High Throughput Sequencing Identifies MicroRNAs Mediating α-Synuclein Toxicity by Targeting Neuroactive-Ligand Receptor Interaction Pathway in Early Stage of Drosophila Parkinson\u27s Disease Model.

Parkinson\u27s disease (PD) is a prevalent neurodegenerative disorder with pathological features including death of dopaminergic neurons in the substantia nigra and intraneuronal accumulations of Lewy bodies. As the main component of Lewy bodies, α-synuclein is implicated in PD pathogenesis by aggregation into insoluble filaments. However, the detailed mechanisms underlying α-synuclein induced neurotoxicity in PD are still elusive. MicroRNAs are ~20nt small RNA molecules that fine-tune gene expression at posttranscriptional level. A plethora of miRNAs have been found to be dysregulated in the brain and blood cells of PD patients. Nevertheless, the detailed mechanisms and their in vivo functions in PD still need further investigation. By using Drosophila PD model expressing α-synuclein A30P, we examined brain miRNA expression with high-throughput small RNA sequencing technology. We found that five miRNAs (dme-miR-133-3p, dme-miR-137-3p, dme-miR-13b-3p, dme-miR-932-5p, dme-miR-1008-5p) were upregulated in PD flies. Among them, miR-13b, miR-133, miR-137 are brain enriched and highly conserved from Drosophila to humans. KEGG pathway analysis using DIANA miR-Path demonstrated that neuroactive-ligand receptor interaction pathway was most likely affected by these miRNAs. Interestingly, miR-137 was predicted to regulate most of the identified targets in this pathway, including dopamine receptor (DopR, D2R), γ-aminobutyric acid (GABA) receptor (GABA-B-R1, GABA-B-R3) and N-methyl-D-aspartate (NMDA) receptor (Nmdar2). The validation experiments showed that the expression of miR-137 and its targets was negatively correlated in PD flies. Further experiments using luciferase reporter assay confirmed that miR-137 could act on specific sites in 3\u27 UTR region of D2R, Nmdar2 and GABA-B-R3, which downregulated significantly in PD flies. Collectively, our findings indicate that α-synuclein could induce the dysregulation of miRNAs, which target neuroactive ligand-receptor interaction pathway in vivo. We believe it will help us further understand the contribution of miRNAs to α-synuclein neurotoxicity and provide new insights into the pathogenesis driving PD

Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production

The rabies Flury Low Egg Passage virus (LEP) has been widely used as a seed virus to generate inactive vaccine. Here, we established a reverse genetic system for LEP and generated a recombinant LEP virus (rLEP-G) that carries two identical G genes. This recombinant virus showed similar properties to those of LEP with respect to in vitro growth, neurotropism index, and virulence in mice. rLEP-G produced 4.3-fold more G protein than did LEP in BHK-21 cells. The inactivated vaccine generated from rLEP-G induced significantly higher virus neutralization titers in mice and dogs than those produced in response to LEP-derived vaccine. Our results suggest that rLEP-G is an improved seed virus candidate for inactivated rabies virus vaccine manufacture

Newcastle disease virus-vectored Nipah encephalitis vaccines induce B and T cell responses in mice and long-lasting neutralizing antibodies in pigs

AbstractNipah virus (NiV), a member of the Paramyxoviridae family, causes deadly encephalitis in humans and huge economic losses to the pig industry. Here, we generated recombinant avirulent Newcastle disease virus (NDV) LaSota strains expressing the NiV G and F proteins respectively (designated as rLa-NiVG and rLa-NiVF), and evaluated their immunogenicity in mice and pigs. Both rLa-NiVG and rLa-NiVF displayed growth properties similar to those of LaSota virus in chicken eggs. Co-infection of rLa-NiVG and rLa-NiVF caused marked syncytia formation, while intracerebral co-inoculation of these viruses in mice showed they were safe in at least one mammalian species. Animal immunization studies showed rLa-NiVG and rLa-NiVF induced NiV neutralizing antibody responses in mice and pigs, and F protein-specific CD8+ T cell responses in mice. Most importantly, rLa-NiVG and rLa-NiVF administered alone or together, induced a long-lasting neutralizing antibody response in pigs. Recombinant rLa-NiVG/F thus appear to be promising NiV vaccine candidates for pigs and potentially humans

