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Comparing downstream qPCR and STR profile results of diluted samples using different direct lysis methods
(2025) Morin, Emma Nancy; Cotton, Robin W.
The forensic analysis of deoxyribonucleic acid (DNA) aims to procure a profile from DNA found on evidence samples or collected from known persons in order to establish linkages between victims, suspects and/or crime scenes. The end result is an electropherogram created via capillary electrophoresis (CE) that allows analysts to view a short tandem repeat (STR) profile of the DNA. DNA extraction is the first step in forensic DNA analysis, and direct lysis is often the preferred method for use with forensic samples, which are often degraded and low template. Direct lysis is colloquially known as the “quick and dirty” lysis method, as it is typically faster, and usually only requires one tube, meaning potential Polymerase Chain Reaction (PCR) inhibitors remain in the tube along with the lysate. Therefore, a strong contender for a direct lysis kit to be used on forensic samples is capable of producing high quality profiles even in the presence of potential inhibitors.
Blood and semen are two body fluids commonly encountered at crime scenes and used as forensic DNA evidence. Both of these cell sources, however, pose challenges to the use of direct lysis. Blood contains heme, a PCR inhibitor, and sperm is made up of disulfide bonds, which require the use of a reducing agent in order to be broken for cellular lysis.
The purpose of this study was to analyze and compare the ability of two different direct lysis kits to extract DNA from diluted blood and semen samples, and to eventually produce STR profiles.
A potential approach for treating chronic pain in neuroblastoma patients
(2025) Mosharraf, Marfia; Feng, Hui; Zachariou, Venetia
Neuroblastoma is the most common malignancy diagnosed in the first year of life. The complexity of neuroblastoma cases and with the majority of cases being classified as high-risk, the prognosis is unfavorable and the efficacy of current therapies is limited. The difficulties with treatment can prevent many patients with neuroblastoma from finding relief from the neuropathic pain. This study explores the expression of histone deacetylase genes involved in neuropathic pain, hdac1, hdac4, and hdac6 in a zebrafish model for neuroblastoma. The expression of hdac1 and hdac6 was found to decrease in the neuroblastoma model of zebrafish. In the hindbrain and spinal cord, the expression of hdac4 and hdac6 contrasted with each other. In the zebrafish hindbrain, hdac4 expression was elevated and there were lower levels of hdac6 expression. The spinal cord had reduced expression of hdac4 and increased expression of hdac6. The changes in expression may be attributed to the long-term stress from chronic pain in the zebrafish model of neuroblastoma or for neuroprotection from inflammatory signaling. Although a significant relationship was found between neuroblastoma and hdac expression, further studies that include different testing methods and a positive pain model are needed to clarify this relationship.
Neutrophil elastase regulates cultured aortic smooth muscle cell phenotype
(2025) Nagle, Benjamin; Jiang, Zhen; Deeney, Jude T.
BACKGROUND: Abnormal remodeling of the aortic wall—characterized by extracellular matrix (ECM) accumulation, fibrosis, and vascular calcification—plays a crucial role in arterial stiffening, atherosclerosis, and related cardiovascular diseases. A key factor driving these processes is the phenotypic switching of vascular smooth muscle cells (VSMCs), which are typically quiescent and contractile but can transform into synthetic, fibrotic, or osteogenic states under pathological conditions. Inflammatory stimuli are among the most potent activators of this plasticity. Neutrophil elastase (NE), a serine protease secreted by activated neutrophils, is recognized for its matrix-degrading capabilities and has been linked to fibrosis in the liver, lung, and adipose tissues. However, its direct impact on human aortic smooth muscle cells (hASMCs) and its ability to activate canonical TGF-β1 or BMP pathways relevant to vascular remodeling remain largely unexplored. This study aimed to investigate the effects of NE on SMAD signaling and phenotypic programming in hASMCs under fibrotic and pro-calcific conditions.
METHODS: Primary hASMCs were cultured under standard conditions and then transitioned into contractile-induction media (containing 1% FBS, insulin, ascorbic acid, and heparin) for 24–48 hours to reduce baseline phenotypic variability and better mimic the quiescent state of medial VSMCs. Cells were then treated with NE (5–15 nM) in either fibrotic (low-serum) or osteogenic (calcifying) media formulations. Gene expression was assessed by quantitative PCR (qPCR), normalized to GAPDH and 36B4, and analyzed using the ΔΔCt method. Immunofluorescence (IF) was used to visualize cytoskeletal organization, nuclear translocation of MRTF-A and RUNX2. To determine pathway specificity, small-molecule inhibitors targeting ALK5 (TGF-β1 receptor) and ALK2/3 (BMP receptors) were applied in parallel with NE treatment. Morphological changes were documented using brightfield imaging, and quantification of nuclear fluorescence intensity was performed using ImageJ.
RESULTS: NE treatment under fibrotic conditions resulted in robust activation of the canonical TGF-β1 signaling pathway via ALK5. NE also upregulated multiple fibrosis-associated genes. In parallel, NE disrupted F-actin stress fibers and reduced MRTF-A nuclear localization, suggesting that impaired mechanotransduction acts as an additional modulator of gene expression. Under calcifying conditions, NE promoted expression of osteogenic transcription factors RUNX2 and SOX9, as well as other calcification-related genes. These changes were blunted by ALK2/3 inhibition, indicating that NE acts through BMP signaling. NE significantly upregulated BMP2 and ID1, while BMP4 was slightly downregulated, indicating selective ligand modulation. Notably, IF imaging revealed increased nuclear RUNX2 protein following NE treatment, confirming transcriptional and translational commitment to osteogenic reprogramming.
CONCLUSION: This study shows that NE is a potent driver of ASMC phenotypic switching, acting through both ALK5–SMAD3 and ALK2/3–SMAD1/5 signaling pathways. NE promotes fibrotic remodeling by enhancing ECM gene expression and impairing cytoskeletal regulation, while also initiating an osteogenic transcriptional program under conditions of calcification. These findings describe NE’s potential role in mediating inflammatory vascular remodeling and position ALK5 or ALK2/3 signaling as a critical intersection between inflammation, fibrosis, and calcification. Additional research is necessary to determine the mechanisms by which NE regulates these pathways.
S.A.M.E.N.A. domestic violence organization providing services while navigating Hindu nationalism in the US
(2025) Patel, Aakash A.; Barnes, Linda; Laird, Lance
This qualitative study connects the intersection of Hindu Nationalism and US institutions in the lives of South Asian, Middle Eastern, and North African (SAMENA) anti-domestic violence advocates as they provide services to their clients. Their domestic violence organization is courageous in tackling the stigmatized issue of domestic violence in SAMENA communities. Domestic violence is stigmatized in these communities in part because of the gender roles placed on women in the family. The SAMENA Domestic Violence organization helps clients with immigration services, restraining orders, economic empowerment, English literacy, and emotional and mental support. Nevertheless, these services are shaped by Hindu Nationalism and US institutions, which create barriers to receiving the help that domestic violence survivors need. I argue that Hindu Nationalism is a growing conservative framework which affects immigrant domestic violence organizations that work with SAMENA communities. This research analyzes three aspects of a Boston-area organization’s work tackling domestic violence within the context of this framework: 1. The organization’s relationship with law enforcement, the judicial system, and the social perception of SAMENA immigrants. 2. How the organization presents itself to community members and potential funders. 3. The stories that the organization emphasizes as they provide services to survivors. The police take on the role of gatekeepers to potential clients. The Judicial system focuses on physical violence and conflicts with the advocate’s mission to consider immigration, emotional, and mental abuse. Hindu Nationalism further stigmatizes LGBTQ and Arab community members, shaping how the organization presents itself to clients and to funders. Advocates focus on the barriers to helping clients through outreach and housing. SAMENA anti-domestic violence advocates come together in acts of solidarity with each other and acts of resistance to these systems of influence.
Sea urchin morphogenesis: teratogenesis and P-bodies
(2025) Lion, Alexandra Theresa; Bradham, Cynthia A.
