Petrology and reflectance spectroscopy of lunar meteorite Yamato 981031: Implications for the source region of the meteorite and remote-sensing spectroscopy

Combined mineralogy and reflectance spectroscopy of lunar meteorite Yamato (Y) 981031 were investigated to determine its possible source region. Mineralogical observations indicate that Y981031 is a mixture of mafic mare and feldspathic highland components. Y981031 has abundant mineral fragments and lithic clasts in a comminuted matrix. Although the most of the lithic clasts are pyroxene-dominant basaltic clasts, some plagioclase-rich lithic fragments are also present. High- and low-Ca pyroxene grains with wide compositional variations are included in the breccia. Since high-Ca pyroxene (Wo43En40Fs17 to Wo29En23Fs48) and a part of Fe-rich low-Ca pyroxene are found in pyroxene-dominant basaltic clasts, they were derived from mare materials. In contrast, abundant Mg-rich low-Ca pyroxene (approximately Wo10En63Fs27) is of highland origin because their chemical compositions resemble highland low-Ca pyroxene. Fusion crust glass compositions (TiO2=0.50-0.77wt and FeO=11.7-15.4wt) suggest that source mafic components of Y981031 have very low-Ti (VLT) affinity. In comparison with global remote-sensing data, the above TiO2 and FeO concentrations resemble those of the VLT affinity in Mare Frigoris and adjacent maria. Thus, we propose that Y981031 was launched from this area. Modified gaussian model analysis of reflectance spectrum shows absorption features of high-Ca pyroxene (mare-origin) and Mg-rich low-Ca pyroxene (highland-origin), and enables us to observe separately mineralogical characteristics of each end member of Y981031 as the soil mixture

Binding of Ala-scanning analogs of ω-conotoxin MVIIC to N- and P/Q-type calcium channels

Abstractω-Conotoxin MVIIC binds to P/Q-type calcium channels with high affinity and N-type channels with low affinity. To reveal the residues essential for subtype selectivity, we synthesized Ala-scanning analogs of MVIIC. Binding assays using rat cerebellar P2 membranes suggested that Thr11, Tyr13 and Lys2 are essential for binding to both N- and P/Q-type channels, whereas Lys4 and Arg22 are important for binding to P/Q-type channels. These results suggest that MVIIC interacts with P/Q-type channels via a large surface, in good agreement with previous observations using chimeric analogs

Welfare Cost of Inflation and Income Risks in an Incomplete Market Model: Application to the Japanese Economy Welfare Costs of Inflation and Income Risks in an Incomplete Market Model: Application to the Japanese Economy *

Abstract This paper quantitatively investigates the welfare costs of inflation and idiosyncratic and aggregate income risks in a Bewley-type incomplete market model. A calibrated model of the Japanese economy in the 1990s indicates that money growth generated a larger welfare cost equivalent to 0.334% of real GDP, than the estimated shoe-leather cost 0.2%, and that the cost of inflation was amplified through an increase in unemployment risk. The model also indicates that longer unemployment duration spells, and the presence of heterogeneous agents, augment the welfare costs of income risk. Finally, the aggregate risk of the business cycle is found to be of little importance to welfare

Reactivation of hyperglycemia-induced hypocretin (<i>HCRT)</i> gene silencing by <i>N</i>-acetyl-d-mannosamine in the orexin neurons derived from human iPS cells

<p>Orexin neurons regulate critical brain activities for controlling sleep, eating, emotions, and metabolism, and impaired orexin neuron function results in several neurologic disorders. Therefore, restoring normal orexin function and understanding the mechanisms of loss or impairment of orexin neurons represent important goals. As a step toward that end, we generated human orexin neurons from induced pluripotent stem cells (hiPSCs) by treatment with <i>N</i>-acetyl-d-mannosamine (ManNAc) and its derivatives. The generation of orexin neurons was associated with DNA hypomethylation, histone H3/H4 hyperacetylation, and hypo-<i>O</i>-GlcNAcylation on the <i>HCRT</i> gene locus, and, thereby, the treatment of inhibitors of SIRT1 and OGT were effective at inducing orexin neurons from hiPSCs. The prolonged exposure of orexin neurons to high glucose in culture caused irreversible silencing of the <i>HCRT</i> gene, which was characterized by H3/H4 hypoacetylation and hyper-<i>O</i>-GlcNAcylation. The DNA hypomethylation status, once established in orexin neurogenesis, was maintained in the <i>HCRT</i>-silenced orexin neurons, indicating that histone modifications, but not DNA methylation, were responsible for the <i>HCRT</i> silencing. Thus, the epigenetic status of the <i>HCRT</i> gene is unique to the hyperglycemia-induced silencing. Intriguingly, treatment of ManNAc and its derivatives reactivated <i>HCRT</i> gene expression, while inhibitors SIRT1 and the OGT did not. The present study revealed that the <i>HCRT</i> gene was silenced by the hyperglycemia condition, and ManNAc and its derivatives were useful for restoring the orexin neurons.</p

Binding of chimeric analogs of w-conotoxin MVIIA and MVIIC to the N-and P/Q-type calcium channels

International audienceDespite their high sequence homology, the peptide neurotoxins ¢o-conotoxin MVIIA and MVIIC selectively block N-and P/Q-type calcium channels, respectively. To study the recognition mechanism of calcium channel subtypes, two chimeric analogs of ¢o-conotoxin MVIIA and MVIIC were synthesized by exchanging their N-and C-terminal halves. Binding assay for both N-and P/Q-type calcium channels showed that amino acid residues restricted to the N-terminal half are important for the recognition of N-type channels, whereas essential residues for P/Q-type channel recognition are widely spread over the whole ¢o-conotoxin molecule

A novel homozygous variant in MICOS13

Abstract Background Mitochondrial DNA depletion syndrome (MTDPS) is part of a group of mitochondrial diseases characterized by a reduction in mitochondrial DNA copy number. Most MTDPS is caused by mutations in genes that disrupt deoxyribonucleotide metabolism. Methods We performed the whole‐exome sequencing of a hepato‐encephalopathy patient with MTDPS and functional analyses to determine the clinical significance of the identified variant. Results Here, whole‐exome sequencing of a patient presenting with hepato‐encephalopathy and MTDPS identified a novel homozygous frameshift variant, c.13_29del (p.Trp6Profs*71) in MICOS13. MICOS13 (also known as QIL1, MIC13, or C19orf70) is a component of the MICOS complex, which plays crucial roles in the maintenance of cristae junctions at the mitochondrial inner membrane. We found loss of MICOS13 protein and fewer cristae structures in the mitochondria of fibroblasts derived from the patient. Stable expression of a wild‐type MICOS13 cDNA in the patients fibroblasts using a lentivirus system rescued mitochondrial respiratory chain complex deficiencies. Conclusion Our findings suggest that the novel c.13_29del (p.Trp6Profs*71) MICOS13 variant causes hepato‐encephalopathy with MTDPS. We propose that MICOS13 is classified as the cause of MTDPS

Apomorphine is a potent inhibitor of ferroptosis independent of dopaminergic receptors

Abstract Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of PTSG2 and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors