Life Sciences Commons^™

Pioneer Factors Compete For Epigenetic Factors In Switching Stem Cell Fates, Yihao Yang

Student Theses and Dissertations

During development, progenitor cells can activate one cell fate while simultaneously silencing another, a process that is tightly regulated in adult tissues. However, this process is often derailed in diseases such as cancers, leading to uncontrolled growth and malignancy. At the crossroads of fate-switching, pioneer factors are a class of transcription factors equipped to bind cognate motifs in closed chromatin. Once they access the closed chromatin, pioneer factors can either act as transcriptional activators or repressors of cell fates by recruiting co-activators or co-repressors. Nevertheless, whether and how a single factor can simultaneously silence the old fate while activating the …

Influence Of Mouse Motor Cortex On Vocal Musculature, César D. M. Vargas

Student Theses and Dissertations

Learned vocal communication and spoken language are complex behaviors we have long sought to understand. Studying the neurobiology of speech and language will be advanced by investigating its component traits in model organisms. Most vertebrates share common brainstem circuits for vocalization, and they produce innate vocal repertoires over which the animals have little to no control. Vocal learners can imitate heard sounds, and thus have a high degree of control over their vocalizations. Vocal learning species have a direct projection from the pallial forebrain to the brainstem vocal motor neurons, which facilitate their vocal dexterity. Songbirds have been the standard …

Neural Population Dynamics Underlying Encoding Of Time In The Cortico-Striatal Circuit, Francisca Martínez Traub

Student Theses and Dissertations

Interval timing, the ability to accurately measure elapsed time between events, is critical for generating appropriate behavioral responses. Research conducted over the past decades has implicated the cortico-striatal-thalamic loop in time encoding,suggesting that the cortex utilizes high-dimensional dynamics to represent time. The dorsal lateral region of the striatum (d1St) is a key structure involved in interval timing,where neurons exhibit dynamic firing rate patterns that encode elapsed time, enabling animals to make perceptual judgments about time intervals. However, it is unlikely that this striatal activity is self-generated, pointing towards cortical afferent inputs as the driving force behind it. This thesis aims …

Developing Easysci, A High-Throughput And Low-Cost Single-Cell Genomic Technique, To Study Aging And Alzheimer's Disease In Human And Mouse Brain, Andras Sziraki

Student Theses and Dissertations

Previous single-cell methods are limited by their relatively low throughput and high costs. This prevents most laboratories from performing large-scale cell profiling, complicating the understanding of rare cell type contributions to aging and disease. Moreover, these methods often focus on the 3' end of genes. Without capturing the complete gene body coverage, these technologies have limited detection of specific isoforms. To address these limitations, we extensively optimized a combinatorial indexing-based framework to develop EasySci. We used EasySci to study cell population dynamics associated with aging and Alzheimer's disease in the mammalian brain. This dataset recovered approximately 1.5 million single-cell transcriptomes …

Cells That Kill: The Chemosensory Cell Types Of Aedes Aegypti Mosquitoes, Olivia Victoria Goldman

Student Theses and Dissertations

The ability to detect and respond to environmental cues is the fundamental start of any brain function, computation, or behavior. For my doctoral work, I studied chemosensation in the Aedes aegypti mosquito, which can detect cues including human odor, carbon dioxide, and insect repellents. Mosquitoes are human's deadliest predator, causing 700,000 deaths every year through the transmission of malaria parasites and arboviruses including dengue. My research has focused on the molecular underpinnings of mosquito chemosensory cell types. In olfaction, research following the cloning of the first odorant receptors in1991 has shown that each mouse olfactory sensory neuron (OSN) expresses a …

Discovery And Optimization Of A Family Of Naturally Encoded Antibiotic Compounds That Evade Antibiotic, Adam Rosenzweig

Student Theses and Dissertations

Antibacterial resistant infections are an ongoing global health emergency. To combat this,novel potent antibiotics with unique modes of action are required. The classic arsenal of antibiotics used in clinical settings are largely natural products discovered by bulk fermentation of bacterial species isolates that are then extracted and purified to yield a bioactive compound.Unfortunately, this discovery pipeline no longer produces novel molecules, thus new discovery methodologies are essential to continue to identify antibiotic clinical candidate molecules. In the modern era, coupling natural product discovery with sequencing technologies has proven to bean efficient and fruitful method of identifying secondary metabolite natural products …

