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Investigating the effects of maternal separation on the locus coeruleus and negative affective behaviors in adulthood
Get PDFEarly life stress or childhood trauma is associated with psychiatric disorders later in life. However, it is unclear what potential neurobiological changes lead those who become exposed to early life stress to experience these behavioral changes in adulthood. The locus coeruleus norepinephrine (LC-NE) system is an important neuromodulatory system for stress-induced behaviors. We sought to determine if the LC-NE system is influenced by early life stress and plays a role in early life stress-induced changes in adult behavior in mice. Using maternal separation stress (MSS) as our early life stress paradigm, we analyzed LC spontaneous baseline activity across the lifespan, expression of genes related to LC function in adulthood, and adult behaviors related to stress. We saw an increase in LC baseline activity during early development and adulthood. Additionally, the genes for the alpha2a adrenergic receptor and dopamine beta-hydroxylase mRNA levels were decreased in the LC. Next, we tested whether stress-related behaviors during adulthood and observed that male MSS mice increased in exploratory behavior and locomotion in both the elevated-plus maze and the open field test. During the forced swim test, an assessment that measures coping strategies, MSS mice significantly increased immobility time compared to the no MSS group. Due to the increase in immobility in MSS mice, we determined that MSS causes an increase in the use of passive coping strategies versus active coping strategies. We attempted to reverse the effect of MSS on immobility by inhibiting the LC during the forced swim test but ultimately saw no change. We suspect that the lack of LC control over the coping strategy within the forced swim test after MSS is due to the MSS-induced dysregulation of the LC. Consequently, we sought to test whether no MSS and MSS mice respond to the forced swim following LC excitation. We saw no significant differences in immobility in either groups, however, there was a trending decrease in immobility in the no MSS group after LC activation. This trending result in no MSS mice after LC stimulation is the inverse of no MSS mice after LC inhibition, showing that driving LC activity up or down can drive opposite behavioral effects during the forced swim test. In summary, the increase in exploratory behavior and locomotion in MSS mice may be assumed to be a resilient type of behavior or even an impulsive type of behavior, though these concepts merit further testing. Additionally, it is clear that MSS mice prefer passive coping strategies in the forced swim test. The effect of early life stress on locus coeruleus function and adult behavior should be further analyzed to determine potential future therapeutic solutions for those who have experienced trauma in early life
Dominant tree species as a driver of forest herb community assembly: The peculiar case of pawpaw (Asimina triloba)
Get PDFUnderstanding the drivers of community assembly is a key goal in ecology and conservation. One way to better understand community assembly is to understand how the presence or absence of dominant species– highly abundant species with a proportionally large effect on the ecosystem–affects assembly. This approach allows for a more generalized understanding of community assembly based on the presence or abundance of one species rather than pairwise interactions among all species in a community. In forests, studies on dominant tree species have focused on how they affect patterns of species diversity. In contrast, surprisingly little is known about how dominant species influence key processes of community assembly, such as non-random (deterministic) selection resulting from niche differences among species, random (stochastic) changes in species relative abundance (ecological drift), and dispersal. Additionally, the herbaceous layer of forests often does not receive as much attention as dynamics among trees, despite herbs making up a majority of the species diversity in temperate forests. Thus, my dissertation focuses on how a geographically widespread and locally dominant tree species–pawpaw (Asimina triloba, Annonaceae)–affects the assembly, biodiversity, and abundance of forest understory herbs in a temperate oak-hickory forest. My dissertation aims to accomplish three goals: 1) determine how the presence of dominant species influences patterns of herb species composition, diversity, and abundance across spatial scales, 2) determine how dominant species alter the relative strength of the high-level assembly processes of selection, ecological drift, and dispersal to produce these patterns, and 3) elucidate the biological mechanisms by which dominant species are altering these patterns and processes. In Chapter 2, I determined the relative importance of deterministic and stochastic processes in assembling the herbaceous layer inside and outside of pawpaw patches by using a combination of observed local diversity (alpha-diversity), local community size (total abundance of all species), and observed and null-model simulated compositional variation (beta-diversity). I found that inside pawpaw patches, there was lower local diversity, lower community size and lower abundances (higher rarity) of a large number of herb species, and beta-diversity that was both