Abstract: Parkinson?s disease (PD) is a neurodegenerative disorder resulting in loss of motor function stemming primarily from the loss of dopaminergic (DAergic) neurons within the substantia nigra (SN). Several studies have demonstrated elevated levels of intracellular iron in the Parkinsonian SN but whether this is causatively involved in dopaminergic SN cell death has been controversial. We previously reported that iron chelation via expression of the body?s major iron sequestering protein, ferritin, protects against DAergic SN neurodegeneration associated with the PD-inducing neurotoxin MPTP in young mice1. The aim of our current research is towards exploring whether iron elevation in young animals contributes to PD pathology via its activation of the enzyme prolyl hydroxylase (PH). When activated, PH can act as an inhibitor of hypoxiainducing factor 1 alpha (HIF-1?), a transcription factor which activates various genes involved in both protection against oxidative stress and in regulation of cellular iron metabolism. In our studies, inhibition of PHD by the specific inhibitor 3,4-dihydroxybenzoate (DHB) in vivo resulted in the stabilization of cytosolic HIF- 1? and significantly protected against MPTP-induced nigral dopaminergic cell loss. MPTP alone results in a significant increase in striatal iron levels that was found to be attenuated by co-treatment with DHB. In addition to HIF activation, we observed up-regulation of several downstream HIF-dependent genes including the mitochondrial antioxidant MnSOD and the iron regulatory protein HO-1 which has recently been demonstrated to contribute to cellular iron efflux. Additionally, MPTP-induced decreases in the iron export protein ferroportin were found to revert back to normal in the presence of DHB. In vitro, the HIF pathway was found to be activated in dopaminergic midbrain-derived rat N27 cells grown at 3% oxygen treated with two PHD inhibitors, DHB and DOMG, and an iron chelator, SIH. Concordant with in vivo data, MPP+ elicited an increase in total intracellular iron that was attenuated in the presence of DHB. In addition, MPP+ administration resulted in a concentration-dependent increase in levels of the iron import protein TfR that was significantly reduced in the presence of DHB. Taken together, data from this study suggest that the protection against MPTP neurotoxicity as a consequence of iron chelation may be mediated by inhibition of PH and subsequent increases in cellular HIF-1? levels that in turn activates genes involved in both protection against increased oxidative stress and dysregulation of cellular iron homeostasis. This study provides novel data extending the therapeutic aspects of HIF protein to a PD model of neurodegeneration and may prove beneficial in other diseases associated with metal-induced oxidative stress such as Alzheimer?s disease and multiple sclerosis.

Abstract: Completion of the Great Lakes-St. Lawrence Seaway 50 years ago linked ports on all five of the Laurentian Great Lakes to the global shipping trade. The Seaway increased international trade in the Great Lakes region but there were tradeoffs, mostly due to transoceanic freighters inadvertently importing aquatic invasive species via ballast water discharges. In this session, I examine the role of public policy in preventing transoceanic vessels from importing invasive species into the lakes during the Seaways first 50 years. I will discuss efforts by government agencies in the U.S. and Canada to address this problem and missed opportunities to slow the rate of aquatic invasive species entering the lakes via the ballast water vector. Finally, I will explain why the number of shipborne aquatic invasive species discovered in the Great Lakes increased after the U.S. and Canada passed laws designed to stem the tide of invaders. Keywords: Invasive species, Ballast, Policy making.

