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Motor axon degeneration is a critical but poorly understood event leading to weakness and muscle atrophy in motor neuron diseases. Here, we investigated oxidative stress-mediated axonal degeneration in mice lacking the antioxidant enzyme, Cu,Zn superoxide dismutase (SOD1). We demonstrate a progressive motor axonopathy in these mice and show that Sod1(-/-)(More)
Nrf-2 is a redox-sensitive transcription factor that is activated by an oxidative signal in the cytoplasm but has a critical cysteine that must be reduced to bind to DNA in the nucleus. The glutathione (GSH) and thioredoxin (TRX) systems have overlapping functions in thiol/disulfide redox control in both the cytoplasm and the nucleus, and it is unclear(More)
Uncontrolled inflammatory responses in the immature gut may play a role in the pathogenesis of many intestinal inflammatory syndromes that present in newborns or children, such as necrotizing enterocolitis (NEC), idiopathic inflammatory bowel diseases (IBD), or infectious enteritis. Consistent with previous reports that murine intestinal function matures(More)
Paraquat, N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine, and rotenone have been shown to reproduce several features of Parkinson's disease in animal and cell culture models. Although these chemicals are known to perturb dopamine homeostasis and induce dopaminergic cell death, their molecular mechanisms of action are not well defined. We have previously shown(More)
BACKGROUND Familial hemiplegic migraine (FHM) is a rare, dominantly inherited subtype of migraine with transient hemiplegia during the aura phase. Mutations in at least three different genes can produce the FHM phenotype. The mutated FHM genes code for ion transport proteins that animal and cellular studies have associated with disturbed ion homeostasis,(More)
Tumor necrosis factor-a (TNF-a) is a cytokine that is involved in numerous pathologies, in part through stimulation of the mitochondrial production of reactive oxygen species (ROS). Previous studies show that in addition to mitochondrial superoxide dismutase-and glutathione-dependent systems, mitochondria also contain thioredoxin-2 (Trx2), an antioxidant(More)
BACKGROUND Methanol (CH3OH) is believed to be teratogenic based on rodent studies. The mouse is more sensitive than the rat, but mechanisms of toxicity and identification of teratogenic metabolites are uncertain. METHODS Rat and mouse whole embryo cultures are used to distinguish toxicity of CH3OH and its metabolites, formaldehyde (HCHO) and formate(More)
The mechanisms by which enteric commensal microbiota influence maturation and repair of the epithelial barrier are relatively unknown. Epithelial restitution requires active cell migration, a process dependent on dynamic turnover of focal cell-matrix adhesions (FAs). Here, we demonstrate that natural, commensal bacteria stimulate generation of reactive(More)
The recommended strategy for management of dyspepsia is empirical treatment with an H2-blocking drug, followed by endoscopy if the symptoms do not respond or recur. We compared two strategies for the management of dyspepsia--treatment based on the results of prompt endoscopy (group 1) and empirical H2-blocker treatment with diagnostic endoscopy only in(More)