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Influence Of Environmental Gradients On Genomic Variation In Pediatric Commensals And Pathogens, Sanjam Sawhney May 2023

Influence Of Environmental Gradients On Genomic Variation In Pediatric Commensals And Pathogens, Sanjam Sawhney

Arts & Sciences Graduate Student Theses and Dissertations

Microbes interact with humans in a myriad of ways. They come together in the human gut to form complex communities that collectively transform and individually evolve in response to changing environmental conditions. Individual microbes can also cause human infection and escape antibiotic clearance through acquisition and development of novel resistance mechanisms. In this thesis, I chronicle the relationships between microbes and humans across two axes: from complex communities to single isolates, and from targeted studies of pediatric populations vulnerable to microbiome perturbations and pathogen challenge, to broader human and animal cohorts spanning colonizing and diagnostic environments.In Chapter 2, I extensively …

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Eng 3001-600 Advanced Composition, Tim Engles May 2023

Eng 3001-600 Advanced Composition, Tim Engles

Summer 2023

No abstract provided.

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Deformation Of Hydrous Magnesium Silicates In Subduction Zone Environments, Charis Madeleine Horn May 2023

Deformation Of Hydrous Magnesium Silicates In Subduction Zone Environments, Charis Madeleine Horn

Arts & Sciences Graduate Student Theses and Dissertations

Hydrous magnesium silicates form primarily from the interaction of seawater with the oceanic lithosphere and are drawn down into the mantle by subducting slabs at convergent margins. It is thought that they hold an important control over several aspects of the subduction multisystem, with implications for many different subduction zone processes. In particular, the hydrous magnesium silicates serpentine and talc exhibit unusual rheological and anisotropic properties. To explore the effects of these minerals on global subduction zones, we conducted three separate studies on talc (Mg3Si4O10(OH)2) and two of the serpentine group minerals (Mg3Si2O5(OH)4), lizardite and antigorite. Firstly, to understand the …

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A Mechanistic Study Of Err Α/Γ Agonists For Treatment Of Metabolic Dysfunction In Heart Failure, Mckenna Lael Losby May 2023

A Mechanistic Study Of Err Α/Γ Agonists For Treatment Of Metabolic Dysfunction In Heart Failure, Mckenna Lael Losby

Arts & Sciences Graduate Student Theses and Dissertations

Heart failure is the leading cause of death in the United States and current therapeutic interventions fail to reverse the disease progression. In the failing heart, pathological cardiac remodeling leads to disease progression: a process characterized by hypertrophy, inflammation, fibrosis, and metabolic remodeling. By pharmacologically targeting the nuclear hormone receptors estrogen receptor-related receptor α and γ (ERRα and γ), it may be possible to reverse the array of metabolic pathways that are pathologically inhibited in the failing heart. Fatty acids are the primary fuel source of the adult heart that generate the ATP required for each contraction; however, in heart …

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Examining Therapeutic Targets For Central Nervous System Autoimmune Disease, Sindhu Manivasagam May 2023

Examining Therapeutic Targets For Central Nervous System Autoimmune Disease, Sindhu Manivasagam

Arts & Sciences Graduate Student Theses and Dissertations

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) that leads to demyelination, axonal damage, and neuronal loss. Patients are typically diagnosed early in adulthood and due to the chronic nature of the disease, will continue to develop symptoms over their lifetime. Currently available therapeutics for MS focus on symptomatic relief and reduce severity of relapses; however, they are unable to prevent disease progression or promote recovery. Therefore, there is a critical need to understand the biological mechanisms driving neuroinflammatory and neurodegenerative processes in MS and to translate these findings into novel therapeutic strategies.Here we …

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An Investigation Of Second-Site Non-Complementation Among Motile Cilia Genes In Chlamydomonas Reinhardtii, Gervette M. Penny May 2023

An Investigation Of Second-Site Non-Complementation Among Motile Cilia Genes In Chlamydomonas Reinhardtii, Gervette M. Penny

Arts & Sciences Graduate Student Theses and Dissertations

ABSTRACT OF THE DISSERTATIONAn Investigation of Second-Site Non-Complementation among Motile Cilia Genes in Chlamydomonas reinhardtii by Gervette M. Penny Doctor of Philosophy in Biology and Biomedical Sciences Molecular Genetics and Genomics Washington University in St. Louis, 2023 Professor Susan K. Dutcher, ChairMotile cilia are complex microtubule-based organelles used by eukaryotic cells for locomotion or directing fluid flow. In humans, motile cilia defects cause primary ciliary dyskinesia (PCD), characterized by neonatal respiratory distress, recurrent lung infections, bronchiectasis, and low nitric oxide. Situs inversus and/or male infertility are present in about 50% of cases. PCD inheritance is recessive; both copies (alleles) of …

