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Neuronal injury resulting from glutamate receptor-mediated excitotoxicity has been implicated in a wide spectrum of neurological disorders. Following dramatic results in the preclinical setting, anti-excitotoxic neuroprotective agents have been used in clinical trials for stroke and head injury, but the results have generally been unsuccessful. Hence, alternative targets in the excitotoxic cascade appear to be required. Poly(ADP-ribosyl)ation has been linked to the pathogenesis of numerous disorders of the CNS, including excitotoxicity and ischemic injury. A presumed cascade of glutamate receptor activation leading to excessive free radical formation, DNA damage and then overactivation of PARP-1 is based on studies with drugs that block these various steps. Along this classical view, experiments in our laboratory have shown that the intracellular depletion of ATP and NAD induced by PARP-1 overactivation leads to necrotic cell death in ischemic and excitotoxic models and that PARP-1 inhibitors are protective against necrotic but not apoptotic neuronal death. Therefore, it appears reasonable to propose PARP-1 inhibitors as useful therapeutic agents in pathological brain conditions where necrosis predominates. [ABSTRACT FROM AUTHOR]

We report on the specification and analysis of VICE, a hypothetical cell with a genome as basic as possible. We used an enhanced version of the π-calculus and a prototype running it to study the behaviour of VICE. The results of our experimentation in silico confirm that our virtual cell "survives" in an optimal environment and shows a behaviour similar to that of real prokaryotes. [ABSTRACT FROM AUTHOR]

Apoptosis, or programmed cell death, represents in cell biology a functional program as important as cell growth or differentiation. Programmed cell death is of basic importance for the development of multicellular organisms and its basic mechanisms are conserved during the evolution of metazoa. Mammalian cells exhibit several different apoptotic pathways that converge to a common endpoint. Each pathway is triggered by a different stimulus: growth factor default, irradiation, induction of the p53 oncosuppressor protein, glucocorticoid hormones (in lymphocytes), ligand binding to Fas/APO (CD95), or tumor necrosis factor receptor (TNF-R), perforin secreted by cytotoxic T cells (reviewed by Hale et al. [1]). As opposed to necrosis, apoptosis is a "clean" process: as the cell shrinks, the cell membrane turns into the "apoptotic shell," the nucleus is condensed and reduced in volume, and eventually the cell disappears from the tissue, due to phagocytosis by neighboring cells or professional phagocytes, such as macrophages. [ABSTRACT FROM AUTHOR]