Abstract: Zinc (Zn) is required as a catalytic, structural and regulatory ion for enzymes, proteins and transcription factors and is thus a key trace element in many homeostatic mechanisms of the body. Vitamins like riboflavin, nicotinic acid, thiamine, folic acid and ascorbic acid have functional groups capable of forming complexes with Zn. However, the interaction of water-soluble vitamins with Zn has not received much attention. Methods: We have examined the Zn-vitamin interactions at a variety of conditions like different Zn concentrations, different cell and protein models and under normal and oxidative stress (OS) conditions. The interactions were studied in vitro, by using erythrocytes under deficient, normal and excess Zn states. Results: Under Zn-deficient state, thiamine significantly enhanced the erythrocyte Zn uptakes (p<0.05), whereas ascorbic acid and riboflavin inhibited it (p<0.05). In another study, an in vitro erythrocyte Zn uptake was compared among healthy and diabetic subjects and it was found that Zn uptakes of healthy subjects were 17-52% higher than those for diabetic subjects. Furthermore, erythrocyte super oxide dismutase, plasma ascorbic acid and status of riboflavin were negatively correlated with Zn uptakes in healthy subjects (p<0.01). These interactions were also studied in precision cut rat liver slices, where it was found that folic acid showed inhibitory effect on Zn uptake under both normal and OS conditions as seen by dose response curves. Ascorbic acid showed marked enhancing effect on Zn uptake under OS. These in vitro interactions were confirmed in vivo using male Wistar rats. The 21 days old rats were used to examine the effect of niacin supplementation on Zn absorption under chronic OS generated by tert-butyl hydro peroxide at a dose of 0.2 mM/Kg body weight. Niacin supplementation increased the Zn absorption and improved antioxidant enzyme profile. The albumin being the major Zn carrier protein in plasma and the albumin bound Zn (ABZn) comprises 80% plasma Zn. Folic acid and thiamine significantly enhanced the ABZn (p<0.010), while nicotinic acid inhibited Zn binding to albumin. Conclusions: These results collectively suggest that vitamins are playing an important role in distribution of circulating Zn among albumin, blood cells and liver and giving a new dimension to their functionality in Zn metabolism in health and disease conditions.

Abstract: Recent epidemiological evidence indicates that consumption of plant-based foods and beverages can reduce the risk of cardiovascular disease. Our research group has measured the total phenolic antioxidants in fruits, vegetables, beverages, grains, nuts, oils and spices. We have determined US per capita consumption of these antioxidants using USDA data. Beverages provide the majority of the antioxidants in the US diet. We have shown that individual phenols found in plant foods and beverages are more powerful antioxidants when compared to antioxidant vitamins on a molecule to molecule basis using LDL+VLDL oxidation as a heart disease model. Our research group has used the cholesterol/saturated fat-fed hamster model which in 10-12 weeks produces arterial foam cells, the early sign of atherosclerosis. Citrus extract, grape seed extract, berry extract, green and black tea, grape juice, red wine, beer, and cocoa powder have been found to significantly inhibit the hamster atherosclerosis process by both hypolipemic and antioxidant mechanisms. Fat and sugar produce oxidative stress in the postprandial state and this is a risk factor for a myocardial infarction in humans. We have demonstrated that phenols in cranberry juice or chocolate significantly inhibit this oxidative stress and that high fructose corn syrup, fat and sugar are post-prandial pro-oxidants. After subject drank grape juice, red wine, green or black tea and coffee, these beverages provided post-prandial antioxidant protection of LDL+VLDL. Greater consumption of plant foods and beverage is suggested as a means to decrease the risk of heart disease.

Abstract: Maps of climatological circulation in Lake Michigan are presented for the first time. They are based on ten years continuous modeling of lake hydrodynamics from 1998-2007 using observed meteorological data as the forcing function. Model results show a remarkably stable large-scale cyclonic circulation pattern during both stratified and unstratified conditions. Lakeaveraged mean current speed is about 2 cm/s, but currents can reach 10 cm/s in some locations. The model results are confirmed by long-term current observations.

Abstract: Lipoid proteinosis (hyalinosis cutis et mucosae) is a rare, autosomal recessive disease. Main clinicopathological features comprise skin and mucous membrane infiltration and scarring with deposition of hyaline material. Lipoid proteinosis (LP) results from pathogenic mutations in the glycoprotein extracellular matrix protein 1 (ECM1) gene. In this study, we describe two consanguineous Pakistani families suffering from lipoid proteinosis. The disease phenotype in both families was mapped to ECM1 locus on chromosome 1q21.2. The mutation screening of 10 exonic regions of ECM1 genes were amplified by using intronic forward and reverse primers. SSCP and direct DNA sequencing analysis of ECM1 revealed a novel homozygous 62bp insertion.