STAT1/3 signaling suppresses axon degeneration and neuronal cell death through regulation of NAD+-biosynthetic and consuming enzymes

Nicotinamide adenine dinucleotide (NAD)+-biosynthetic and consuming enzymes are involved in various intracellular events through the regulation of NAD+ metabolism. Recently, it has become clear that alterations in the expression of NAD+-biosynthetic and consuming enzymes contribute to the axonal stability of neurons. We explored soluble bioactive factor(s) that alter the expression of NAD+-metabolizing enzymes and found that cytokine interferon (IFN)-γ increased the expression of nicotinamide nucleotide adenylyltransferase 2 (NMNAT2), an NAD+-biosynthetic enzyme. IFN-γ activated signal transducers and activators of transcription 1 and 3 (STAT1/3) followed by c-Jun N-terminal kinase (JNK) suppression. As a result, STAT1/3 increased the expression of NMNAT2 at both mRNA and protein levels in a dose- and time-dependent manner and, at the same time, suppressed activation of sterile alpha and Toll/interleukin receptor motif-containing 1 (SARM1), an NAD+-consuming enzyme, and increased intracellular NAD+ levels. We examined the protective effect of STAT1/3 signaling against vincristine-mediated cell injury as a model of chemotherapy-induced peripheral neuropathy (CIPN), in which axonal degeneration is involved in disease progression. We found that IFN-γ-mediated STAT1/3 activation inhibited vincristine-induced downregulation of NMNAT2 and upregulation of SARM1 phosphorylation, resulting in modest suppression of subsequent neurite degradation and cell death. These results indicate that STAT1/3 signaling induces NMNAT2 expression while simultaneously suppressing SARM1 phosphorylation, and that both these actions contribute to suppression of axonal degeneration and cell death

Turbulence Spreading into an Edge Stochastic Magnetic Layer Induced by Magnetic Fluctuation and Its Impact on Divertor Heat Load

Turbulence spreading into the edge stochastic magnetic layer induced by magnetic fluctuation is observed at the sharp boundary region in the large helical device. The density fluctuation excited at the sharp boundary region with a large pressure gradient does not propagate into the boundary region due to the blocking of turbulence spreading by the large second derivative of the pressure gradient. Once the magnetic fluctuation appears at the boundary, the density fluctuation begins to penetrate the edge stochastic layer and the second derivative of the pressure gradient also decreases. The increase of density fluctuation in this layer results in the broadening and reduction of the peak divertor heat load. It is demonstrated that magnetic fluctuation plays a key role in controlling the turbulence spreading at the boundary of plasma which contributes to the reduction of divertor heat load

Idobata-Nagaya: a community housing solution for socially isolated older adults following the great East Japan earthquake

IntroductionFollowing the Great East Japan Earthquake, the living environment of socially isolated older adults has become a pressing concern. In response, Nagaya, a collective housing program, was established in Soma City, Fukushima, Japan to address social isolation among older adults and support their long-term health. This study aimed to identify characteristics of individuals in Nagaya and examine the sustainability of this initiative.MethodsWe conducted a retrospective analysis of residents who were relocated to Nagaya, emphasizing their characteristics, the continuity of their stay in Nagaya, and their care certification levels, using data up to December 31, 2022. We employed Kaplan–Meier curves to analyze the duration for which residents continued to reside in Nagaya and the time leading up to the requiring care-level certification.ResultsOf 65 people who moved to Nagaya after the disaster, 30 people (46.2%) continued to live there, 21 (32.3%) died during their stay, and 14 (21.5%) moved out. The overall duration of occupancy averaged 6.39 years (SD 3.83 years). The proportion of requiring care-level certification occurrences per person-year was 0.0577 for those without care certification and 0.3358 for those with requiring support level at the time of moving in.ConclusionIn summary, Nagaya-style communal housing may offer suitable living environments for older adults with diverse needs during disasters and serve as a valuable tool for developing public policies in aging societies

Confinement improvement during detached phase with RMP application in deuterium plasmas of LHD

