ABSTRACT
A role for beta-amyloid precursor protein (beta-APP) in the development of Alzheimer's disease has been indicated by genetics, and many conditions in which beta-APP is raised have been associated with an increased risk of Alzheimer's disease or an Alzheimer's-like pathology. Inflammatory events may also contribute to Alzheimer's disease. Here we investigate whether a secreted derivative of beta-APP (sAPP-alpha) can induce inflammatory reactions in microglia, which are brain cells of monocytic lineage. We found that treatment with sAPP-alpha increased markers of activation in microglia and enhanced their production of neurotoxins. The ability of sAPP-alpha to activate microglia was blocked by prior incubation of the protein with apolipoprotein E3 but not apolipoprotein E4, a variant associated with an increased risk for Alzheimer's. A product of amyloidogenic beta-APP processing (sAPP-beta) also activated microglia. Because sAPP-beta is deficient in the neuroprotective activity shown by sAPP-alpha, our results indicate that increased amyloidogenic processing could adversely affect the balance of sAPP activities that determine neuronal viability.
Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/metabolism , Apolipoproteins E/metabolism , Microglia/metabolism , Peptide Fragments/metabolism , Animals , Cell Death , Cell Line , Gene Expression Regulation , Humans , Inflammation/metabolism , Interleukin-1/biosynthesis , Interleukin-1/genetics , Microglia/cytology , NF-kappa B/metabolism , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase/genetics , RatsABSTRACT
Determining occupational health and safety risks posed by emerging technologies is difficult because of limited statistics. Nevertheless, estimates of such risks must be constructed to permit comparison of various technologies to identify the most attractive processes. One way to estimate risks is to use statistics on related industries. Based on process labor requirements and associated occupational health data, risks to workers and to society posed by an emerging technology can be calculated. Using data from the California semiconductor industry, this study applies a five-step occupational risk assessment procedure to four processes for the fabrication of photovoltaic cells. The validity of the occupational risk assessment method is discussed.
Subject(s)
Occupational Diseases/epidemiology , California , Humans , Occupational Diseases/mortality , Risk , TechnologyABSTRACT
The dinoflagellate Glenodinium hallii was investigated for its sterol composition. Five of the six sterols were isolated and identified as cholest-5en-3beta-ol, (24xi)-24-methylcholest-5-en-3beta-ol, stigmasta-5,22-dien-3beta-ol, (22E,24R)-4 alpha, 23, 24-trimethyl-5 alpha-cholest-22-en-3 beta-ol, and 4 alpha, 23 xi, 24 xi-trimethyl-5 alpha-cholestan-3 beta-ol.