Digital Commons Network^™

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 …

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 …

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 …

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 …

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 …

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 …

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) …

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, …

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, …

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 …

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 …

Inflammation And Reward-Related Neural And Behavioral Phenotypes, Erin Bondy

Arts & Sciences Graduate Student Theses and Dissertations

Anhedonia transcends psychiatric diagnostic boundaries (e.g., depression, schizophrenia, PTSD) and is a marker of severe dysfunction and treatment resistance. Convergent evidence from non-human animal models and initial human studies suggests that elevated inflammatory signaling may induce anhedonia. However, the mechanisms underlying this association and the specific forms of reward processing that may be affected remain largely unknown. Here, two studies were conducted examining whether variability in reward-related brain measures and behavior may plausibly contribute to inflammation-related differences in reward processing. In the first study, data from children of European American ancestry of the Adolescent Brain Cognitive Development (ABCD) study of …

Understanding The Spectrum Of Dnmt3a Mutations In Neurodevelopmental Disease, Diana Christian Beard

Arts & Sciences Graduate Student Theses and Dissertations

Epigenetic mechanisms are critical for precisely controlling gene expression programs to allow for the development and function of the brain, and disruptions of these processes are highly associated with neurodevelopmental disease. DNA methylation is one mechanism used to regulate gene expression, and neurons employ a unique form of DNA methylation particularly at CA dinucleotides (mCA), that is not widely observed in other somatic cell types. The DNA methyltransferase DNMT3A is required to establish mCA, and mutations in DNMT3A are associated with autism spectrum disorder (ASD) and an overgrowth and intellectual disability disorder called Tatton-Brown Rahman Syndrome (TBRS). However, it remains …

Mechanisms And Consequences Of Microtubule-Based Symmetry Breaking In Plant Roots, Natasha Anriel Bilkey

Arts & Sciences Graduate Student Theses and Dissertations

Directional growth in plants is primarily determined by the axis of cell expansion, which is specified by the net orientation of cortical microtubules. Microtubules guide the deposition of cellulose and other cell wall materials. In rapidly elongating cells, transversely oriented microtubules create material anisotropy in the cell wall that prevents radial cell expansion, channeling cell expansion in the longitudinal direction. Mutations perturbing microtubule organization frequently lead to aberrant cell growth in land plants, with some mutations leading to helical growth patterns (called ‘twisted mutants’), often in roots. This phenotype manifests as right-handed or left-handed twisting of cell files along the …

Zebrafish Swim Capacity, Gait, And Posture During Innate Spinal Cord Repair, Nicholas Oliver Jensen

Arts & Sciences Graduate Student Theses and Dissertations

Adult zebrafish are capable of anatomical and functional recovery following severe spinal cord injury. Significant advances for understanding the cellular and molecular mechanisms of innate spinal cord repair are best supported by accurate assessment of swim function. This study introduces neuromuscular-associated measurements derived from gait and posture, compares new and classical functional measurements longitudinally, and provides a comprehensive correlative analysis of various functional and cellular regeneration outputs. It also explores trajectories of functional regeneration through tensor decomposition and demonstrates that swim function at 2 weeks post-injury can be used to predict 8-week regeneration outcomes. By establishing swim quality metrics which …

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 …

Spike-Timing-Dependent Plasticity Alters Sensory Network Connectivity, Adalee Lube

Arts & Sciences Graduate Student Theses and Dissertations

A fundamental question in neuroscience is: how does a sensory system optimize detection of behaviorally relevant stimuli, when those stimuli and the sensory environment are constantly changing? Spike-timing-dependent plasticity (STDP), in which synapse strength changes based on the relative timing of pre- and post-synaptic spiking, has been implicated in changes in neuronal connectivity thought to underlie learning and memory. Synaptic strength changes caused by STDP have been shown in optic tectum, visual cortex, hippocampus, and other brain regions in vitro across many organisms like fish, frogs, and mice. Although it is possible that STDP mechanisms underlie changes in sensory neuron …

Three Essays On Public Attitudes Toward Federal Agencies, Zoe Ang

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation is composed of three papers on public attitudes toward US federal agencies. In the first, entitled ``Political Influences of Public Attitudes toward Federal Agencies,'' I argue that individuals rely on agency-adjacent political information to form their attitudes because bureaucratic politics are relatively low-salience and individuals hold little specific knowledge with which to evaluate agencies. Using nationally representative surveys administered from 2007 to 2018, I find that individuals rely on political information to evaluate agencies. Copartisanship with the president and one's ideology, and to a lesser extent partisanship, influence attitudes toward agencies; this effect persists over time but varies …

Wild Plant–Pathogen Interactions Across Gradients Of Urbanization And Latitude, Quinn N. Fox

Arts & Sciences Graduate Student Theses and Dissertations

In light of large-scale urbanization and rising global temperatures, it is essential to understand how environmental and climatic changes impact the ecology and evolution of species interactions. This thesis investigates interactions between wild plants and their pathogens across gradients in land use and latitude, and specifically tests the effects of multiple scales of climate variation on such interactions. In this work, I focused on a system of common herbaceous plants in the genus Plantago and their fungal powdery mildew pathogens. I studied their interactions across an urbanization gradient transecting the metropolitan area of St. Louis, Missouri and along a latitudinal …

Development Of Myelin In Wolfram Syndrome, Olga Reine Neyman

Arts & Sciences Graduate Student Theses and Dissertations

Wolfram syndrome is a rare, autosomal recessive disease traditionally characterized by juvenile onset insulin dependent diabetes, optic atrophy, deafness, and neurodegeneration often beginning in childhood and adolescence. The disease is caused by mutations in WFS1, which encodes for the protein wolframin and is associated with endoplasmic (ER) stress-mediated apoptosis. ER stress-related dysfunction may inhibit production of myelin during neurodevelopment in Wolfram syndrome, as active and developing oligodendrocytes are more vulnerable to ER stress than mature ones. It is known that white matter tracts are compromised in the disease, but many questions related to the vulnerability of myelin and its impact …

Novel Bites, Fatima Elkabti

Arts & Sciences Graduate Student Theses and Dissertations

No abstract provided.

