Blood pressure, brain lesions and cognitive decline in patients with atrial fibrillation.

Background: The influence of atrial fibrillation (AF) and blood pressure (BP) on brain lesions and cognitive function is unclear. We aimed to investigate the association of BP with different types of brain lesions and cognitive decline in patients with AF.

Methods: Overall, 1,213 AF patients underwent standardized brain magnetic resonance imaging at baseline and after 2 years, as well as yearly neurocognitive testing.

Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection.

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S.

as a model for unraveling unique molecular features of epilepsy elicited by human GABA transporter 1 variants.

Mutations in the human γ-aminobutyric acid (GABA) transporter 1 (hGAT-1) can instigate myoclonic-atonic and other generalized epilepsies in the afflicted individuals. We systematically examined fifteen hGAT-1 disease variants, all of which dramatically reduced or completely abolished GABA uptake activity. Many of these loss-of-function variants were absent from their regular site of action at the cell surface, due to protein misfolding and/or impaired trafficking machinery (as verified by confocal microscopy and de-glycosylation experiments).

Identification and characterization of the Fasciola hepatica sodium- and chloride-dependent taurine transporter.

The parasitic liver fluke Fasciola hepatica infests mainly ruminants, but it can also cause fasciolosis in people, who ingest the metacercariae encysted on plants. The drug of choice to treat fasciolosis is triclabendazole (TBZ), which has been on the market for several decades. This is also true for the other available drugs.

ChemDoodle Web Components: HTML5 toolkit for chemical graphics, interfaces, and informatics.

ChemDoodle Web Components (abbreviated CWC, iChemLabs, LLC) is a light-weight (~340 KB) JavaScript/HTML5 toolkit for chemical graphics, structure editing, interfaces, and informatics based on the proprietary ChemDoodle desktop software. The library uses and WebGL technologies and other HTML5 features to provide solutions for creating chemistry-related applications for the web on desktop and mobile platforms. CWC can serve a broad range of scientific disciplines including crystallography, materials science, organic and inorganic chemistry, biochemistry and chemical biology.

An o-aminoanilide analogue of 1α,25-dihydroxyvitamin D(3) functions as a strong vitamin D receptor antagonist.

Vitamin D receptor (VDR) antagonists have therapeutic potential in treatment of allergic conditions and hypercalcemia driven by granulomatous diseases. We have identified an o-aminoanilide analogue of the hormonal form of vitamin D with a dienyl side chain that functions as a strong VDR antagonist. Modeling studies indicate that antagonism arises from side chain rigidity, when compared to a more flexible saturated analogue, which interferes with H12 folding/alignment.

Effects of various small-molecule anesthetics on vesicle fusion: a study using two-photon fluorescence cross-correlation spectroscopy.

Currently, the molecular mechanism for membrane fusion remains unconfirmed. The most compelling suggested mechanism is the stalk hypothesis, which states that membrane fusion proceeds via stalk formation/hemifusion, among other steps. Because the stalk would have a very high radius of curvature, small lipophilic molecules could enhance fusion by lowering the energy barrier to stalk formation.

A quantum dot-labeled ligand-receptor binding assay for G protein-coupled receptors contained in minimally purified membrane nanopatches.

A robust method to directly measure ligand-receptor binding interactions using fluorescence cross-correlation spectroscopy (FCCS) is described. The example receptor systems demonstrated here are the human micro-opioid receptor, a representative G protein-coupled receptor (GPCR), and Streptavidin, but these general protocols can be extended for the analysis of many membrane receptors. We present methods for the preparation of GPCR-containing membrane nanopatches that appear to have the shapes of nanovesicles, labeling of proteins in membrane vesicles, in addition to the coupling of quantum dots (QDs) to peptide ligands.

Two-photon excitation fluorescence cross-correlation assay for ligand-receptor binding: cell membrane nanopatches containing the human micro-opioid receptor.

Current ligand-receptor binding assays for G-protein coupled receptors cannot directly measure the system's dissociation constant, Kd, without purification of the receptor protein. Accurately measured Kd's are essential in the development of a molecular level understanding of ligand-receptor interactions critical in rational drug design. Here we report the introduction of two-photon excitation fluorescence cross-correlation spectroscopy (TPE-FCCS) to the direct analysis of ligand-receptor interactions of the human micro opioid receptor (hMOR) for both agonists and antagonists.

Ganglioside partitioning and aggregation in phase-separated monolayers characterized by bodipy GM1 monomer/dimer emission.

The distribution of Bodipy GM1 in monolayers of binary and ternary lipid mixtures with coexisting fluid and ordered phases has been examined using a combination of atomic force microscopy and near-field scanning optical microscopy. Monolayers deposited at high (30 mN/m) and low (5 or 10 mN/m) surface pressures were examined and compared to those containing the same concentration of unlabeled ganglioside. Measurements of monomer and dimer Bodipy emission were used to distinguish aggregated from dilute ganglioside levels.

Transition from nanodomains to microdomains induced by exposure of lipid monolayers to air.

The morphology of monolayers prepared from ternary lipid mixtures that have coexisting fluid phases has been examined by atomic force microscopy for samples transferred to mica before and after exposure to air. Mixtures of 1,2-dioleoyl-sn-glycero-3-phosphocholine and cholesterol with either egg sphingomyelin or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine were studied at several surface pressures. Both lipid mixtures have a combination of small islands and large microdomains at low surface pressure (5-10 mN/m) for monolayers deposited in either air or nitrogen.