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A Pilot Study Of Hand Autografts Treated With Autologous Skin Cell Suspension, Paige Deville, Jeffrey E. Carter, Madeline Lechtenberg, Herbert A. Phelan May 2023

A Pilot Study Of Hand Autografts Treated With Autologous Skin Cell Suspension, Paige Deville, Jeffrey E. Carter, Madeline Lechtenberg, Herbert A. Phelan

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

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Essays On Health Care Payment Incentives, David Adam Schwartzman May 2023

Essays On Health Care Payment Incentives, David Adam Schwartzman

Olin Business School Graduate Student Theses and Dissertations

This dissertation studies how payment incentives in health care change clinician and patient behavior and how different “value-based” payment models may impact outcomes. In Chapter 1, I explore optimal design of healthcare payment models in the presence of market frictions to targeting benefits. I leverage a natural experiment where an employer introduces Direct Primary Care, a form of care delivery where clinicians are paid a capitated monthly fee for high-touch access to a bundle of primary care services. This model modifies moral and behavioral hazard incentives for both patients and clinicians while changing the trade-off between preventive investments and downstream …

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Maternal-Fetal Circadian Communication During Pregnancy, Keenan Bates May 2023

Maternal-Fetal Circadian Communication During Pregnancy, Keenan Bates

Arts & Sciences Graduate Student Theses and Dissertations

Circadian rhythms in gene expression and hormones are ubiquitous across species and across cell types. Circadian rhythms depend on a transcription-translation negative feedback loop that drives many daily rhythms in behavior and physiological processes. Circadian rhythms regulate many aspects of reproduction, such as fetal development and birth timing. Mammalian pregnancy presents a unique situation with circadian rhythms in the mom and, eventually, in the fetus. Prior studies showed that circadian rhythms develop in utero and that maternal signals, such as glucocorticoids, may act to entrain or drive daily rhythms in the fetus. However, there remains considerable debate about when and …

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Circumventing Drug Resistance With Small Molecule Inhibitors Of Mycobacterium Tuberculosis, Gregory Alexander Harrison May 2023

Circumventing Drug Resistance With Small Molecule Inhibitors Of Mycobacterium Tuberculosis, Gregory Alexander Harrison

Arts & Sciences Graduate Student Theses and Dissertations

The disease tuberculosis caused by Mycobacterium tuberculosis (Mtb) remains a global health threat, and the antibiotic resistance crisis challenges our ability to treat Mtb infections. For example, out of the approximately 10 million cases of tuberculosis each year, an estimated 10.7% of new cases and 27.2% of previously treated cases are resistant to the frontline antibiotic isoniazid (INH). There is a clear need for new therapies that enhance our current regimen and target these genetically resistant strains.Identifying ways to enhance the antimicrobial activity of INH has the potential to significantly improve the efficacy of frontline treatment regimens. To this end, …

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The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen May 2023

The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen

Arts & Sciences Graduate Student Theses and Dissertations

Recent human genetic studies have associated mutations in a gene called Myelin Transcription Factor 1 Like (MYT1L) with neurodevelopmental disorders (NDDs). Patients with MYT1L loss of function (LoF) mutations (MYT1L Syndrome patients) demonstrate shared symptoms such as microcephaly, attention deficit and hyperactivity disorder (ADHD), and obesity. Despite prior studies showing MYT1L overexpression facilitates neuronal differentiation in vitro, its functions in vivo, especially in the mammalian brain, and how its mutation leads to human disease pathology remains poorly understood. Here, I established the first mouse model of MYT1L Syndrome mimicking a patient specific LoF mutation. I found mice with Myt1l heterozygous …

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The Evolutionary And Comparative Elements Of Social Roles, Jake A. Funkhouser May 2023

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. …

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The Role Of Mavs And Interferon-Lambda In Regulating Astrovirus And Norovirus Infections, Heyde Makimaa May 2023

The Role Of Mavs And Interferon-Lambda In Regulating Astrovirus And Norovirus Infections, Heyde Makimaa

