SMN promotes mitochondrial metabolic maturation during myogenesis by regulating the MYOD-miRNA axis

脊髄性筋萎縮症における骨格筋病変の発症メカニズムの一部を解明. 京都大学プレスリリース. 2023-01-17.Pathogenesis of skeletal muscle lesions in spinal muscular atrophy. 京都大学プレスリリース. 2023-02-17.Spinal muscular atrophy (SMA) is a congenital neuromuscular disease caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although the primary cause of progressive muscle atrophy in SMA has classically been considered the degeneration of motor neurons, recent studies have indicated a skeletal muscle–specific pathological phenotype such as impaired mitochondrial function and enhanced cell death. Here, we found that the down-regulation of SMN causes mitochondrial dysfunction and subsequent cell death in in vitro models of skeletal myogenesis with both a murine C2C12 cell line and human induced pluripotent stem cells. During myogenesis, SMN binds to the upstream genomic regions of MYOD1 and microRNA (miR)-1 and miR-206. Accordingly, the loss of SMN down-regulates these miRs, whereas supplementation of the miRs recovers the mitochondrial function, cell survival, and myotube formation of SMN-deficient C2C12, indicating the SMN-miR axis is essential for myogenic metabolic maturation. In addition, the introduction of the miRs into ex vivo muscle stem cells derived from Δ7-SMA mice caused myotube formation and muscle contraction. In conclusion, our data revealed novel transcriptional roles of SMN during myogenesis, providing an alternative muscle-oriented therapeutic strategy for SMA patients

Search for two-neutrino double electron capture on 124^{124}Xe with the XMASS-I detector

Double electron capture is a rare nuclear decay process in which two orbital electrons are captured simultaneously in the same nucleus. Measurement of its two-neutrino mode would provide a new reference for the calculation of nuclear matrix elements whereas observation of its neutrinoless mode would demonstrate lepton number violation. A search for two-neutrino double electron capture on $^{124}$Xe is performed using 165.9 days of data collected with the XMASS-I liquid xenon detector. No significant excess above background was observed and we set a lower limit on the half-life as $4.7 \times 10^{21}$ years at 90% confidence level. The obtained limit has ruled out parts of some theoretical expectations. We obtain a lower limit on the $^{126}$Xe two-neutrino double electron capture half-life of $4.3 \times 10^{21}$ years at 90% confidence level as well.Comment: 6 pages, 3 figures, accepted for publication in Physics Letters

Direct dark matter search by annual modulation in XMASS-I

A search for dark matter was conducted by looking for an annual modulation signal due to the Earth's rotation around the Sun using XMASS, a single phase liquid xenon detector. The data used for this analysis was 359.2 live days times 832 kg of exposure accumulated between November 2013 and March 2015. When we assume Weakly Interacting Massive Particle (WIMP) dark matter elastically scattering on the target nuclei, the exclusion upper limit of the WIMP-nucleon cross section 4.3$\times$10$^{-41}$cm$^2$ at 8 GeV/c$^2$ was obtained and we exclude almost all the DAMA/LIBRA allowed region in the 6 to 16 GeV/c$^2$ range at $\sim$10$^{-40}$cm$^2$. The result of a simple modulation analysis, without assuming any specific dark matter model but including electron/$\gamma$ events, showed a slight negative amplitude. The $p$-values obtained with two independent analyses are 0.014 and 0.068 for null hypothesis, respectively. we obtained 90\% C.L. upper bounds that can be used to test various models. This is the first extensive annual modulation search probing this region with an exposure comparable to DAMA/LIBRA.Comment: 5 pages, 4 figure

Search for solar axions in XMASS, a large liquid-xenon detector

XMASS, a low-background, large liquid-xenon detector, was used to search for solar axions that would be produced by bremsstrahlung and Compton effects in the Sun. With an exposure of 5.6ton days of liquid xenon, the model-independent limit on the coupling for mass $\ll$ 1keV is $|g_{aee}|< 5.4\times 10^{-11}$ (90% C.L.), which is a factor of two stronger than the existing experimental limit. The bounds on the axion masses for the DFSZ and KSVZ axion models are 1.9 and 250eV, respectively. In the mass range of 10-40keV, this study produced the most stringent limit, which is better than that previously derived from astrophysical arguments regarding the Sun to date