ALS-Related Mutant SOD1 Aggregates Interfere with Mitophagy by Sequestering the Autophagy Receptor Optineurin

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive demise of motor neurons. One of the causes of familial ALS is the mutation of the gene encoding superoxide dismutase 1 (SOD1), which leads to abnormal protein aggregates. How SOD1 aggregation drives ALS is still poorly understood. Recently, ALS pathogenesis has been functionally implicated in mitophagy, specifically the clearance of damaged mitochondria. Here, to understand this mechanism, we investigated the relationship between the mitophagy receptor optineurin and SOD1 aggregates. We found that mutant SOD1 (mSOD1) proteins associate with and then sequester optineurin, which is required to form the mitophagosomes, to aggregates in N2a cells. Optineurin recruitment into mSOD1 aggregates resulted in a reduced mitophagy flux. Furthermore, we observed that an exogenous augmentation of optineurin alleviated the cellular cytotoxicity induced by mSOD1. Taken together, these studies demonstrate that ALS-linked mutations in SOD1 interfere with the mitophagy process through optineurin sequestration, suggesting that the accumulation of damaged mitochondria may play a crucial role in the pathophysiological mechanisms contributing to ALS

Spine-like Joint Link Mechanism to Design Wearable Assistive Devices

When we develop wearable assistive devices, comfort and support are two main issues that need to be considered. In conventional design approaches, the degree of freedom of the wearer’s joint movements tends to be oversimplified. Accordingly, the wearer’s motion becomes restrained and bone/ligament injuries might occur in case of an unexpected fall. To mitigate these issues, this paper proposes a novel joint link mechanism inspired by a human spine structure as well as functionalities. The key feature of the proposed spine-like joint link mechanism is that hemispherical blocks are concatenated via flexible synthetic fiber lines so that their concatenation stiffness can be adjusted according to a tensile force. This feature has a great potentiality for designing a wearable assistive device that can support aged people’s sit-to-stand action or augment spinal motion by regulating the concatenation stiffness. In addition, the concatenated hemispherical blocks enable the wearer to move his/her joint with full freedom, which in turn increases the wearer’s mobility and prevents joint misalignment. The experimental results with a testbed and a pilot wearer substantiated that the spine-like joint link mechanism can serve as a key component in the design of wearable assistive devices for better mobility

Effect of Fluoroethylene Carbonate on Electrochemical Performances of Lithium Electrodes and Lithium-Sulfur Batteries

The positive impact of a fluoroethylene carbonate (FEC) solvent on the interfacial stability of Li metal electrodes and the electrochemical performance of lithium-sulfur (Li-S) cells is investigated. To confirm the effects of FEC on electrolyte decomposition and cell resistance, the surface chemistry and impedance of an Li electrode cycled in electrolytes with and without a FEC solvent are investigated using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), time of flight secondary ion mass spectrometry (ToF-SIMS), and electrochemical impedance spectroscopy. A protective layer with a FEC solvent for the formation of robust SET and carbonate-based solvents for the suppression of polysulfide attack against an Li anode was formed on the Li anode by UV-curing polymerization. It is found that the protective layer with FEC effectively suppresses the significant overcharge by the shuttle process of polysulfide species and improves cycling performance of Li-S cells.close6

Production of High-Purity Tantalum Metal Powder for Capacitors Using Self-Propagating High-Temperature Synthesis

In this study, high-purity tantalum metal powder was manufactured via self-propagating high-temperature synthesis. During the process, Ta2O5 and Mg were used as the raw material powder and the reducing agent, respectively, and given that combustion rate and reaction temperature are important factors that influence the success of this process, these factors were controlled by adding an excessive mass of the reducing agent (Mg) i.e., above the chemical equivalent, rather than by using a separate diluent. It was confirmed that Ta metal powder manufactured after the process was ultimately manufactured 99.98% high purity Ta metal powder with 0.5 μm particle size. Thus, it was observed that adding the reducing reagent in excess favored the manufacture of high-purity Ta powder that can be applied in capacitors

Effects of ZrO2 and Al2O3 Addition on the Physical Properties of Cu-Mo-Cr Alloy by Liquid Phase Sintering

In this study, the effect of the addition of ZrO2 and Al2O3 ceramic powders to Cu-Mo-Cr alloy was studied by examining the physical properties of the composite material. The ceramic additives were selected based on the thermodynamic stability calculation of the Cu-Mo-Cr alloys. Elemental powders, in the ratio Cu:Mo:Cr = 60:30:10 (wt.%), and approximately 0-1.2 wt.% of ZrO2 and Al2O3 were mixed, and a green compact was formed by pressing the mixture under 186 MPa pressure and sintering at 1250°C for 5 h. The raw powders were evenly dispersed in the mixed powder, as observed by scanning electron microscopy. After sintering, the microstructures, densities, electrical conductivities, and hardness of the composites were evaluated. We found that the addition of ZrO2 and Al2O3 increased the hardness and decreased the electrical conductivity and density of the composites

Optimal proteinuria target for renoprotection in patients with IgA nephropathy.

BACKGROUND: Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown. METHODS: We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR. RESULTS: During a median follow-up duration of 65 (12-154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3-0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0-2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0-2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3-0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (-0.41±1.68 vs. -0.73±2.82 ml/min/1.73 m2/year, P = 0.03). CONCLUSION: In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3-0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN

Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy

AbstractIgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.11Ysciescopu