APP Processing Induced by Herpes Simplex Virus Type 1 (HSV-1) Yields Several APP Fragments in Human and Rat Neuronal Cells

Lifelong latent infections of the trigeminal ganglion by the neurotropic herpes simplex virus type 1 (HSV-1) are characterized by periodic reactivation. During these episodes, newly produced virions may also reach the central nervous system (CNS), causing productive but generally asymptomatic infections. Epidemiological and experimental findings suggest that HSV-1 might contribute to the pathogenesis of Alzheimer's disease (AD). This multifactorial neurodegenerative disorder is related to an overproduction of amyloid beta (Aβ) and other neurotoxic peptides, which occurs during amyloidogenic endoproteolytic processing of the transmembrane amyloid precursor protein (APP). The aim of our study was to identify the effects of productive HSV-1 infection on APP processing in neuronal cells. We found that infection of SH-SY5Y human neuroblastoma cells and rat cortical neurons is followed by multiple cleavages of APP, which result in the intra- and/or extra-cellular accumulation of various neurotoxic species. These include: i) APP fragments (APP-Fs) of 35 and 45 kDa (APP-F35 and APP-F45) that comprise portions of Aβ; ii) N-terminal APP-Fs that are secreted; iii) intracellular C-terminal APP-Fs; and iv) Aβ1-40 and Aβ1-42. Western blot analysis of infected-cell lysates treated with formic acid suggests that APP-F35 may be an Aβ oligomer. The multiple cleavages of APP that occur in infected cells are produced in part by known components of the amyloidogenic APP processing pathway, i.e., host-cell β-secretase, γ-secretase, and caspase-3-like enzymes. These findings demonstrate that HSV-1 infection of neuronal cells can generate multiple APP fragments with well-documented neurotoxic potentials. It is tempting to speculate that intra- and extracellular accumulation of these species in the CNS resulting from repeated HSV-1 reactivation could, in the presence of other risk factors, play a co-factorial role in the development of AD

Comparative studies of the stability of various fluids under electrical discharge and thermal stresses

It is a well-known fact that the service reliability of power transformers largely depends upon the condition of the dielectric fluid. The steady deterioration (under the influence of the multiple stresses) of the insulation has an important impact on the condition of the transformers themselves. This contribution reports some investigations on some commercially available ester, silicone and mineral oil fluids. Some of their physicochemical properties are studied by submitting them to various stresses: electrical, thermal and oxidation. Many comparisons are made according to the quality test results of mineral oil, as it is very familiar to the transformer industry. A new technique using a reactive free radical reagent, 2,2-diphenyl-1- picrylhydrazyl (DPPH), added to both new oil for reference purposes and different aged oil to assess free radical concentration is presented. The gassing tendency under either thermal or electrical stress, along with the physicochemical properties of the fluids, is affected; it is assessed with the production of oxidative aging by-products. The gassing performance characteristics of natural ester fluids are far superior to those of conventional mineral oil. A significant reduction in insulation aging rate was observed with synthetic ester fluids