Oxidative Stress Conditions Result in Trapping of PHF-Core Tau (297–391) Intermediates

Funding: This work was supported by funding from Alzheimer’s Society [345 (AS-PG-16b-010)] awarded to L.C.S. and funding M.B.M. Y.K.A.-H. is supported by WisTa Laboratories Ltd. (PAR1596). The work was supported by ARUK South Coast Network. G.B. was supported by European Molecular Biology Organisation (EMBO) Short-Term Fellowship award (EMBO-STF 7674). LCS is supported by BBSRC [BB/S003657/1]. Acknowledgments: TEM work was performed at the University of Sussex’s Electron microscopy imaging centre (EMC), funded by the School of Life Sciences, the Wellcome Trust (095605/Z/11/A, 208348/Z/17/Z) and the RM Phillips Trust. The authors thank Pascale Schellenberger for valuable support.Peer reviewedPublisher PD

Dityrosine cross-links are present in alzheimer's disease-derived Tau Oligomers and Paired Helical Filaments (PHF) which Promotes the stability of the PHF-core Tau (297–391) in vitro

A characteristic hallmark of Alzheimer's Disease (AD) is the pathological aggregation and deposition of tau into paired helical filaments (PHF) in neurofibrillary tangles (NFTs). Oxidative stress is an early event during AD pathogenesis and is associated with tau-mediated AD pathology. Oxidative environments can result in the formation of covalent dityrosine crosslinks that can increase protein stability and insolubility. Dityrosine cross-linking has been shown in Aβ plaques in AD and α-synuclein aggregates in Lewy bodies in ex vivo tissue sections, and this modification may increase the insolubility of these aggregates and their resistance to degradation. Using the PHF-core tau fragment (residues 297 – 391) as a model, we have previously demonstrated that dityrosine formation traps tau assemblies to reduce further elongation. However, it is unknown whether dityrosine crosslinks are found in tau deposits in vivo in AD and its relevance to disease mechanism is unclear. Here, using transmission electron microscope (TEM) double immunogold-labelling, we reveal that neurofibrillary NFTs in AD are heavily decorated with dityrosine crosslinks alongside tau. Single immunogold-labelling TEM and fluorescence spectroscopy revealed the presence of dityrosine on AD brain-derived tau oligomers and fibrils. Using the tau (297–391) PHF-core fragment as a model, we further showed that prefibrillar tau species are more amenable to dityrosine crosslinking than tau fibrils. Dityrosine formation results in heat and SDS stability of oxidised prefibrillar and fibrillar tau assemblies. This finding has implications for understanding the mechanism governing the insolubility and toxicity of tau assemblies in vivo

Structural and Electrochemical Characterization of Nanostructured Titanium Thin Films Prepared by DC Magnetron Sputtering with Supported Discharge

In this study, nanostructured titanium (Ti) thin films were prepared by direct current magnetron sputtering (diode mode) and supported discharge (triode mode) on a stainless steel substrate. The X-ray diffraction pattern shows a preferred orientation (002) plane and exhibits a hexagonal cubic structure for the film prepared at a lower working pressure (0.7 Pa). The electrical resistivity was found to be 15 mu ohm-cm. The scanning electron microscopy analysis indicates that the coatings in triode mode have agglomerates with larger grains compared to the DC magnetron sputtering diode mode. The surface topography was examined by atomic force microscopy. The electrochemical studies of the Ti thin films coated at a lower working pressure (0.7 Pa) provide evidence for better corrosion resistance

Low-resistive Tin (II) Sulfide Thin Films for Nontoxic and Low-cost Solar Cell Devices

Tin (II) sulfide (SnS) thin films have been developed on highly conductive indium doped tin oxide (ITO) substrates by using thermal evaporation technique at optimized deposition conditions. Here, SnS films were deposited at a substrate temperature of 300 degrees C by maintaining 14 cm distance between source to substrates with a rate of deposition of 1-2 nms(-1) and film thickness of 500 nm. Then, the crystal structure, morphology, electrical, and optical properties along with chemical composition of SnS films have been investigated and discussed in view of their potential applications in photovoltaic technology. The obtained results reveal that SnS films grown on ITO substrates have (111) as preferential orientation crystals with different sizes. These films are highly rough-in surface morphology, and exhibited very low-electrical resistivity in the order of 10(-3) Omega cm. These films also exhibited direct optical band gap and transmittance of about 60%. From these investigations we emphasized that SnS films deposited on ITO substrates could be adopted as an absorber layer for the development of solar cell devices or active component for other multifunctional devices

