Analysis of Charging of the HTV-4 Based on On-Orbit Data

After three H-II transfer vehicles (HTVs) had finished their mission to resupply the International Space Station (ISS), NASA requested data of the HTV\u27s potential to evaluate the charging/discharging process that occurs when the HTV docks to the ISS. To measure these data, a new instrument was installed on the fourth HTV. This instrument allows us to measure the HTV-4 surface potential relative to the surrounding plasma, and is called advanced technology on-orbit test instrument for space environment-mini (ATOTIE-mini). The ATOTIE-mini observed the HTV\u27s local potential in the orbit for more than one month. The measured potential during the HTV solo-flight phase varied between -30 and -60 V in sunlight and was about 0 V in eclipse conditions. The HTV\u27s potential during the time when it was docked to the ISS followed the ISS\u27s potential with an almost constant offset of about 10 V. The data measured by ATOTIE-mini are consistent with those measured by the floating potential measurement unit on the ISS, and thus are considered reliable. The HTV\u27s potential level itself was acceptable for ISS. Note that the solar array panels can generate up to approximately 120 V, which is much larger than the absolute potential range in sunshine. We analyze the potential distribution on the HTV surface by a multi-utility spacecraft charging analysis tool, because ATOTIE-mini can only observe one point on the HTV surface. The analysis results are discussed with respect to the flight attitude

Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy

Primary auditory neurons (PANs) play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs), comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs). The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs

Analysis of Charging of the HTV-4 Based on On-Orbit Data

After three H-II transfer vehicles (HTVs) had finished their mission to resupply the International Space Station (ISS), NASA requested data of the HTV's potential to evaluate the charging/discharging process that occurs when the HTV docks to the ISS. To measure these data, a new instrument was installed on the fourth HTV. This instrument allows us to measure the HTV-4 surface potential relative to the surrounding plasma, and is called advanced technology on-orbit test instrument for space environment-mini (ATOTIE-mini). The ATOTIE-mini observed the HTV's local potential in the orbit for more than one month. The measured potential during the HTV solo-flight phase varied between -30 and -60 V in sunlight and was about 0 V in eclipse conditions. The HTV's potential during the time when it was docked to the ISS followed the ISS's potential with an almost constant offset of about 10 V. The data measured by ATOTIE-mini are consistent with those measured by the floating potential measurement unit on the ISS, and thus are considered reliable. The HTV's potential level itself was acceptable for ISS. Note that the solar array panels can generate up to approximately 120 V, which is much larger than the absolute potential range in sunshine. We analyze the potential distribution on the HTV surface by a multi-utility spacecraft charging analysis tool, because ATOTIE-mini can only observe one point on the HTV surface. The analysis results are discussed with respect to the flight attitude

The Hepatitis B Virus Genotype Affects the Persistence of Viral Replication in Immunodeficient NOG Mice.

At least eight genotypes of Hepatitis B virus (HBV) have been identified. HBV genotype C is the most common genotype in Japan, although the incidence of HBV genotype A is increasing. The reason underlying the differences in viral multiplication of the HBV genotypes is unclear, especially in vivo. The purpose of this study was to elucidate the differences in HBV load and the persistence of viremia in vivo between genotypes A and C.Immunodeficient NOG mice were transfected by hydrodynamic injection with the HBV expression plasmids pHBA1.2 or pHBC1.2, which contain overlength (1.2-mer) copies of the genomes of HBV genotype A or C, respectively.One day after transfection, the number of HBcAg-positive hepatocytes and serum HBV DNA levels were similar between mice transfected with pHBA1.2 and pHBC1.2. Serum levels of HBV DNA, HBsAg and HBeAg in mice transfected with pHBA1.2 were maintained over 5 months. In contrast, those in mice with pHBC1.2 gradually decreased over time and reached undetectable levels within 3 months after transfection. HBcAg-stained hepatocytes were detected in mice transfected with pHBA1.2, but not pHBC1.2, 5 months post-transfection. Double-staining immunohistochemistry revealed that the number of cleaved caspase3-stained, HBcAg-positive hepatocytes in the pHBC1.2-transfected mice was higher than in the pHBA1.2-transfected mice 3 days post-transfection. Moreover, the plasmid DNA and covalently closed circular DNA levels were decreased in the livers of pHBC1.2-transfected mice. These results suggested that hepatocytes expressing HBV genotype C were eliminated by apoptosis in the absence of immune cells more often than in hepatocytes expressing HBV genotype A.Immunodeficient mice transfected with HBV genotype A develop persistent viremia, whereas those transfected with HBV genotype C exhibit transient viremia accompanied by apoptosis of HBV-expressing hepatocytes. This differences may affect the clinical courses of patients infected with HBV genotypes A and C