Isolation and gene analysis of interferon α-resistant cell clones of the hepatitis C virus subgenome

AbstractHepatitis C virus (HCV) proteins appear to play an important role in IFN-resistance, but the molecular mechanism remains unclear. To clarify the mechanism in HCV replicon RNA harboring Huh-7 cells (Huh-9-13), we isolated cellular clones with impaired IFNα-sensitivity. Huh-9-13 was cultured for approximately 2 months in the presence of IFNα, and 4 IFNα-resistant cell clones showing significant resistances were obtained. When total RNA from clones was introduced into Huh-7 cells, the transfected cells also exhibited IFNα-resistance. Although no common mutations were present, mutations in NS3 and NS5A regions were accumulated. Transactivation of IFNα and IFNα-stimulated Stat-1 phosphorylation were reduced, and the elimination of HCV replicon RNA from the clones restored the IFNα signaling. These results suggest that the mutations in the HCV replicon RNA, at least in part, cause an inhibition of IFN signaling and are important for acquisition of IFNα resistance in Huh-9-13

Comparison of the effects of losartan vs. ramipril on several adipocytokines and vascular remodeling biomarkers

金沢大学医学系研究

Room-Temperature Electron Spin Transport in a Highly Doped Si Channel

We report on the first demonstration of generating a spin current and spin transport in a highly doped Si channel at room temperature (RT) using a four-terminal lateral device with a spin injector and a detector consisting of an Fe/MgO tunnel barrier. Spin current was generated using a nonlocal technique, and spin injection signals and Hanle-type spin precession were successfully detected at 300 K, thus proving spin injection with the elimination of spurious signals. The spin diffusion length and its lifetime at RT were estimated to be 0.6 \"im and 1.3 ns by the Hanle-type spin precession, respectively.Comment: 14 pages, 4 Figure

Lower FEV1 in non-COPD, nonasthmatic subjects: association with smoking, annual decline in FEV1, total IgE levels, and TSLP genotypes

Few studies have investigated the significance of decreased FEV1 in non-COPD, nonasthmatic healthy subjects. We hypothesized that a lower FEV1 in these subjects is a potential marker of an increased susceptibility to obstructive lung disease such as asthma and COPD. This was a cross-sectional analysis of 1505 Japanese adults. We divided the population of healthy adults with no respiratory diseases whose FEV1/FVC ratio was ≥70% (n = 1369) into 2 groups according to their prebronchodilator FEV1 (% predicted) measurements: <80% (n = 217) and ≥80% (n = 1152). We compared clinical data – including gender, age, smoking habits, total IgE levels, and annual decline of FEV1 – between these 2 groups. In addition, as our group recently found that TSLP variants are associated with asthma and reduced lung function, we assessed whether TSLP single nucleotide polymorphisms (SNPs) were associated with baseline lung function in non-COPD, nonasthmatic healthy subjects (n = 1368). Although about half of the subjects with lower FEV1 had never smoked, smoking was the main risk factor for the decreased FEV1 in non-COPD, nonasthmatic subjects. However, the subjects with lower FEV1 had a significantly higher annual decline in FEV1 independent of smoking status. Airflow obstruction was associated with increased levels of total serum IgE (P = 0.029) and with 2 functional TSLP SNPs (corrected P = 0.027–0.058 for FEV1% predicted, corrected P = 0.015–0.033 for FEV1/FVC). This study highlights the importance of early recognition of a decreased FEV1 in healthy subjects without evident pulmonary diseases because it predicts a rapid decline in FEV1 irrespective of smoking status. Our series of studies identified TSLP variants as a potential susceptibility locus to asthma and to lower lung function in non-COPD, nonasthmatic healthy subjects, which may support the contention that genetic determinants of lung function influence susceptibility to asthma

Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice

A close correlation between atherosclerosis, inflammation, and osteoporosis has been recognized, although the precise mechanism remains unclear. The growth factor progranulin (PGRN) is expressed in various cells such as macrophages, leukocytes, and chondrocytes. PGRN plays critical roles in a variety of diseases, such as atherosclerosis and arthritis by inhibiting Tumor Necrosis Factor-α (TNF-α) signaling. The purpose of this study was to investigate the effect of PGRN on bone metabolism. Forty-eight-week old female homozygous PGRN knockout mice (PGRN-KO) (n = 8) demonstrated severe low bone mass in the distal femur compared to age- and sex-matched wild type C57BL/6J mice (WT) (n = 8) [BV/TV (%): 5.8 vs. 16.6; p < 0.001, trabecular number (1/mm): 1.6 vs. 3.8; p < 0.001]. In vitro, PGRN inhibited TNF-α-induced osteoclastogenesis from spleen cells of PGRN-KO mice. Moreover, PGRN significantly promoted ALP activity, osteoblast-related mRNA (ALP, osteocalcin) expression in a dose-dependent manner and up-regulated osteoblastic differentiation by down-regulating phosphorylation of ERK1/2 in mouse calvarial cells. In conclusion, PGRN may be a promising treatment target for both atherosclerosis and inflammation-related osteoporosis.Noguchi T., Ebina K., Hirao M., et al. Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice. Biochemical and Biophysical Research Communications 465, 638 (2015); https://doi.org/10.1016/j.bbrc.2015.08.077

Subaru High-Dispersion Spectroscopy of Narrow-Line Region in the Seyfert Galaxy NGC 4151

We report on a study of forbidden emission-line spectrum of nearby Seyfert 1.5 galaxy NGC 4151 based on the high-resolution (R ~ 45,000) optical spectrum obtained by using the High Dispersion Spectrograph boarded on the Subaru Telescope. The profile parameters such as the emission-line widths, the velocity shifts from the recession velocity of the host galaxy, and the asymmetry indices, for emission lines including very faint ones such as [Ar IV]4712,4740 and [Fe VI]5631,5677 are investigated. Statistically significant correlations between the measured profile parameters and the critical densities of transitions are found while there are no meaningful correlations between the profile parameters and the ionization potentials of ions. By comparing the results with photoionization model calculations, we remark that a simple power-law distribution of the gas density which is independent of the radius from the nucleus cannot explain the observed correlation between the emission-line widths and the critical densities of the transitions. Taking the additional dense gas component expected to exist at the innermost of the narrow-line region into account, the observed correlations between the emission-line width and the critical density of the transitions can be understood since high-critical-density emission lines can arise at such relatively inner regions even if their ionization potentials are low. The observed correlation between the blueshift amounts of emission lines and the critical densities of the ions is also explained if such dense gas clouds located closer to the nucleus have larger outflowing velocities.Comment: 19 pages and 1 separate jpeg figure. Accepted for publication in A