Journal of African Christian Biography: v. 10, no. 3-4: Separate cover file (PDF), print-ready

The full issue of Journal of African Christian Biography: v. 10, no. 3-4 is available at: https://hdl.handle.net/2144/5171

Immune protein interactions with microglia: contributors to both synapse loss and myelin damage in the aging rhesus monkey brain

2024Normal aging is characterized by cognitive decline in learning, memory, and executive function even in the absence of neurodegenerative diseases such as Alzheimer’s disease (AD). Although originally believed to be a result of neuron loss, the source of cognitive decline during normal aging is now understood to reflect damage sustained by neurons, particularly disruption of the insulative myelin sheath around the axon and disruption of synaptic connections. As a result of myelin pathology, white matter volume is lost, and axon conduction is disrupted leading to loss of cortical connectivity. Concurrently, gray matter volume loss occurs due to the combined loss of myelin and synapses and atrophy of dendrites, resulting in decreased synaptic transmission between neurons and ultimately cortical disconnection. Although the underlying cause of this damage is unknown, increasing neuroinflammation is likely involved as it renders microglia reactive, disrupting proper maintenance of myelin and synaptic homeostasis. With age, the ability of microglia to clear myelin debris declines and it has been shown that myelin debris impedes remyelination by oligodendrocytes. Additionally, secretion of proinflammatory molecules increases, making microglia more sensitive to inflammatory stimuli, resulting in an exaggerated inflammatory response. This exaggerated response may lead to aberrant engulfment and phagocytosis of both myelin and synapses during normal aging, ultimately leading to cognitive decline. Microglia engulfment is regulated through innate immune signals that either promote or inhibit phagocytosis. Two key components in this regulation are the initiatory signal of the classical complement cascade, C1q, that signals “eat me” to initiate engulfment of targets and the inhibitory neuroimmune regulatory protein CD47 that signals “don’t eat me” to prevent engulfment. The overall goal of this dissertation study was to investigate regional differences in innate immune signals C1q and CD47 in the aging brain, where microglial homeostatic function deteriorates under neuroinflammatory conditions. To do this, immunofluorescence (IF) was used to examine changes in C1q and CD47 in relation to synapse loss in the dorsolateral prefrontal cortex (dlPFC) gray matter, myelin damage in the cingulum bundle white matter, and cognitive decline in the normal aging rhesus monkey. Modeling human aging with the rhesus monkey is a highly translatable model as monkeys have extended lifespans, a gray to white matter ratio comparable to humans, and a similar pattern of cognitive impairment in learning and memory tasks during aging. First, using IF on archived brain sections collected from a large cohort of behaviorally tested monkeys, we found that synapses identified by PSD95 decreased with age, and existing PSD95+ synapses had increased colocalization of C1q along with decreased CD47 colocalization in dlPFC gray matter. However, gray matter microglia did not show age-related changes in morphology or expression of C1q, likely indicating a process other than conventional phagocytosis by which microglia engulf synapses. Next, these immune signals were investigated in cingulum bundle white matter, where IF showed colocalization of C1q with myelin increased with age. In contrast CD47 showed decreased colocalization with myelin from young to middle age but then increased in the oldest subjects. In aging white matter, IF revealed an increase in the number of microglia with hypertrophic morphology along with in the phagocytic activation marker Gal-3, changes that may reflect microglial reactivity. Further, RNAscope in situ hybridization revealed C1qA mRNA expression increased in white matter microglia with age, while CD47 mRNA expression decreased in oligodendrocytes, likely making them more vulnerable to attack by microglia. Importantly, these changes in C1q, CD47, and microglia reactivity are associated with age-related cognitive decline. Finally, microglia engulfment of myelin and synapses was investigated in relation to changes in C1q, CD47, and downstream complement components. IF and spectral confocal reflectance (SCoRe) microscopy, which enables visualization of myelin, revealed increased microglial engulfment of myelin in aging white matter and increased synaptic engulfment in aging gray matter. Electron microscopy confirmed that C1q and CD47 both colocalize to synaptic structures and to myelin. At the molecular level, quantitative polymerase chain reaction showed differences in upregulation of downstream complement molecules, where aging white matter had upregulated expression of C1q and CR1 genes that mediate phagocytosis. In contrast, aging gray matter showed increased expression of C4b which has been implicated in excess synapse loss. Together, these results provide strong evidence that C1q and CD47 immune signaling are dysregulated during aging and likely contribute to synapse loss, myelin damage, and microglia reactivity, and thus presents a novel target for therapies aimed at slowing cognitive decline