Cellular And Circuit Consequences Of A Genetic Locus For Attention, Zachary Gershon

Student Theses and Dissertations

Animals are constantly bombarded by any number of sensory inputs but have a limited capacity with which to process them. A mechanism for filtering, prioritizing, and directing mental assets is required to prevent sensory overload, enable meaningful comprehension, and allow for further action. Attention is the process of directing cognitive resources toward specific stimuli, which can be dispensed in a top-down manner to carry out higher-order cognitive functions. However, despite extensive and careful study at the molecular, cellular, and, circuit scales, unifying principles have been challenging to elicit. In this thesis, I aimed to provide a new perspective by taking …

Single-Molecule Studies Of Cftr Gating And Pharmacology, Jesper Bøegh Levring

Student Theses and Dissertations

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel expressed in the apical membrane of epithelial tissues. Alterations in CFTR that disrupt activity cause cystic fibrosis, a fatal disease which is characterized by systemic salt and fluid dysregulation. By contrast, hyperactivation of CFTR is central to pathogenesis in secretory diarrhea and autosomal dominant polycystic kidney disease. Electrophysiological properties of CFTR have been analyzed for decades. The structure of CFTR, determined in two globally distinct conformations, underscores its evolutionary relationship with other ATP-binding cassette transporters. However, direct correlations between the essential functions of CFTR and extant structures are lacking …

Proteomic Analysis Of Wnt Signaling And Metabolism Of Fibrolamellar Hepatocellular Carcinoma, James Knox

Student Theses and Dissertations

Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer that primarily affects young adults and adolescents.Although characterized as a subvariant of hepatocellular carcinoma (HCC), we have shown it is distinct based on its pathogenesis, patient population and drug response. Our lab has identified a fusion gene DNAJB1::PRKACA that is found in almost all FLC tumor samples sequenced to date. The fusion gene when expressed in mouse liver is sufficient to generate FLC, and elimination of the fusion transcript kills human tumors. The fusion results from a ~400kb deletion on chromosome 19, beginning after the first exon ofDNAJB1, which …

Anterior Cingulate Function Across Multiple-Time Scales Shapes Learning And Memory, Josue Manuel Regalado

Student Theses and Dissertations

We are constantly learning from our everyday experiences about the people we are with, the things we do,where we are, and how we feel. If deemed significant enough,we may choose to remember what we learn for the rest of our lives.For my doctoral work, I studied how a part of the neocortex, the anterior cingulate cortex (ACC),has critical functions across multiple time-scales,from minutes to days-long learning,to weeks-long memory consolidation.The prefrontal cortex, and particularly the ACC portion, is known to be important for goal-directed learning, especially as the relationship between our actions (including effort) and their outcomes (including value) has to …

Dissecting The Roles Of Cancer Cell Lipid Metabolism In Tumor Progression And Immune Evasion, Mariluz Soula

Student Theses and Dissertations

Lipids, along with nucleic acids, carbohydrates, and proteins, are essential biomolecules.These diverse hydrophobic metabolites are composed of fatty acids and include sterols, phospholipids, and glycerides. Lipids can be broken down to fuel energy demands, form the structural basis of all membranes, and can both act as signaling molecules themselves and regulate signaling by impacting membrane fluidity and receptor stability. Given the diverse and essential functions of lipids for normal cell function, it is no surprise that cancer cells leverage lipid metabolic pathways to fuel uncontrolled growth and proliferation and evade cell death. Indeed, enhanced lipid availability has been implicated in …

Recall Germinal Center And Antibody Responses, Ariën Schiepers

Student Theses and Dissertations

Repeated exposure to viruses or their antigens elicits anamnestic antibody responses that produce antibodies that are of greater magnitude and affinity compared to those induced after primary exposure to antigen.The anamnestic nature of the response is a result of the recall of memory B cells (MBCs) that have undergone clonal expansion and affinity maturation in germinal centers(GCs) during the primary response. Upon antigen re-encounter ("boosting"), MBCs, aided by enhanced help from memory T cells, efficiently differentiate into antibody-secreting plasma cells. At the same time, boosting induces recall GCs that could in principle either further affinity mature primary-derived MBCs or engage …

Strain Variation As A Window Into The Neural Logic Of Drosophila Mate Choice, Anna Ryba

