Impairment of adult hippocampal neural progenitor proliferation by methamphetamine: role for nitrotyrosination

Methamphetamine (METH) abuse has reached epidemic proportions, and it has become increasingly recognized that abusers suffer from a wide range of neurocognitive deficits. Much previous work has focused on the deleterious effects of METH on mature neurons, but little is known about the effects of METH on neural progenitor cells (NPCs). It is now well established that new neurons are continuously generated from NPCs in the adult hippocampus, and accumulating evidence suggests important roles for these neurons in hippocampal-dependent cognitive functions. In a rat hippocampal NPC culture system, we find that METH results in a dose-dependent reduction of NPC proliferation, and higher concentrations of METH impair NPC survival. NPC differentiation, however, is not affected by METH, suggesting cell-stage specificity of the effects of METH. We demonstrate that the effects of METH on NPCs are, in part, mediated through oxidative and nitrosative stress. Further, we identify seventeen NPC proteins that are post-translationally modified via 3-nitrotyrosination in response to METH, using mass spectrometric approaches. One such protein was pyruvate kinase isoform M2 (PKM2), an important mediator of cellular energetics and proliferation. We identify sites of PKM2 that undergo nitrotyrosination, and demonstrate that nitration of the protein impairs its activity. Thus, METH abuse may result in impaired adult hippocampal neurogenesis, and effects on NPCs may be mediated by protein nitration. Our study has implications for the development of novel therapeutic approaches for METH-abusing individuals with neurologic dysfunction and may be applicable to other neurodegenerative diseases in which hippocampal neurogenesis is impaired

Discontinuous CFRP-jacketing of masonry columns

Existing masonry columns are often susceptible to cracking due to overloading. Moreover, their fragility under earthquakes’ forces is of particular concern in seismic-prone regions. In order to mitigate these structural deficiencies, Fiber Reinforced Polymers (FRPs) are commonly used for external confinement. Full-jacketing, by means of FRP-wrapping is recognized to be very effective in improving the load bearing capacity and the ductility of masonry columns. Unfortunately, long-term effects seem to be detrimental for the masonry core, since its breathability is obstructed by the polymeric resin. Thus, a discontinuous application of the FRP-confinement appears to be more indicated in stone-masonry columns, allowing the humidity cycles to recur. On the other hand, the discontinuous wrapping negatively affects the confinement effectiveness, since both confined and unconfined masonry regions participate in the bearing capacity. In this sense, the present research is aimed to study the discontinuous confinement of half-scale masonry columns by means of Carbon-FRP strips. Unconfined and confined specimens were tested under uniaxial compression. The CFRP-confinement was studied by investigating the lateral strain in the confined and unconfined portions of the specimens. The results are reported and discussed in the paper in terms of failure modes, axial stress-strain and axial stress versus lateral strain relationships. The outcomes are reasonably convenient for a proper analytical interpretation of the phenomenon

Discontinuous FRP-Confinement of Masonry Columns

Recent seismic events, all over the world, demonstrated that masonry constructions are prone to brittle collapses when shear or compression capacity is reached. It is clear that, in many real cases, masonry columns need to be strengthened for enhancing their load-carrying capacity and to develop a more ductile response. The Fiber Reinforced Polymers (FRPs) confinement of masonry columns is a well-known technique that may produce these advantages. Unfortunately, full-wrapping insulates the column from the environment; so interstitial humidity can easily occur and cause the acceleration of the masonry's decay. In order to prevent it, partial-confinement is commonly assessed instead of total-jacketing. For this reason, a research was led, consisting of an experimental and theoretical study focused on the discontinuous FRP-confinement. Thus, two different series of masonry columns were confined with Glass-FRP (GFRP) and Carbon-FRP (CFRP) strips bonded to the column with an epoxy resin. Different schemes of FRP-wrapping were investigated by means of uniaxial compression tests. Moreover, an analytical method for the prediction of the experimental results was also provided. The proposed model was based on the relationship between the different lateral deformations of the confined and unconfined regions (experimentally recorded by using strain gauges). The new iterative procedure was found able to provide theoretical stress vs. strain curves; which demonstrated to accurately match the experimental recordings. The proposed model was also validated by parametric analyses, presented in the paper