A model of motor and sensory axon activation in the median nerve using surface electrical stimulation

Surface electrical stimulation has the potential to be a powerful and non-invasive treatment for a variety of medical conditions but currently it is difficult to obtain consistent evoked responses. A viable clinical system must be able to adapt to variations in individuals to produce repeatable results. To more fully study the effect of these variations without performing exhaustive testing on human subjects, a system of computer models was created to predict motor and sensory axon activation in the median nerve due to surface electrical stimulation at the elbow. An anatomically-based finite element model of the arm was built to accurately predict voltages resulting from surface electrical stimulation. In addition, two axon models were developed based on previously published models to incorporate physiological differences between sensory and motor axons. This resulted in axon models that could reproduce experimental results for conduction velocity, strength-duration curves and activation threshold. Differences in experimentally obtained action potential shape between the motor and sensory axons were reflected in the models. The models predicted a lower threshold for sensory axons than motor axons of the same diameter, allowing a range of sensory axons to be activated before any motor axons. This system of models will be a useful tool for development of surface electrical stimulation as a method to target specific neural functions.     

Biomarkers of marine pollution observed in species of mullet living in two eastern Mediterranean harbours

The activities of enzymes associated with xenobiotic metabolism and or oxidative processes, and the levels of aromatic DNA adducts, have been determined in the livers of grey mullet Oedalechilus labeo and Lisa ramada living in two eastern Mediterranean harbours. Glutathione peroxidase GSH P activity was 2.5 times higher 9 IU g-1 liver and glutathione reductase GSSG R activity was twice as high 2.5 IU g-1 liver in fish from the more polluted harbour at Mersin than in the harbour near Erdemli. Superoxide dismutase SOD activity was 25 lower 4.3 IU g-1 liver in the more polluted harbour. The concentrations of glutathione and malondialdehyde varied both with species and environment by a factor of 2.5-3. DNA adducts in liver were determined by 32P postlabelling. In Oedalechilus labeo in the more polluted harbour, adduct levels were 258 21 adducts per 108 nucleotides mean SE ; two groups of Lisa ramada were distinguished having 261 48 and 30 6 adducts per 108 nucleotides, respectively. The average adduct level in a group of mullet of mixed species in the less polluted harbour was 3.3 2.3 adducts per 108 nucleotides. The results illuminate the ability of mullet to live in contaminated marine environments, and show that enzyme activities and liver DNA adduct levels can serve as indicators of marine pollution.     

The dare gene: steroid hormone production, olfactory behavior, and neural degeneration in Drosophila.

Steroid hormones mediate a wide variety of developmental and physiological events in insects, yet little is known about the genetics of insect steroid hormone biosynthesis. Here we describe the Drosophila dare gene, which encodes adrenodoxin reductase (AR). In mammals, AR plays a key role in the synthesis of all steroid hormones. Null mutants of dare undergo developmental arrest during the second larval instar or at the second larval molt, and dare mutants of intermediate severity are delayed in pupariation. These defects are rescued to a high degree by feeding mutant larvae the insect steroid hormone 20-hydroxyecdysone. These data, together with the abundant expression of dare in the two principal steroid biosynthetic tissues, the ring gland and the ovary, argue strongly for a role of dare in steroid hormone production. dare is the first Drosophila gene shown to encode a defined component of the steroid hormone biosynthetic cascade and therefore provides a new tool for the analysis of steroid hormone function. We have explored its role in the adult nervous system and found two striking phenotypes not previously described in mutants affected in steroid hormone signaling. First, we show that mild reductions of dare expression cause abnormal behavioral responses to olfactory stimuli, indicating a requirement for dare in sensory behavior. Then we show that dare mutations of intermediate strength result in rapid, widespread degeneration of the adult nervous system.     

Dopamine D3 receptor antagonists: The quest for a potentially selective PET ligand. Part one: Lead identification

The synthesis and SAR of a new series of potent and selective dopamine D₃ receptor antagonists is reported.     

Examining mummichog growth and movement: Are some individuals making intra-season migrations to optimize growth?

We used a combination of field experiments and stable isotopes to examine mummichog growth and movement within a New England estuary. We documented physical and biological patterns within the estuary by caging individually-marked fish in enclosures at four locations along a coastal river and measuring environmental parameters (e.g., salinity, tidal inundation) and fish characteristics (e.g., gut-contents, growth, and stable isotope values) at each location. The upstream location was fresh (1 ppt) at low tide, and the downstream location was saline at high tide (32 ppt). The upstream and downstream locations had more tidal inundation than the intermediate location. Fish gut contents were dominated by terrestrial insects at the upstream location, by algae and detritus at the intermediate locations, and by aquatic insects at the downstream location. Fish grew fastest at the upstream location and slowest at the downstream location. Stable isotope values (δ¹³C and δ¹⁵N) of fish held in cages were significantly different at upstream, intermediate, and downstream locations. We transferred fish from one location to another in order to document how stable isotope values change when fish switch diets by moving within this estuary. Because differences in rates at which different tissue types approach the isotopic value of new diet sources can be used as a way to estimate the time since diet shift, we used the δ¹³C and δ¹⁵N values of liver and muscle as indicators of short term previous diet (liver) and longer term previous diet (muscle). We collected wild (uncaged) mummichogs from each location, and we compared their liver and muscle isotope values to values of fish that were transferred among locations. When fish were transferred from one location to another, their stable isotope values were intermediate between expected values at the previous and current locations. The liver approached stable isotope values representative of current location faster than muscle. Wild fish showed greater variation in stable isotope values than fish held in cages. Wild fish from the upstream location showed patterns in liver and muscle stable isotope values that were consistent with patterns in fish that were transferred from the downstream location to the upstream location (∼ 10 km away). These patterns in stable isotope values could have multiple causes including intra-season movement between downstream and upstream locations.