SARS-CoV-2 N-protein induces the formation of composite α-synuclein/N-protein fibrils that transform into a strain of α-synuclein fibrils

The presence of deposits of alpha-synuclein (αS) fibrils in the cells of the brain is a hallmark of several α-synucleinopathies, including Parkinson's disease. As most disease cases are not familial, it is likely that external factors play a role in the disease onset. One of the external factors that may influence the disease onset is viral infection. It has recently been shown in in vitro assays that in the presence of SARS-Cov-2 N-protein, αS fibril formation is faster and proceeds in an unusual two-step aggregation process. Here, we show that faster fibril formation is not due to the SARS-CoV-2 N-protein-catalysed formation of an aggregation-prone nucleus. Instead, aggregation starts with the formation of a population of mixed αS/N-protein fibrils with low affinity for αS. Mixed amyloid fibrils, composed of two different proteins, have not been observed before. After the depletion of N-protein, fibril formation comes to a halt, until a slow transformation into fibrils with characteristics of a pure αS fibril strain occurs. This transformation into a strain of αS fibrils subsequently results in a second phase of fibril growth until a new equilibrium is reached. We hypothesize that this fibril strain transformation may be of relevance in the cell-to-cell spread of the αS pathology and disease onset

Elimination of adsorptive behaviour of biomolecules at the glass-solution interface in fluorescence correlation spectroscopy

We study adsorptive behaviour of biomolecules at the glass-solution interface in fluorescence correlation spectroscopy (FCS), and propose a negatively charged coating to eliminate the adsorption of molecules. In this article, we demonstrate confocal microscopic measurements on Cy3.5-90-mer-ssDNA and Cy3.5-90-bp-dsDNA in different solutions, and use two polymers – poly (acrylic acid, sodium salt) and poly (sodium 4-styrenesulfonate) to produce the negatively charged coating on glass coverslips. This technology enables more stable FCS measurements in extremely low concentration samples and reveals that the adsorptive behaviour of biomolecules is responsible for sudden disappearance of many iomolecules in low concentration solutions

Interplay between Heavy Fermions and Crystal Field Excitation in Kondo Lattices. Low-Temperature Thermodynamics and Inelastic Neutron Scattering Spectra of CeNiSn

The microscopic theory of interaction between the heavy fermions and the crystal field excitations in Kondo lattices is presented. It is shown that the heavy-fermion spectrum scaled by the Kondo temperature $T_K$ can be modified by the crystal field excitations with the energy $\Delta_{CF}$ provided the inequality $\Delta_{CF}<T_K$ is realized. On the base of general description of excitation spectrum the detailed qualitative and quantitative explanation of anisotropic inelastic neutron scattering spectra and low-temperature specific heat of orthorhombic CeNiSn is given. The theory resolves the apparent contradiction between the metallic conductivity and the gap-wise behavior of thermodynamic properties and spin response of CeNiSn at low temperatures.Comment: 24 pages (LaTeX), 12 Postscript figures, submitted to Phys.Rev.

Factors Affecting European Farmers’Participation in Biodiversity Policies

This article reports the major findings from an interdisciplinary research project that synthesises key insights into farmers’ willingness and ability to co-operate with biodiversity policies. The results of the study are based on an assessment of about 160 publications and research reports from six EU member states and from international comparative research.We developed a conceptual framework to systematically review the existent literature relevant for our purposes. This framework provides a common structure for analysing farmers’ perspectives regarding the introduction into farming practices of measures relevant to biodiversity. The analysis is coupled and contrasted with a survey of experts. The results presented above suggest that it is important to view support for practices oriented towards biodiversity protection not in a static sense – as a situation determined by one or several influencing factors – but rather as a process marked by interaction. Financial compensation and incentives function as a necessary, though clearly not sufficient condition in this process

