Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease

Research by Klein and co-workers suggests that the inhibition of GSK-3beta by small molecules may offer an important strategy in the treatment of a number of central nervous system (CNS) disorders including Alzheimer's disease, Parkinson's disease, and bipolar disorders. Based on results from kinase-screening assays that identified a staurosporine analogue as a modest inhibitor of GSK-3beta, a series of 3-indolyl-4-indazolylmaleimides was prepared for study in both enzymatic and cell-based assays. Most strikingly, whereas we identified ligands having poor to high potency for GSK-3beta inhibition, only ligands with a Ki value of less than 8 nM, namely maleimides 18 and 22, were found to inhibit Tau phosphorylation at a GSK-3beta-specific site (Ser 396/404). Accordingly, maleimides 18 and 22 may protect neuronal cells against cell death by decreasing the level of alpha-Syn protein expression. We conclude that the GSK-3beta inhibitors described herein offer promise in defending cells against MPP+-induced neurotoxicity and that such compounds will be valuable to explore in animal models of Parkinson's disease as well as in other Tau-related neurodegenerative disease states.     

Formation of magnesia-spinel inclusions

Research on magnesia spinel in steel and the fracture of magnesite linings from laboratory and industrial melts is reviewed. The mineralogical composition of spinelide globules is considered. The transformation of periclase to magnesia spinel is described, with particular focus on the processes by which MgO · Al₂O₃ is formed.     

Al— Be alloys: Multipurpose metallic composite materials

The article is devoted to composite materials created on the basis of the technology of light alloys and developments of the All-Russia Institute of Aircraft Materials concerning beryllium alloys with a high modulus of elasticity. The competitiveness of such composite materials is determined by the high level of the specific strength properties, which exceed, in some cases, the characteristics of powder materials of a similar composition and approach the properties of titanium alloys and steels.Translated from Metallovedenie i Termicheskaya Obrabotka Metallov, No. 9, pp. 23 – 26, September, 1996.     

Efficiency of process methods for improving the surface quality and fatigue strength of gas-turbine engine disks of the KhN73MBTYu-VD alloy

The results of the present study suggest that a fatigue limit of the crown interslot projections of gas-turbine engine disks made of the KhN73MBTYu-VD alloy can be raised by subjecting the surface layer of the disk slots to ultrasonic hardening with balls. We attribute this to a removal of abrasive grits left by previous machining, to a decrease in depletion of the surface in alloying elements, and a simultaneous improvement in uniformity of the stress-strain state of various sections of the surface of a slot. Translated from Problemy Prochnosti, No. 5, pp. 126–133, September–October, 1998.