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.     

Active glycation in neurofibrillary pathology of Alzheimer disease: N(epsilon)-(carboxymethyl) lysine and hexitol-lysine.

Advanced glycation end products are a diverse class of posttranslational modifications, stemming from reactive aldehyde reactions, that have been implicated in the pathogenesis of a number of degenerative diseases. Because advanced glycation end products are accelerated by, and result in formation of, oxygen-derived free radicals, they represent an important component of the oxidative stress hypothesis of Alzheimer disease (AD). In this study, we used in situ techniques to assess N(epsilon)-(Carboxymethyl)lysine (CML), the predominant advanced glycation end product that accumulates in vivo, along with its glycation-specific precursor hexitol-lysine, in patients with AD as well as in young and aged-matched control cases. Both CML and hexitol-lysine were increased in neurons, especially those containing intracellular neurofibrillary pathology in cases of AD. The increase in hexitol-lysine and CML in AD suggests that glycation is an early event in disease pathogenesis. In addition, because CML can result from either lipid peroxidation or advanced glycation, while hexitol-lysine is solely a product of glycation, this study, together with studies demonstrating the presence of 4-hydroxy-2-nonenal adducts and pentosidine, provides evidence of two distinct oxidative processes acting in concert in AD neuropathology. Our findings support the notion that aldehyde-mediated modifications, together with oxyradical-mediated modifications, are critical pathogenic factors in AD.     

Oral Presentations OP01: Neurodegenerative Diseases. BCL‐W Plays a key neuroprotective role in Alzheimer's disease

The mechanisms underlying neuronal degeneration in Alzheimer's disease (AD) are very controversial and none more so than whether apoptosis plays a role. Although neurons in AD face a wide assortment of apoptogenic stimuli, the temporal dichotomy between the acuteness of apoptosis vs. the chronicity of AD suggests that apoptosis should be extremely rare in AD. In this regard, survival factor(s) must be involved. In this study, we investigated Bcl‐w, a pro‐survival member of the Bcl‐2 family. Although expressed at low levels in brains of control cases, Bcl‐w is significantly up‐regulated in AD as shown by both immunocytochemistry and immunoblot analysis. Astonishingly, increased Bcl‐w was found to be associated with neurofibrillary pathologies in AD, which was further demonstrated by an EM study. Since neuronal death in AD is thought to be triggered by increased production of amyloid‐β (Aβ), it was interesting to find that exposure of human M17 neuroblastoma cells to Aβ1–42 (1 nm ?10 μm ) dramatically up‐regulates Bcl‐w protein levels. Such increases may be a protective response that attenuates apoptotic processes. Consistent with this, transfected M17 cells overexpressing Bcl‐w were protected from both STS‐induced and Aβ‐induced apoptosis compared to vector‐transfected controls. Notably, both tau phosphorylation and p38 is inhibited in Bcl‐w transfected cells which may contribute to the neuroprotective role of Bcl‐w. Taken together, these set of in vitro and in vivo results suggest that Bcl‐w plays an important protective role in neurons in the AD brain.     

Correlated Electrophysiological and Ultrastructural Studies of a Crustacean Motor Unit

Structural and functional interrelationships between the pre- and postsynaptic elements of a singly motor innervated crab muscle (stretcher of Hyas araneus L.) were examined using electrophysiological and electron microscopic techniques. Excitatory postsynaptic potential (EPSP) amplitude at 1 Hz was found to be inversely related to the extent of facilitation, and directly related both to the amount of transmitter released at 1 Hz and the muscle fiber input resistance (R_in). The extent of facilitation (F_e), taken as the ratio of the EPSP amplitude at 10 Hz to that 1 Hz, was inversely related to muscle fiber R_in, τ_m, and sarcomere length. Sarcomere length was directly related to R_in and τ_m. The excitatory nerve terminals of low F_e muscle fibers had larger neuromuscular synapses than did those of high F_e fibers. Inhibitory axo-axonal synapses were more often found in low F_e muscle fibers. These structural features may account for the greater release of transmitter at low frequencies from the low F_e nerve terminals as well as provide for a greater amount of presynaptic inhibition of low F_e muscle fibers. The implications of these findings for the development and physiological performance of the crustacean motor unit are discussed. It is proposed that both nerve and muscle fiber properties may be determined by the developmental pattern of nerve growth.     

Almost a spider: a 305-million-year-old fossil arachnid and spider origins

Spiders are an important animal group, with a long history. Details of their origins remain limited, with little knowledge of their stem group, and no insights into the sequence of character acquisition during spider evolution. We describe a new fossil arachnid, Idmonarachne brasieri gen. et sp. nov. from the Late Carboniferous (Stephanian, ca 305–299 Ma) of Montceau-les-Mines, France. It is three-dimensionally preserved within a siderite concretion, allowing both laboratory- and synchrotron-based phase-contrast computed tomography reconstruction. The latter is a first for siderite-hosted fossils and has allowed us to investigate fine anatomical details. Although distinctly spider-like in habitus, this remarkable fossil lacks a key diagnostic character of Araneae: spinnerets on the underside of the opisthosoma. It also lacks a flagelliform telson found in the recently recognized, spider-related, Devonian–Permian Uraraneida. Cladistic analysis resolves our new fossil as sister group to the spiders: the spider stem-group comprises the uraraneids and I. brasieri. While we are unable to demonstrate the presence of spigots in this fossil, the recovered phylogeny suggests the earliest character to evolve on the spider stem-group is the secretion of silk. This would have been followed by the loss of a flagelliform telson, and then the ability to spin silk using spinnerets. This last innovation defines the true spiders, significantly post-dates the origins of silk, and may be a key to the group''s success. The Montceau-les-Mines locality has previously yielded a mesothele spider (with spinnerets). Evidently, Late Palaeozoic spiders lived alongside Palaeozoic arachnid grades which approached the spider condition, but did not express the full suite of crown-group autapomorphies.     

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.     

Survival and abundance of polar bears in Alaska’s Beaufort Sea, 2001–2016

The Arctic Ocean is undergoing rapid transformation toward a seasonally ice‐free ecosystem. As ice‐adapted apex predators, polar bears (Ursus maritimus) are challenged to cope with ongoing habitat degradation and changes in their prey base driven by food‐web response to climate warming. Knowledge of polar bear response to environmental change is necessary to understand ecosystem dynamics and inform conservation decisions. In the southern Beaufort Sea (SBS) of Alaska and western Canada, sea ice extent has declined since satellite observations began in 1979 and available evidence suggests that the carrying capacity of the SBS for polar bears has trended lower for nearly two decades. In this study, we investigated the population dynamics of polar bears in Alaska''s SBS from 2001 to 2016 using a multistate Cormack–Jolly–Seber mark–recapture model. States were defined as geographic regions, and we used location data from mark–recapture observations and satellite‐telemetered bears to model transitions between states and thereby explain heterogeneity in recapture probabilities. Our results corroborate prior findings that the SBS subpopulation experienced low survival from 2003 to 2006. Survival improved modestly from 2006 to 2008 and afterward rebounded to comparatively high levels for the remainder of the study, except in 2012. Abundance moved in concert with survival throughout the study period, declining substantially from 2003 and 2006 and afterward fluctuating with lower variation around an average of 565 bears (95% Bayesian credible interval [340, 920]) through 2015. Even though abundance was comparatively stable and without sustained trend from 2006 to 2015, polar bears in the Alaska SBS were less abundant over that period than at any time since passage of the U.S. Marine Mammal Protection Act. The potential for recovery is likely limited by the degree of habitat degradation the subpopulation has experienced, and future reductions in carrying capacity are expected given current projections for continued climate warming.