Early developmental patterning and morphogenesis are fundamental processes that are still not well understood. Perturbations to aspects of these processes can result in a range of disorders including cancer, intellectual disability, and physical disabilities. These perturbations can occur due to the environment in which the embryos are developing or due to genetic alterations arising within the embryo. The first half of this thesis uses the embryos of the sea urchin Lytechinus variegatus (Lv) to examine the effects of exposure to per and polyfluoryl alkyl substances (PFAS) on development. PFAS are environmental toxicants that have adverse health outcomes in exposed animals, including cancer, kidney and liver disorders, defects to developmental morphogenesis and neurogenesis. I compared perfluorooctanoic acid (PFOA), a “legacy” PFAS which has been mostly phased out of use, and hexafluoropropylene oxide dimer acid (Gen X), a short-chain PFAS which is still in current industrial use. I found that Gen X has earlier and more severe teratogenic effects than PFOA, refuting its status as a safe PFAS. I also found that the window of effect for each chemical and resulting skeletal patterning defects suggest that PFOA directly impacts skeletal patterning, while Gen X acts earlier and affects dorsal-ventral specification. Given the persistence of these chemicals in the environment, this is an ecologically important finding which indicated that Gen X use should be curtailed or halted. The second part of this thesis examines the functional role for the RNA helicase DEAD-box helicase 6 (DDX6) in sea urchin development. DDX6 is required for the formation of processing bodies (P-bodies), which are cytoplasmic liquid-liquid phase separated compartments involved in mRNA repression and sequestration of RNAs and proteins. DDX6 and P-bodies are required for major phenotypic transitions including epithelial-to-mesenchymal transition, maternal-to-zygotic transition, and the entry and exit from pluripotency; DDX6 plays a role in numerous disorders including cancer, viral hepatitis, and intellectual disability. I found that DDX6 is necessary for normal morphogenesis of the embryo and larva, with DDX6 perturbations impacting the gut, mesoderm, skeleton, and nervous system. These results indicate that DDX6 plays a role in patterning of all three germ layers and suggest that DDX6 is involved in the gene regulatory network that reflects the instructive signaling between the ectoderm and PMCs during skeletal patterning. While a role for DDX6 in early neural development has been identified in mouse embryos, this is the first study to show that DDX6 is necessary for normal patterning. Together, these findings expand our knowledge of pattern-regulating components in the sea urchin embryo, and further demonstrate the utility of those patterns as sensors for environmental teratogens.
Assessing oral health in a New Mexican sample of opioid and non-opioid users from the New Mexico decedent image database
(2025) Poplavska, Elizabeth; Tallman, Sean D.; Moore, Tara L.
Chronic opioid use and opioid-related overdose deaths have been a continuous health epidemic in the United States in the last quarter century, with waves of increased and decreased use fluctuating over time. Research to combat this epidemic takes into account the intersectionality of how an individual's biological, social, psychological, and neurological factors interact and influence opioid usage. Both synthetic opioids, such as fentanyl and methadone, and natural opioids such as morphine and codeine, can adversely affect an individual's health and can result in mortality. Forensic anthropologists who work in a medicolegal setting are involved in analyzing skeletal and dental remains to determine the biological profile of an induvial, which includes the estimation of age, sex, stature, and ancestry. A close examination of specific skeletal markers in combination with any associated relevant and contextual data available can reveal certain circumstances surrounding an individual's death, as well as how they lived. This study examined oral health, specifically antemortem tooth loss (AMTL), dental caries, and crown restorations, in deceased individuals who do and do not have a documented medical history of opioid use from the New Mexico Decedent Image Database (NMDID). The oral health of individuals who used opioids was compared to individuals who have no recorded opioid use through visual examination of computed tomography scans (CT) to explore if there is a relationship between