higher and closer to the null (stochastic) expectation compared to outside pawpaw patches, all suggesting that community assembly is more random inside pawpaw patches, though deterministic assembly still plays an important role. In Chapter 3, I investigated how pawpaw influences deterministic or stochastic assembly through abiotic selection or effects on community size. I used variation partitioning to explain herb composition as a function of local environmental conditions (light levels, soil properties, fire disturbance) and spatial processes (geographic distance) inside and outside pawpaw patches. I found that local environmental conditions explain less variation in herb composition inside compared to outside pawpaw patches, suggesting weaker niche selection (species sorting) and stronger ecological drift inside pawpaw patches with smaller community size. Community size increased with light availability, suggesting that pawpaws increase ecological drift by decreasing light availability and increasing rarity of herb species inside pawpaw patches. Soil variables were significant predictors of herb composition, suggesting that spatially variable selection outside of pawpaw patches is associated with species sorting along local soil-resource gradients, but that pawpaws weaken these plant-soil associations. Finally in Chapter 4, I experimentally tested the degree to which the rarity of three herb species inside pawpaw patches is caused by three types of recruitment limitation: seed limitation, establishment limitation, and limited reproduction (flowering). In one herb species (Desmodium glutinosum), I found that local abundances are seed-limited across both patch types, but that pawpaw does not appear to alter the degree of seed limitation. There was some evidence for establishment limitation for Desmodium glutinosum seedlings being higher inside pawpaw patches, but establishment for transplanted seedlings was not significantly different in the pawpaw patches for any of the three species. Flowering was significantly reduced inside pawpaw patches for two of the three species investigated. This suggests that recruitment inside pawpaw patches is most limited by reproduction and that the presence of pawpaws may promote source-sink dynamics. Together, my dissertation illustrates how a locally dominant tree species increases stochastic community assembly, alters abiotic conditions and species sorting, and increases local rarity of forest herbs by limiting establishment and reproduction. While pawpaw trees are part of a healthy landscape, their impact on understory herbs should not be ignored in land-management plans and conservation. These findings could potentially be generalizable to other dominant species across forest types and other ecosystems
Molecular Mechanisms of Enzymes Driving Antibiotic Resistance and Virulence
No full textAntibiotics are facing significant challenges due to the emergence of resistance and the slow pace of discovery. A deeper understanding of the enzymes responsible for antibiotic resistance and virulence is important to address this growing threat. This dissertation focuses on investigating key enzymatic mechanisms underlying tetracycline resistance and tabtoxin biosynthesis. Specifically, a series of inhibitors, including two covalent inhibitors, were rationally designed and synthesized to target tetracycline destructases, with the goal of restoring the efficacy of tetracycline antibiotics through combination therapy. In parallel, the early steps of tabtoxin biosynthesis were explored. A SAM-dependent enzyme TblA was found to exhibit unexpected cyclopropane synthase activity, expanding the known catalytic repertoire of this enzyme family. These findings provide new insights into antibiotic resistance and biosynthetic enzymes, offering promising strategies for combating antibiotic resistance and expanding our knowledge of enzyme functions
Examining Light-Circadian Interactions in Regulation of Amyloid Plaque Pathology
Get PDFCircadian disruption has long been appreciated as a downstream consequence of Alzheimer’s Disease in humans. However, an upstream role for circadian disruption in regulating AD pathology remains an open question. The mammalian circadian system is hierarchical, with cellular clocks – driven largely by BMAL1 – synchronized by the hypothalamic SCN (suprachiasmatic nucleus) via a combination of hormonal and synaptic cues. To assess the relative contributions of each component to Alzheimer’s Disease pathology, we crossed mice harboring either microglial (Cx3cr1/Lyz2-Cre) or GABAergic (VGAT-iCre, expressed in more than 95% of the SCN) BMAL1-knockout to mouse models of Aβ aggregation (5xFAD; APP/PS1-21), which is thought to be the initiating event in AD pathogenesis. Ablation of BMAL1 in microglia failed to consistently alter plaque aggregation, suggesting that the myeloid circadian clock is dispensable for parenchymal Aβ accumulation. In contrast, inhibitory BMAL1-knockout using VGAT-iCre disrupted rhythmic behavior, physiology, and Aβ processing in a light-dependent manner, resulting in reduced plaque load and plaque-associated phospho tau. These studies shed light on the respective roles of microglial and GABAergic circadian clocks in mediating the molecular pathogenesis of AD, and they suggest a reevaluation of the proposed positive feedback loop between circadian rhythm disruption and Alzheimer’s Disease pathology
