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Sources And Consequences Of Cell-To-Cell Variability In Gene Expression, Avinash Ramu

Arts & Sciences Graduate Student Theses and Dissertations

Gene expression is a stochastic process. A population of genetically identical cells grown in an identical environment can express different amounts of any given gene. This cell-to-cell variability in gene expression often underlies important phenotypic differences between cells. If we understand the sources of cell-to-cell variability in gene expression this can help uncover the mechanisms of transcription. The core of this thesis is split into two chapters related to cell-to-cell variability in gene expression. I first examine the sources and impact of cell-to-cell variability on a specific phenotype, a signaling pathway response. In the next chapter I discuss the results …

Development And Validation Of A Uplc-Ms/Ms Method To Investigate The Plasma Pharmacokinetics Of A KCa2.2/KCa2.3 Positive Allosteric Modulator In Mice, Mohammad Asikur Rahman, Devaraj Venkatapura Chandrashekar, Young-Woo Nam, Basir Syed, David Salehi, Hamidreza Montazeri Aliabadi, Miao Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Rationale

There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of K_Ca2.2/K_Ca2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently-developed positive allosteric modulator of K_Ca2.2/K_Ca2.3 channels (compound 2q) in mouse plasma.

Methods

Mouse plasma samples (10 μL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar internal …

Solo Dance In Greek And Roman Comedy, Marleigh Anderson

Arts & Sciences Graduate Student Theses and Dissertations

In the first full-length study focusing exclusively on comic solo dance, I argue for the presence and significance of solo dance in both Greek and Roman comedy. My dissertation aims to answer two driving questions: where does solo dance (broadly defined as dance by actors) occur in extant Greek and Roman comedy, and how does such dancing contribute to the plays? The introduction lays out my methodology for approaching these questions. My study then moves from what can be known with certainty (definite solo dance scenes and references to dance) to what requires more speculation (likely dance scenes). Chapter one, …

Dissecting Tau Isoform Control And Modeling Tauopathies In Directly-Reprogrammed Neurons, Lucia Capano

Arts & Sciences Graduate Student Theses and Dissertations

Tauopathies are a family of neurodegenerative disorders whose pathology include intracellular tau aggregates, synaptic dysfunction, and neuronal death. Advanced age is the strongest risk factor for developing a tauopathy, independent of a predisposing mutation, therefore the ability to study tauopathies in adult human neurons is vital to understand the age-associated changes which underly disease onset. Tau, the protein product of the gene Microtubule Associated Protein Tau (MAPT), is expressed highly in neurons. There are six tau isoforms whose splicing control and expression is both developmentally and tightly regulated, with only one isoform expressed in fetal brain and all six expressed …

Multi-Scalar Contributions To Sex Differences In Brain Tumor Incidence And Outcome, Lauren Broestl

Arts & Sciences Graduate Student Theses and Dissertations

Nearly all complex human diseases exhibit some degree of sex difference in incidence, age of onset, disease severity, and/or response to treatment. Sex differences are observed in a wide range of nervous system disorders, including neurodevelopmental disorders, psychiatric diseases, neuroimmunological disorders, neurodegenerative diseases, and central nervous system (CNS) tumors. Males have increased incidence rates for most CNS tumor types. Sex differences in brain tumor incidence rates are observed in studies from around the world, across a wide range of cultures, in both pediatric and adult populations, and even extend to other species. Males also have decreased survival from brain tumors, …

Restoring The Mechanoresponsiveness Of Aged Bone To Mechanical Loading, Christopher John Chermside-Scabbo

Arts & Sciences Graduate Student Theses and Dissertations

Osteoporosis—a disease of low bone mass and a predisposition to fracture—remains a pressing public health burden. Osteoporotic fractures occur in 1 in 3 women and 1 in 5 men over the age of 50, at a cost of more than $22 billion annually in the US. To prevent osteoporotic fractures, we need additional strategies to increase bone formation and reverse the disease. A potent strategy to increase bone formation is mechanical loading. However, with aging, bone becomes less responsive to the same stimulus. Because we do not fully understand the age-related decrease in bone mechanoresponsiveness, we have been unable to …

