The presence of valine at residue 129 in human prion protein accelerates amyloid formation

The polymorphism at residue 129 of the human PRNP gene modulates disease susceptibility and the clinicopathological phenotypes in human transmissible spongiform encephalopathies. The molecular mechanisms by which the effect of this polymorphism are mediated remain unclear. It has been shown that the folding, dynamics and stability of the physiological, alpha-helix-rich form of recombinant PrP are not affected by codon 129 polymorphism. Consistent with this, we have recently shown that the kinetics of amyloid formation do not differ between protein containing methionine at codon 129 and valine at codon 129 when the reaction is initiated from the a-monomeric PrPC-like state. In contrast, we have shown that the misfolding pathway leading to the formation of beta-sheet-rich, soluble oligomer waS favoured by the presence of methionine, compared with valine, at position 129. In the present work, we examine the effect of this polymorphism on the kinetics of an alternative misfolding pathway, that of amyloid formation using partially folded PrP allelomorphs. We show that the valine 129 allelomorph forms amyloids with a considerably shorter lag phase than the methionine 129 allelomorph both under spontaneous conditions and when seeded with pre-formed amyloid fibres. Taken together, our studies demonstrate that the effect of the codon 129 polymorphism depends on the specific misfolding pathway and on the initial conformation of the protein. The inverse propensities of the two allelomorphs to misfold in vitro through the alternative oligomeric and amyloidogenic pathways could explain some aspects of prion diseases linked to this polymorphism such as age at onset and disease incubation time. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

Associating sporadic, foodborne illness caused by Shiga toxin-producing Escherichia coli with specific foods : a systematic review and meta-analysis of case-control studies

Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health issue, with foodborne transmission causing >1 million illnesses worldwide each year. We conducted a systematic review and meta-analysis (PROSPERO registry # CRD42017074239), to determine the relative association of different food types with sporadic illnesses caused by STEC. Searches were conducted from 01 August to 30 September 2017, using bibliographic and grey literature databases, websites and expert consultation. We identified 22 case-control studies of sporadic STEC infection in humans, from 10 countries within four World Health Organization subregions, from 1985 to 2012. We extracted data from 21 studies, for 237 individual measures in 11 food categories and across three status types (raw or undercooked, not raw and unknown). Beef was the most significant food item associated with STEC illness in the Americas and Europe, but in the Western Pacific region, chicken was most significant. These findings were not significantly moderated by the raw or cooked status of the food item, nor the publication year of the study. Data from the African, South-East Asian and Eastern Mediterranean subregions were lacking and it is unclear whether our results are relevant to these regions

A novel minimal in vitro system for analyzing HIV-1 Gag mediated budding

A biomimetic minimalist model membrane was used to study the mechanism and kinetics of cell-free in vitro HIV-1 Gag budding from a giant unilamellar vesicle (GUV). Real time interaction of Gag, RNA and lipid leading to the formation of mini-vesicles was measured using confocal microscopy. Gag forms resolution limited punctae on the GUV lipid membrane. Introduction of the Gag and urea to a GUV solution containing RNA led to the budding of mini-vesicles on the inside surface of the GUV. The GUV diameter showed a linear decrease in time due to bud formation. Both bud formation and decrease in GUV size were proportional to Gag concentration. In the absence of RNA, addition of urea to GUVs incubated with Gag also resulted in subvesicle formation but exterior to the surface. These observations suggest the possibility that clustering of GAG proteins leads to membrane invagination even in the absence of host cell proteins. The method presented here is promising, and allows for systematic study of the dynamics of assembly of immature HIV and help classify the hierarchy of factors that impact the Gag protein initiated assembly of retroviruses such as HIV.Comment: 27 pages, 9 Figures and 0 Table

Analytic Representation of The Dirac Equation

In this paper we construct an analytical separation (diagonalization) of the full (minimal coupling) Dirac equation into particle and antiparticle components. The diagonalization is analytic in that it is achieved without transforming the wave functions, as is done by the Foldy-Wouthuysen method, and reveals the nonlocal time behavior of the particle-antiparticle relationship. We interpret the zitterbewegung and the result that a velocity measurement (of a Dirac particle) at any instant in time is, as reflections of the fact that the Dirac equation makes a spatially extended particle appear as a point in the present by forcing it to oscillate between the past and future at speed c. From this we infer that, although the form of the Dirac equation serves to make space and time appear on an equal footing mathematically, it is clear that they are still not on an equal footing from a physical point of view. On the other hand, the Foldy-Wouthuysen transformation, which connects the Dirac and square root operator, is unitary. Reflection on these results suggests that a more refined notion (than that of unitary equivalence) may be required for physical systems

Dispersion Relations for Bernstein Waves in a Relativistic Pair Plasma

A fully relativistic treatment of Bernstein waves in an electron-positron pair plasma has remained too formidable a task owing to the very complex nature of the problem. In this article, we perform contour integration of the dielectric response function and numerically compute the dispersion curves for a uniform, magnetized, relativistic electron-positron pair plasma. The behavior of the dispersion solution for several cases with different plasma temperatures is highlighted. In particular, we find two wave modes that exist only for large wavelengths and frequencies similar to the cyclotron frequency in a moderately relativistic pair plasma. The results presented here have important implications for the study of those objects where a hot magnetized electron-positron plasma plays a fundamental role in generating the observed radiation.Comment: 8 pages, 8 figures, Accepted for publication by Phys. Rev. E with minor change

Nitrogen-vacancy singlet manifold ionization energy

The singlet states of the negatively-charged nitrogen-vacancy centers in diamond play a key role in its optical spin control and readout. In this work, the hitherto unknown ionization energy of the singlet is measured experimentally and found to be between 1.91-2.25 eV. This is obtained by analyzing photoluminescence measurements incorporating spin control and NV charge state differentiation, along with simulations based on the nitrogen-vacancy's master equation. This work establishes a protocol for a more accurate estimate of this ionization energy, which can possibly lead to improved read-out methods

The luminosities of backsplash galaxies in constrained simulations of the Local Group

We study the differences and similarities in the luminosities of bound, infalling and the so-called backsplash (Gill et al. 2005) galaxies of the Milky Way and M31 using a hydrodynamical simulation performed within the Constrained Local UniversE Simulation (CLUES) project. The simulation models the formation of the Local Group within a self-consistent cosmological framework. We find that even though backsplash galaxies passed through the virial radius of their host halo and hence may have lost a (significant) fraction of their mass, their stellar populations are hardly affected. This leaves us with comparable luminosity functions for infalling and backsplash galaxies and hence little hope to decipher their past (and different) formation and evolutionary histories by luminosity measurements alone. Nevertheless, due to the tidal stripping of dark matter we find that the mass-to-light ratios have changed when comparing the various populations against each other: they are highest for the infalling galaxies and lowest for the bound satellites with the backsplash galaxies in-between.Comment: 9 pages, 10 figures, 1 table, accepted for publication in MNRA