Exposure to air pollution is a major and often overlooked risk factor for cardiovascular disease, the leading cause of death worldwide. Particulate matter (PM), a common component of air pollution, has been implicated in promoting reactive oxygen species (ROS) production and inflammation. In response to ROS and inflammation, macrophages can upregulate Heme oxygenase-1 (HO-1), an antioxidant and anti-inflammatory enzyme. However, the effects of ultrafine particles (UFP) and whether HO-1 can modulate UFP-induced inflammation is not well understood. To investigate ROS generation following UFP exposure, RAW 264.7 macrophages were pretreated with UFPs for 24 hours. ROS levels were then measured and compared to controls using fluorescent microscopy with dichlorofluorescein (DCF) as a probe. A dihydroethidium (DHE) assay was also used to evaluate superoxide production. We hypothesize that ROS levels will be elevated in the UFP exposed cells compared to controls. To investigate the role of HO-1 on modulating inflammation, bone marrow-derived macrophages (BMDMs) were cultured from HO-1 knockout and HO-1 over-expressing mice and treated with UFPs for 24 hours. Inflammation will be assessed via qPCR of various cytokines. We expect that HO-1 overexpressing cells will exhibit reduced inflammation compared to HO-1 knockout cells. Elucidating the role of HO-1 may identify new therapeutic targets against inflammatory disease and inform public health strategies aimed at reducing the impact of air pollution.

This abstract has been withheld from publication.

In natural populations, multiple stressors experienced early in life have lasting consequences on adult fitness. While cumulative early life adversity (ELA) is known to affect physiological health, less is known about how it affects behavior. More research is needed on whether cumulative ELA has long-term impacts on behaviors with important fitness trade-offs, such as vigilance and other antipredator behaviors. Alarm calling is a key antipredator behavior that can help the caller or others but at a cost to the caller. We used a cumulative adversity index (CAI) previously developed for yellow-bellied marmots (Marmota flaviventer) to determine whether an individual’s CAI score is associated with their propensity to alarm call or their call quality. After fitting generalized mixed models, we found no relationship between CAI score and alarm calling propensity in natural environments, nor did we observe an association between CAI score and call noisiness. However, among marmots who called when live-trapped, those with higher CAI scores were significantly less likely to call. Our findings suggest that cumulative ELA’s impacts on risk-taking behavior depend on context. In especially stressful situations, marmots that experienced considerable stressors growing up may become more risk-averse. This study is one of the first contributions towards a better understanding of how cumulative ELA affects individuals’ responses to risk and their assessments of fitness trade-offs.

Multiple system atrophy (MSA) and Lewy body diseases such as Parkinson's disease share a pathological hallmark: aggregation of α-synuclein into β-sheet-rich fibrils. Cryo-EM has revealed that MSA-associated fibrils adopt a conformation structurally distinct from Lewy body fibrils, forming within oligodendrocytes and exhibiting roughly 1,000-fold greater seeding potency. Yet no current diagnostic can reliably distinguish MSA from Lewy body synucleinopathies in living patients, as existing capture agents recognize generic amyloid features rather than conformation-specific surfaces. Here, de novo computational design is applied to generate protein binders that selectively recognize the MSA fibril fold. Using a patient-authentic recombinant MSA α-synuclein structure from the Peng lab, surface-exposed side grooves unique to the MSA conformation are identified, scaffolds generated with RFdiffusion, sequences optimized with LigandMPNN, and designs filtered through AlphaFold3. Top candidates will be screened by yeast surface display and FACS, with sequential negative selection against α-synuclein monomers and Lewy body fibrils enforcing conformational specificity, followed by bio-layer interferometry to quantify affinity and selectivity. Successful binders would enable the first strain-specific capture agents for blood-based MSA diagnostics and establish a generalizable pipeline for targeting disease-specific fibril conformers.

Black Americans experience a disproportionate burden of chronic health conditions, including hypertension, diabetes, cardiovascular disease, and obesity. These health disparities are closely linked to chronic stress exposure and broader social inequalities. One biological measure used to understand the physiological consequences of stress is allostatic load (AL), which reflects the cumulative wear and tear on the body resulting from repeated stress responses. Despite growing research on stress and health, less is known about how early-life trauma contributes to physiological stress accumulation among Black Americans specifically. This study examines the relationship between childhood trauma and adult allostatic load using data from the Nashville Stress and Health Study (2011–2014). By evaluating trauma exposure across the life course, this study investigates whether early-life adversity predicts higher physiological stress in adulthood. Specifically, this research asks: how does childhood trauma shape adult allostatic load among Black Americans, and through what pathways does stress become biologically embedded over time? Addressing this question helps clarify how early-life experiences contribute to persistent racial disparities in health outcomes and informs public health interventions aimed at reducing the long-term consequences of trauma.