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Preservation of enzyme activity and antigenicity after mutagenesis of the membrane anchoring domain of GAD65

The smaller isoform of glutamic acid decarboxylase, GAD65, is an important autoantigen implicated in the pathogenesis of type 1 diabetes whereas the larger isoform, GAD67 appears to play no major role. The primary difference between the two isoforms resides in the N-terminal part of the molecule including the GAD65 membrane-anchoring domain. The aim of this study was to generate mutants of the mem

Low-dose streptozotocin induces sustained hyperglycemia in Macaca nemestrina

The potential for using macaques to create a nonhuman diabetic model was investigated. The significant objectives were to determine a) prognosis of STZ induced permanent beta cell destruction in nonhuman primates, and b) the potential to use STZ treated animals in a model of autoimmune diabetes by following adoptively transferred lymphocytes into MHC identical macaques. Beta cell impairment was ac

Bag-limits på torsk i Öresund

Fritidsfisket är en viktig källa till rekreation samtidigt som företag inom fisketurism bidrar till utvecklingen av de kustnära regionerna. Sedan januari 2017 regleras fritidsfisket på torsk i västra Östersjön av en bag-limit. Det innebär att det är tillåtet att ta hem högst fem torskar per dag (tre under lekperioden, februari-mars). I det berörda området är många fisketurismföretag så kallade tur

Low serum conditions for in vitro generation of human macrophages with macrophage colony stimulating factor

Animal serum is often used to generate human macrophages in vitro. Since fetal calf serum (FCS) may complicate antigen uptake, processing and presentation on HLA molecules, we tested the ability of M-CSF to generate macrophages at low fetal calf serum conditions. Peripheral blood monocytes from 12 individuals were cultured 1-4 days with 0-100 ng/ml macrophage colony stimulating factor (M-CSF) at e

Glucose-regulated insulin expression in diabetic rats

Retroviral vectors encoding glucose-responsive promoters driving furin expression may provide an amplified, glucose-regulated secretion of insulin. We constructed LhI*TFSN virus to encode a glucose-regulatable transforming growth factor α promoter controlling furin expression with a viral LTR promoter driving constitutive expression of furin-cleavable human proinsulin. Autologous BB rat vascular s

Gene and Cell-Replacement Therapy in the Treatment of Type 1 Diabetes : How High Must the Standards Be Set?

Recent advances in molecular and cell biology may allow for the development of novel strategies for the treatment and cure of type 1 diabetes. In particular, it is now possible to envisage restoration of insulin secretion by gene or cell-replacement therapy. The β-cell is, however, remarkably sophisticated, and many of the features of this highly differentiated secretory cell will have to be faith

Autoimmune type 1 diabetes : Resolved and unresolved issues

Based on the presence of autoantibodies and a strong HLA linkage, type 1 diabetes is now classified as a chronic autoimmune disease. Many issues, however, remain unresolved. Although autoantibodies to GAD65, IA-2, and insulin are clearly markers for this disease, it is not known whether they contribute to pathogenesis or are simply the response to an existing underlying destructive process. Based

Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population

Objective. Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. Design. A population-based follow-up cohort study. Setting. Participants visited the primary health care cen

A novel monoclonal antibody specific for the N-terminal end of GAD65

We describe a novel monoclonal antibody raised towards the N-terminus of the 65 kDa isoform of glutamate decarboxylase (GAD65). This N-GAD65 mAb is highly specific for GAD65 and can be used in a wide range of applications such as Western blot analysis, immunoprecipitation and immunocytochemistry. Full-length cDNAs coding for N-GAD65 mAb heavy and light chains were cloned and characterized by nucle

Induction of islet allotolerance in nonhuman primates

Recent clinical trials have pioneered the successful use of a nonsteroidal immunosuppressive regimen and established a basis for application in a routine clinical setting. In this study, a single islet transplant was not sufficient to regulate blood glucose levels, and a second transplant became necessary. A similar observation was made in our macaque islet transplant study, where animals after th

Proportional–Integral Controller Design for Combustion-Timing Feedback, from n-Heptane to iso-Octane in Compression-Ignition Engines

The problem of designing robust and noise-insensitive PI controllers for pressure-sensor based combustion-timing control was studied through simulation. Different primary reference fuels (PRF) and operating conditions were studied. The simulations were done using a physics-based, control-oriented model with an empirical ignition-delay correlation. It was found that the controllable region, in-betwThe problem of designing robust and noise-insensitive PI controllers for pressure-sensor based combustion-timing control was studied through simulation. Different primary reference fuels (PRF) and operating conditions were studied. The simulations were done using a physics-based, control-oriented model with an empirical ignition-delay correlation. It was found that the controllable region, in-betw

Increased galanin expression in the celiac ganglion of BB diabetic rats

BB rats lose >50% of their islet sympathetic nerve terminals soon after diabetes onset, markedly impairing the glucagon response to activation of these nerves. In this study, we sought evidence that this degree of disease-induced nerve terminal damage affected their neuronal cell bodies. Increased galanin expression was used as a marker of the change of phenotype that occurs in neuronal cell bodie

Evidence of a functional role for mast cells in the development of type 1 diabetes mellitus in the biobreeding rat

Human type 1 diabetes mellitus (T1DM) arises through autoimmune destruction of pancreatic β cells and is modeled in many respects by the lymphopenic and spontaneously diabetic BioBreeding (BB) DRlyp-lyp rat Previously, preonset expression profiling of whole DRlyp-lyp pancreatic lymph nodes (PLN) revealed innate immune activity, specifically that of mast cells and eosinophils. Furthermore, we obser

An extension of digital volume correlation for multimodality image registration

The question of registering two images (or image volumes) acquired with different modalities, and thus exhibiting different contrast, at different positions is addressed based on an extension of global digital image (or volume) correlation. A specific comparison metric is introduced allowing the signature of the different phases to be related. A first solution consists of a Gaussian mixture to des

Oxidation of a Dimethoxyhydroquinone by Ferrihydrite and Goethite Nanoparticles : Iron Reduction versus Surface Catalysis

Hydroquinones are important mediators of electron transfer reactions in soils with a capability to reduce Fe(III) minerals and molecular oxygen, and thereby generating Fenton chemistry reagents. This study focused on 2,6-dimethoxy hydroquinone (2,6-DMHQ), an analogue to a common fungal metabolite, and its reaction with ferrihydrite and goethite under variable pH and oxygen concentrations. Combined

Stages of PPP and principal–agent conflicts : the Swedish water and sewerage sector

The focus of this article is on public–private partnerships (PPPs). The aim is to both theoretically and empirically illustrate PPP agency problems in four PPP stages, as well as to identify potentially relevant solutions to the agency problems. The study employed a longitudinal case study of one PPP in a municipality in southern Sweden. Through an analysis based on interviews, observations, and d

Translating sustainable and smart city strategies into performance measurement systems

This paper shows how sustainable and smart strategies can be implemented in cities and how these strategies influence, and are influenced by, performance measurement systems. Drawing upon the Foucauldian notion of governmentality, the authors present the case of Gothenburg in Sweden, where they interviewed the key actors involved in a new sustainability strategy. Translating strategy into performa