Mapping of possible prion protein self-interaction domains using peptide arrays

Background  

The common event in transmissible spongiform encephalopathies (TSEs) or prion diseases is the conversion of host-encoded protease sensitive cellular prion protein (PrP^C) into strain dependent isoforms of scrapie associated protease resistant isoform (PrP^Sc) of prion protein (PrP). These processes are determined by similarities as well as strain dependent variations in the PrP structure. Selective self-interaction between PrP molecules is the most probable basis for initiation of these processes, potentially influenced by chaperone molecules, however the mechanisms behind these processes are far from understood. We previously determined that polymorphisms do not affect initial PrP^C to PrP^Sc binding but rather modulate a subsequent step in the conversion process. Determining possible sites of self-interaction could elucidate which amino acid(s) or amino acid sequences contribute to binding and further conversion into other isoforms. To this end, ovine – and bovine PrP peptide-arrays consisting of 15-mer overlapping peptides were probed with recombinant sheep PrP^C fused to maltose binding protein (MBP-PrP).     

Strongly nonlinear luminescence in oxidized porous silicon films

Partially oxidized free-standing porous silicon films show a strongly superlinear increase in photoluminescence (PL) intensity above a threshold cw excitation intensity of 10 W/cm². The PL-intensity increase can be expressed by a power law with n9 as a function of the excitation intensity. The PL-peak wavelength of this emission is slightly redshifted from that at low-excitation levels. These changes are fully reversible and reproducible, but not observed in samples on substrate. We attribute this behavior to thermal reexcitation of carriers trapped at the dangling bond states in initially nonluminescent Si nanocrystallites.     

Studies on photoinduced effects in pulse-electrodeposited Ag/Hg-1212/CdSe hetero-nanostructures

Metal/superconductor/semiconductor (Ag/Hg-1212/CdSe) hetero-nanostructures have been fabricated using pulse-electrodeposition technique and are characterized by X-ray diffraction (XRD), full-width at half-maximum (FWHM) and scanning electron microscopy (SEM) studies. The junction capacitance of Ag/Hg-1212, Hg-1212/CdSe and Ag/Hg-1212/CdSe heterojunctions is measured in dark and under laser irradiation at room temperature. The nature of the junction formed and built-in-junction potentials were determined. The increase in carrier concentration across the junction due to photo-irradiation has been observed.     

Effect of laser irradiation of C-V characteristics of electrodeposited Ag/Tl-2223/CdSe hetero-nanostructures

One of the innovative technological directions for the high-temperature superconductors has been persued by fabricating the heteroepitaxial multilayer structures such as superconductor-semiconductor heterostructures. In the present investigation, metal/superconductor/semiconductor (Ag/Tl-2223/CdSe) hetero-nanostructures have successfully been fabricated using dc electrodeposition technique and were characterized by X-ray diffraction (XRD), full-width at half-maximum (FWHM) and scanning electron microscopy (SEM) studies. The measurement of junction capacitance as a function of biasing voltage was used for the estimation of junction built-in-potential (V _D) and to study the charge distribution in a heterojunction. The Mott-Schottky plots were measured for each junction in dark and under the photo-irradiation. The effect of laser irradiation on C-V characteristics of hetero-nanostructure has been studied.     

Photoluminescence and electroluminescence from porous silicon

The properties and origins of the red, blue and infrared photoluminescence bands of porous silicon are reviewed and discussed in the light of the models that have been proposed to explain the experimental and theoretical results. The red band is due to quantum confinement possibly supplemented by surface states; the blue band is linked to the presence of silicon dioxide; the infrared band is correlated with dangling bonds and bandgap luminescence in large crystallites. The fabrication and characterization of light-emitting devices made of porous silicon are reported and discussed with respect to critical issues such as the device stability, efficiency, modulation speed, emission wavelength, and compatibility with microelectronic processing.     

Glycopeptide and Oligosaccharide Libraries

Despite the burgeoning interest in the various biological functions and consequent therapeutic potential of the vast number of oligosaccharides found in nature on glycoproteins and cell surfaces, the development of combinatorial carbohydrate chemistry has not progressed as rapidly as expected. The reason for this imbalance is rooted in the difficulty of oligosaccharide assembly and analysis that renders synthesis a rather cumbersome endeavor. Parallel approaches that generate series of analogous compounds rather than real libraries have therefore typically been used. Since generally low affinity is obtained for interactions between carbohydrate receptors and modified oligosaccharides designed as mimetics of natural carbohydrate ligands, glycopeptides have been explored as alternative mimics. Glycopeptides have been proven in many cases to be superior ligands with higher affinity for a receptor than the natural carbohydrate ligand. High-affinity glycopeptide ligands have been found for several types of receptors including the E-, P-, and L-selectins, toxins, glycohydrolases, bacterial adhesins, and the mannose-6-phosphate receptor. Furthermore, the assembly of glycopeptides is considerably more facile than that of oligosaccharides and the process can be adapted to combinatorial synthesis with either glycosylated amino acid building blocks or by direct glycosylation of peptide templates. The application of the split and combine approach using ladder synthesis has allowed the generation of very large numbers of compounds which could be analyzed and screened for binding of receptors on solid phase. This powerful technique can be used generally for the identification and analysis of the complex interaction between the carbohydrates and their receptors.     

An experimental and theoretical analysis of molecular separations by diffusion through ultrathin nanoporous membranes

Diffusion based separations are essential for laboratory and clinical dialysis processes. New molecularly thin nanoporous membranes may improve the rate and quality of separations achievable by these processes. In this work we have performed protein and small molecule separations with 15 nm thick porous nanocrystalline silicon (pnc-Si) membranes and compared the results to 1- and 3- dimensional models of diffusion through ultrathin membranes. The models predict the amount of resistance contributed by the membrane by using pore characteristics obtained by direct inspection of pnc-Si membranes in transmission electron micrographs. The theoretical results indicate that molecularly thin membranes are expected to enable higher resolution separations at times before equilibrium compared to thicker membranes with the same pore diameters and porosities. We also explored the impact of experimental parameters such as porosity, pore distribution, diffusion time, and chamber size on the sieving characteristics. Experimental results are found to be in good agreement with the theory, and ultrathin membranes are shown to impart little overall resistance to the diffusion of molecules smaller than the physical pore size cutoff. The largest molecules tested experience more hindrance than expected from simulations indicating that factors not incorporated in the models, such as molecule shape, electrostatic repulsion, and adsorption to pore walls, are likely important.