Individual And Social Influences On Cigarette Smoking During Pregnancy, Alexandra Noel Houston-Ludlam

Arts & Sciences Graduate Student Theses and Dissertations

Population-level trends on sociodemographic risk factors for cigarette smoking during pregnancy (SDP) and outcomes for offspring exposed to maternal SDP are well established. However, the more complex task of understanding individual risk-prediction, including differences by maternal race/ethnicity, and its clinical application, remains incomplete. Characterizing the relative influence of environmental and individual characteristics as risk or protective factors for continued SDP is a necessary next step for informing individual- and public health-level interventions to produce successful smoking cessation prior to pregnancy, substantially reducing smoking-related mortality in child-bearing people. In this dissertation, I wanted to explore how multiple levels of influence, from …

The Evolutionary And Comparative Elements Of Social Roles, Jake A. Funkhouser

Arts & Sciences Graduate Student Theses and Dissertations

In human societies, individuals who hold social roles are recognized by others as possessing context- or task-specific proficiencies and skills. The social roles that are arguably unique to our societies confer many functional benefits, however multidisciplinary interests in the topic lack an evolutionary framework that allows for the comparative elements and emergence of social roles to be investigated. In this research, we put forth four elements of social roles in societies that can be compared across species: those that are context-specific, expressed over time, offer functional advantages, and individuals who hold social roles are recognized by conspecifics as possessing characteristics. …

A Torsion Balance Search For Long-Range Interactions Coupling To Baryons And Leptons And Cosmic Ray Transport For Spatially And Temporally Continuous And Discrete Sources, Dawson Huth

Arts & Sciences Graduate Student Theses and Dissertations

Part I: The expectation of new physics motivates more stringent tests of our current best understanding of gravitation, General Relativity (GR). Many theories proposing new physics predict the violation of Einstein’s equivalence principle, a set of criteria which must hold for GR to be valid. A torsion balance instrument was designed and operated to detect any violation of the equivalence principle. The motivations for performing such an experi- ment, instrument design, operational principles, data collected and subsequent analysis are described in detail in this thesis. After 51 days of continuous data collection experimental upper bounds on the violation of the …

Identification And Characterization Of Targets Of Metastasis In High-Grade Serous Ovarian Cancer, Emilee Nicole Kotnik

Arts & Sciences Graduate Student Theses and Dissertations

High-Grade Serous Ovarian Cancer (HGSC) is a highly metastatic cancer with the majority of patients presenting in advanced stages. Currently there are limited targeted treatment options for patients, especially for women with high metastatic tumor burdens. In order to improve patient outcomes, we have aimed to identify and characterize novel targets of metastasis utilizing sequencing from patient tumors and a functional genomic screen. First, we identified genetic alterations of metastasis and short survival by characterizing the genomic and transcriptomic alterations of primary and metastatic tumors in HGSC patients from 23 short-term survivors (overall survival (OS) <3.5 years) and 16 long-term survivors (OS >5 years). We compared somatic …

The Effect Of Oxytocin Receptor Genetic Variants On Oxytocin Response, Manasi Malik

Arts & Sciences Graduate Student Theses and Dissertations

Oxytocin is a nonapeptide hormone that modulates social behavior, mediates the lactation reflex, and induces and strengthens uterine contractions. Each year, oxytocin is administered to about half of laboring patients for induction and augmentation, and to almost all patients for prevention of post-partum hemorrhage – a total of four million patients per year in the United States alone. However, response to oxytocin varies widely between individuals, and complications including uterine hyperstimulation, uterine atony, required Cesarean section, and postpartum hemorrhage can arise from either excessive or inadequate oxytocin response. To avoid these adverse events, it is critically important to identify individuals …

How Can One Be Happy? Conteuses’ Lessons On Proper Conduct And Mentality In The Court Society Of Louis Xiv, Zhiyuan Meng

Arts & Sciences Graduate Student Theses and Dissertations

“How can one be happy?” is an age-old question that has been asked countless times throughout history. The answer, however, varies considerably according to when and where the question is asked. In seventeenth-century French court society, marked by patriarchal and monarchical domination, the key to happiness depends heavily upon the individual’s gender and social position. This dissertation examines three cross-dressed heroines in fairy tales written by first-generation French storytellers at the end of the seventeenth century. Their adventures as male chevaliers are conducive to the evaluation of advice for an audience of both genders from aristocratic and high bourgeois backgrounds …

