Aqueous solutions of super reduced polyoxotungstates as electron storage systems.

Due to the increasing energy density demands of battery technology, it is vital to develop electrolytes with high electron storage capacity. Polyoxometalate (POM) clusters can act as electron sponges, storing and releasing multiple electrons and have potential as electron storage electrolytes for flow batteries. Despite this rational design of clusters for high storage ability can not yet be achieved as little is known about the features influencing storage ability.

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas.

Objective: To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth.

Research Design And Methods: Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members.

Acute Recurrent Pancreatitis in a Child With INS-Related Monogenic Diabetes and a Heterozygous Pathogenic CFTR Mutation.

Given the close anatomical and physiological links between the exocrine and endocrine pancreas, diseases of 1 compartment often affect the other through mechanisms that remain poorly understood. Pancreatitis has been associated with both type 1 and type 2 diabetes, but its association with monogenic diabetes is unknown. Patients heterozygous for pathogenic CFTR variants are cystic fibrosis carriers and have been reported to have an increased risk of acute pancreatitis.

Insight on Diagnosis and Treatment From Over a Decade of Research Through the University of Chicago Monogenic Diabetes Registry.

Monogenic diabetes is a category of diabetes mellitus caused by a single gene mutation or chromosomal abnormality, usually sub-classified as either neonatal diabetes or maturity-onset diabetes of the young (MODY). Although monogenic diabetes affects up to 3.5% of all patients with diabetes diagnosed before age 30, misdiagnosis and/or improper treatment occurs frequently.

Effective Storage of Electrons in Water by the Formation of Highly Reduced Polyoxometalate Clusters.

Aqueous solutions of polyoxometalates (POMs) have been shown to have potential as high-capacity energy storage materials due to their potential for multi-electron redox processes, yet the mechanism of reduction and practical limits are currently unknown. Herein, we explore the mechanism of multi-electron redox processes that allow the highly reduced POM clusters of the form {MO} to absorb electrons in aqueous solution, focusing mechanistically on the Wells-Dawson structure X[PWO], which comprises 18 metal centers and can uptake up to 18 electrons reversibly ( = 18) per cluster in aqueous solution when the countercations are . This unconventional redox activity is rationalized by density functional theory, molecular dynamics simulations, UV-vis, electron paramagnetic resonance spectroscopy, and small-angle X-ray scattering spectra.

Exploring the Geometric Space of Metal-Organic Polyhedrons (MOPs) of Metal-Oxo Clusters.

Metal organic polyhedra (MOPs) such as coordination cages and clusters are increasingly utilized across many fields, but their geometrically selective assembly during synthesis is nontrivial. When ligand coordination along these polyhedral edges is arranged in an unsymmetrical mode or the bridging ligand itself is nonsymmetric, a vast combinatorial space of potential isomers exists complicating formation and isolation. Here we describe two generalizable combinatorial methodologies to explore the geometrical space and enumerate the configurational isomers of MOPs with discrimination of the chiral and achiral structures.

Novel dominant K channel mutations in infants with congenital hyperinsulinism: Validation by in vitro expression studies and in vivo carrier phenotyping.

Inactivating mutations in the genes encoding the two subunits of the pancreatic beta-cell K channel, ABCC8 and KCNJ11, are the most common finding in children with congenital hyperinsulinism (HI). Interpreting novel missense variants in these genes is problematic, because they can be either dominant or recessive mutations, benign polymorphisms, or diabetes mutations. This report describes six novel missense variants in ABCC8 and KCNJ11 that were identified in 11 probands with congenital HI.

Mechanism of pharmacochaperoning in a mammalian K channel revealed by cryo-EM.

ATP-sensitive potassium (K) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β-cells to maintain glucose homeostasis. Mutations that impair channel folding or assembly prevent cell surface expression and cause congenital hyperinsulinism.

Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in Type 1 Diabetes as Revealed by Comparison With GCK-MODY (MODY2).

