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Reactive oxygen species (ROS) are important second messengers generated in response to many types of environmental stress. In this setting, changes in intracel-lular ROS can activate signal transduction pathways that influence how cells react to their environment. In sepsis, a dynamic proinflammatory cellular response to bacterial toxins (e.g.(More)
Adeno-associated virus (AAV) is a single-stranded DNA parvovirus that causes no currently known pathology in humans. Despite the fact that this virus is of increasing interest to molecular medicine as a vector for gene delivery, relatively little is known about the cellular mechanisms controlling infection. In this study, we have examined endocytic and(More)
Cerebellar Purkinje cells were ablated by the specific expression of diphtheria toxin in these cells in transgenic mice. Purkinje cell degeneration during early postnatal development shows a zonally restricted pattern which has been exploited in order to look for local secondary effects. The most obvious early effect is the alignment of gaps in the Purkinje(More)
Members of the En and Wnt gene families seem to play a key role in the early specification of the brain territory that gives rise to the cerebellum, the midhindbrain junction. To analyze the possible continuous role of the En and Wnt signaling pathway in later cerebellar patterning and function, we expressed En-2 ectopically in Purkinje cells during late(More)
Extracellular signal regulated kinases (ERKs) are key regulatory proteins that mediate cell survival, proliferation and differentiation. Reactive oxygen species (ROS) may play a role in activation of the ERK pathway. Since mitochondria are a major source of ROS, we investigated whether mitochondrial-derived ROS play a role in ERK activation. Diazoxide, a(More)
Numerous environmental influences have been demonstrated to enhance recombinant adeno-associated virus (rAAV) transduction. Such findings are the foundation of developing new and innovative strategies to improve the efficiency of rAAV as a gene therapy vector. Several of these environmental factors included genotoxic stresses such as UV and y irradiation as(More)
Several types of environmental damage including UV, hydroxyurea and ionizing irradiation have been shown to augment rAAV transduction. Current hypotheses suggest that these environmental stimuli lead to the enhanced production and/or activation of cellular factors important in the conversion of single-stranded DNA genomes to expressible forms. However, the(More)
To explore the role of Engrailed proteins in development of the cerebellum, Engrailed-2 (En-2) was ectopically expressed in cerebellar Purkinje cells from the late embryonic stage into adulthood. The fundamental organization of Purkinje cell sagittal zones as revealed by the "early onset" markers L7-beta-gal and cadherin-8 was found to be virtually(More)
We have previously demonstrated that a short sequence element (L7ATE) within the proximal promoter of a Purkinje cell-specific gene, pcp-2(L7), is required for the normal pattern of expression of the gene in the cerebellum of transgenic mice. The presence of a series of TAAT sequence motifs in this element suggested its interaction with homeodomain(More)
Numerous environmental stimuli alter cell functions by the induction of intracellular reactive oxygen species, such as superoxide and hydrogen peroxide (H2O2). These redox alterations can change the activity of kinases and phosphatases responsible for controlling intracellular signal transduction cascades important in determining how cells react to their(More)