatic islets. Lessons from spontaneous obesity-prone and non-obese type 2 diabetes in rats.

The role of islet GPR40 protein in the pathogenesis of diabetes is unclear. We explored the influence of GPR40 protein levels on hormone secretion in islets from two rat models of spontaneous type 2 diabetes displaying either hyperlipidaemia or hyperglycaemia. GPR40 expression was analysed by confocal microscopy, Western blot and qPCR in islets from preobese Zucker (fa/fa) rats, diabetic Goto-Kaki

Water diffusion and free volume in hydrophilic polymers

Popular Abstract in Swedish Vid vattenabsorption i en polymer antas vattenmolekylerna röra sig genom polymeren via små kaviteter, som inte upptas av polymermolekylerna och dess termiska vibrationer. Den ej upptagna volymen, som de små kaviteterna representerar kallas fri volym. Storleken på kaviteterna liksom andra egenskaper hos polymeren såsom andelen kristallin fas ändras kontinuerligt i takt mDuring moisture uptake in polymers, the diffusion of the water molecules is believed to occur via unoccupied voids. These voids are called free volume cavities and their sizes are continuously altered when the moisture content in the polymer is enhanced. Not only the free volume cavity sizes, but also other polymer properties such as the degree of crystallinity, are changed as a consequence of moi

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with

Perspective : An extension of the STROBE statement for observational studies in nutritional epidemiology (STROBE-nut): Explanation and elaboration

Nutritional epidemiology is an inherently complex and multifaceted research area. Dietary intake is a complex exposure and is challenging to describe and assess, and links between diet, health, and disease are difficult to ascertain. Consequently, adequate reporting is necessary to facilitate comprehension, interpretation, and generalizability of results and conclusions. The STrengthening the Repo

Influence of a HTR2B stop codon on glucagon homeostasis and glucose excursion in non-diabetic men

Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This