Warwick Data Store : a data structure abstraction library

With the increasing complexity of memory architectures and scientific applications, developing data structures that are performant, portable, scalable, and support developer productivity, is a challenging task. In this paper, we present Warwick Data Store (WDS), a lightweight and extensible C++ template library designed to manage these complexities and allow rapid prototyping. WDS is designed to abstract details of the underlying data structures away from the user, thus easing application development and optimisation. We show that using WDS does not significantly impact achieved performance across a variety of different scientific benchmarks and proxy-applications, compilers, and different architectures. The overheads are largely below 30% for smaller problems, with the overhead deceasing to below 10% when using larger problems. This shows that the library does not significantly impact the performance, while providing additional functionality to data structures, and the ability to optimise data structures without changing the application code

Hard Interactions of Quarks and Gluons: a Primer for LHC Physics

In this review article, we develop the perturbative framework for the calculation of hard scattering processes. We undertake to provide both a reasonably rigorous development of the formalism of hard scattering of quarks and gluons as well as an intuitive understanding of the physics behind the scattering. We emphasize the importance of logarithmic corrections as well as power counting of the strong coupling constant in order to understand the behavior of hard scattering processes. We include "rules of thumb" as well as "official recommendations", and where possible seek to dispel some myths. Experiences that have been gained at the Fermilab Tevatron are recounted and, where appropriate, extrapolated to the LHC.Comment: 118 pages, 107 figures; to be published in Reports on Progress in Physic

Fluorescence correlation spectroscopy of the binding of nucleotide excision repair protein XPC-hHr23B with DNA substrates

The interaction of the nucleotide excision repair (NER) protein dimeric complex XPC-hHR23B, which is implicated in the DNA damage recognition step, with three Cy3.5 labeled 90-bp double-stranded DNA substrates (unmodified, with a central unpaired region, and cholesterol modified) and a 90-mer single-strand DNA was investigated in solution by fluorescence correlation spectroscopy. Autocorrelation functions obtained in the presence of an excess of protein show larger diffusion times (τ d) than for free DNA, indicating the presence of DNA-protein bound complexes. The fraction of DNA bound (θ), as a way to describe the percentage of protein bound to DNA, was directly estimated from FCS data. A significantly stronger binding capability for the cholesterol modified substrate (78% DNA bound) than for other double-stranded DNA substrates was observed, while the lowest affinity was found for the single-stranded DNA (27%). This is in accordance with a damage recognition role of the XPC protein. The similar affinity of XPC for undamaged and 'bubble' DNA sub

Cytotoxic lymphocytes in B-cell chronic lymphocytic leukemia

The occurrence of cytotoxic lymphocyte subpopulations (i.e., CD 16+, CD57+ and cytotoxic CD 8+) was studied in the peripheral blood of 18 B-cell chronic lymphocytic leukemia (B-CLL) patients. The absolute numbers of CD 57+, CD 16+ and cytotoxic CD 8+ lymphocytes were increased in the peripheral blood of untreated patients as compared with healthy donors, suggesting a causal relation with the accumulation of malignant B-cells. For 5 B-CLL patients and 5 hematological normal donors, the lymphocyte subpopulations in peripheral blood, lymph nodes and bone marrow were determined. A significant immune response was observed in the lymph nodes of the patients, as reflected by the CD 3+ lymphocytes, which were 1.7–27 times larger in the patients lymph nodes than in their peripheral blood and bone marrow. In contrast, with peripheral blood this was mainly caused by an increase in CD 4+ lymphocytes. The CD 57 lymphocytes in the lymph nodes of the patients had abnormal orthogonal light-scattering signals and an abnormal density of CD 57+ receptors in comparison with their peripheral blood CD 57+ lymphocytes or the CD57+ lymphocytes in the peripheral blood, bone marrow and tonsils of the hematological normal donors. This study shows that although a significant increase of cytotoxic lymphocytes in the peripheral blood of B-CLL patients is observed, the actual distributions of the non-malignant lymphocytes can be quite different at the actual tumor sites, i.e., bone marrow and lymph node