Mapping paths to equitable dental care: a study on the practice locations of oral health sciences graduates and underserved communities

2024The Master's in Oral Health Sciences (OHS) program, a collaborative initiative between Boston University's Graduate Medical Sciences and the Henry M. Goldman School of Dental Medicine, has been instrumental since its establishment in 2005 in providing a pathway for students from underrepresented backgrounds to gain admission to dental school. Designed to strengthen academic qualifications for entry into dental school, this program has been crucial in fostering diversity within the dental profession.Access to dental care is a critical public health concern, particularly in underserved or economically impoverished areas. This research endeavors to explore the career trajectories of pre-dental students who successfully completed the OHS program, pursued dental education, and subsequently became practicing dentists. Our primary objective is to evaluate the geographical distribution of these dental graduates, with a specific focus on whether they returned to similar hometowns or cities to their own upbringing, especially those marked by underservice in dental care. Data for this study were sourced from deidentified OHS matriculation and graduation records. A comprehensive dataset, including demographic information such as race, ethnicity, gender, disadvantaged and first-generation status, OHS admission years, and career status, was compiled. Underrepresented minority (URM) status, encompassing Black or African American, Hispanic or Latino, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander, was a key focus within the dataset. Furthermore, student career outcomes post-dental school were gathered from online platforms, including social media networks and LinkedIn. The study evaluated data from 276 students enrolled in the OHS program between 2005 and 2018. This cohort presented a diverse range of demographics, including 47.5% male and 52.2% female, 16.3% disadvantaged, 10.1% first generation students and 28.3% from groups under-represented in dentistry enabling an in-depth examination of career outcomes for students from historically underrepresented racial and ethnic backgrounds. Through an examination of the practice locations of OHS graduates, we have observed a significant proportion opting to practice in areas marked by dental care shortages and socioeconomic challenges. Specifically, among the 276 OHS graduates, a substantial proportion, accounting for 41.7% of the total, chose to practice in underserved areas. Among the 45 OHS graduates categorized by their disadvantaged status, 42.2% of the graduates opted to practice in underserved areas, aligning their practice locations with the communities they grew up (although not statistically significant (χ2 (1) = 0.007, p = 0.9341). Further, among the 78 graduates from underrepresented groups, an even larger percentage, 57.7 %, opted to work in underserved areas. The results indicated that there was a statistically significant association between URM status and their likelihood of working in underserved areas, χ2 (1) = 0.0007, p = 11.489. The results not only shed light on the success of the OHS Pathway Program in enhancing diversity within the dental profession but also revealed a distinctive preference among graduates to return to underserved communities to practice. Additionally, the study underscores the significance of pathway programs and the importance of enrichment programming to support disadvantaged and underrepresented students. These are key to the success of the MS in Oral Health Sciences program. By providing mentorship, academic and professional development resources, and social support, through enrichment and a near-peer mentoring program, not only do graduates' gain professional development but also build the academic and self-confidence they need to be successful in dental school and beyond. Training in such a culture cultivates a sense of social responsibility and commitment to community and addressing disparities. Further investigation is necessary to understand the factors contributing to dental outcome difference and to explore long-term career outcomes, particularly in terms of location preferences for serving communities in need. This study underscores the correlation between OHS graduate students and their preferences to serve in areas with underserved populations, encouraged by a strong foundation in the OHS Pathway Program. It emphasizes the growing importance of creating pathway programs similar to OHS to enhance diversity within the dental profession and address healthcare disparities

Journal of African Christian Biography: v. 4, no. 1: Booklet, no cover (A4 format), print-ready

