Amyotrophic lateral sclerosis (ALS), characterized by degeneration of spinal motor neurons, consists of sporadic and familial forms. One cause of familial ALS is missense mutations in the superoxide dismutase 1 (SOD1) gene. Iron accumulation occurs in the CNS of both forms of ALS; however, its contribution to the pathogenesis of ALS is not known. We examined the role of iron in a transgenic mouse line overexpressing the human SOD1 G37R mutant. We show that multiple mechanisms may underlie the iron accumulation in neurons and glia in SOD1 G37R transgenic mice. These include dysregulation of proteins involved in iron influx and sensing of intracellular iron; iron accumulation in ventral motor neurons secondary to blockage of anterograde axonal transport; and increased mitochondrial iron load in neurons and glia. We also show that treatment of SOD1 G37R mice with an iron chelator extends life span by 5 weeks, accompanied by increased survival of spinal motor neurons and improved locomotor function. These data suggest that iron chelator therapy might be useful for the treatment of ALS.
ABSTRACT:The electrical conductivity of polymeric materials can be increased by the addition of carbon fillers, such as carbon fibers and graphite. The resulting composites could be used in applications such as interference shielding and electrostatic dissipation. Electrical conductivity models are often proposed to predict the conductivity behavior of these materials in order to achieve more efficient material design that could reduce costly experimental work. The electrical conductivity of carbon-filled polymers was studied by adding four single fillers to nylon 6,6 and polycarbonate in increasing concentrations. The fillers used in this project include chopped and milled forms of polyacrylonitrile (PAN) carbon fiber, Thermocarb TM Specialty Graphite, and Ni-coated PAN carbon fiber. Material was extruded and injection-molded into test specimens, and then the electrical conductivity was measured. Data analysis included a comparison of the results to existing conductivity models. The results show that the model proposed by Mamunya, which takes into account the filler aspect ratio and the surface energy of the filler and polymer, most closely matched the conductivity data. This information will then be used in the development of improved conductivity models.
This is the first comprehensive study from Germany showing a high prevalence of TEM-, CTX-M- and SHV-type ESBLs in Enterobacteriaceae isolated from retail chicken meat. The high rate of coresistance to different classes of antibiotics in the ESBL producers might reflect the common veterinary usage of these and related substances. There is an urgent need to further evaluate the role of poultry in the transmission of highly resistant ESBL-producing bacteria in humans.
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