In order to explore the compatibility of good core plasma performance with divertor heat load mitigation, the interaction between cold edge plasma and core plasma transport, including the edge transport barrier (ETB), has been analysed in the divertor detachment discharges of deuterium plasmas in LHD with resonant magnetic perturbation (RMP) field application. The RMP application introduces a widened edge stochastic layer and sharp boundary in the magnetic field structure between the confinement region and the edge stochastic layer. The widened edge stochastic layer enhances impurity radiation and provides stable detachment operation as compared with the case without RMP. It is found that ETB is formed at the confinement boundary at the onset of detachment transition. However, as the detachment deepens, the resistive pressure gradient-driven MHD mode is excited, which degrades the ETB. At the same time, however, the core transport decreases to keep global plasma stored energy (Wp) unchanged, showing clear core-edge coupling. After a gradual increase of density fluctuation during the MHD activity, a spontaneous increase of Wp and the recovery of ETB are observed while the detachment is maintained. Then, the coherent MHD mode ceases and ELM-like bursts appear. In the improved mode, impurity decontamination occurs, and the divertor heat load increases slightly. Key controlling physical processes in the interplay between core and cold edge plasma are discussed. A comparison between deuterium and hydrogen plasmas shows that hydrogen plasmas exhibit similar features to the deuterium ones in terms of density and magnetic fluctuations, impurity decontamination towards higher confinement, etc. But most of the features are modest in the hydrogen plasmas and thus no clear confinement mode transition with clear ETB formation is defined. Better global confinement is obtained in the deuterium plasmas than the hydrogen ones at a higher radiation level

Observation of a reduced-turbulence regime with boron powder injection in a stellarator

In state-of-the-art stellarators, turbulence is a major cause of the degradation of plasma confinement. To maximize confinement, which eventually determines the amount of nuclear fusion reactions, turbulent transport needs to be reduced. Here we report the observation of a confinement regime in a stellarator plasma that is characterized by increased confinement and reduced turbulent fluctuations. The transition to this regime is driven by the injection of submillimetric boron powder grains into the plasma. With the line-averaged electron density being kept constant, we observe a substantial increase of stored energy and electron and ion temperatures. At the same time, the amplitude of the plasma turbulent fluctuations is halved. While lower frequency fluctuations are damped, higher frequency modes in the range between 100 and 200 kHz are excited. We have observed this regime for different heating schemes, namely with both electron and ion cyclotron resonant radio frequencies and neutral beams, for both directions of the magnetic field and both hydrogen and deuterium plasmas

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

Isotope effects on transport in LHD

Isotope effects are one of the most important issues for predicting future reactor operations. Large helical device (LHD) is the presently working largest stellarator/helical device using super conducting helical coils. In LHD, deuterium experiments started in 2017. Extensive studies regarding isotope effects on transport have been carried out. In this paper, the results of isotope effect studies in LHD are reported. The systematic studies were performed adjusting operational parameters and nondimensional parameters. In L mode like normal confinement plasma, where internal and edge transport barriers are not formed, the scaling of global energy confinement time (τE) with operational parameters shows positive mass dependence (M0.27; where M is effective ion mass) in electron cyclotron heating plasma and no mass dependence (M0.0) in neutral beam injection heating plasma. The non-negative ion mass dependence is anti-gyro-Bohm scaling. The role of the turbulence in isotope effects was also found by turbulence measurements and gyrokinetic simulation. Better accessibility to electron and ion internal transport barrier (ITB) plasma is found in deuterium (D) plasma than in hydrogen (H). Gyro kinetic non-linear simulation shows reduced ion heat flux due to the larger generation of zonal flow in deuterium plasma. Peaked carbon density profile plays a prominent role in reducing ion energy transport in ITB plasma. This is evident only in plasma with deuterium ions. New findings on the mixing and non-mixing states of D and H particle transports are reported. In the mixing state, ion particle diffusivities are higher than electron particle diffusivities and D and H ion density profiles are almost identical. In the non-mixing state, ion particle diffusivity is much lower than electron diffusivity. Deuterium and hydrogen ion profiles are clearly different. Different turbulence structures were found in the mixing and non-mixing states suggesting different turbulence modes play a role