Arts & Sciences Graduate Student Theses and Dissertations

Although they globally cause viral gastroenteritis in children, astroviruses are understudied due to the lack of well-defined animal models. While muAstVs chronically infect immunodeficient mice, a culture system and understanding of their pathogenesis is lacking. Here, we describe a platform to cultivate muAstV using air–liquid interface (ALI) cultures derived from mouse enteroids, which support apical infection and release. Chronic muAstV infection occurs in the small intestine and correlates with higher IFN-λ expression. MuAstV stimulates IFN-λ production in ALI, recapitulating our in vivo findings. We demonstrate that goblet cells and enterocytes are targets for chronic muAstV infection in vivo, and that …

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Circadian Protein Bmal1 Regulates Astrocyte Activation And Protein Degradation In Health And Disease, Celia Augusta Mckee May 2023

Circadian Protein Bmal1 Regulates Astrocyte Activation And Protein Degradation In Health And Disease, Celia Augusta Mckee

Arts & Sciences Graduate Student Theses and Dissertations

The circadian clock regulates gene transcription to control daily rhythms in cellular function, behavior, and disease. Circadian dysfunction is a symptom of aging and neurodegenerative diseases, and recent studies suggest reciprocal regulation between impaired clock function and neurodegeneration. In addition to the clock regulating neuronal activity, non-neuronal glia cells of the brain also possess functional circadian clocks which control their responses to daily oscillations in brain activity, cellular stress, and metabolism. Astrocytes directly support brain function through synaptic interactions, neuronal metabolic support, neuroinflammatory regulation, and control of neurovascular coupling at blood and cerebrospinal fluid (CSF) barriers. Emerging evidence suggests that …

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Identification And Characterization Of Targets Of Metastasis In High-Grade Serous Ovarian Cancer, Emilee Nicole Kotnik May 2023

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 …

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Multi-Omics Understanding Of Heterogeneity, Progression, And Therapeutic Vulnerabilities In Kidney Disease And Cancer, Yize Li May 2023

Multi-Omics Understanding Of Heterogeneity, Progression, And Therapeutic Vulnerabilities In Kidney Disease And Cancer, Yize Li

Arts & Sciences Graduate Student Theses and Dissertations

Kidney disease and cancer are both highly heterogeneous diseases, meaning that they exhibit significant variability in their underlying causes, mechanisms, progression, and responses to therapy. Traditional approaches to studying these diseases have focused on individual molecular or cellular pathways, which can provide limited information on the complexity of the disease. By combining multi-omics technologies, we can gain a more comprehensive understanding of the molecular and cellular changes that occur in kidney disease and cancer and identify new therapeutic targets and personalized treatment options.As a kidney disease, clear cell renal cell carcinomas (ccRCCs) represent ~75% of RCC cases and account for …

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Roles Of The Transcription Factors Bcl6, Irf2, And Notch2 In Myeloid Development, Kevin William O'Connor May 2023

Roles Of The Transcription Factors Bcl6, Irf2, And Notch2 In Myeloid Development, Kevin William O'Connor

Arts & Sciences Graduate Student Theses and Dissertations

Development of immune cells is orchestrated by expression of transcription factors which function to control differentiation of progenitor populations and survival of mature cells. Nonclassical monocytes are a population of myeloid cells which patrol the bloodstream and are thought to maintain vascular endothelium. Conventional dendritic cells (cDCs) are antigen-presenting myeloid cells which serve to activate naïve T cells during infections. cDCs are further differentiated into cDC1s capable of cross-presenting exogenous antigens to activate CD8 T cells and cDC2s which are thought to play essential roles in activating Th2 and Th17 responses. These disparate cells originate from a shared bone marrow …

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Understanding Thermotolerance In Photosynthetic Cells: From Green Algae To Land Plants, Erin Marie Mattoon May 2023

Understanding Thermotolerance In Photosynthetic Cells: From Green Algae To Land Plants, Erin Marie Mattoon

Arts & Sciences Graduate Student Theses and Dissertations

Global temperatures are increasing, causing damage to crop plants, algae, and reducing food and biofuel production. To meet increasing demand for food and energy, we must engineer thermotolerant crops and algae that will thrive in the increasingly warm environment. However, there are many things we do not understand about how photosynthetic cells cope with high temperatures. Primarily, we do not fully understand which genes are required for thermotolerance and how different intensities and durations of high temperature periods may change this list. In this thesis, I employed high-throughput, quantitative, and genomic approaches including transcriptomics, proteomics, and genome-wide pooled mutant screens …

