Hepatitis C Virus-specific T-cell Response Correlates with Hepatitis Activity and Donor IL28B Genotype Early after Liver Transplantation

It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At＞3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-specific immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect

An isomorphous replacement method for efficient de novo phasing for serial femtosecond crystallography.

SACLAのX線自由電子レーザーを用いた新規タンパク質立体構造決定に世界で初めて成功. 京都大学プレスリリース. 2015-09-14.Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) holds great potential for structure determination of challenging proteins that are not amenable to producing large well diffracting crystals. Efficient de novo phasing methods are highly demanding and as such most SFX structures have been determined by molecular replacement methods. Here we employed single isomorphous replacement with anomalous scattering (SIRAS) for phasing and demonstrate successful application to SFX de novo phasing. Only about 20,000 patterns in total were needed for SIRAS phasing while single wavelength anomalous dispersion (SAD) phasing was unsuccessful with more than 80,000 patterns of derivative crystals. We employed high energy X-rays from SACLA (12.6 keV) to take advantage of the large anomalous enhancement near the LIII absorption edge of Hg, which is one of the most widely used heavy atoms for phasing in conventional protein crystallography. Hard XFEL is of benefit for de novo phasing in the use of routinely used heavy atoms and high resolution data collection

Gamma-ray irradiation effects on optical coatings and polarizers for edge Thomson scattering system in ITER

This paper reports the gamma-ray irradiation effects on optical coatings and polarizers to be used in the ITERedge Thomson scattering system (ETS). Outside a diagnostic port-plug, in the Interspace, a total dose of the orderof 1 MGy is expected through 20 years of ITER operation. In this study, gamma-ray irradiation experiments wereperformed up to 10 MGy. A high peak power laser beam, i.e. a pulse energy of 5 J and a pulse duration of∼4 ns,is needed for a Thomson scattering measurement in ITER. Laser-induced damage threshold (LIDT) of anti-re-flection (AR) and high-reflection (HR) coatings at the laser wavelengths after gamma-ray irradiation were in-vestigated. LIDT of AR coating for 0° injections was more likely higher for the irradiated samples at a wavelengthof 1064 nm. Regarding HR coatings, LIDT was not noticeably degraded by gamma-ray irradiation. Regardingpolarizers, no degradation of transmission and extinction ratio was observed at visible and near infrared wa-velength ranges when a wire-grid polarizer substrate is made of fused silica. Since a signal of ETS is almostlinearly polarized, a wire-grid polarizer enables to improve signal to noise ratio of electron temperature anddensity measurements by Thomson scattering in ITER