worse oral health outcomes and opioid use. Additionally, the relationship between opioid use and oral health was assessed through a structural vulnerability framework, drawing attention to specific skeletal and dental biomarkers and interpreting them in relation to embodied forms of inequity (Winburn et al. 2022b). The study sample consisted of 242 individuals (f=62; m=180) from the NMDID, of which 92 individuals had available sociodemographic information including adult socioeconomic status (SES), tobacco usage, drinking status, and education level. The CT images were downloaded and visualized using a medical imaging viewer, OsiriX MD, and recorded the presence, absence and count of each oral health variable on the mandibular and maxillary dental arch. It was hypothesized that opioid users will show higher rates of AMTL, dental caries, and crown restorations than non-opioid users, and that opioid use or non-opioid use can be predicted by an individual's sex, age, presence or absence of AMTL, dental caries, and crown restorations, ethnicity, tobacco usage, drinking status, education level, and SES. Pearson's Chi-square, Binary Logistic Regression, Kruskal-Wallis, and a Mann-Whitney U test were used to produce probabilities for the data, which comprised of the final sample size (n=242), and a known sociodemographic subset (n=92). Overall, results found that opioid use is not significantly associated with an increased amount of AMTL, dental caries, and crown restorations. It was also found that current everyday tobacco usage predicts opioid use. These results indicate that looking at a few dental biomarkers cannot predict whether or not someone is an opioid user; however, if someone is an opioid user, there is a significant association that they also use tobacco. Assessing oral health in forensic anthropology within a New Mexican sample addresses questions of “why” these associations are being seen rather than “what” is being seen and contributes to the evolving nature of the field by taking into account how social and political forces can impact an individual's health, especially those in socially and structurally marginalized and oppressed.
Addressing Black maternal health disparities in Woonsocket, Rhode Island
(2025) Ndiaye, Fatu; Dominguez, M. Isabel; Sen, Sarbattama
Due to systemic racism, socioeconomic disparity, and restricted access to high-quality healthcare, Black women in the US experience disproportionately high rates of maternal morbidity and mortality. Communities like Woonsocket, Rhode Island that have some of the highest rates of delayed prenatal care, preterm births, and low birthweight infants in the state, are particularly affected by these inequities. Through a community-based study carried out in collaboration with the Rhode Island Department of Health and the WATCH Coalition, this thesis investigates asset-based interventions to reduce poor maternal health outcomes among low-income and Black mothers in Woonsocket. This research thesis explores how systemic, socioeconomic, and academic barriers relate and affect maternal health disparities among Black mothers in Woonsocket, Rhode Island, and how community driven interventions can address these disparities. Secondary data demonstrates significant risk factors in Woonsocket that contribute to local gaps in maternal health outcomes across race and socioeconomic status, such as access to reproductive health care, financial instability, and educational disparities. Data collected from a focus group of Woonsocket mothers reveal the values, priorities, and strengths of local women that can be leveraged to promote maternal wellness. The findings of this research informed the development of The Watchful Moms Initiative, a peer-led, asset-focused program that offers parenting, financial literacy, and workforce development training. Through its train-the-trainer methodology, The Watchful Moms Initiative empowers participants to become community educators, helping to ensure the initiative’s sustainability and cultural relevance. This thesis concludes that investing in community-based interventions and creating structural change are essential to mitigate maternal health disparities. Programs like Watchful Moms provide a model for enhancing maternal health outcomes through local collaboration and elevating the voices of Black and low-income mothers.
Noise and inductive bias in generalization: insights from humans, rodents, and computational models of decision-making and abstract reasoning
(2025) Do, Quan; Hasselmo, Michael E.; Scott, Benjamin B.