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The Monumentalization Of The Past: German Humanist Patriotism And Source Use, 1488–1582, Justin Meyer May 2023

The Monumentalization Of The Past: German Humanist Patriotism And Source Use, 1488–1582, Justin Meyer

Arts & Sciences Graduate Student Theses and Dissertations

The development of a patriotic discourse among German Renaissance humanists emerged from a humanist desire to memorialize the past by gathering information from the sources of German history and geography. Prevailing scholarly arguments explain the emergence of this discourse as a result of cultural conflict with Italian humanists who reproached the Germans for their barbarity. This explanation, which I call the Conflict Model, is inadequate as a means to explain the phenomenon of this patriotism because it relies on too few sources. This dissertation rests on a far more expansive source base in which cultural conflict is a limited but …

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Dynamics Of Epithelial Differentiation Following Intestinal Villus Injury, Takahiro Erick Ohara May 2023

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 …

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Essays On Macroeconomics, Zheliang Zhu May 2023

Essays On Macroeconomics, Zheliang Zhu

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation has three chapters. The first chapter examines the information transmissionfrom the central bank to the private sector regarding the public signal interest rate. The second chapter presents a proposed belief-driven Taylor rule and analyzes the rule’s impact on private expectation anchoring and social welfare loss. The third chapter studies the relationship between corporate Environmental, Social, and Governance (ESG) practices and their associated financing costs. Omitted proofs in each chapter are presented in the last section of each chapter.In the first chapter, we study the information transmission from the central bank to theprivate sector regarding the public signal interest …

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Mechanisms Of Transcription Regulation By Card In Mycobacterium, Dennis Xiaoqian Zhu May 2023

Mechanisms Of Transcription Regulation By Card In Mycobacterium, Dennis Xiaoqian Zhu

Arts & Sciences Graduate Student Theses and Dissertations

Mycobacterium tuberculosis (Mtb) is an important human pathogen that is responsible for over 1 million deaths each year. As a bacterial pathogen, Mtb is highly adapted to survival within the host environment, which imposes numerous environmental stresses on the bacteria. To survive these challenges, Mtb utilizes a network of transcription factors to adapt its gene expression and physiology. CarD is an essential transcription factor in mycobacteria that binds directly to RNA polymerase (RNAP) rather than DNA sequence motifs on the chromosome. Prior mechanistic studies of CarD’s function in mycobacteria have been limited to studies of CarD’s effects on individual kinetic …

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Abundances Of Ultra-Heavy Cosmic Ray Nuclei With Calet, Wolfgang Vaughn Zober May 2023

Abundances Of Ultra-Heavy Cosmic Ray Nuclei With Calet, Wolfgang Vaughn Zober

Arts & Sciences Graduate Student Theses and Dissertations

This work describes the determination of the relative abundances of the Galactic Cosmic-Ray (GCR) nuclei from Z=9 through Z=40, with preliminary measurements up to Z=44, using the Calorimetric Electron Telescope (CALET) on board the International Space Station (ISS). This analysis will compare results with the top-of-atmosphere abundances from the balloon-borne SuperTIGER and top-of-instrument abundances from the space missions, ACE-CRIS and HEAO-3. This analysis also provides insight into the potential opportunities and challenges for a future SuperTIGER-like mission on the ISS.Our analysis looks at work on two separate but complementary aspects of the Ultra-Heavy (UH) analysis in CALET. CALET has a …

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A Framework For Investigating Random Ensembles Of Structured Ecosystems And Quantifying Their Emergent Coarse-Grainability, Jacob Moran May 2023

A Framework For Investigating Random Ensembles Of Structured Ecosystems And Quantifying Their Emergent Coarse-Grainability, Jacob Moran

Arts & Sciences Graduate Student Theses and Dissertations

The interface between statistical physics and theoretical ecology has a long history, employing powerful concepts such as ensemble approaches and typicality to study emergent properties of ecosystems. This of course raises the question of what ensembles are useful to describe the typical behaviors of evolution and ecology, but so far, the traditional context of high-diversity ecology has considered ensembles of random, unstructured ecosystems. Although much insight has been gained in this regime, one naturally wonders how representative are random ensembles of real, natural ecosystems that are arguably atypical and highly structured by evolution. Moreover, the question of coarse-graining ecosystems has …