Faster, Higher, Stronger: Modern Methodologies for the Calibration, Exploration, and Utilization of Agent-Based Models
No full textIncreases in computing power and availability have led to the widespread use and adoption of agent-based models (ABMs) in the physical, biological, and social sciences. At their core, ABMs represent a novel paradigm for scientific inquiry: their micro-level specification allows for the simulation of the individual components of a system which yields a deeper understanding of dynamic processes such as contagion and adaptive decision-making when used appropriately. However, several hurdles exist when attempting to use ABMs to their full potential. In this thesis, we will explore and address several challenges in designing and utilizing ABMs, with a focus on applying state-of-the-art optimization techniques to aid in ABMs ability to recover empirical phenomena, identify optimal interventions, and explore richer social and behavioral dynamics
Developing Aerosol Representation in Atmospheric Modeling
No full textAmbient aerosols affect climate and air quality in the Earth system. Global chemical transport models used to study these impacts require an accurate representation of aerosols in terms of shape, composition, and vertical distribution. For example, despite having a complex morphology, mineral dust is often treated as spherical particles in these models. This can lead to errors in optical properties calculations, trace gas retrievals, and heterogeneous chemistry. Similarly, inaccurate representation of the vertical distribution of smoke particles in these models can lead to uncertainties in air quality assessments. Aerosol composition also plays a critical role in determining radiative forcing and atmospheric visibility. This dissertation addresses these challenges by developing improved aerosol representations within the GEOS-Chem global chemical transport model. Through a combined theoretical and observational framework, this work advances the modeling of ambient aerosols to better reflect their physical and chemical complexity, thereby enhancing our understanding of their climate and air quality impacts. The dissertation includes three studies. The first study aims to use the spheroidal model as an effective dust shape to study how the optical properties, such as extinction efficiency and phase function, deviate from the previously assumed spherical shape. Subsequently, the study examines how the updated optical properties affect the scattering weights and air mass factor (AMF) used for NO2 retrievals over the urban city of Riyadh. The impact of shape and surface complexities (pores) on dust surface area, reaction, and diffusion parameters is also examined using a theoretical framework based on surface fractal dimension and porosity. The findings emphasize the use of non-sphericity and surface heterogeneity in atmospheric modelling. The second study aims to improve the vertical distribution of smoke aerosols during wildfire events by implementing satellite-constrained plume heights in the high-performance configuration of GEOS-Chem (GCHP). A Gaussian vertical profile is used for aerosol mass distribution, and the resulting satellite-derived surface-level PM2.5 concentrations are compared against ground-based observations. The results demonstrate that incorporating plume height information significantly enhances the accuracy of air quality assessments during wildfire events. The third study focuses on understanding the role of aerosol chemical composition in determining the mass scattering efficiency using measurements from Surface PARTiculate mAtter Network (SPARTAN). The study finds that the hygroscopic species such as secondary inorganic aerosols, organics, and sea salt considerably affect mass scattering efficiency. Sea salt, in particular, emerges as a significant contributor to mass scattering efficiency across all sites. In contrast, mineral dust is not a major contributor even in dust-prone regions. This underscores the important role of relative humidity in particle growth and thereby, in light scattering. Together, these studies provide a more physically grounded and observationally validated framework for representing aerosols in global chemical transport models, leading to improved assessments of their climate and air quality impacts
Old Frames on New Media: Health Misinformation in Black Digital Communities
No full textGrowing evidence suggests that health misinformation has the potential to proliferate on social media. However, our understanding of the problem’s magnitude continues to evolve. Despite several studies on health misinformation and Black communities in the United States (U.S.), few of these studies characterize misinformation within digital settings. This dissertation seeks to address this gap by: 1) synthesizing the literature on health misinformation and Black communities to identify prevalent misinformation topics and claims, characteristics of exposure to and belief in these topics and claims, and successful intervention strategies; 2) quantifying and characterizing the volume of COVID-19 misinformation on Black Twitter during the initial weeks of the pandemic; and (3) advancing our understanding of the network of accounts that shared COVID-19 misinformation on Black Twitter during the initial weeks of the pandemic. Regarding the first aim, a scoping review provides important context for Aims 2 and 3. It suggests that misinformation beliefs in Black communities are common