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).     

Design of molecular two-photon probes for in vivo imaging. 2H-Benzo[h]chromene-2-one derivatives

2H-Benzo[h]chromene-2-one derivatives showing appreciable water solubility, significant two-photon cross sections, high photostability, cell permeability, low toxicity, and ability to be converted to a protein TP probe have been developed by incorporating all of the needed functions within a small molecule.     

On the loss of ethylene from [C3H7O]+ ions of structure \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm CH}_{\rm 3} {\rm CH}_{\rm 2} \mathop {{\rm CHOH}}\limits^{\rm + } $\end{document}

The results of some ³C and ²H labelling experiments plus some measurements of reaction thermochemistry and translational energy releases, permit a significant simplification of the mechanistic pathways by which [C₃H₇O]⁺ ions of structure fragment by loss of C₂H₄. The relationships between these ions and some of their isomeric forms are explored and clarified.     

Specific and random fragmentations in the mass spectra of some neopentyl compounds

The mass spectra of neopentyl alcohol, bromide and chloride and some ¹³C and ²H labelled analogues have been studied. Most fragmentations of the molecular ions of these compounds occur by simple bond cleavages and do not involve rearrangement before fragmentation. We propose that in the [M ? CH₃]⁺ fragment ions, seven of the eight hydrogen atoms and all four carbon atoms are involved in randomisation when an ethylene molecule is ejected. The eighth hydrogen atom (which comes from a methyl group) is probably associated with the heteroatom. The neopentylcation, observed only in the mass spectrum of the bromide, fragments mainly by loss of an ethylene molecule, also containing randomly selected hydrogen and carbon atoms. The [C₄H₇]⁺ ion also was observed to undergo complete atom scrambling.     

Low-energy 3He+ ion scattering spectroscopy studies of D2 adsorption on W(211)

Direct physical evidence for occupation of a trough site by the β₂ state of deuterium adsorbed on W(211) has been obtained by angle-resolved ³He⁺/D(ads) ion-scattering spectroscopy (ISS) in combination with LEED/Auger. The W(211) surface is composed of close-packed 〈111〉 rows of W atoms separated by a wide channel. Previous thermal desorption studies have shown two clearly resolved hydrogen states: β₁ desorbing with a temperature maximum of ca. 60°C, and β₂ at ca. 400°C. Analyses of flash desorption, work-function, adsorption kinetics, stoichiometry and mixed adsorption further indicated that the more tightly bound β₂ form occupies a deep-trough position. In the present study, ISS polar-angle profiles were taken at an incident energy of 306 eV. With only the β₂ state populated, a ³He⁺ beam parallel to the close-packed 〈111〉 rows was found to scatter from D(ads) with a cutoff angle close to grazing incidence while for the perpendicular direction D(ads) scattering is observed only for angles greater than 18° away from grazing incidence. These measurements are consistent with the corrugated W(211) geometry and with the proposed β₂-D trough-site model.     

Enhanced diffraction from a grating on the surface of a negative-index metamaterial

We show by numerical simulation as well as by measurements on negative-index metamaterial wedge samples, that the unavoidable stepping of the refraction interface-due to the finite unit-cell size inherent to metamaterials-can give rise to a well-defined diffracted beam in addition to the negatively refracted beam. The direction of the diffracted beam is consistent with elementary diffraction theory; however, the coupling to this higher order beam is much larger than would be the case for a positive index material. The results confirm recent theoretical predictions of enhanced diffraction for negative-index grating surfaces.     

Anechoic chamber qualification: traverse method,inverse square law analysis method,and nature of test signal

Qualification of anechoic chambers is intended to demonstrate that the chamber supports the intended free-field environment within some permissible tolerance bounds. Key qualification issues include the method used to obtain traverse data, the analysis method for the data, and the use of pure tone or broadband noise as the chamber excitation signal. This paper evaluates the relative merits of continuous versus discrete traverses, of fixed versus optimal reference analysis of the traverse data, and of the use of pure tone versus broadband signals. The current practice of using widely space discrete sampling along a traverse is shown to inadequately sample the complexity of the sound field extant with pure tone traverses, but is suitable for broadband traverses. Continuous traverses, with spatial resolution on the order of 15% of the wavelength at the frequency of interest, are shown to be necessary to fully resolve the spatial complexity of pure tone qualifications. The use of an optimal reference method for computing the deviations from inverse square law is shown to significantly improve the apparent performance of the chamber for pure tone qualifications. Finally, the use of broadband noise as the test signal, as compared to pure tone traverses over the same span, is demonstrated to be a marginal indicator of chamber performance.     

Isotope variations in white-tailed kites from various habitats in California: possible limitations in assessing prey utilization and population dynamics

White-tailed kite (Elanus leucurus) populations in the 1930s were close to extirpation in the United States. But by the 1940s, an upward trend towards recovery was apparent and continued to their current stable population levels. These dramatic fluctuations in kite numbers may have been related to changes in rodent prey populations due to the conversion of native habitats to agriculture. To address this question, we evaluated the use of stable isotope analysis in determining if a shift in diet could be isotopically differentiated in current and historic kite populations. We first compared delta13C, delta15N, and delta34S values from present-day kite flight feathers and prey fur samples from four locations in California. The total ranges of isotope values for kite and their rodent prey were similar within each site. Carbon isotope values ranged from -27.1 to -22.2 per thousand in Arcata, -26.1 to -16.9 per thousand in Davis, -27.0 to -15.0 per thousand in Cosumnes, and -28.2 to -11.6 per thousand in Santa Barbara. Nitrogen isotope values ranged from 3.2 to 15.7 per thousand in Arcata, 2.8 to 12.7 per thousand in Davis, 4.0 to 15.7 per thousand in Cosumnes, and 1.7 to 20.0 per thousand in Santa Barbara. Sulfur isotope values ranged from -7.8 to 12.4 per thousand in Arcata, -1.1 to 9.2 per thousand in Davis, 0.7 to 10.9 per thousand in Cosumnes, and -8.6 to 15.6 per thousand in Santa Barbara. Carbon, nitrogen, and sulfur isotope values at each site reflect typical trophic enrichments due to physiological processes. At each site, delta13C and delta15N values reflected the influence of a predominantly C3 or a mixed C3/C4 plant community. Sulfur isotope values reflect the influence of predominant marine or terrestrial sulfur sources at each site. However, variability in isotope values may limit the usefulness of such analyses for addressing prey utilization and population dynamics.