Student Theses and Dissertations

Drosophila males perform robust, stereo typed courtship routines which have been studied for over a century to understand the genetic and neural underpinnings of flexible, hard-wired behavior. Courtship–particularly on the crowded wild food patches where flies congregate to mate–is a dynamic interaction between a male and surrounding potential partners that requires he integrate multiple sensory cues to direct his efforts efficiently and appropriately. While the behavior follows a similar basic pattern across Drosophila, it can contain elements that are higly species-specific. Here, we described marked variation in one aspect of male courtship preference among inbred lines of the widely studied …

Transcriptomic Signatures Of Projection Class Neurons For Vocal Control, Stephanie Joy Marcus

Student Theses and Dissertations

Vocal learning is the ability to modify acoustic structure and syntax of vocalizations. This rare trait is thought to have independently evolved three times in birds and five times in mammals. Vocal learning species exhibit an underlying convergence in brain circuitry, including a direct, forebrain-to-brainstem projection critical for the motor production of learned vocalizations. The remarkable convergence in fore brain vocal circuitry is associated with convergent molecular specializations. In characterizing specializations for vocal motor control across species, we can expand our knowledge of vocal learning and the evolution of this trait. In the first section of this thesis, I generated …

Neural Mechanisms Of Homeostatic Need And Reward, Bowen Tan

Student Theses and Dissertations

Feeding, drinking, sleep, mating, fighting, and parenting are instinct behaviors essential for animal survival. Brain has evolved sophisticated cell types and circuits that encode or fulfill the need states for food, water, sleep, sex, aggression and parenting. These need-sensing neurons monitor both environmental cues and interoceptive conditions to elicit appropriate and specific behavioral programs towards restoration of these needs. The homeostatic control of these need states further enables animals to maintain their survival strength and adapt to the environment. In contrast,dysregulation of these need-sensing neurons causes diseases such as obesity and sleep disorders,both of which are key risk factors for …

Use Of Genetically Encoded Tools To Interrogate Mechanisms Of Glutathione Homeostasis From Mitochondria To Mice, Rebecca Timson

Student Theses and Dissertations

Glutathione is an evolutionarily ancient molecule that underlies many critical biological processes across all categories of life. It acts as a cofactor in some metabolic reactions, modifies proteins to modulate their activity, and participates in detoxification of xenobiotic compounds. Despite these wide-ranging functions, glutathione is best known as an antioxidant. Some consider it akin to the fountain of youth because it decreases throughout the course of aging while oxidative damage accumulates.In addition to aging, glutathione dysregulation occurs in a plethora of diseases, including neurodegenerative diseases like Alzheimer's and Parkinson's Disease, liver disease, and metabolic disease, among others. However, the specific …

Structural Mechanisms Of F-Actin Mechanochemical Regulation And Flexible Network Assembly, Matthew J. Reynolds

Student Theses and Dissertations

The actin cytoskeleton integrates physical and chemical cues from a cell's environment to instruct its behavior, coordinating processes including cell migration, organelle dynamics, and endocytosis. Actin-binding proteins (ABPs) specify actin filament (F-actin) organization to build micron-scale networks which power these cell dynamics. Interactions between ABPs and F-actin are regulated by both biochemical processes and mechanical forces. The mechanisms mediating this interplay remain unclear at the protein structural level. Newly polymerized F-actin hydrolyzes bound ATP to produce metastable ADP-Pi–F-actin, which persists for minutes before phosphate release to yield long-lived ADP–F-actin. I determined cryo-EM structures of both ADP–F-actin and ADP-Pi–F-actin with sufficient …

Fate, Phases, And Form In Vertebrate Organ Morphogenesis-Uncovering A Role Of Morphogenesis At The Supracellular Scale, Sichen Yang

Student Theses and Dissertations

How morphology unfolds from fertilization to birth is one of the most fundamental questions in the life sciences. Self-organization in embryonic development, whereby organs robustly adopt forms through intrinsic processes, is a central feature that remains enigmatic. To achieve greater clarity of such processes, new conceptual and experimental approaches may be needed. Much of work in developmental biology in the past three to four decades has focused on cell and subcellular levels of organization. In line with work of some key conceptual thinkers, we revisit the notions of epigenetics. Rather than confining it to the molecular mechanisms of chromatin remodeling, …

Towards A Better Understanding Of Facial Movements: Computational Models For Perception, Characterization, And Neural Production, Yanis Tazi