Although insulin resistance consistently occurs with type 1 diabetes, its predominant driver is uncertain. We therefore determined the relative contributions of hyperglycemia and iatrogenic hyperinsulinemia to insulin resistance using hyperinsulinemic-euglycemic clamps in three participant groups ( = 10/group) with differing insulinemia and glycemia: healthy control subjects (euinsulinemia and euglycemia), glucokinase-maturity-onset diabetes of the young (GCK-MODY; euinsulinemia and hyperglycemia), and type 1 diabetes (hyperinsulinemia and hyperglycemia matching GCK-MODY). We assessed the contribution of hyperglycemia by comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes.

Functional characterization of activating mutations in the sulfonylurea receptor 1 (ABCC8) causing neonatal diabetes mellitus in Asian Indian children.

Background: Gain-of-function of ATP-sensitive K (K ) channels because of mutations in the genes encoding SUR1 (ABCC8) or Kir6.2 (KCNJ11) is a major cause of neonatal diabetes mellitus (NDM). Our aim is to determine molecular defects in K channels caused by ABCC8 mutations in Asian Indian children with NDM by in vitro functional studies.

Coupling d Ir(III) and d Pt(II) Chromophores.

Two classes of widely studied luminescent metal complexes are octahedral d (i.e., Ir) and square planar d (i.

Methods for Characterizing Disease-Associated ATP-Sensitive Potassium Channel Mutations.

The ATP-sensitive potassium (K) channel formed by the inwardly rectifying potassium channel Kir6.2 and the sulfonylurea receptor 1 (SUR1) plays a key role in regulating insulin secretion. Genetic mutations in KCNJ11 or ABCC8 which encode Kir6.

Anti-diabetic drug binding site in a mammalian K channel revealed by Cryo-EM.

Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides.

Gallium(III)-Containing, Sandwich-Type Heteropolytungstates: Synthesis, Solution Characterization, and Hydrolytic Studies toward Phosphoester and Phosphoanhydride Bond Cleavage.

The gallium(III)-containing heteropolytungstates [Ga4(H2O)10(β-XW9O33)2](6-) (X = As(III), 1; Sb(III), 2) were synthesized in aqueous acidic medium by reaction of Ga(3+) ions with the trilacunary, lone-pair-containing [XW9O33](9-). Polyanions 1 and 2 are isostructural and crystallized as the hydrated sodium salts Na6[Ga4(H2O)10(β-AsW9O33)2]·28H2O (Na-1) and Na6[Ga4(H2O)10(β-SbW9O33)2]·30H2O (Na-2) in the monoclinic space group P21/c, with unit cell parameters a = 16.0218(12) Å, b = 15.

Identification and molecular characterization of HNF1B gene mutations in Indian diabetic patients with renal abnormalities.

Heterozygous mutations of the HNF1B gene (HNF1B-MODY or MODY5) are associated with a wide clinical spectrum of renal and extrarenal disease without clear genotype-phenotype correlation. In this study, we investigated the prevalence of HNF1B gene mutations in young Indian diabetic patients with various renal abnormalities. Fifty unrelated young diabetic patients, who also had renal abnormalities, were selected from the electronic records of a large diabetes centre in Chennai, in southern India.

Novel ABCC8 (SUR1) gene mutations in Asian Indian children with congenital hyperinsulinemic hypoglycemia.

Congenital hyperinsulinemic hypoglycemia (HI) is a heterogeneous genetic disorder of insulin secretion characterized by persistent hypoglycemia, most commonly associated with inactivating mutations of the β-cell ATP-sensitive K(+) channel (K(ATP) channel) genes ABCC8 (encoding SUR1) and KCNJ11(encoding Kir6.2). This study aimed to screen the mutations in the genes associated with congenital HI in Asian Indian children.

Glucokinase gene mutations (MODY 2) in Asian Indians.

Background And Aim: Heterozygous inactivating mutations in the glucokinase (GCK) gene cause a hyperglycemic condition termed maturity-onset diabetes of the young (MODY) 2 or GCK-MODY. This is characterized by mild, stable, usually asymptomatic, fasting hyperglycemia that rarely requires pharmacological intervention. The aim of the present study was to screen for GCK gene mutations in Asian Indian subjects with mild hyperglycemia.