J. J. Schmidt

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Neonatal mice resist the lethal effect of Waglerin-1. Because Waglerin-1 blocks the nicotinic acetylcholine receptor of mature end-plates, the appearance of lethality may result from the epsilon- for gamma-subunit substitution. In support of this hypothesis, adult knockout (KO) mice lacking the gene coding for the epsilon-subunit resist the lethal effect of(More)
Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of(More)
Optimization of a serotype-selective, small-molecule inhibitor of botulinum neurotoxin serotype A (BoNTA) endopeptidase is a formidable challenge because the enzyme-substrate interface is unusually large and the endopeptidase itself is a large, zinc-binding protein with a complex fold that is difficult to simulate computationally. We conducted multiple(More)
Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism that could afflict large, unprotected populations if the toxin were employed in an act of bioterrorism. Current post-exposure therapy is limited to symptomatic treatment or passive immunization that is effective for treating infant botulism at a cost(More)
A targeted drug carrier (TDC) is described for transferring functional proteins or peptides into motor nerve terminals, a pivotal locus for therapeutics to treat neuromuscular disorders. It exploits the pronounced selectivity of botulinum neurotoxin type B (BoNT/B) for interacting with acceptors on these cholinergic nerve endings and becoming internalized.(More)
Although the neuromuscular nicotinic acetylcholine receptor (nAChR) is one of the most intensively studied ion channels in the nervous system, the differential roles of fetal and adult subtypes of the nAChR under normal and pathological conditions are still incompletely defined. Until recently, no pharmacological tools distinguished between fetal and adult(More)
There have been made efforts to develop technologies for low health literate users and evaluate them for effectiveness. We address how technology improves health literacy by identifying salient technical features to support health literacy processes and the specific needs of user populations. A systematic review of 45 published studies on technology to(More)
The neuromuscular effects of a peptide toxin (peptide I) from venom of Trimeresurus wagleri were investigated using the rat extensor digitorum longus muscle/peroneal nerve preparation. Sub-micromolar concentrations depressed endplate currents (EPCs) produced in response to nerve stimulation. Since quantal content of EPCs was not altered, it appears that the(More)
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