Dynamics Of Epithelial Differentiation Following Intestinal Villus Injury, Takahiro Erick Ohara

Arts & Sciences Graduate Student Theses and Dissertations

Millions of finger-like structures called villi line the small intestine, providing an enormous surface area for rapid and efficient nutrient absorption. Collapse of the villus architecture, known as villus atrophy, is often observed in response to pathogen invasion, inflammation, medications, and ischemia due to loss of intestinal epithelial cells, resulting in symptoms of diarrhea and malabsorption. Though removal of the inciting agent generally allows for near complete tissue recovery, some individuals take longer to restore their villi, a condition known as persistent villus atrophy, for reasons that are unknown. How intestinal villi cope with tissue damage and re-establish their structure …

Essays In International Reserves And Sovereign Risk, Rocio E. Suarez

Arts & Sciences Graduate Student Theses and Dissertations

Since the 1990s, international reserves accumulation has particularly surged in emerging economies. What are the rationals behind this rise and the implications of international reserves accumulation for emerging economies? Chapter 1 of the dissertation, titled The Effects of Reserves Accumulation on Sovereign Default Under Terms of Trade Shocks, studies what is the value of holding international reserves in emerging economies when they experience fluctuations in their terms of trade and the sovereign debt is denominated in foreign currency. Firstly, I document stylized facts regarding a sample of emerging economies over the period 1997-2019 and find that there is a negative …

Identifying Molecular Targets Of Adar1 Dependency In Breast Cancer, Sua Ryu

Arts & Sciences Graduate Student Theses and Dissertations

Innate immunity is a fundamental defense mechanism against non-self. Similar to its role in pathogenic infections, innate immunity is capable of eliminating cancerous cells by activating cytotoxic inflammatory signaling. Adenosine deaminase acting on RNA 1 (ADAR1) is a key regulator of cell-intrinsic innate immunity. ADAR1 converts adenosines to inosines on double-stranded RNAs (dsRNAs), altering dsRNA structure and its interactive properties. This suppresses cytoplasmic sensing of immunogenic dsRNA and activation of the type I interferon (IFN) signaling pathway. Frequently, suppressing endogenous dsRNA from triggering cytotoxic inflammatory signaling is essential for cancer cell survival. This is known as ADAR1 dependency, which has …

The Role Of Ns1 In Flavivirus Immunity And Pathogenesis, Alex W. Wessel

Arts & Sciences Graduate Student Theses and Dissertations

ABSTRACT OF THE DISSERTATIONThe Role of NS1 in Flavivirus Immunity and Pathogenesis by Alex W. Wessel Doctor of Philosophy in Biology and Biomedical Sciences Immunology Washington University in St. Louis, 2023 Professor Michael Diamond, Chair Flaviviruses are a genus of enveloped, arthropod-transmitted RNA viruses that include clinically relevant pathogens such as yellow fever, dengue, Zika, and West Nile viruses. These viruses cause a spectrum of potentially life-threatening diseases including hepatitis, vascular shock, congenital abnormalities, and encephalitis. Dengue virus, alone, infects up to 390 million individuals in any given year, and its endemic regions continue to expand along with the geographical …

Evaluating The Function Of Dnmt3a Mutations Associated With Acute Myeloid Leukemia And Dnmt3a Overgrowth Syndrome, Yang Li

Arts & Sciences Graduate Student Theses and Dissertations

Heterozygous loss-of-function mutations in the DNMT3A gene are the most common cause of clonal hematopoiesis, and among the most common initiating events for Acute Myeloid Leukemia (AML). Meanwhile, mutant DNMT3A cause an overgrowth syndrome, DNMT3A Overgrowth Syndrome (DOS, also known as Tatten-Brown-Rahmen syndrome, TBRS). Amino acid R882H mutation is the most frequent variance of DNMT3A, while the rest of the mutations spread out on the entire gene of DNMT3A. Over 70% of DNMT3A mutants cause loss of function change. A reduction of DNMT3A activity causes a canonical, focal hypomethylation phenotype in hematopoietic cells, which is associated with immortalization of hematopoietic …