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Wide-Field Optical Imaging Of Neurological Disorders And Sleep In Mice, Lindsey M. Brier May 2023

Wide-Field Optical Imaging Of Neurological Disorders And Sleep In Mice, Lindsey M. Brier

Arts & Sciences Graduate Student Theses and Dissertations

Neuroimaging has revolutionized the way in which we understand the hierarchical organization of the amazingly complex, interconnected human brain. Neuroimaging techniques, like functional magnetic resonance imaging (fMRI), have provided high quality structural and functional data, providing multiple in-depth analyses and biomarkers of disease processes. In animal models, mechanistic studies can uncover root pathologies that aren’t explorable in humans. In mice, brain functional connectivity (FC) can be measured via Optical Intrinsic Signal (OIS) imaging – a modality that measures vascular reactivity as a surrogate for neural activity via quantification of fluctuations in oxygenated-hemoglobin (similar to the blood oxygen level dependent (BOLD) …

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The “Dread Sex Cases:” Community, Citizenship, And The Regulation Of Adult Theaters In The 1970s, Erin Barry May 2023

The “Dread Sex Cases:” Community, Citizenship, And The Regulation Of Adult Theaters In The 1970s, Erin Barry

Arts & Sciences Graduate Student Theses and Dissertations

Through an innovative examination of scale (local, state, and national regulatory structures), space (the location of theaters, the spatial arrangements inside them) and place (the cities and suburbs in which these battles took place), my dissertation on the regulation of adult theaters in the 1970s raises compelling questions about sexuality, space and the various levels at which citizenship is enacted and policed. I utilize three Supreme Court cases, Paris Adult Theater v. Slaton, which dealt with consent and the application of community standards, Erznoznik v. Jacksonville, which addressed bans on nudity and pornography at drive-in theaters, and Young v. American …

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Pastoralism As Institutions: Modeling The Pastoral Landscape In Tibet In The Second And First Millennium Bc, Xinzhou Chen May 2023

Pastoralism As Institutions: Modeling The Pastoral Landscape In Tibet In The Second And First Millennium Bc, Xinzhou Chen

Arts & Sciences Graduate Student Theses and Dissertations

Previous archaeological research has made significant advances in our understanding of the chrono-spatial patterns of ancient human occupation of the Tibetan Plateau based on archaeobotanical, zooarchaeological, and material cultural analysis. The surge of archaeological data in prehistoric Tibet calls for further analysis of the potential social and environmental forces that shaped the prehistoric landscapes of Tibet. This dissertation presents a synthetic analysis of the role of pastoralism in shaping the economy, materiality, and mobility of Tibetan societies in the second and first millennium BC. Based on both previously published archaeological evidence and my own analysis of newly documented archaeological data, …

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Histamine Production By Airway Resident Haemophilus Species Induces Rhinitis, Michael Lint May 2023

Histamine Production By Airway Resident Haemophilus Species Induces Rhinitis, Michael Lint

Arts & Sciences Graduate Student Theses and Dissertations

Allergic rhinitis is one of the most common chronic illnesses in America, affecting more than 60 million people each year. Allergies develop when sensitization to an environmental allergen result in the production of antigen-specific IgE. Subsequent exposure to the allergen, detected by IgE, then binds to the surface of mast cells triggering the release of inflammatory mediators particularly histamine, which contribute to characteristic allergic symptoms of nasal itching, sneezing, and wheezing. Although fundamental mechanisms underlying allergy development have been previously characterized, recent research has implicated commensal bacteria residing in the respiratory tract in contributing to the development of allergic inflammation, …

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The Influence Of The Gut Microbiota On Asthma In School-Aged Children And Adults, Naomi Grace Wilson May 2023

The Influence Of The Gut Microbiota On Asthma In School-Aged Children And Adults, Naomi Grace Wilson

Arts & Sciences Graduate Student Theses and Dissertations

Asthma is a common respiratory disease with a highly heterogeneous pathophysiology. The human gut microbiota, comprising of all the microorganisms that inhabit the gastrointestinal tract, is linked to the development of asthma and can alter airway inflammation in animal models. The idea that the gut microbiota can have bidirectional cross-talk with the lung, such as gut dysbiosis affecting lung disease, is termed the gut-lung axis. While the gut microbiota of early life has been an area of particular interest for asthma pathogenesis research, the effect of its taxonomic and functional composition after asthma diagnosis is less clear. This dissertation employs …

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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 May 2023

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 …

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