Both Breast Cancer Gene 1 (BRCA1) and Partner and Localizer of BRCA 2 (PALB2) interact through their coiled-coil domains and are critical for proper functioning of DNA repair through homologous recombination. Individuals who carry pathogenic variants in either protein have an increased risk of developing breast cancer. Multiple variations of unknown significance (VUS) have been documented within the coiled-coil region of each protein, meaning a person carries a variation in either BRCA1 or PALB2 but there is not enough data to know the clinical significance of those variants. In this study, we analyzed the structural effects of five proline VUS within the binding region of BRCA1 and PALB2, three variants that have been discovered in patients and two variants that have not yet been discovered in patients. We used a known benign valine variant and a known pathogenic proline variant as our negative and positive controls, respectively. Because proline variants are known to disrupt protein structure, we hypothesize the proline variants will inhibit coiled-coil formation and, in turn, disrupt interaction between BRCA1 and PALB2. Each coiled-coil construct was generated in vitro and its structure analyzed using circular dichroism first individually and then in the presence of its wild-type binding partner. While all proline variants affected the structure of BRCA1, they had different degrees of impact depending on where they are located in the coiled-coil. This suggests that proline variants impact the ability of BRCA1 to form a coiled-coil in the presence of PALB2 and may be pathogenic. Notably, however, the BRCA1 proline variants seem to cause different structural changes from the pathogenic PALB2 proline variant. This prompts further research to determine the structural effects on the residue level and to correlate structural changes with functional changes.

Alzheimer’s disease (AD) is a neurodegenerative disease that is the most common cause of dementia. There is currently no cure for AD, which means the best alternative is developing preventative strategies, such as adoption of the Mediterranean diet (MD), which has been shown to reduce risk of AD development and mortality. In comparison, a typical American diet has been shown to increase risk of AD development. Although the ability of dietary factors to alter the propensity of development of AD is well established, the mechanisms through this is mediated is unknown. One largely unexplored mechanism of dietary-induced AD prevalence is epigenetic modification to genes associated with AD. The most studied epigenetic modification, DNA methylation of cytosines, has been known to alter gene expression levels. Therefore, this study aims to determine whether dietary influences can induce epigenetic modifications, and subsequently modify expression of genes associated with AD. To do this, DNA was extracted from hippocampal tissue of mice on either a MD or TAD, as well as their offspring who were consuming a control diet. The offspring were included to determine if differential methylation patterns are heritable, thereby implicating transgenerational effects and predisposition to AD development or protection. An epigenetic array was used to identify loci that were differentially methylated between diets, and qPCR was used to determine if differential methylation resulted in significant differences in gene expression. No loci were found to be significantly differentially methylated (p-val<0.0001) with an effect size of 10% or more, nor differentially expressed upon qPCR analysis.

As antibiotic resistance increases and antibiotic development dwindles, new antimicrobial agents are needed. Recent advances in nanoscale engineering have increased interest in metal oxide nanoparticles, particularly zinc oxide nanoparticles, as antimicrobial agents. Zinc oxide nanoparticles are particularly promising due to their broad-spectrum antibacterial activity and low production cost. Despite many studies demonstrating the effectiveness of zinc oxide nanoparticles, the antibacterial mechanism is still unknown. Previous work has implicated the role of reactive oxygen species such as hydrogen peroxide, physical damage of the cell envelope, and/or release of toxic Zn2+ ions as possible mechanisms of action. To evaluate the role of these proposed methods, we assessed the susceptibility of S. aureus mutant strains, ΔkatA and ΔmprF, to zinc oxide nanoparticles. These assays demonstrated that hydrogen peroxide and electrostatic interactions are not crucial for mediating zinc oxide nanoparticle toxicity. Instead, we find that a soluble factor accumulates in Mueller Hinton Broth over time that mediates toxicity and that removal of Zn2+ through chelation reverses this toxicity. Furthermore, we find that the physical separation of zinc oxide nanoparticles and bacterial cells using a semi-permeable membrane still allows for growth inhibition. We conclude that soluble Zn2+ is the primary mechanism by which zinc oxide nanoparticles mediate toxicity in Mueller Hinton Broth. Future work investigating how factors such as particle morphology (e.g., size, polarity, surface defects) and media contribute to Zn2+ dissolution could allow for the synthesis of zinc oxide nanoparticles that possess chemical and morphological properties best suited for antibacterial efficacy.

The spread of red imported fire ants (Solenopsis invicta; RIFA) has frequently been cited as a factor contributing to the decline of the Texas horned lizard (Phrynosoma cornutum; THL). Two hypotheses for this are: 1) direct lizard mortality due to RIFA, and 2) displacement of THL’s main food source, harvester ants (Pogonomyrmex spp.), by RIFA. A new third hypothesis suggests that the invasion of RIFA could be causing a decline in hatchling THL food resources, as their diet is mainly composed of small ant species. Many studies have attempted widespread treatment to eradicate RIFA; however, this could have unintended consequences for non-target ant species that THL depend on. Using a targeted application method, we sought to reduce RIFA populations over the summers of 2022 and 2023 at four sites located at Mason Mountain Wildlife Management in central Texas, a locality with an ongoing THL reintroduction program. At each site, hot dog baits were placed 5 meters apart in 10x10 grids. At treatment sites, one teaspoon of Amdro (a common ant poison) was applied to baits with RIFA thirty minutes after placement. After Amdro was applied, baits were left for 30 minutes and then collected. Treatments were repeated monthly May – August. The effects of each targeted poisoning were evaluated using pitfall traps and ant abundance measurements from baits. Results showed that treatment may have decreased RIFA abundance for both years and had variable effects on hatchling food abundance. Future studies will increase sample size to better detect potential treatment effect.

Approximately 1 in 9 Americans over the age of 65 has Alzheimer’s disease (AD). As the size of this age group is expected to more than double by 2040, the AD prevalence is likewise predicted to increase rapidly. Two key risk factors for late-onset AD include poor diet and obesity. Therefore, long-term nutritional strategies could potentially reduce the development of hallmark AD biomarkers, such as amyloid beta (Aβ), later in adulthood. Researchers have found that diets extremely rich in saturated fats are associated with increased Aβ production in both the cortex and hippocampus of rodents. Conversely, plant-based Mediterranean diets (MD) that are plentiful in unsaturated fatty acids were shown to mitigate Aβ in rodents.

The relationship between diet and AD biomarkers has been explored in prior animal research, yet most studies utilize extremely high fat diets (40-60% kcal fat) or supplement with individual MD nutritional components. To address these limitations, we designed comprehensive, macronutrient-matched Mediterranean and typical American diets (TAD) that mimic human diets in Mediterranean regions and the U.S., respectively. C57BL/6J mice were weaned onto one of the two diets at postnatal day 21. Following 6 months of diet consumption, we found that the TAD increased soluble Aβ1-42 in the brain. Additionally, mice on the TAD had excess hepatic lipid deposition, which is a hallmark of insulin resistance and metabolic dysregulation, a comorbidity linked to AD risk.