Alzheimer’s Disease (AD) is the most common form of dementia that mainly impacts the brain, specifically inducing neuronal cell death in the central nervous system. AD is characterized by the secretion of the protein Tau, and the formation of plaques made up of Beta-amyloid protein. Tau and Beta-amyloid plaques activate the secretion of inflammatory cytokines by microglial cell. The resulting inflammation triggers neuronal cell death, which leads to damage and cognitive decline over time. The cytokines secreted by microglial cells activate the Nf-kB signaling pathway. Activation of Nf-kB results in gene expression and secretion of TNF-a, a cytokine known to be associated with inflammation. This leads to a feedback mechanism that results in greater inflammation.
Our lab has demonstrated that a variety of anti-inflammatory compounds derived from IDT (iso-indolin dithione), targets the Nf-kB pathway by reducing the levels of TNF-a at the protein/translational level. BV-2 cells, a mouse microglial cell line were used in this study. Inflammation was stimulated by exposing these cells to LPS to trigger the activation of the Nf-kB signaling pathway. We hypothesize that the drugs tested reduce levels of TNF-a secreted by BV-2 mouse microglial cells, and therefore, block the development of disease-associated CNS inflammation seen in Alzheimer’s disease

Bacillus anthracis is a gram-positive bacterial pathogen that causes the deadly infectious disease anthrax. Bacillus anthracis contains two plasmids, pX01, and pX02. These plasmids were found to be necessary for the virulence of B. anthracis. However, Bacillus anthracis contains over 5,000 chromosomal genes and we believe that there are additional virulence genes that have yet to be discovered. Our lab constructed a transposon mutant library with random disruptions in the B. anthracis Sterne genome to screen for novel virulence factors. This library has been successfully used to identify the chromosomal genes clpX and yceGH and show their importance for B. anthracis virulence. To find additional novel virulence genes, we used the same transposon library and screened around 1,000 mutants using hydrogen peroxide, a reactive oxygen species (ROS). ROS are involved in the immune defense and the mutants that are attenuated in its presence may have a disrupted gene that contributes to the pathogenicity of B. anthracis. We obtained two mutants that were repeatedly susceptible to hydrogen peroxide in vitro. To determine the virulence of these mutants in an animal model, we will be performing an in vivo assay using the waxworm, Galleria Mellonella. Mutants that have reduced virulence in G. mellonella will be further tested to determine the location of the transposon in the genome to find out which genes are disrupted. The findings of this research could be used as potential therapeutic drug targets and could offer insight into the mechanisms that B. anthracis uses for its pathogenesis.

Mercury (Hg) is released by coal-burning power plants and artisanal gold mines into the atmosphere. Mercury deposited from the atmosphere into aquatic ecosystems can be converted into a neurotoxic form, methyl mercury (MeHg). In aquatic ecosystems, Hg biomagnifies which can affect organisms feeding at higher trophic positions. However, monitoring Hg in the environment to assess the risk to biota is not straightforward. For example, measuring Hg in sediment may not reflect the amount of Hg bioaccumulating in organisms. This difference in the Hg in the sediment and the amount bioaccumulating is partly determined by the bioavailability of Hg. Measuring bioavailability is very complex so sentinels can be used to detect Hg in food chains. Sentinels are defined as organisms that accumulate Hg within their tissues without significant adverse effects. Riparian spiders have been proposed as sentinels. Riparian spiders eat emerging aquatic insects which transport Hg from aquatic ecosystems and because of this, riparian spiders are sentinels of aquatic Hg contamination. The objective of this study was to measure Hg levels in wolf spiders (family: Lycosidae). From May 2021- June 2021, spiders were collected at four sites, two on the Clear Fork and two on the West Fork of the Trinity River, and the spiders were preserved in 95% ethanol. The spiders were sorted based on sex and their body size was measured. Hg will be analyzed using direct mercury analysis. This study attempts to determine the effect of sex and body size on the amount of Hg in wolf spiders, factors that have not been assessed previously. It also attempts to detect differences in the concentration of Hg between the Clear Fork and the West Fork of the Trinity River.

In the pathogenesis of neurodegenerative inflammatory diseases, such as Alzheimer’s disease, there is an abnormal buildup of redox metal ions that associate with β-amyloid plaques and convert oxygen into oxygen radicals. These radicals are highly reactive with cellular components and lead to oxidative stress that induces damage and death of neuronal cells which is associated with the cognitive decline of Alzheimer’s disease. Bifunctional macrocyclic compounds with antioxidant properties are a promising potential therapeutic to reduce levels of reactive oxygen species (ROS) and increase neuronal cell survival via the ability to chelate dysregulated metal ions and radical scavenging. In this project, novel macrocyclic compounds were tested for their efficacy in reducing intracellular levels of H2O2-induced ROS and H2O2-induced cytotoxicity. Intracellular ROS levels and cell survival were quantified in FRDA and BV-2 cells using the DCFH-DA and MTT cytotoxicity assays.

Alzheimer’s disease (AD) is often associated with chronic inflammation and cognitive dysfunction. In studying how AD-like pathologies change and affect learning and memory, our lab aims to optimize an object location memory (OLM) testing paradigm in mice. Briefly, a mouse is placed into an arena with two identical objects for a training session. Four hours later, one of the objects is moved to a novel location, and the mouse is placed back into the arena for the testing session. Because mice exhibit a preference for novelty, memory is assessed as the amount of time the mouse spends exploring the moved object divided by the total time spent exploring both objects. Our goal is to identify testing parameters that make this task both accurate and efficient for our lab’s use, as we will add this learning paradigm to a battery of behavioral tests to be used in future experiments. In the current study, the OLM protocol will be performed twice according to two different experimental timelines that test the effects of adding an additional training session to the original protocol.