The full issue of Journal of African Christian Biography: v. 4, no. 1 is available at: https://hdl.handle.net/2144/3567

Econometrically-estimated weather sensitivities and projections of mid-century climate change impacts on economic systems

2025By 2050, global food and energy production systems will face critical pressure. The supply of crop is to be impacted through secular shocks to land productivity whose uncertain implications balance between weather change-driven crop yield declines modulated by farmers’ adaptation and the potentially offsetting effect of CO2 fertilization (CFE). In temperate mega-cities, sectors’ fuel demand sensitivity and the physical properties of buildings will determine the extent to which future shifts in extreme heat and cold-season temperatures alter energy demand. The final co-occurrence of energy insecurity and climate change, because it reduces households’ adaptation capacity to outdoor temperatures, poses significant health concerns.This dissertation quantifies climate change impacts on human economic systems: agriculture, energy and health. In the three sectors, we highlight how the balance of forces has played out historically and geographically and what, given both supply and demand determinants, the likely socio-economic implications are circa-2050. First, we use a panel dataset of gridded annual crop yields and investigate the global temperature, precipitation, CFE and irrigation responses of four crops responsible for 75% of world’s calorie intake. Projecting climatically-driven changes, by coupling our estimated elasticities with an ensemble of climate model midcentury simulations, we find substantial agreement on average weather-driven crop yield losses offset by CFE. We suggest that previous agricultural productivity estimates may have overstated technical progress by failing to distinguish it from the underlying contribution of CO2. Second, we elucidate heterogeneity in the demand responses to temperature of different fuels in conjunction with the sector building stock demography of temperate NYC. Combining building-level monthly electricity and gas disclosures with high spatial- and temporal-resolution weather data and hourly-downscaled climate forecasts, we predict net aggregate energy changes and decompose future fuel, sector and season disparities. Third, we review the literature assessing energy insecurity effects on health. Our hypothesis is that gaps in energy use for adaptation to temperature extremes produce health inequities at all developmental stages. Beyond individual risk factors, we look at structurally interconnected drivers and show that the poorest populations are most likely to bear the burdens of conflicting mitigation and adaptation efforts in the warming future

Race differences in prayer among Black and White Americans with chronic low back pain

2024The burden of chronic low back pain (cLBP) in America disproportionately affects Black Americans. This unequal burden may in part, be due to differences in coping, including religious coping. Research examining prayer as a coping strategy for pain has been scant and predominantly focused on White populations. Previous literature has suggested that active prayer, compared to passive prayer, may yield more favorable pain-related outcomes. However, no prior study has examined the relationship between race, type of prayer, and pain outcomes among people with cLBP. Thus, the present study sought to examine racial differences in prayer as a coping strategy for chronic pain between Black and White adults with cLBP and the relationship between prayer and pain among these individuals. In a diverse sample of 29 participants aged 18-85 with non-specific cLBP, the 17-item Pain-related PRAYER Scale (PPRAYERS) was used to assess participants’ engagement in active, passive, and neutral prayer to cope with pain. Pain intensity and interference were assessed using the 11-item Brief Pain Inventory (BPI). Results indicated that Black participants endorse more frequent use of active (p=0.02; d=0.92), passive (p=0.01; d=1.05), and neutral prayer (p=0.01; d=0.72) compared to White participants. There was also a significant race difference in pain intensity (p=0.04; d=0.75), such that Black participants reported greater pain intensity than White participants. However, there were no differences in pain interference (p=0.29; d=0.23). Furthermore, active prayer, passive prayer, and neutral prayer were not significantly correlated with pain intensity (ρ=0.22, p>0.05; ρ=0.31, p>0.05; ρ=0.16, p>0.05) or pain interference (ρ=0.10, p>0.05; ρ=0.19, p>0.05; ρ=0.06, p>0.05). This study provides novel insights into racial differences in the experience of pain.2027-09-26T00:00:00

Association between total amyloid beta plasma levels (AB 42/40, AB42 and AB40) and amyloid burden as measured by AB-PET SUVr levels

