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Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria

In eukaryotes, iron-sulfur clusters are essential cofactors for numerous physiological processes, but these clusters are primarily biosynthesized in mitochondria. Previous studies suggest mitochondrial ABCB7-type exporters are involved in maturation of cytosolic iron-sulfur proteins. However, the molecular mechanism for how the ABCB7-type exporters participate in this process remains elusive. Here

PcoB is a defense outer membrane protein that facilitates cellular uptake of copper

Copper (Cu) is one of the most abundant trace metals in all organisms, involved in a plethora of cellular processes. Yet elevated concentrations of the element are harmful, and interestingly prokaryotes are more sensitive for environmental Cu stress than humans. Various transport systems are present to maintain intracellular Cu homeostasis, including the prokaryotic plasmid-encoded multiprotein pc

Mesenchymal heterogeneity in the adult human lung

The human lung is a complex tissue consisting of a heterogeneous mix of different structures and cells, each which a specific role that together contribute to the primary function of the organ: the gas exchange. Different mesenchymal cells populate the interstitial areas around airways and blood vessels and form the connective tissue together with the extracellular matrix. Fibroblasts constitute o

Disposal Behaviour and Local Support Systems

Disposal behaviour represent the last phase in the consumption cycle. From an environmental point of view it is extremely important to know the factors behind individual behaviour in waste handling. There are several aspects of interest, for example willingness of waste separation and re-use of products. The aim of this article is to analyse the importance of environmental concern, disposal behavi

Evidence for neural contribution to islet effects of DPP-4 inhibition in mice

It has been suggested that neural mechanisms may contribute to effects of the incretin hormones, and, therefore, also to the effects of dipeptidyl peptidase (DPP-4) inhibition. We therefore examined whether muscarinic mechanisms are involved in the stimulation of insulin secretion by DPP-4 inhibition. Fasted, anesthetized mice were given intraperitoneal saline or the muscarinic antagonist atropine

Incretin hormone receptors are required for normal beta cell development and function in female mice

The incretin hormones, glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), potentiate insulin secretion and are responsible for the majority of insulin secretion that occurs after a meal. They may also, however, have a fundamental role in pancreatic beta cell development and function, independently of their role in potentiating insulin secretion after a meal. Th

Efficacy of lixisenatide in patients with type 2 diabetes : A post hoc analysis of patients with diverse β-cell function in the GetGoal-M and GetGoal-S trials

Aims: To evaluate the impact of β-cell function on the efficacy of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes (T2D). Materials and methods: In this post hoc analysis, patients from the Phase 3 GetGoal-M and GetGoal-S clinical trials randomized to lixisenatide 20. μg once daily were stratified into quartiles by baseline β-cell func

Developmental programming : State-of-the-science and future directions: Summary from a Pennington Biomedical symposium

OBJECTIVE: On December 8-9, 2014, the Pennington Biomedical Research Center convened a scientific symposium to review the state-of-the-science and future directions for the study of developmental programming of obesity and chronic disease. The objectives of the symposium were to discuss: (i) past and current scientific advances in animal models, population-based cohort studies, and human clinical

Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest exp

CFTR in pancreatic islets

AbstractCystic fibrosis (CF) is caused by mutations in the anion channel and protein regulator CFTR. The most common co-morbidity in CF is CF-related diabetes (CFRD) affecting ~50% of adult patients. The etiopathology of CFRD is largely unknown but the destruction of the exocrine pancreas is thought to contribute. However, the hypothesis that CFTR has a direct role in the endocrine pancreas has no

Genetic Determinants of Dyslipidemia

Dyslipidemia is a chronic deviation from normal blood lipid levels that can lead to atherosclerosis and other cardiovascular diseases; dyslipidemia and its sequelae are caused by the complex interplay of genetic and environmental factors. Although circulating concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein chole

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

Roles of unconventional ion channels and insulin granule structure in the pathogenesis of type-2 diabetes

T2D is the most widespread endocrine disease. In conventional stimulus secretion coupling increased blood glucose is metabolized causing an increased intracellular level of ATP and closure of the KATP channels, and this, in turn, depolarizes the cell membrane leading to the opening of voltage-gated Ca2+ channels, the influx of Ca2+ and exocytosis of insulin granules. This model has become almost a

Amino acids and the changing face of the α-cell

Glucagon has long been defined by its glucogenic action and as a result α-cells have been characterised based largely on their interaction with glucose. Recent findings have challenged this preconception, bringing to the fore the significant role glucagon plays in amino acid breakdown and underlining the importance of amino acids in glucagon secretion. The challenge that remains is defining the me

Race/Ethnicity and Gender Representation in Hematology and Oncology Editorial Boards : What is the State of Diversity?

Introduction: Women and underrepresented groups in medicine hold few academic leadership positions in the field of hematology/oncology. In this study, we assessed gender and race/ethnicity representation in editorial board positions in hematology/oncology journals. Materials and Methods: Editorial leadership board members from 60 major journals in hematology and oncology were reviewed; 54 journals

α-cell electrophysiology and the regulation of glucagon secretion

Glucagon is the principal glucose-elevating hormone that forms the first-line defence against hypoglycaemia. Along with insulin, glucagon also plays a key role in maintaining systemic glucose homeostasis. The cells that secrete glucagon, pancreatic α-cells, are electrically excitable cells and use electrical activity to couple its hormone secretion to changes in ambient glucose levels. Exactly how

The Apparent Organ-Specificity of Amyloidogenic ApoA-I Variants Is Linked to Tissue-Specific Extracellular Matrix Components

Apolipoprotein A-I (ApoA-I) amyloidosis is a rare protein misfolding disease where fibrils of the N-terminal domain of the protein accumulate in several organs, leading to their failure. Although ApoA-I amyloidosis is systemic, the different amyloidogenic variants show a preferential tissue accumulation that appears to correlate with the location of the mutation in the protein sequence and with th