A study of the visualization of proton relay in cellulase by neutron crystallography.

Objective: The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported agestandardized rate of 63.6 per 100 000 women. Methods: The Japanese Guidelines for Breast Cancer Screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for populationbased and opportunistic screenings were formulated. Results: Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. Conclusions: Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness.

Biophysical parameters and L-band polarimetry synthetic aperture radar observation data were taken for 59 test sites in Tomakomai national forest, which is located in the northern part of Japan. Correlations between the derived σ 0 HH , σ 0 HV , and σ 0 VV and the biophysical parameters are investigated and yield the following results. 1) The above-ground biomass-σ 0 curves saturate above 50 tons/ha for σ 0 VV , 100 tons/ha for σ 0 HH , and over 100 tons/ha for σ 0 HV when all forest species are included in the curves. 2) The σ 0 HH -above-ground biomass curve for one forest species indicates a higher saturation level than that for the other forest species. Dependence on the forest species was absent for VV polarization and low for HV polarization.3) A simple three-component scattering model indicates that volume scattering accounts for 80%-90% when the above-ground biomass exceeds 50 tons/ha. The surface-scattering components are up to ∼20% for young stands, and the volume-scattering components are down to 70%. The origin of the dependency among the forest species was examined for the σ 0 HH -above-ground biomass. It is concluded that a possible cause of the dependency is the different characteristics of the stands rather than forest species.Index Terms-Forestry, synthetic aperture radar (SAR).

The dipeptidyl aminopeptidase BII (DAP BII) belongs to a serine peptidase family, S46. The amino acid sequence of the catalytic unit of DAP BII exhibits significant similarity to those of clan PA endopeptidases, such as chymotrypsin. However, the molecular mechanism of the exopeptidase activity of family S46 peptidase is unknown. Here, we report crystal structures of DAP BII. DAP BII contains a peptidase domain including a typical double β-barrel fold and previously unreported α-helical domain. The structures of peptide complexes revealed that the α-helical domain covers the active-site cleft and the side chain of Asn330 in the domain forms hydrogen bonds with the N-terminus of the bound peptide. These observations indicate that the α-helical domain regulates the exopeptidase activity of DAP BII. Because S46 peptidases are not found in mammals, we expect that our study will be useful for the design of specific inhibitors of S46 peptidases from pathogens.

Gamma-secretase plays an important role in the development of Alzheimer disease (AD). Gamma-secretase activity is enriched in autophagic vacuoles and it augments amyloid-beta (Abeta) synthesis. Autophagy-lysosomal dysfunction has been implicated in AD, but whether gamma-secretase activity is affected by autophagy remains unclear. Here we report that gamma-secretase activity is enhanced in basal autophagy-disturbed cells through the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) kinase, general control nonderepressible 2 (GCN2). Presenilin-1 (PS1) expression was increased even in the presence of nutrients in autophagy-related 5 knockdown (Atg5KD) human embryonic kidney (HE K293) cells expressing a short hairpin RNA as well as in chloroquine-treated HE K293 cells. However, PS1 expression induction was prevented in GCN2KD and ATF4KD cells. Furthermore, Atg5KD cells showed an increase in Abeta production and Notch1 cleavage. These were reduced by an autophagy inducer, resveratrol. Thus, we conclude that the autophagy-lysosomal system regulates gamma-secretase activity through GCN2.