This dissertation investigates how variability (“noise”) and priors (“inductive biases”) interact to support—or impair—generalization across biological and artificial systems. Chapter 1 (Introduction) situates this inquiry within existing theory and empirical work in cognitive science, neuroscience, and machine learning. It reviews classic and contemporary models of decision making and abstract reasoning, defines key constructs (noise, inductive bias, generalization), and outlines the overarching research questions and methodological approach that guide the subsequent empirical and computational studies. Chapter 2 develops a novel online, nonverbal evidence-accumulation game for humans inspired by pulse-based rodent tasks. Across hundreds of participants trained either with explicit instructions or solely via reward-based feedback, both groups learned equally rapidly and adopted comparable decision strategies. Behavioral modeling revealed that internal noise scales nonlinearly with evidence—mirroring animal findings but contradicting classical diffusion accounts of human perception. These results challenge prevailing theories of human evidence accumulation and demonstrate the value of feedback-driven paradigms for studying populations unable to rely on verbal instructions. Chapter 3 adapts the evidence-accumulation game for adolescents with autism spectrum disorder (ASD) and their typically developing siblings. ASD participants exhibited slower learning and altered perceptual integration, correlating with social and adaptive symptom severity. Critically, artificial neural networks endowed with increased noise reproduced these ASD-like deficits, suggesting a mechanistic link between neural variability and learning impairment. Chapter 4 establishes a rat experimental paradigm of abstract generalization using the same pulse-based evidence-accumulation task. Rats trained under curricula that restrict stimulus–action pairings generalized to novel pulse sequences according to a hybrid Exemplar-to-Prototype learning model. In this framework, internal noise broadens perceptual experience, facilitating transfer beyond the training set. Ongoing pilots with EEG and optogenetic perturbations aim to uncover the neural circuits mediating these effects. Chapter 5 presents an algorithmic one-shot rule-learning model for Raven’s Progressive Matrices–style tasks. Applied to a simplified Raven’s task designed for human behavioral and neuroimaging studies, the model achieves near–human-level performance in the symbolic condition, expresses discovered rules explicitly, and generalizes to perceptual problems with continuous patterns. These results highlight how algorithmic inductive biases can yield rapid abstraction and inform both cognitive theory and the design of more flexible AI systems. Chapter 6 introduces a Graph Neural Network (GNN) framework to capture the abstract representations underlying human reasoning. Tested on a modified Abstraction and Reasoning Corpus (ARC) with human subjects, the GNN ingests graphs encoding multiple relationship types and levels of abstraction, successfully reproducing human solution patterns. By exploring the learned representation space, we identify topological features that predict both reasoning success and characteristic error modes, providing a bridge between representational geometry and circuit-like implementations. Conclusions: Together, these six chapters illuminate how noise and inductive bias jointly promote—or impede—flexible generalization across humans, rodents, and machines. By integrating cross-species behavioral paradigms, neurophysiological measurements, algorithmic and statistical models, and deep neural networks, this work advances our understanding of the mechanisms that enable robust decision-making and abstract reasoning in both typical and neurodivergent brains and guides the development of more adaptable artificial agents.
Evaluating the therapeutic and ethical dimensions of psilocybin for major depressive disorder
(2025) Bhatnagar, Girija; Trinkaus Randall, Vickery; Graboski, Corrie
Major depressive disorder (MDD) remains a leading cause of disability worldwide, with many patients experiencing limited response to conventional treatments. Psilocybin, a psychedelic compound found in certain mushroom species, has recently gained clinical interest for its potential to produce rapid and sustained antidepressant effects, particularly among individuals with treatment-resistant depression (TRD). This literature review critically examines current evidence on the mechanisms, clinical outcomes, and therapeutic framework of psilocybin-assisted psychotherapy (PAP) in the treatment of MDD. Acting through serotonergic and glutamatergic pathways, psilocybin appears to promote neuroplasticity, disrupt rigid patterns of negative thinking, and alter neurocircuitry often implicated in depression. When administered in supportive clinical settings, it can facilitate emotional breakthroughs and improve cognitive flexibility, contributing to its therapeutic impact. Studies have shown that even one or two administrations of psilocybin can lead to meaningful reductions in symptoms. Certain methodological limitations remain, such as small sample sizes and narrow inclusion criteria. This review also explores the ethical and practical barriers of clinically integrating PAP, including issues related to informed consent, access, standardization, and therapeutic boundaries. While psilocybin is not a universal solution, it represents a promising avenue for individuals unresponsive to standard care.