2024OBJECTIVE: Currently, an official diagnosis of Alzheimer’s disease (AD) involves expensive brain scans. Thus, these diagnostic tools are inefficient for targeting large populations and individuals with limited resources. The overarching objective of this thesis project was to explore the association between plasma total Aβ levels (Aβ 42/40, Aβ42 and Aβ40) and amyloid burden as measured by Aβ-PET SUVr levels in a subset of participants screened in the A4 trial. Ultimately, this project aimed to uncover if blood Aβ biomarkers yielded comparable diagnostic results to PET scans. The first goal was to utilize appropriate statistics to determine whether there is a correlation between blood-based Aβ biomarkers and PET SUVr levels. The second goal was to analyze the relationship between blood-based amyloid beta biomarkers and PET positive and negative groups. METHODS: The first statistical analysis involved a Spearman Correlation test, which aimed to explore the relationship between Aβ blood-plasma levels and PET SUVr levels. Notably, this test can determine the strength of the correlation between blood-based Aβ biomarkers and PET SUVr levels. The second statistical test was a logistic regression model that aimed to build a prediction model and assess its potential clinical utility for AD screening. Before conducting the test, the SUVr quantities were assigned into a binary positive or negative scale based on an individual’s official AD diagnosis. RESULTS: Using the Spearman Correlation, I found that the Aβ40 was not correlated with PET SUVr levels since the coefficient value (ρ) = 0.042. Conversely, the Aβ42 showed a weak negative correlation with a ρ value of -0.14. Additionally, the Aβ 42/40 ratio exhibited the strongest correlation between all three scatterplots with a ρ value of -0.29. Individuals who were APOE e4 carriers consistently exhibited elevated PET SUVr levels compared to APOE e4 non-carriers when controlling for Aβ 42/40 levels and age. Regarding the logistic regression model, the results display the logistical regression model outperformed the Aβ 42/40 biomarker when comparing sensitivity for each specificity point. However, this attribution is based on the selection of the Youden index point. Based on the Area Under the Curve (AUC), the Aβ 42/40 has an AUC of 0.67 which provides moderate accuracy. Moreover, the logistic regression model which incorporates Aβ 42/40, age, and APOE e4 status has a significantly better AUC of 0.747. CONCLUSION: In conclusion, Aβ 42 and Aβ 42/40 exhibited weak correlations with PET SUVr levels with the strongest being Aβ 42/40 ratio. Additionally, APOE e4 carriers displayed elevated PET SUVr levels for all ranges of Aβ 42/40 and age with a 95% confidence interval. Furthermore, the logistical regression model that accounted for Aβ 42/40 ratio, APOE e4 gene, and age resulted in a higher AUC compared to solely the Aβ 42/40 ratio. Ultimately, the journey toward developing effective diagnostic tools for Alzheimer's disease may require refinement of multiple blood-based biomarkers to achieve optimal predictive power and clinical utility

Efficacy of dialectical behavior therapy for parents with a child with acute mental health needs

2025This study aims to examine treatment outcomes for primary caregivers receiving a virtual dialectical behavioral therapy intervention. Caregivers recruited for this study are seeking treatment to support themselves, and their child, who was experiencing acute mental health needs such as suicidality, aggression, and self-harm. Data on several outcome measures were analyzed at three time points (post intervention, three months into treatment, and six months into treatment) to assess how this intervention supports caregivers. Results contribute to the discussion on the importance of virtual treatment, caregiver focused interventions, and how family focused interventions can have positive effects for direct participants (e.g., parents) as well other members within the family system, even if they are not directly involved in treatment themselves

Investigation of the pyruvate: ferredoxin oxidoreductase and its redox partner, ferredoxin