and consistently themed across vastly different health topics (e.g., HIV/AIDS, COVID-19, and reproductive health), misinformation topics (e.g., origins, transmission, treatment), and over time, suggesting deeply entrenched frames of government and medical mistrust. Furthermore, the results of this review demonstrate that specific subgroups may be more susceptible to misinformation than their counterparts, suggesting the importance of tailoring interventions to specific audiences. However, among the gaps identified by this scoping review, few studies examine Black communities in digital settings, despite several studies referencing social media as a source of misinformation. Regarding the second and third aims, a case study extends existing research by characterizing discourse about COVID-19 on Black Twitter, one of many U.S.-centric Black digital communities, during the initial weeks of the pandemic. To achieve this, a large sample of tweets referring to COVID-19 as “the Rona,” #Rona, or #theRona—a colloquialism widely used among Black communities in the U.S. during the pandemic—was described using traditional approaches and social network analysis. A descriptive analysis of misinformation volume and themes reveals that COVID-19 misinformation was plentiful but less prevalent than other COVID-19 information on Black Twitter; however, misinformation received more retweets. Misinformation claims overlapped with mainstream media and misinformation but were often spun in ways that were specific to Black experiences and culture. Moreover, a close reading of tweets revealed that specific claims and frames (e.g., government and medical mistrust) overlapped those described in the Aim 1 scoping review, which largely correspond to offline settings. Social network analysis demonstrated that, during most weeks, the retweet network that shared COVID-19 misinformation and the retweet network that shared other COVID-19 information were both fragmented. These networks consisted of several hubs, where many others retweeted a single account, and several smaller fragments involving two or more accounts. Among these networks, a sizable proportion of accounts questioned or opposed misinformation, and involvement of accounts with relatively large followings promoted tweet diffusion. The empirical studies in this dissertation align variably with existing literature on health misinformation and social media, contributing to a more nuanced understanding of the health misinformation landscape within Black communities in the U.S. In combination with future research, insights from these studies may inform the development and evaluation of tailored, culturally relevant interventions designed to reduce misinformation diffusion, exposure, and acceptance, and to better reach Black digital communities with accurate health information
Can You Hear the Music? Reexamining the Gender Gap in Physics
No full textExamining the gender gap in physics through looking at physics’ reliance on “physical intuition” and how it impacts women in physics. Among STEM disciplines, physics stands out for its persistent and striking gender imbalance. While gender disparities exist across all science fields, physics consistently reports some of the lowest levels of female participation. According to a 2017-2021 study by the American Physical Society, only 23% of bachelor’s degrees were awarded to women, in stark contrast to 42% in math, 52% in chemistry, and 64% in biological sciences. This sharp divide highlights how physics remains uniquely gendered, even within the broader context of male dominated fields. While the gender gap in physics is widely acknowledged, its underlying causes are less rigorously proven and agreed upon
Disagreement and Historical Argument or How Not to Think About Removal
No full textScholars have debated the reach of the President’s power to remove government officers for over one hundred years. This old fight is now suddenly urgent as President Trump asserts far-reaching powers to control the federal bureaucracy and the Supreme Court transforms Unitary Executive Theory into caselaw. Yet the scholarly case for an indefeasible presidential removal power has never been weaker.This Essay continues an ongoing conversation about how to read some critical early republic evidence about removal. It briefly recapitulates the stakes of the disagreement before offering in-depth analyses of developments in Pennsylvania removal practice, including a reading of the Council of Censors’ Report from 1784. Along the way, it responds to some recent criticisms of our work by Professors Saikrishna Prakash and Aditya Bamzai.The Essay makes two overarching arguments: First, there was no consensus in the early republic that the executive power included an indefeasible power of removal. Second, legal historians must take dissensus seriously. Historical disagreement is a fact that lawyers wishing to make legal meaning out of history need to confront. In this case, it straightforwardly undermines the notion there was a shared understanding in the early republic that the executive power included an indefeasible power of removal
Data for Social Impact - Data Persona Worksheet
No full textDeveloped in collaboration with Amelia Parnell and drawing upon the framework from Parnell\u27s 2021 book You Are a Data Person: Strategies for Using Analytics on Campus, this worksheet facilitates exploration of data identity and the identification of data personas