Targeting the Mitochondrial Protein VDAC1 as a Potential Therapeutic Strategy in ALS

Impaired mitochondrial function has been proposed as a causative factor in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), caused by motor neuron degeneration. Mutations in superoxide dismutase (SOD1) cause ALS and SOD1 mutants were shown to interact with the voltage-dependent anion channel 1 (VDAC1), affecting its normal function. VDAC1 is a multi-functional channel located at the outer mitochondrial membrane that serves as a mitochondrial gatekeeper controlling metabolic and energetic crosstalk between mitochondria and the rest of the cell and it is a key player in mitochondria-mediated apoptosis. Previously, we showed that VDAC1 interacts with SOD1 and that the VDAC1-N-terminal-derived peptide prevented mutant SOD1 cytotoxic effects. In this study, using a peptide array, we identified the SOD1 sequence that interacts with VDAC1. Synthetic peptides generated from the identified VDAC1-binding sequences in SOD1 directly interacted with purified VDAC1. We also show that VDAC1 oligomerization increased in spinal cord mitochondria isolated from mutant SOD1^G93A mice and rats. Thus, we used the novel VDAC1-specific small molecules, VBIT-4 and VBIT-12, inhibiting VDAC1 oligomerization and subsequently apoptosis and associated processes such as ROS production, and increased cytosolic Ca²⁺. VBIT-12 was able to rescue cell death induced by mutant SOD1 in neuronal cultures. Finally, although survival was not affected, VBIT-12 administration significantly improved muscle endurance in mutant SOD1^G93A mice. Therefore, VBIT-12 may represent an attractive therapy for maintaining muscle function during the progression of ALS.     

Enhancing the design and performance of a gate-all-around (GAA) charge plasma nanowire field-effect transistor with the help of the negative-capacitance technique

A gate-all-around charge plasma nanowire field-effect transistor (GAA CP NW FET) device using the negative-capacitance technique is introduced, termed the GAA CP NW negative-capacitance (NC) FET. In the face of bottleneck issues in nanoscale devices such as rising power dissipation, new techniques must be introduced into FET structures to overcome their major limitations. Negative capacitance is an efficient effect that can be incorporated into a device to enhance its performance for low-power applications and help to reduce the operating voltage. The Landau–Khalatnikov equation can be applied in such cases to obtain the effective bias. To determine the effects of negative capacitance, lead zirconate titanate (PZT) ferroelectric material, a ceramic material with perovskite properties, is adopted as a gate insulator. This approach diminishes the supply voltage and reduces the power dissipation in the device. Excluding their polarization properties, ferroelectric materials are similar to dielectric materials, and PZT offers abundant polarization with improved reliability and a higher dielectric capacitance. Without proper tuning of the thickness of the PZT material, hysteresis behavior mat occur. Hence, the thickness of the PZT material (t_FE) is an essential parameter to optimize the device performance and achieve a reduced threshold voltage for the GAA CP NW NC-FET device proposed herein. Furthermore, varying the thickness of the PZT ferroelectric material can also enhance the performance. When using the highest values of t_FE, improved outcomes with an analogously lower operating voltage are observed. The effects of varying t_FE on the performance characteristics of the device including the drain current, transconductance, polarized charge, etc. are also interpreted herein.

     

A proposed criteria to identify wind turbine drivetrain bearing loads that induce roller slip based white-Etching cracks

Forschung im Ingenieurwesen - In this article, the type of roller slip behavior that may result in the formation of white-etching cracks (WECs) in wind turbine gearbox bearings is identified....     

Determination of correlation properties of moving diffuser by spectral analyses of the scattered light emerging from two pinholes

Abstract

Correlation properties of light scattered by a moving diffuser are determined by studying the spectral characteristics of the light that emerges from two pinholes placed after the diffuser. These properties are used to determine the correlation functions of the heights of diffuser surface and the speed of the diffuser. The phase of the light on the two pinholes after it has passed through the moving diffuser, is also determined.     

Antifungal activity of five different essential oils in vapour phase for the control of Colletotrichum gloeosporioides and Lasiodiplodia theobromae in vitro and on mango

Mango fruit has high commercial value; however, major postharvest losses are encountered throughout the supply chain due to postharvest diseases. These results lead to the search for natural fungicide for postharvest diseases control. The antifungal effects of five essential oils (thyme, clove, cinnamon, anise and vitex) were assessed by disc volatilisation method. Thyme oil vapours at 5 μL per Petriplate, and clove and cinnamon oil at 8 μL per Petriplate showed 100% growth inhibition of mango pathogens in vitro. GC/MS analysis of essential oil showed thymol (23.88), o‐cymol (23.88) and terpinolene (23.88) as the major constituents of thyme oil. Clove and cinnamon oils contain 3‐allyl‐2‐methoxyphenol (37.42%) and benzofuran 3‐methyl (17.97%), respectively. Thyme oil as a fumigant at 66.7 μL L^?1 showed a significant (P < 0.05) inhibition on postharvest pathogens of mango fruits stored at 25 °C for 6 days. Results of our study suggest the possibility of using thyme oil as an alternate natural fungicide to manage postharvest diseases in mango.     

Information technology adoption and continuance: A longitudinal study of individuals’ behavioral intentions

Extant research on information technology (IT) adoption and continuance has not adequately modeled the times of adoption by individuals. This study argues that individuals adopt an innovation at different times and are likely to be influenced by different factors over time. The theoretical models are empirically validated using data gathered at three points in time through surveys of 132 users of a new innovation. The results indicate that the innovation attributes and individual characteristics influence individuals’ intentions to adopt the innovation during the early stage, and the innovation attributes and contextual factors impact the individuals’ intentions during the later stage.