"I'M Fat As Fuck:" Fat Black Women's Self-Perception And Modes Of Resistance, Savannah Henderson

Senior Honors Papers / Undergraduate Theses

While many past scholars have positioned Black women as not having significant body image anxieties, Black women’s experiences with racism, sexism, and fatphobia is deeply rooted in historical narratives of the “acceptable body.” As a result, body image anxieties are prominent among Black women of size. My project investigates the historical and contemporary positioning of self-defined fat Black women and thoroughly interrogates the assumption that they do not have significant body image anxieties. Through the employment of 14 interviews, my project explores how fat Black women perceive their bodies and navigate the world. Additionally, using Lizzo’s media presence as a …

Structural Insights Into Ligand Recognition And Selectivity Of Somatostatin Receptors, Guizhen Fan, Eugenia Mileykovskaya, William Dowhan

Faculty, Staff and Student Publications

Cardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of this lipid-protein interaction is still lacking. To address the essential role of cardiolipin in supercomplex organization, we report cryo-EM structures of a wild type supercomplex (IV

Bans On Bags Or Bans On Bans?: A Home Rule Analysis Of Recent Attempts In Ohio To Enact Legislation Eliminating Plastic Bags From Stores, Christine Mika, Karin Mika

Cleveland State Law Review

This Article addresses how Ohio’s Home Rule provision in the Ohio Constitution has played out as legislators grapple with efforts to ban plastic bags from stores. It discusses the complexities of the Home Rule doctrine in Ohio, especially as it relates to the competing authority of state, county, and municipal governments. The Article discusses the history of Home Rule in Ohio, and the pre-emptive relationships between the competing governmental entities stemming from the existence of County and Municipal Charters that also grant legislative powers. It explains that the opting out of plastic bag bans by Ohio municipalities is a valid …

From Instability To Civil Liberties: Nonviolent Resistance In Afghanistan, Rachel L. Knowles

Master's Theses

When people have a fundamental issue at stake, giving in is not an option. For these types of conflict, when people’s rights are being violated, when their countries are occupied, or when they are oppressed and humiliated, they need a powerful way to persist and fight back. Oftentimes when people are left with no choice they will use the terrible and destructive nature of violence. For decades nonviolent resistance (NVR) movements have been associated with Gandhi and Martin Luther King, but people have been using nonviolent action for years. In fact, NVR has been a part of political life for …

Cardiac Pericytes Mediate The Remodeling Response To Myocardial Infarction, Kamal Ss Kolluri, David Wong, Kevin D Shih, Kai Fang, Arash Pezhouman, Lingjun Wang, Ali Daraei, Matthew D Tran, Elle M Rathbun, Kimberly N Burgos Villar, Maria L Garcia-Hernandez, Thanh Td Pham, Charles J Lowenstein, M Luisa Iruela-Arispe, S Thomas Carmichael, Eric M Small, Reza Ardehali

Faculty, Staff and Students Publications

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac …

Kras Hijacks The Mirna Regulatory Pathway In Cancer

Faculty, Staff and Students Publications

Extensive studies have focused on the misregulation of individual miRNAs in cancer. More recently, mutations in the miRNA biogenesis and processing machinery have been implicated in several malignancies. Such mutations can lead to global miRNA misregulation, which may promote many of the well-known hallmarks of cancer. Interestingly, recent evidence also suggests that oncogenic Kristen rat sarcoma viral oncogene homolog (KRAS) mutations act in part by modulating the activity of members of the miRNA regulatory pathway. Here, we highlight the vital role mutations in the miRNA core machinery play in promoting malignant transformation. Furthermore, we discuss how mutant KRAS can simultaneously …

#Notyourmammy: Explicating The Experiences Of Black Women Graduate Students As Learners And Laborers In American Academia, Kristian Ashley Contreras