The Effect Of Ionization Density In Applications Of Radiation Detection, Dosimetry, And Therapy, Daniel Mulrow

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation covers a wide range of topics but is linked by the common theme of radiation interacting with materials and studying the result of those interactions. The introduction describes the fundamentals of how radiation interacts with material and how we are able to detect that radiation and the application of how we use those interactions in radiation oncology. The thesis starts with a chapter detailing the temperature dependence of the photophysics in two organic scintillators. This chapter is the foundation for a future study that will look the degree to which these scintillators can distinguish between gammas and neutrons …

Columbus, Nebraska: Southern Housing Development Design Proposal, Ryan Weyers, Caiden Dynek, Alex Papa, Brexton Robertson, Kaden Perala

Honors Program: Senior Projects (Public)

The following paper proposes the design and creation of a new housing development in the city of Columbus, Nebraska in a lot to the south of the city and directly north of the Columbus wastewater treatment plant. The goal of this proposal is to provide readers with confidence that our company is the most qualified to complete the project and will create the safest, most comfortable, most efficient, and most cost-effective final design. This proposal seeks to offer a solution to the lack of affordable housing for the growing workforce in Columbus. In order to arrive at this solution, each …

Anillin And Dunk: The Conserved And Non-Conserved Players Regulating Myosin Dynamics In Drosophila Cleavage, Jiayang Chen

Dartmouth College Ph.D Dissertations

Cleavage is a common process during early embryogenesis. Similar to conventional cytokinesis, Drosophila cellularization, a unique form of cleavage, requires precise regulation of non-muscle myosin II ("myosin") at cleavage furrows, where myosin forms an interconnected basal array before reorganizing into individual cytokinetic rings. However, how myosin is regulated through both conserved and cellularization-specific mechanisms during this special form of cytokinesis remains unclear.

In my first project, I investigated the molecular mechanisms by which the cellularization-specific zygotic gene dunk regulates myosin at the basal array. I identified anillin (Scraps in Drosophila), a conserved scaffolding protein in cytokinesis, as the primary …

Piezoelectric And Conductive Polymer Based Flexible Devices Enabling Cardiovascular Health Sensing And Energy Harvesting, Andrew Closson

Dartmouth College Ph.D Dissertations

Piezoelectric materials show great promise for low-power wearable and implantable sensing, but their rigidity makes it challenging to integrate them with biological tissue. To address this, researchers have started exploring polymer-based functional materials that offer flexibility and are suitable for interfacing with the human body. However, these materials are still in their early stages, and a framework is necessary to illustrate how these materials, in conjunction with novel fabrication techniques and device designs, can enable the development of multi-functional sensing and energy harvesting devices.

This thesis utilizes highly scalable fabrication methods for functional polymers to build and test a flexible …

Evaluating Abiotic And Biotic Factors Affecting Plant Succession Processes At Malheur Lake, Beth Boos, Sammy L. King

LSU Master's Theses

Arid wetlands are diverse systems that provide habitat for a variety of flora and fauna, including stopover and breeding habitat for migratory birds. In the western United States, these wetlands support a network of stopover sites on the Pacific Flyway, and due primarily to wetland loss and alterations, these areas are becoming more isolated. Malheur Lake is a shallow endorheic lake in eastern Oregon that supported a robust emergent marsh throughout most of the 20^th century. However, following large scale flooding in the 1980s, emergent vegetation was extirpated and has only reestablished in small patches. Our objective was to …

Development And Validation Of An Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry 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 …

Effect Of Obesity And Insulin Resistance On Glucose And Fatty Acid Metabolism, Chao Cao

WUSM Theses and Dissertations – All Programs

In people with obesity, insulin resistance of glucose and fatty acid metabolism is common and it is thought that insulin resistance of fatty acid metabolism is involved in causing insulin resistance of glucose metabolism and subsequently hyperglycemia through a mechanism referred to as “lipotoxicity”. However, in many individuals with obesity and insulin resistance fasting plasma glucose and free fatty acid (FFA) concentrations are not elevated. It is widely believed that pancreatic beta-cells detect the need to increase insulin secretion in order to compensate for the impaired insulin action caused by insulin resistance in these people, whereas beta-cell dysfunction results in …

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 …

A Call For The Legalization Of Two Sustainable Means Of Final Disposition In Ohio, Aimee Sheetz

Cleveland State Law Review

Several states currently have laws that allow for alkaline hydrolysis as an alternative to burial or cremation. A few states also allow for the composting of human remains. People are choosing these means of disposition for themselves and their loved ones due to environmental, financial, and societal reasons. Ohio currently does not allow either of these methods to be performed within the state. There have been attempts to legalize alkaline hydrolysis in Ohio. This Note calls for the legalization of both methods of disposition by including them in the Ohio Revised Code. This would provide clarity to the Ohio Board …