The State of the Region: Hampton Roads 2006

This is Old Dominion University\u27s seventh annual State of the Region report. While it represents the work of many people connected in various ways to the university, the report does not constitute an official viewpoint of Old Dominion, or it\u27s president, Roseann Runte. The report maintains the goal of stimulating thought and discussion that ultimately will make Hampton Roads an even better place to live. We are proud of our region\u27s many successes, but realize that it is possible to improve our performance. In order to do so, we must have accurate information about where we are and a sound understanding of the policy options open to us.https://digitalcommons.odu.edu/economics_books/1012/thumbnail.jp

Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy

Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid βâ glucosidase), with consequent cellular accumulation of glucosylceramide (GLâ 1). The disease is managed by intravenous administrations of recombinant glucocerebrosidase (imiglucerase), although symptomatic patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy (ERT) is not an option may also be treated by substrate reduction therapy (SRT) with miglustat. To determine whether the sequential use of both ERT and SRT may provide additional benefits, we compared the relative pharmacodynamic efficacies of separate and sequential therapies in a murine model of Gaucher disease (D409V/null). As expected, ERT with recombinant glucocerebrosidase was effective in reducing the burden of GLâ 1 storage in the liver, spleen, and lung of 3â monthâ old Gaucher mice. SRT using a novel inhibitor of glucosylceramide synthase (Genzâ 112638) was also effective, albeit to a lesser degree than ERT. Animals administered recombinant glucocerebrosidase and then Genzâ 112638 showed the lowest levels of GLâ 1 in all the visceral organs and a reduced number of Gaucher cells in the liver. This was likely because the additional deployment of SRT following enzyme therapy slowed the rate of reaccumulation of GLâ 1 in the affected organs. Hence, in patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genzâ 112638 could potentially be used as a convenient maintenance therapy. In patients naïve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147062/1/jimd0281.pd

A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease

An approach to treating Gaucher disease is substrate inhibition therapy which seeks to abate the aberrant lysosomal accumulation of glucosylceramide. We have identified a novel inhibitor of glucosylceramide synthase (Genz-112638) and assessed its activity in a murine model of Gaucher disease (D409V/null). Biochemical characterization of Genz-112638 showed good potency (IC(50) approximately 24nM) and specificity against the target enzyme. Mice that received drug prior to significant accumulation of substrate (10 weeks of age) showed reduced levels of glucosylceramide and number of Gaucher cells in the spleen, lung and liver when compared to age-matched control animals. Treatment of older mice that already displayed significant amounts of tissue glucosylceramide (7 months old) resulted in arrest of further accumulation of the substrate and appearance of additional Gaucher cells in affected organs. These data indicate that substrate inhibition therapy with Genz-112638 represents a viable alternate approach to enzyme therapy to treat the visceral pathology in Gaucher diseas

Exclusion of deer affects responses of birds to woodland regeneration in winter and summer

Using an exclosure experiment in managed woodland in eastern England, we examined species and guild responses to vegetation growth and its modification by deer herbivory, contrasting winter and the breeding season over 4 years. Species and guild responses, in terms of seasonal presence recorded by multiple point counts, were examined using generalized linear mixed models. Several guilds or migrant species responded positively to deer exclusion and none responded negatively. The shrub-layer foraging guild was recorded less frequently in older and browsed vegetation, in both winter and spring. Exclusion of deer also increased the occurrence of ground-foraging species in both seasons, although these species showed no strong response to vegetation age. The canopy-foraging guild was unaffected by deer exclusion or vegetation age in either season. There was seasonal variation in the responses of some individual resident species, including a significantly lower occurrence of Eurasian Wren Troglodytes troglodytes and European Robin Erithacus rubecula in browsed vegetation in winter, but no effect of browsing on those species in spring. Ordinations of bird assemblage compositions also revealed seasonal differences in response to gradients of vegetation structure generated by canopy-closure and exclusion of deer. Positive impacts of deer exclusion in winter are probably linked to reduced thermal cover and predator protection afforded by browsed vegetation, whereas species that responded positively in spring were also dependent on a dense understorey for nesting. The effects on birds of vegetation development and its modification by herbivores extend beyond breeding assemblages, with different mechanisms implicated and different species affected in winter

Modelling the distribution of the invasive Roesel’s bush-cricket (Metrioptera roeselii) in a fragmented landscape

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