Assessment of Mechanical Properties, Residual Stresses and Diffusible Hydrogen of Longitudinal Weld in Electric Water Heater Tanks

The core technique of electric storage water heaters is the manufacture of the tanks, and the welding technique is the key technology of the tank manufacture. A company producing water heaters received feedback from its after-sales that a large quantity of water leakage from the tanks was found in the market. A follow-up on the manufacturing site by the researchers showed that the position of the water leakage defects mostly happens in the welds of the tanks. Series of experiments were conducted to investigate the mechanical properties, residual stress, and diffusible hydrogen content of the longitudinal weld of the tank. Results of the mechanical properties showed that both the micro-hardness and the tensile strength of the welds are higher than the base metal. There are higher residual compressive stresses in the weld center and the adjacent-weld zone. Vertical residual compressive stress decreases first and then increases (149 MPa–28 MPa–134 MPa) from the weld ends to the middle, whilst the transversal stress decreases continuously (332 MPa~240 MPa) from the weld center to the heat affected zone. After enameling, the longitudinal welds’ peak micro-hardness of coarse grained region reduces by 30.9 HV1, and the average micro-hardness of the HAZ reduces by 5 HV1. The average vertical residual compressive stress difference of the same test points reduces from 270.6 MPa to 20.4 MPa. It proves that enameling can improve the mechanical property of the longitudinal welds

Experimental Analysis of Grease Friction Properties on Sliding Textured Surfaces

There is comprehensive work on the tribological properties and lubrication mechanisms of oil lubricant used on textured surfaces, however the use of grease lubrication on textured surfaces is rather new. This research article presents an experimental study of the frictional behaviours of grease lubricated sliding contact under mixed lubrication conditions. The influences of surface texture parameters on the frictional properties were investigated using a disc-on-ring tribometer. The results showed that the friction coefficient is largely dependent on texture parameters, with higher and lower texture density resulting in a higher friction coefficient at a fixed texture depth. The sample with texture density of 15% and texture depth of 19 μm exhibited the best friction properties in all experimental conditions because it can store more grease and trap wear debris. The reduction of friction is mainly attributable to the formation of a stable grease lubrication film composed of oil film, transfer film and deposited film, and the hydrodynamic pressure effect of the surface texture, which increases the mating gap and reduces the probability of asperity contact. This result will help in understanding the tribological behaviour of grease on a textured surface and in predicting the lubrication conditions of sliding bearings for better operation in any machinery

Effect of textured DLC coatings on tribological properties of titanium alloy under grease lubrication

To improve the tribological properties of titanium alloy surface and promote the functional application of titanium alloy, the synergistic anti-friction and wear-resistant effect of laser micro-textures and diamond-like carbon (DLC) coatings on titanium alloy surface under grease lubrication were investigated in this paper. Micro-textures and DLC coatings were fabricated on the surface of titanium alloy by Nd:YAG laser and magnetron sputtering technology. Effects of different surface treatment methods and micro-textures parameters on tribological properties of titanium alloy samples was studied. The results showed that, compared with the smooth titanium alloy sample, the friction coefficient of micro-textured sample, DLC coated sample and textured DLC coated sample decreased by 43.7%, 75.8%, 80.6% respectively. The surface of textured coated titanium alloy had the best tribological properties with a friction coefficient of 0.0799. The wear on the surface of the titanium alloy sample treated by laser micro-textures and DLC coatings was obviously improved. Compared with the severe adhesive wear on the surface of the titanium alloy sample, the surface of the textured coated titanium alloy sample was slightly scratched, and the wear volume was decreased by 97.5%. Meanwhile, DLC coatings with 30% textures density and 20 μ m textures depth showed the best anti-friction effect as well as the optimal hydrodynamic lubrication effect. Under the condition of grease lubrication, the surface of textured DLC coated titanium alloy substrate presented favorable anti-friction and wear-resistance effects, which revealed that reasonable micro-textures density and depth could more effectively exert the lubricating and anti-friction properties of textured DLC coatings