Cell culture and in vivo analyses of cytopathic hepatitis C virus mutants

AbstractHCV-JFH1 yields subclones that develop cytopathic plaques (Sekine-Osajima Y, et al., Virology 2008; 371:71). Here, we investigated viral amino acid substitutions in cytopathic mutant HCV-JFH1 clones and their characteristics in vitro and in vivo. The mutant viruses with individual C2441S, P2938S or R2985P signature substitutions, and with all three substitutions, showed significantly higher intracellular replication efficiencies and greater cytopathic effects than the parental JFH1 in vitro. The mutant HCV-inoculated mice showed significantly higher serum HCV RNA and higher level of expression of ER stress-related proteins in early period of infection. At 8weeks post inoculation, these signature mutations had reverted to the wild type sequences. HCV-induced cytopathogenicity is associated with the level of intracellular viral replication and is determined by certain amino acid substitutions in HCV-NS5A and NS5B regions. The cytopathic HCV clones exhibit high replication competence in vivo but may be eliminated during the early stages of infection

Photoinduced swing of a diarylethene thin broad sword shaped crystal:a study on the detailed mechanism

We report a swinging motion of photochromic thin broad sword shaped crystals upon continuous irradiation with UV light. By contrast in thick crystals, photosalient phenomena were observed. The bending and swinging mechanisms are in fact due to molecular size changes as well as phase transitions. The first slight bending away from the light source is due to photocyclization-induced surface expansion, and the second dramatic bending toward UV incidence is due to single-crystal-to-single-crystal (SCSC) phase transition from the original phase I to phase IIUV. Upon visible light irradiation, the crystal returned to phase I. A similar SCSC phase transition with a similar volume decrease occurred by lowering the temperature (phase IIItemp). For both photoinduced and thermal SCSC phase transitions, the symmetry of the unit cell is lowered; in phase IIUV the twisting angle of disordered phenyl groups is different between two adjacent molecules, while in phase IIItemp, the population of the phenyl rotamer is different between adjacent molecules. In the case of phase IIUV, we found thickness dependent photosalient phenomena. The thin broad sword shaped crystals with a 3 mu m thickness showed no photosalient phenomena, whereas photoinduced SCSC phase transition occurred. In contrast, large crystals of several tens of mu m thickness showed photosalient phenomena on the irradiated surface where SCSC phase transition occurred. The results indicated that the accumulated strain, between isomerized and non-isomerized layers, gave rise to the photosalient phenomenon

国立大学における「実践的医療薬学教育プログラム」の現状

The six-year pharmacy program started in April 2006 in Japan. In the new program, students in the fifth year of the pharmacy course undergo a long-term practice experience (pharmacy clerkship) in community pharmacy and hospital pharmacy settings as compulsory 20 course credits. The new pharmacy practice experience started in May 2010. A start of the new system was a chance as for beginning movement, thus we conducted the questionnaire survey for the following steps. The finding obtained from our questionnaires indicated that many universities had already planned to execute new approaches, such as an advanced practice at outpatient units, an with medical students, and so on

国立大学における「実践的医療薬学教育プログラム」の現状

The six-year pharmacy program started in April 2006 in Japan. In the new program, students in the fifth year of the pharmacy course undergo a long-term practice experience (pharmacy clerkship) in community pharmacy and hospital pharmacy settings as compulsory 20 course credits. The new pharmacy practice experience started in May 2010. A start of the new system was a chance as for beginning movement, thus we conducted the questionnaire survey for the following steps. The finding obtained from our questionnaires indicated that many universities had already planned to execute new approaches, such as an advanced practice at outpatient units, an with medical students, and so on