Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor

Alzheimer-disease-associated beta-amyloid (A beta) is produced by sequential endoproteolysis of beta-amyloid protein precursor (beta APP): the extracellular portion is shed by cleavage in the juxtamembrane region by beta-amyloid-cleaving enzyme (BACE)/beta-secretase, after which it is cleaved by presenilin (PS)/gamma-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces A beta generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce A beta production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces A beta generation without affecting BACE or PS/gamma-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and beta APP, which reduces beta-cleavage of beta APP. Therefore, the data demonstrate that Dx-E represents a novel A beta-reducing process which could have fewer side effects than secretase inhibitors. Copyright (C) 2009 S. Karger AG, Base

Design and Demonstration of a Neutron Spin Flipper for a New Neutron Reflectometer SHARAKU at J-PARC

AbstractA new neutron reflectometer SHARAKU with vertical sample-plane geometry was installed on the beam line 17 (BL17) at Materials and Life science experiment Facility (MLF) at J-PARC. Magnetism in a thin magnetic film is one of the main targets on SHARAKU and polarizing devices and neutron spin flippers are required. Since polarized neutrons of wavelength from 0.24nm to 0.64nm can be used on SHARAKU, a neutron spin flipper has to control white neutron beam. A two-coil neutron spin flipper (Drabkin spin flipper) is one of the powerful devices to control neutron spin with white beam. In this study, the two-coil flipper was designed and installed in SHARAKU. Demonstration of the two-coil flipper was also performed and polarization of more than 0.95 with wavelengths ranging from 0.24nm to 0.64nm was obtained

Reduced Expression of the Survivin Gene in PBMC from Silicosis Patients

To explore the mechanism involved in immunological disorders associated with silicosis, the expression of IAP family genes in peripheral blood mononuclear cells from silicosis patients was examined. Relative gene expression was assayed using the multiplex RT-PCR for the XIAP and survivin genes. The correlation between those expression levels and various clinical parameters was then analyzed. The relative expression level of the survivin gene was reduced in silicosis patients as compared with that of healthy volunteers. The expression level of survivin positively correlated with PCO_2 values. These results support the existence of two populations of T lymphocytes in silicosis patients, one resistant to Fas-mediated apoptosis (a self-recognizing long-surviving fraction) and the other one sensitive to silica-induced apoptosis and repeatedly undergoing death and recruitment