Charge Reduction of Membrane Proteins in Native Mass Spectrometry Using Alkali Metal Acetate Salts.

Native mass spectrometry (MS) provides the capacity to monitor membrane protein complexes and noncovalent binding of ligands and lipids to membrane proteins. The charge states produced by native MS of membrane proteins often result in gas-phase protein unfolding or loss of noncovalent interactions. In an effort to reduce the charge of membrane proteins, we examined the utility of alkali metal salts as a charge-reducing agent.

Direct binding of phosphatidylglycerol at specific sites modulates desensitization of a ligand-gated ion channel.

Pentameric ligand-gated ion channels (pLGICs) are essential determinants of synaptic transmission, and are modulated by specific lipids including anionic phospholipids. The exact modulatory effect of anionic phospholipids in pLGICs and the mechanism of this effect are not well understood. Using native mass spectrometry, coarse-grained molecular dynamics simulations and functional assays, we show that the anionic phospholipid, 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG), preferentially binds to and stabilizes the pLGIC, Erwinia ligand-gated ion channel (ELIC), and decreases ELIC desensitization.

Prevalence and risk factors of hand eczema in hospital-based nurses in northern China.

Background/objectives: This study aimed to evaluate the prevalence of hand eczema among nurses in northern China and to analyse associated risk factors.

Methods: A retrospective self-reported questionnaire was designed and distributed to 1322 nurses who were selected from three regional hospitals. Risk factors related to hand eczema in nurses were analysed using multivariable logistic regression.

Secondary consequences of beta cell inexcitability: identification and prevention in a murine model of K(ATP)-induced neonatal diabetes mellitus.

ATP-insensitive K(ATP) channel mutations cause neonatal diabetes mellitus (NDM). To explore the mechanistic etiology, we generated transgenic mice carrying an ATP-insensitive mutant K(ATP) channel subunit. Constitutive expression in pancreatic beta cells caused neonatal hyperglycemia and progression to severe diabetes and growth retardation, with loss of islet insulin content and beta cell architecture.

Differential roles of blocking ions in KirBac1.1 tetramer stability.

Potassium channels are tetrameric proteins that mediate K(+)-selective transmembrane diffusion. For KcsA, tetramer stability depends on interactions between permeant ions and the channel pore. We have examined the role of pore blockers on the tetramer stability of KirBac1.

Random assembly of SUR subunits in K(ATP) channel complexes.

Sulfonylurea receptors (SURs) associate with Kir6.x subunits to form tetradimeric K(ATP) channel complexes. SUR1 and SUR2 confer differential channel sensitivities to nucleotides and pharmacological agents, and are expressed in specific, but overlapping, tissues.

Expression of ATP-insensitive KATP channels in pancreatic beta-cells underlies a spectrum of diabetic phenotypes.

Glucose metabolism in pancreatic beta-cells elevates cytoplasmic [ATP]/[ADP], causing closure of ATP-sensitive K(+) channels (K(ATP) channels), Ca(2+) entry through voltage-dependent Ca(2+) channels, and insulin release. Decreased responsiveness of K(ATP) channels to the [ATP]/[ADP] ratio should lead to decreased insulin secretion and diabetes. We generated mice expressing K(ATP) channels with reduced ATP sensitivity in their beta-cells.

pH regulates endoglucanase expression and virulence of Alternaria alternata in persimmon fruit.

The phytopathogenic fungus Alternaria alternata produces one endo-1,4-beta-glucanase, AaK1, which is an important factor in disease development in persimmon fruit. During growth of A. alternata in media containing acidified yeast extract or cell walls from persimmon fruit, the fungus secreted ammonia and raised the medium pH.