Dissertations - ALL

The #NotYourMammyStudy explored the ways Black women are expected to engage in affective work – the production of feelings or affects that prioritize the needs/expectations of others – while learning in and laboring for White Serving Institutions in American higher education. This interdisciplinary qualitative study utilized a Transnational Black Feminist Framework to draw on the experiences of 28 Black women pursuing terminal graduate degrees at White Serving Institutions (WSIs) with a consideration of how the university exploits Black women through the colonial trope of the Mammy figure. The #NotYourMammyStudy offers an incisive critique of the structures of exploitation within American …

The Body Knows: Embodiment And Whiteness A Rhetorical Analysis Of White Bodies Engaged In Antiracism Work, Otsego County, New York, Kerry Lynn Mess

Theses - ALL

Multiculturalism, diversity, inclusion, equity, antiracism, belonging… The humanities, social sciences, and rhetorical scholarship have all slowly given attention to questions of race and racism. Situated at the intersection of somatic psychology and rhetorical studies, this thesis uses a somatic theory lens to explore how symbolic systems, specifically language and bodies, are intertwined to understand the embodied or material effects of racism we have not yet accounted for. I borrow Karma Chávez’s language of “abstract” and “actual” (2018) to observe the rhetorical dynamics, patterns and strategies, of white bodies accounting for themselves and apply Resmaa Menakem and Douglas Robinson’s somatic theories …

Legacies Of Empire: Museums, Neocolonialism, And Repatriation, Kailey Smith

Theses - ALL

“Legacies of Empire: Museums, Neocolonialism, and Repatriation” examines four European museums and their presentation of African cultural heritage. Analysis of the British Museum, Louvre, Musée du Quai Branly, and the AfricaMuseum uses qualitative methods and is grounded in both critical museology and decolonial theory. In conducting this analysis, I argue that these museums are engaged in various forms of memory manipulation regarding their colonial empires and that the consequent refusal of these spaces to return African cultural heritage taken during the colonial empire perpetuates the supremacy and violence of their taking. Through analysis of the museums themselves, this thesis considers …

Towards Decolonization: Migrated Kenyan Archives And The Politics Of Knowledge Production, Joy Nyokabi Karinge

Theses - ALL

“Towards Decolonization: Migrated Kenyan Archives and the Politics of Knowledge Production” examines ethical questions of archival removal in relation to access to knowledge and the politicization of access. Utilizing a theoretical framework of postcolonial theory, decolonial theory, and epistemic decolonization, this study investigates Kenyan archival holdings within the Foreign and Commonwealth Office files at The National Archives in London and the East African Archives at Syracuse University. Analysis of these archives is conducted using qualitative methods of archival research and interviews. This research reveals British colonial efforts to protect its reputation by migrating, concealing, and destroying archives and to preserve …

The Passing Intensities Of A Neighborhood. Sensing Atmospheres In La Boca, Gabriel Tomas O'Rourke

Theses - ALL

The neighborhood of La Boca, located in the city of Buenos Aires, is an urban space burdened with a story and a unique aesthetic that differentiates it from other barrios in the city. In 2022, I visited this area to walk its streets, with the goal of understanding what elements marked this urban area as a distinctive place in the city. Situated within the rhetoric of space and place, this study relies on the concept of atmospheres developed by Gernot Böhme to account for the way the experience of place is constituted by an interplay between bodies, materiality and spaces. …

Role Of Fish Oil In Paternal Obesity And In Offspring Skeletal Muscle Health, Ligeng Xiong

Theses - ALL

This study investigates the effects of fish oil in father male mice and how it could potentially affect skeletal muscle health of the next generation. Thirty male mice were fed either a low fat diet (LF), High-Fat Diet (HF), and a High-Fat diet supplemented with fish oil (FO) for 10 weeks to mimic paternal obesity. They were then mated with female mice on chow diet and all mice consumed chow diet during gestation and lactation. Offspring mice were supplemented with chow diet for 16 weeks and half of the mice were sacrificed at 8-weeks and rest at 16-weeks to study …

With-In-Through, Rumpelstiltskin Anne Morgan

Theses - ALL

I invite you to join me on a wandering into/besides/returning with ecological-attunement through gatherings, exercises, reflections, and poetry; conversing with the prior as they are as present as the current. Everything has a way of oozing together, losing perceived independence and joining in inter-dependent choreographies.