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The inability to rapidly (within minutes to hours) improve behavioral function after severance of peripheral nervous system axons is an ongoing clinical problem. We have previously reported that polyethylene glycol (PEG) can rapidly restore axonal integrity (PEG-fusion) between proximal and distal segments of cut- and crush-severed rat axons in vitro and in(More)
Both constitutive secretion and Ca(2+)-regulated exocytosis require the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes. At present, little is known about how the SNARE complexes mediating these two distinct pathways differ in structure. Using the Drosophila neuromuscular synapse as a model, we show(More)
Plasmalemmal repair is necessary for survival of damaged eukaryotic cells. Ca(2+) influx through plasmalemmal disruptions activates calpain, vesicle accumulation at lesion sites, and membrane fusion proteins; Ca(2+) influx also initiates competing apoptotic pathways. Using the formation of a dye barrier (seal) to assess plasmalemmal repair, we now report(More)
This study examines the effects of several experimental compounds [melatonin (MEL), cyclosporin A (CsA), glial-derived neurotrophic factor (GDNF), and methylprednisolone (MP)] on polyethylene glycol (PEG)-induced repair in vitro and/or in vivo by plasmalemmal fusion (PEG-fusion) of sciatic axons severed by crushing. As measured by conduction of compound(More)
Behavioral function lost in mammals (including humans) after peripheral nerve severance is slowly (weeks to years) and often poorly restored by 1-2-mm/day, nonspecifically directed outgrowths from proximal axonal stumps. To survive, proximal stumps must quickly repair (seal) plasmalemmal damage. We report that, after complete cut- or crush-severance of rat(More)
Epilepsy is a neurological seizure disorder that affects over 100 million people worldwide. Levetiracetam, either alone, as monotherapy, or as adjunctive treatment, is widely used to control certain types of seizures. Despite its increasing popularity as a relatively safe and effective anti-convulsive treatment option, its mechanism(s) of action are poorly(More)
Methods based on AND/OR graph representations of Boolean relations provide a promising new way of approaching VLSI CAD design automation problems. AND/OR graphs can represent any Boolean network and they allow for systematic reasoning through the application of the technique of recursive learning. An approach to build and analyze AND/OR graphs that makes(More)
To survive, neurons and other eukaryotic cells must rapidly repair (seal) plasmalemmal damage. Such repair occurs by an accumulation of intracellular vesicles at or near the plasmalemmal disruption. Diacylglycerol (DAG)-dependent and cAMP-dependent proteins are involved in many vesicle trafficking pathways. Although recent studies have implicated the(More)
In PLoS Biology, volume 5, issue 4: On page 0801, in the last sentence of the fi rst paragraph of the Results section, " isoleucine " should be replaced with " threonine. " The corrected version is: " Nonetheless, the overall feature emerging from our analysis is that syntaxins with conserved threonine at the +7 layer appear to be selectively involved in(More)
Protein synthesis inhibitors (PSIs) increase the rate of degeneration, as measured by compound action potential (CAP) conduction, in segments of rat PNS and CNS axons. Sciatic axonal segments maintained in vitro in Krebs at 37-38 degrees C generate CAPs for 24 h compared to 8 h for axons exposed to Krebs containing two PSIs, 100 microM anisomycin and/or 35(More)