Temperature-dependent electrical characteristics and carrier transport mechanism of p-Cu2ZnSnS4/n-GaN heterojunctions

This work explores the temperature-dependent electrical characteristics and carrier transport mechanism of Au/p-Cu2ZnSnS4/n-type GaN heterojunction (HJ) diodes with a CZTS interlayer. The electrical characteristics were examined by current-voltage-temperature, turn-on voltage-temperature and series resistance-temperature in the high-temperature range of 300-420 K. It is observed that an exponential decrease in the series resistance (R-S) and increase in the ideality factor (n) and barrier height (phi(b)) with increase in temperature. The thermal coefficient (K-j) is determined to be -1.3 mV K-1 at >= 300 K. The effective phi(b) is determined to be 1.21 eV. This obtained barrier height is consistent with the theoretical one. The characteristic temperature (T-0) resulting from the Cheung's functions dV/d(lnI) vs. I and H(I) vs. I], is seen that there is good agreement between the T-0 values from both Cheung's functions. The relevant carrier transport mechanisms of Au/p-CZTS/n-type GaN HJ are explained based on the thermally decreased energy band gap of n-type GaN layers, thermally activated deep donors and increased further activated shallow donors

Influence of annealing on physical properties of evaporated SnS films

The effect of annealing on the composition, crystal structure, surface features and electro-optical properties of tin mono-sulfide (SnS) films, deposited by thermal evaporation at 300 °C, has been studied. Elemental analysis of the films shows sulfur deficiency, which increases at higher annealing temperatures (T<SUB>a</SUB>). The SnS structure in the as-deposited and annealed films remains orthorhombic. With an increase in T<SUB>a</SUB>, the grain size and the surface roughness are reduced. The electrical resistivity also decreases with increasing T<SUB>a</SUB>. The variation of activation energy and optical parameters with T<SUB>a</SUB> has been explained by taking into account the degree of preferred orientation of the grains. The films annealed at 100 °C show some unusual features compared to those annealed at other temperatures

The effect of substrate surface on the physical properties of SnS films

The effect of substrates on the physical properties of tin mono-sulphide (SnS) films has been studied. The SnS films were deposited using the resistive thermal evaporation method on CORNING 7059 glass, ITO-coated glass, Si wafer and Ag-coated glass substrates. The as-deposited films exhibited nearly stoichiometry between Sn and S elements with a Sn/S at.% ratio of ~1.05. Structural analysis of these films indicated that the films are crystallized in the form of an orthorhombic crystalline structure and showed (1 1 1) as a dominant peak, except for the films grown on Si substrates. Si/SnS films exhibited (0 4 0) as a dominant peak. The ITO/SnS films showed high values of rms roughness (~14.9 nm) and average grain size (~225 nm), along with a low electrical resistivity of 8.9 × 10-3 Ω cm as compared to SnS films grown on glass, Si and Ag substrates. The ITO/SnS films exhibit low resistivity, probably due to the large size of grains, and could be suitable for optoelectronic device applications

Microstructure dependent physical properties of evaporated tin sulfide films

In the field of photovoltaics, semiconductors of the III-V group such as GaAs and InP have been considered as the most efficient absorber materials due to their direct energy band gap and high mobility. In these compounds, arsenic and phosphorus are highly toxic and expensive. In this work we present systematic preparation of low cost SnS thin films and characterize these films to test their suitability for photovoltaic applications. We have observed that the films (with thickness ≅ 0.5 μ m) grown at the substrate temperature of 275°C exhibit a low resistive single SnS phase and have a direct optical band gap of 1.35 eV with an absorption coefficient of ~ 10<SUP>5</SUP> cm<SUP>-1</SUP>. SnS films could be alternative semiconductor materials as absorbers for the fabrication of photovoltaic devices

Thickness Effect on the Physical Properties of Evaporated SnS Films

SnS films with different thicknesses have been deposited on glass substrates at a constant substrate temperature of 300°C. The physical properties of the films were investigated using energy dispersive analysis of X-rays, X-ray diffraction, scanning electron microscopy, atomic force microscopy, van der Pauw method, and Fourier transform infrared spectroscopy measurements at room temperature. The deposited films exhibit only SnS phase with different orientations. We show that the electrical resistivity, activation energy, and optical bandgap of the films depend strongly on the preferred orientation of the SnS films. The electrical resistivity of films decreased with the increase of film thickness. The optical and electrical data of the SnS film are well interpreted with the composition, crystal, and surface structure data