Student Theses and Dissertations

Facial movements are the primary medium for non-verbal communication and involve a complex orchestration of muscles controlled by the brain. The ability to interpret and produce these movements enables the expression of a wide range of emotions and social cues, all essential for social interactions. Despite their significance, the neural mechanisms governing facial movements remain poorly understood, hindered by the complexity of muscle coordination and the limitations of traditional, subjective, and labor-intensive analysis methods. To objectively understand facial motor control, this research adopts a three-pronged approach: 1) Developing and interpreting computational models within a novel multi-task training framework to simultaneously …

The Role Of Gram - Negative Anaerobes In Hidradenitis Suppurativa, Samuel Clay Williams

Student Theses and Dissertations

Hidradenitis Suppurativa is a chronic autoinflammatory disease with unknown triggers.New evidence in the last five years has begun to clarify two parts of the pathogenesis of the disease. These two parts are the fundamental role of keratinocyte inflammation from early through late-stage disease and the role of the microbiome as an antigenic and infectious trigger of pathogenesis. Gram-negative anaerobic bacteria (GNA) such as Prevotella, Porphyromonas, and Fusobacterium are commonly identified in HS lesions, and their prevalence in lesions is associated with HS disease severity. Additionally, newly epithelialized structures called "dermal tunnels" are found in severe disease and are associated with …

Recombination And Excision: Dna Repair Proteins In Prokaryotic Host-Virus Conflicts, Amer Azim Hossain

Student Theses and Dissertations

Bacteriophages, or simply phages, are viruses that infect bacteria. They are the most abundant biological entity on our planet and outnumber bacteria 10:1 in the ocean. In response to this threat, bacteria have evolved a diverse battery of immune systems that prevent infection, which in turn has resulted in the development of numerous counter-defense mechanisms by phages. This evolutionary arms race drives molecular innovations and presents exciting avenues for the discovery of new molecular biology and new biotechnology tools, such as restriction enzymes and CRISPR-Cas9. My thesis investigates how mechanisms of DNA repair, specifically recombination and base excision, have been …

Molecular Mechanisms Of Sensing And Synergy By Anti-Bacteriophage Immune Systems In Staphylococcus, Dalton Van Banh

Student Theses and Dissertations

Viruses parasitize every known life form on the planet for their propagation and spread. To deal with this constant assault, organisms across all domains of life have evolved immune strategies in the form of genetically encoded systems to defend themselves. Immunity can be conceptualized as occurring in three fundamental stages. First, the immune system must identify an invading pathogen— either directly via recognition of a pathogen-associated molecular pattern (PAMP), or indirectly by sensing the perturbation of homeostasis during the process of infection ("guard hypothesis"). Second, this information must be converted into molecular signals to be transmitted to the appropriate compartment …

The Nanomechanics Of Protocadherin 15, A Protein Essential For Human Hearing, Camila M. Villasante

Student Theses and Dissertations

Mechanical force controls the opening and closing of mechanotransductive ion channels atop the hair bundles in the inner ear. A mechanical element called the gating spring modulates the mechanotransduction channel's open probability by changing the force transmitted to the channels. The molecular identity of the gating spring is yet unconfirmed, but a leading candidate is the filamentous tip link connecting the mechanotransduction channel to the tallest neighboring stereocilium. The tip link is essential to mechanotransduction: when it is broken, mechanotransduction is abolished, and when it is allowed to regenerate, mechanotransduction returns. Each tip link comprises four protein molecules: a dimer …

Investigating The Supracellular Processes Underlying Emergent Material Phase Properties During Embryonic Skin Morphogenesis, Karl H. Palmquist

Student Theses and Dissertations

During embryonic development, vertebrate tissues are sculpted by the coordinated behaviors of cells.Vertebrate organs are complex, typically requiring the orchestrated dynamics of hundreds to thousands of cells. Yet, due to their functional significance, the mechanisms underlying organ formation are robust.This implies the need for mechanisms to constrain critical processes during embryogenesis. While much of developmental biology has focused on the aspects of self-organization that relate to patterns of chemicals and molecules across a tissue and their relationship to gene regulatory networks, less attention has been given to the physical mechanisms at play. In particular,it is poorly understood how, in complex …

Plaster Creek Stewards Curb-Cut Rain Garden Social Impacts Study, Eleanor Vander Ark, Laura Luchies

Watershed Reports

As one method of minimizing pollutants in Plaster Creek, Plaster Creek Stewards (PCS) has installed Curb-Cut Rain Gardens (CCRGs) in the downstream neighborhoods of the Plaster Creek Watershed. CCRGs sit in the parkway between the sidewalk and the street, are planted with native plants, and have a cut in the curb to allow the influx of rainwater from the street. These gardens divert polluted rainwater from the creek by catching the water closer to where it falls and allowing it to filter into the ground.