Utilizing functional connectivity to understand reasoning, attention, and spatial navigation
(2025) Isenburg, Kylie; Stern, Chantal
Functional Magnetic Resonance Imaging (fMRI) offers a non-invasive measurement of human brain activity, allowing researchers to replicate decades of essential findings from animal models, while also adding to what we know about human higher-order cognition. Early fMRI work was done using univariate methods. More recently, functional connectivity (FC), a multivariate analysis method, has gained traction because of its ability to assess whole-brain dynamics both during cognitive tasks and at rest. FC during resting-state has resulted in the recognition of well-established and replicated intrinsic functional networks. These functional networks suggest an inherent underlying organization of function in the neurotypical brain. Studies examining these intrinsic networks have increased our understanding of how they reconfigure and/or remain stable during task-state, vary across individuals and different cognitive domains, and contribute to neurological and psychiatric disorders. In this dissertation, I provide three examples of how to use varying methods of FC to probe the network-based neural underpinnings of higher-order cognition. The goals of the 3 studies were to 1) employ a ridge regression machine learning model to use resting-state connectivity (rs-FC) to predict abstract reasoning task-activation across individual participants in the lateral Prefrontal Cortex (PFC), 2) assess the organization of functional brain networks and their nodes in facilitating long-term memory (LTM)-guided and stimulus (STIM)-guided attention, and 3) examine hippocampal to whole-brain connectivity during different phases of a spatial navigation task.
In study 1, I investigated the effectiveness of connectome fingerprinting (CF) trained with rs-FC data during an abstract reasoning task. While previous studies have successfully employed CF on fMRI data using tasks that span sensory processing, motor control, and working-memory, this study served to test its use during a higher-order cognitive task in a highly variable brain area, the lateral PFC. CF was carried out using a nested leave-one-out cross-validation (LOOCV) scheme, resulting in individual activation predictions that were then compared to the group average. The model demonstrated higher prediction accuracy of lateral PFC activation in individual participants than the group average. Further, a subset of nodes generating smaller functional connectomes of only multi-modal brain networks was as accurate as a model using the whole-brain connectome. These results suggest that CF can be used to predict individual activation patterns during higher-order cognition, and that there are key networks whose connectivity patterns contribute to connectome accuracy.
In study 2, I used task-based connectivity to assess the contributions across higher-order brain networks in facilitating LTM-guided attention, a task that requires both internal memory recall and external attentional demands. I employed a general Psychophysiological Interaction (gPPI) model suited for event-related fMRI data to analyze FC of the default mode (DMN), cognitive control (CCN), and dorsal attention (DAN) subnetworks, characterizing large-scale communication between brain regions underlying this process, and a STIM-guided attentional control. The results of this study identified flexible network-based interactions, particularly from the DMN, to facilitate the different components of LTM-guided attention. I found a crucial role for the precuneus and retrosplenial cortex along the posterior midline, between DMN and CCN, in aiding the ability to guide attention based on LTM recall. I identified this posterior midline region as crucial for the integration of exogenous memory and endogenous attention to visual stimuli in the environment. Alternatively, DAN and CCN subnetwork interactions were more important for STIM-guided attention, where DMN played less of a role.
In study 3, I conducted a task-residual FC analysis from the hippocampus during the navigation of a virtual spatial environment. The study assessed two phases of spatial navigation, from acquisition of the routes on day 1 to performance at ceiling accuracy criterion on day 2. Connectivity seeds were generated from 3 hippocampal segments, the head, body, and tail, as the hippocampus is a known hub for spatial navigation. There are few FC studies examining the human hippocampus during spatial navigation, and to our knowledge none looking at this across the different segments of the long axis. This study aimed to identify whole-brain subcortical and network-level connectivity architecture that facilitates the different phases of spatial navigation, from novelty to familiarity. The results suggest a flexible navigation network, where acquisition involves greater connectivity to subcortical basal ganglia, mainly in the striatum, and cortical networks involved in goal-directed attention and cognitive control. During performance, we see a shift in connectivity to cortical networks involved in top-down attention, memory-recall, and somatomotor processing. The hippocampal head showed the most widespread connectivity across the 3 seeds. These findings suggest that flexibility from hippocampal connectivity throughout the whole brain facilitates higher-order spatial navigation.
Together, these projects suggest the use for integrating FC techniques with task-based fMRI to advance our understanding of human cognition. The results show that functional resting-state networks are stable enough to predict underlying properties of task activations (Aim I) while being flexible enough to change their organization to meet task demands (Aims II & III), as resulting from varying methods of FC.