The Giver/ I Never Saw Another Butterfly Lighting Design

https://scholarworks.moreheadstate.edu/student_scholarship_posters/1171/thumbnail.jp

Structural studies of the antioxidant defense enzymes; copper, zinc superoxide dismutase and alkyl hydroperoxide reductase flavoprotein

Oxygen derived radicals are involved in many aspects of life from aging and cell signaling to disease states as diverse as heart disease, diabetes, neurodegeneration and inflammation. Therefore, understanding the function of antioxidant defense proteins and the effects of oxygen derived radicals on protein function is essential to elucidate the role of reactive oxygen species in disease. This thesis describes the X-ray crystallographic structure and biochemical properties of two antioxidant defense enzymes; the N-terminal domain of alkyl hydroperoxide reductase flavoprotein (AhpF) of Salmonella typhimurium and zinc-deficient superoxide dismutase (SOD). In addition, the effect of peroxynitrite on the fluorescence of green fluorescent protein (GFP) was investigated. The N-terminal domain of AhpF has two redox active cysteines that were found to be sensitive to X-ray induced reduction. Additionally, the disulfide redox center had an unusually low redox potential in relation to the pKa of the active site thiols of other thioredoxin family members. The Nterminal domain of AhpF provides a platform to investigate the factors that govern the relationship between the pKa and reduction potential of the active site cysteines. Previous studies have shown that the loss of zinc from Cu,Zn SOD is sufficient to kill motor neurons and is important in the pathogenesis of amyotrophic lateral sclerosis. Structural studies reported herein revealed how zinc organizes the zinc-binding loop (loop IV), electrostatic loop (loop VII), and quaternary structure of SOD. The absence of zinc also increased the susceptibility of zinc-deficient SOD to aggregate in the presence of a reductant. Together these discoveries explain many of the properties that cause zinc-deficient SOD to be toxic to motor neurons. Green fluorescent protein has been proposed as a real-time marker for tyrosine nitration in vivo. We demonstrate that GFP was not sensitive enough to monitor peroxynitrite-mediated nitration in vivo, even with large bolus additions of peroxynitrite totaling 150μM. Hence, measuring the loss of GFP fluorescence in cells has limited utility as a measure of nitrative stress

Discovery of a missense mutation (Q222K) of the APOE gene from the Australian imaging, biomarker and lifestyle study

After age, polymorphisms of the Apolipoprotein E (APOE) gene are the biggest risk factor for the development of Alzheimer\u27s disease (AD). During our investigation to discovery biomarkers in plasma, using 2D gel electrophoresis, we found an individual with and unusual apoE isoelectric point compared to APOE ϵ2, ϵ3, and ϵ4 carriers. Whole exome sequencing of APOE from the donor confirmed a single nucleotide polymorphism (SNP) in exon 4, translating to a rare Q222K missense mutation. The apoE ϵ4 (Q222K) mutation did not form dimers or complexes observed for apoE ϵ2 ϵ3 proteins

OT’s Role in a Technology-Enhanced Care Coordination Service

"Age-Friendly, Smart, Sustainable, and Equitable Technologies for Aging in Place (ASSETs for AIP), is an ongoing, grant-funded demonstration project involving an occupational therapist as part of an interdisciplinary team with a registered nurse and a licensed clinical social worker. Working with a population of community-dwelling older adults and adults with disabilities, the team uses passive motion sensors and smartwatches to remotely monitor clients’ activity and provide guidance for clients to manage their own care needs. In this model, OT plays a crucial role in self-advocacy training, activity analysis, and environmental modification. In this poster, we examine the model of ASSETs for AIP to shed light on the distinct value OT brings to the interdisciplinary care model of technology-enhanced health coaching."--Introductio

ZnII(atsm) is protective in amyotrophic lateral sclerosis model mice via a copper delivery mechanism

AbstractMutations in the metalloprotein Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease for which effective therapeutics do not yet exist. Transgenic rodent models based on over-expression of mutant SOD1 have been developed and these have provided opportunity to test new therapeutic strategies and to study the mechanisms of mutant SOD1 toxicity. Although the mechanisms of mutant SOD1 toxicity are yet to be fully elucidated, incorrect or incomplete metallation of SOD1 confers abnormal folding, aggregation and biochemical properties, and improving the metallation state of SOD1 provides a viable therapeutic option. The therapeutic effects of delivering copper (Cu) to mutant SOD1 have been demonstrated recently. The aim of the current study was to determine if delivery of zinc (Zn) to SOD1 was also therapeutic. To investigate this, SOD1G37R mice were treated with the metal complex diacetyl-bis(4-methylthiosemicarbazonato)zincII [ZnII(atsm)]. Treatment resulted in an improvement in locomotor function and survival of the mice. However, biochemical analysis of spinal cord tissue collected from the mice revealed that the treatment did not increase overall Zn levels in the spinal cord nor the Zn content of SOD1. In contrast, overall levels of Cu in the spinal cord were elevated in the ZnII(atsm)-treated SOD1G37R mice and the Cu content of SOD1 was also elevated. Further experiments demonstrated transmetallation of ZnII(atsm) in the presence of Cu to form the Cu-analogue CuII(atsm), indicating that the observed therapeutic effects for ZnII(atsm) in SOD1G37R mice may in fact be due to in vivo transmetallation and subsequent delivery of Cu

Decreased Serum Zinc Is An Effect Of Ageing And Not Alzheimer\u27s Disease

We examined the distribution of zinc in the periphery (erythrocytes and serum) in a large, well-characterised cohort, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, in order to determine if there is systemic perturbation in zinc homeostasis in Alzheimer’s disease (AD). We observed an age dependent decrease in serum zinc of approximately 0.4% per year. When correcting for the age dependent decline in serum zinc no significant difference between healthy controls (HC), mildly cognitively impaired (MCI) or AD subjects was observed

Rubidium and potassium levels are altered in Alzheimer's disease brain and blood but not in cerebrospinal fluid

Loss of intracellular compartmentalization of potassium is a biochemical feature of Alzheimer's disease indicating a loss of membrane integrity and mitochondrial dysfunction. We examined potassium and rubidium (a biological proxy for potassium) in brain tissue, blood fractions and cerebrospinal fluid from Alzheimer's disease and healthy control subjects to investigate the diagnostic potential of these two metal ions. We found that both potassium and rubidium levels were significantly decreased across all intracellular compartments in the Alzheimer's disease brain. Serum from over 1000 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), showed minor changes according to disease state. Potassium and rubidium levels in erythrocytes and cerebrospinal fluid were not significantly different according to disease state, and rubidium was slightly decreased in Alzheimer's disease patients compared to healthy controls. Our data provides evidence that contrasts the hypothesized disruption of the blood-brain barrier in Alzheimer's disease, with the systemic decrease in cortical potassium and rubidium levels suggesting influx of ions from the blood is minimal and that the observed changes are more likely indicative of an internal energy crisis within the brain. These findings may be the basis for potential diagnostic imaging studies using radioactive potassium and rubidium tracers