As part of a grant from the Michigan Department of Environment, Great Lakes, and Energy …

Human Inborn Errors Of Immunity: Tuberculosis, Autoimmunity, And Beyond, Masato Ogishi

Student Theses and Dissertations

Tuberculosis (TB), a multi-organ infectious disease caused by virulent mycobacteria, most predominantly M. tuberculosis, remains one of the deadliest infectious diseases in human history. Bacillus Calmette-Guérin (BCG) vaccine, first implemented medically in 1921, has remained the only available vaccine for TB, although its protective effect is moderate. TB occurs in 5-10% of individuals exposed to those pathogens, while 90-95% remain asymptomatic (i.e.,latent infection or spontaneous clearance). This surprisingly large inter-individual variability has long attracted the attention of human geneticists. Classical twin-based genetic studies have demonstrated the presence of a substantial genetic risk of developing TB disease between monozygotic twins. Later, …

Effects Of Food Bar Chewing Duration On The Physiologic, Metabolic, And Perceptual Responses To Moderate-Intensity Running, Thomas R. Geaney, Zachary A. Sievert, J. David Branch, Patrick B. Wilson

Exercise Science Faculty Publications

Purpose

Chewing duration can affect food particle size, gastric processing, and postprandial glycemia, but these effects have not been investigated with exercise. This study examined how the chewing duration of a food bar impacts glycemic and metabolic responses, gastrointestinal (GI) symptoms, psychological affect, and performance during endurance running.

Methods

This randomized, unblinded, crossover study had 15 males (35.2 ± 7.4 years, VO_2peak: 56.1 ± 5.2 ml/kg/min) attend three laboratory visits. Visit 1 required a VO_2peak test, 10 min familiarization run at 60% VO2peak, and familiarization time-to-exhaustion (TTE) test (10 min at 90% VO_2peak, followed by …

Probable Extirpation Of The Jackrabbit (Lepus Californicus) From Arkansas, D.B. Sasse

Journal of the Arkansas Academy of Science

The black-tailed jackrabbit (Lepus californicus) was first documented in Arkansas during the modern era in Franklin County in 1927. Over the next few decades records were reported from multiple counties in northwest Arkansas and the species was locally common in Benton, Crawford, and Washington counties in the 1950s. The last Arkansas record documented in the scientific literature was from 1968 and since then there have only been three credible reports, with the last being from the late 1980s. The Arkansas Game and Fish Commission solicited reports of jackrabbits from the public and failed to find evidence of them from a …

Ultrastructure Of The Biflagellated Spermatozoon In The Western Siren, Siren Nettingi (Caudata: Sirenidae), Using Scanning Electron Microscopy, S.E. Trauth

Journal of the Arkansas Academy of Science

I investigated the ultrastructure of the biflagellated spermatozoon of the Western Siren, Siren nettingi, using scanning electron microscopy from salamanders collected in northeastern Arkansas. My primary goal in this study was to reveal the general morphology of the distinctive sperm cell components (two axonemes, two undulating membranes, and two axial fibers), which run nearly the entire length of the spermatozoon. These remarkable gamete structures are found in members of the salamander family Sirenidae and do not conform to spermatozoal ultrastructure of any other salamander species. Moreover, the biflagellated sperm are the end product of an extraordinary assemblage of complex maturation …

History And Distribution Of The Wood Stork (Mycteria Americana) In Arkansas, R. Tumlison, L. Serviss

Journal of the Arkansas Academy of Science

Wood Storks (Mycteria americana) were thought to be common visitors to Arkansas in the early 1900s, but observations declined mid-century. Surveys of citizen science data and other online sources indicate that numbers of unique observations and total counts of birds have increased since 2000. Storks do not breed here, but have been reported in 34 of 75 counties, and appear mostly in August and September. Birds apparently originate from Mexico. Number of observations have increased since 2016, but many of those observations include only a few birds rather than larger flocks.