Tuesday, July 18, 2017

Neuronal metal manganese effect on arginase activity implicated in Huntington's disease

Assistant Professor of Neuroscience Gunnar Kwakye is one of 22 collaborators in this research, from institutions in England, Illinois, Italy, Michigan, New York, Ohio, Pennsylvania, Tennessee and Texas.

Bichell TJV, Wegrzynowicz M, Tipps KG, Bradley EM, Uhouse MA, Bryan M, Horning K, Fisher N, Dudek K, Halbesma T, et al. 2017.

Reduced bioavailable manganese causes striatal urea cycle pathology in Huntington's disease mouse model. Biochimica Et Biophysica Acta-Molecular Basis of Disease 1863(6):1596-604

http://www.sciencedirect.com/science/journal/09254439
sciencedirect.com/science/journal/09254439
Huntington's disease (HD) is caused by a mutation in the huntingtin gene (HIT), resulting in profound striatal neurodegeneration through an unknown mechanism. Perturbations in the urea cycle have been reported in HD models and in HD patient blood and brain. In neurons, arginase is a central urea cycle enzyme, and the metal manganese (Mn) is an essential cofactor. Deficient biological responses to Mn, and reduced Mn accumulation have been observed in HD striatal mouse and cell models. Here we report in vivo and ex vivo evidence of a urea cycle metabolic phenotype in a prodromal HD mouse model. Further, either in vivo or in vitro Mn supplementation reverses the urea-cycle pathology by restoring arginase activity. We show that Arginase 2 (ARG2) is the arginase enzyme present in these mouse brain models, with ARG2 protein levels directly increased by Mn exposure. ARG2 protein is not Teduced in the prodromal stage, though enzyme activity is reduced, indicating that altered Mn bioavailability as a cofactor leads to the deficient enzymatic activity. These data support a hypothesis that mutant HIT leads to a selective deficiency of neuronal Mn at an early disease stage, contributing to HD striatal urea-cycle pathophysiology through an effect on arginase activity. (C) 2017 The Author(s). Published by Elsevier B.V.

Open Access at Sciencedirect

Thursday, July 13, 2017

"Web app for population viability and harvesting analyses." Co-authored by Rich Salter

New publication from Professor Emeritus Richard Salter:
Official Journal of the Resource Modeling Association

Getz WM, Muellerklein OC, Salter RM, Carlson CJ, Lyons AJ, Seidel DP. 2017. A web app for population viability and harvesting analyses. Natural Resource Modeling 30(2):e12120

Abstract:
Population viability analysis (PVA) is used to assess the probability that a biological population will persist for a specified period of time. Such models are typically cast as Markov processes that may include age, stage, sex and metapopulation structures, density-dependence and ecological interaction processes. They may also include harvesting, stocking, and thresholds that trigger interventions. Here we present a PVA web app that includes extensible user-selected options. Specifically, this PVA web app allows for the specification of one to ten age classes, one or two sexes, single population or metapopulation configurations with 2 or 3 subpopulations, as well as density-dependent settings for inducing region-specific carrying capacities. Movement among subpopulations can be influenced by age, metapopulation connectivity, and attractivity of regions based on the relative fitness of the youngest age classes in each region. Simulations can be carried out deterministically or stochastically, with a user-specified combination of demographic and environmental processes. This PVA web app is freely available at http://www.numerusinc.com/webapps/pva for running directly on any browser and device. It is easily modified by users familiar with the NovaModeler Software Platform.

Subscriber access on Wiley Online Library.

Friday, July 07, 2017

Oxidative stress and neurotoxicity in Huntington's disease: publication by G. Kwakye

About NeuroToxicology
New publication from Assistant Professor of Neuroscience Gunnar Kwakye and students in the Kwakye lab:

"Acute exposure to chlorpyrifos caused NADPH oxidase mediated oxidative stress and neurotoxicity in a striatal cell model of Huntington's disease."
Authors:
Gifty A. Dominah, OC'15.; Rachel A. McMinimy, OC'17; Sallay Kallon, OC'17; Gunnar F. Kwakye.
Source:
NeuroToxicology, vol. 60, pp 54-69;  MAY 2017

Subscriber Access on ScienceDirect
Abstract and indexing on PubMed
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