2024On a global scale, Fe–S clusters (among other essential redox cofactors, such as hemes, flavins, or amino acid residues) drive the core metabolic reactions of life by transporting electrons through a suite of redox-active enzymes—the oxidoreductase superfamily (Fuchs, 2011). On a per-active-site basis, these enzymes are the most efficient catalysts for several chemical reactions crucial for renewable energy (storage and usage); thus, understanding their inner workings is paramount for developing alternative, green technologies (Reda et al., 2008; Wang et al., 2014). Therefore, this dissertation examines the mechanistic principles of one class of enzyme catalyst bearing Fe–S clusters, the 2-oxoacid:ferredoxin oxidoreductase (OFOR) enzyme superfamily. Although OFORs are considered reversible enzymes, they appear to have an inherent bias toward either the reductive or oxidative chemistry, often believed to reflect the native function of the enzyme (Li et al., 2016). However, revealing the factors that influence an enzyme’s directionality has been difficult. Therefore, by examining a series of unique OFOR enzymes and mutants, this dissertation addresses the following questions: Given the diversity of OFOR enzymes (i.e., cofactor content, number of subunits, and domain modularity), what factors control catalytic bias of CO2 fixation or evolution? What role does the OFOR’s partner protein, ferredoxin, play in biasing reaction directionality? The electrochemical study of the structurally unique PFOR enzymes from C. tepidum, M. marinus, and M. acetivorans will provide critical information regarding the significance of the domain and structure composition of an OFOR enzyme. It will further reveal whether the native function of the enzyme influences the resting-state reduction potentials of the [4Fe–4S] clusters in the ET chain. Detailed site-directed mutagenesis studies of the Ct PFOR will provide a foundation for understanding the relationship between cluster potentials and ET/catalytic rates of the OFOR family and give insight into the role the protein matrix plays in tuning cluster potentials. Furthermore, electrocatalytic studies of the Ct PFOR/Fd system will provide an example of how the identity of a partner protein could direct or support enzyme catalysis and elucidate factors that contribute to successful intermolecular-ET. Understanding how Fd characteristics influence catalysis applies to many other biological systems, including the chemistry of hydrogenases or nitrogenases. Finally, the study of the Fe proteins from the nitrogenase provides insight into the thermodynamic driving force that initiates nitrogen fixation in the catalytic component of the nitrogenase, further improving our understanding of how the nitrogenase accomplishes its chemistry.2027-02-07T00:00:00

Advanced quantum structures for infrared detectors

2025Type-II superlattices (T2SLs) have emerged as promising alternatives to the more established bulk material systems for infrared (IR) photodetection. This is due to predicted fundamental advantages, such as the tunability of the band gap and theoretically reduced Auger recombination rates. However, the superiority of these materials has not been experimentally realized, prompting the need for further investigation. A bottleneck in the development of improved superlattice (SL) structures and devices is the cost in time and resources required to prototype and characterize these materials as well as incomplete knowledge of the material properties and physical phenomena that characterize these structures. Therefore, the field would greatly benefit from simulation methodologies that enable the development of advanced T2SL materials. In this work, the field of IR photodetection is reviewed highlighting the most common T2SLs structures currently being experimentally implemented. A quantum transport model that includes the necessary physical mechanisms to model carrier transport in these structures will be presented. The results of an investigation on the extraction of vertical carrier mobility, a property important for carrier collection, from quantum transport simulations is presented for an example T2SL. It is demonstrated thatcarrier transport in these structures can be highly coherent. In this case, the apparent mo-bility is suppressed due to ballistic resistance, requiring care when predicting the intrinsic mobility of these materials. The best method of mobility extraction is one that considers the dependence of the resistance on device length. This method was applied to predict the quantum efficiency (QE) in curved focal-plane arrays composed of n-type mid-wave InAs/InAsSb and InAs/GaSb structures subjected to the effects of superlattice disorder and external strain imposed by the curving procedure. It is demonstrated that the external strain has a minimal impact on the QE relative to disorder in both structures suggesting the device design could be viable. Additionally, it was found that large magnitudes of positive axisymmetric strain could result in enhanced hole transport. Finally, a comprehensive investigation is presented that probed for optimized n-type long-wave InAsSb/InAsSb SL structures, a material known to result in low QE devices, for various substrate lattice constants. Several structures were found demonstrating hole mobilities with greater resilience to SL disorder providing potential candidates for future prototyping