?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA

Direct Detection of Dark Matter in Supersymmetric Models

We evaluate neutralino-nucleon scattering rates in several well-motivated supersymmetric models, and compare against constraints on the neutralino relic density, BF( b\to s\gamma ) as well as the muon anomalous magnetic moment a_\mu . In the mSUGRA model, the indirect constraints favor the hyperbolic branch/focus point (HB/FP) region of parameter space, and in fact this region is just where neutralino-nucleon scattering rates are high enough to be detected in direct dark matter search experiments! In Yukawa unified SUSY SO(10) models with scalar mass non-universality, the relic density of neutralinos is almost always above experimental bounds, while the corresponding direct detection rates are below experimental levels. Conversely, in five dimensional SO(10) models where gauge symmetry breaking is the result of compactification of the extra dimension, and supersymmetry breaking is communicated via gaugino mediation, the relic density is quite low, while direct detection rates can be substantial.Comment: 25 page latex file including 18 EPS figures; revised version with references added and cross sections rescaled; figures changed. A copy of the paper with better resolution figures can be found at http://www.hep.fsu.edu/~belyaev/projects/directz1

Intestinal Absorption and First-Pass Metabolism of Polyphenol Compounds in Rat and Their Transport Dynamics in Caco-2 Cells

<div><h3>Background</h3><p>Polyphenols, a group of complex naturally occurring compounds, are widely distributed throughout the plant kingdom and are therefore readily consumed by humans. The relationship between their chemical structure and intestinal absorption, transport, and first-pass metabolism remains unresolved, however.</p> <h3>Methods</h3><p>Here, we investigated the intestinal absorption and first-pass metabolism of four polyphenol compounds, apigenin, resveratrol, emodin and chrysophanol, using the <em>in vitro</em> Caco-2 cell monolayer model system and <em>in situ</em> intestinal perfusion and <em>in vivo</em> pharmacokinetic studies in rats, so as to better understand the relationship between the chemical structure and biological fate of the dietary polyphenols.</p> <h3>Conclusion</h3><p>After oral administration, emodin and chrysophanol exhibited different absorptive and metabolic behaviours compared to apigenin and resveratrol. The differences in their chemical structures presumably resulted in differing affinities for drug-metabolizing enzymes, such as glucuronidase and sulphatase, and transporters, such as MRP2, SGLT1, and P-glycoprotein, which are found in intestinal epithelial cells.</p> </div

Effects of deposition time and post-deposition annealing on the physical and chemical properties of electrodeposited CdS thin films for solar cell application

CdS thin films were cathodically electrodeposited by means of a two-electrode deposition system for different durations. The films were characterised for their structural, optical, morphological and compositional properties using x-ray diffraction (XRD), spectrophotometry, scanning electron microscopy (SEM) and energy dispersive x-ray (EDX) respectively. The results obtained show that the physical and chemical properties of these films are significantly influenced by the deposition time and post-deposition annealing. This influence manifests more in the as-deposited materials than in the annealed ones. XRD results show that the crystallite sizes of the different films are in the range (9.4 – 65.8) nm and (16.4 – 66.0) nm in the as-deposited and annealed forms respectively. Optical measurements show that the absorption coefficients are in the range (2.7×104 – 6.7×104) cm-1 and (4.3×104 – 7.2×104) cm-1 respectively for as-deposited and annealed films. The refractive index is in the range (2.40 – 2.60) for as-deposited films and come to the value of 2.37 after annealing. The extinction coefficient varies in the range (0.1 – 0.3) in asdeposited films and becomes 0.1 in annealed films. The estimated energy bandgap of the films is in the range (2.48 – 2.50) eV for as-deposited films and becomes 2.42 eV for all annealed films. EDX results show that all the films are S-rich in chemical composition with fairly uniform Cd/S ratio after annealing. The results show that annealing improves the qualities of the films and deposition time can be used to control the film thickness. Keywords: Electrodeposition; two-electrode system; CdS; annealing; deposition time; thin-film

Diversity arrays technology (DArT) markers in apple for genetic linkage maps

Diversity Arrays Technology (DArT) provides a high-throughput whole-genome genotyping platform for the detection and scoring of hundreds of polymorphic loci without any need for prior sequence information. The work presented here details the development and performance of a DArT genotyping array for apple. This is the first paper on DArT in horticultural trees. Genetic mapping of DArT markers in two mapping populations and their integration with other marker types showed that DArT is a powerful high-throughput method for obtaining accurate and reproducible marker data, despite the low cost per data point. This method appears to be suitable for aligning the genetic maps of different segregating populations. The standard complexity reduction method, based on the methylation-sensitive PstI restriction enzyme, resulted in a high frequency of markers, although there was 52–54% redundancy due to the repeated sampling of highly similar sequences. Sequencing of the marker clones showed that they are significantly enriched for low-copy, genic regions. The genome coverage using the standard method was 55–76%. For improved genome coverage, an alternative complexity reduction method was examined, which resulted in less redundancy and additional segregating markers. The DArT markers proved to be of high quality and were very suitable for genetic mapping at low cost for the apple, providing moderate genome coverage

Synthesis and Photoluminescence Property of Silicon Carbide Nanowires Via Carbothermic Reduction of Silica

Silicon carbide nanowires have been synthesized at 1400 °C by carbothermic reduction of silica with bamboo carbon under normal atmosphere pressure without metallic catalyst. X-ray diffraction, scanning electron microscopy, energy-dispersive spectroscopy, transmission electron microscopy and Fourier transformed infrared spectroscopy were used to characterize the silicon carbide nanowires. The results show that the silicon carbide nanowires have a core–shell structure and grow along <111> direction. The diameter of silicon carbide nanowires is about 50–200 nm and the length from tens to hundreds of micrometers. The vapor–solid mechanism is proposed to elucidate the growth process. The photoluminescence of the synthesized silicon carbide nanowires shows significant blueshifts, which is resulted from the existence of oxygen defects in amorphous layer and the special rough core–shell interface

Copper Deficiency Induced Emphysema Is Associated with Focal Adhesion Kinase Inactivation

Background: Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1a) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein crosslinking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK). Methodology: To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA). Principal Findings: Copper depletion caused emphysematous changes, decreased HIF-1a activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim. Conclusions: These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema