Life Sciences Commons^™

Self-Organization Of Microtubule And Associated Protein Map65, Sumon Sahu

Dissertations - ALL

One of the most fascinating micron-scale structures in the biological world is the cell cytoskele- ton, with numerous components of different sizes, shapes, and geometries working together. How the local interactions of these macromolecules and polymers in nano-scale help self- organize into this higher-order micron-scale structure remains an open question in the field of biophysics. In this thesis, via a minimal two-protein in vitro system containing cytoskeletal fiber microtubule and associated protein MAP65, I try to address self-organization through passive entropic force mechanisms. I use techniques like protein purification, light microscopy, and image analysis to quantify my results. First, I …

Rooting For The Home Team: Arbuscular Mycorrhizas And Root Traits In Native And Invasive Woody Shrubs, Alexander Ebert

Dissertations - ALL

Exotic species invasions present a global issue that is expected to worsen with the extreme conditions brought about by global climate change and anthropogenic disturbance. Invasive plant species in particular exhibit ecological, economic, and cultural effects on contemporary issues such as biodiversity, ecosystem processes and global food security. Understanding the factors governing both the invasion process and the species that become invasive are important tools for lessening the impacts of plant invasion, as well as preventing future invasions. This dissertation focuses on belowground aspects of these invasive species, including linking arbuscular mycorrhizal fungi (AMF) to invader growth responses, investigating the …

A Common Garden Experiment Suggests Local Adaptation In Stomata Size But Not Stomata Density In Common Milkweed (Asclepias Syriaca), Alyssa Gundel

Undergraduate Theses and Capstone Projects

Local adaptation is a common process that occurs in organisms with wide geographic ranges to maximize fitness in different environments. One specific species that has been shown to have certain locally adapted traits is Common Milkweed, Asclepias syriaca. A handful of these traits include height, stem count, number of leaves, and length and width of the leaves. The size and density of stomata, the pores underneath the leaf used for gas exchange and transpiration, may also be influenced by environmental conditions; however, this relationship has not been studied in common milkweed. In order to analyze population-level differences in the density …

Functional Comparison Of Raw 264.7 Cells And Murine Bone Marrow-Derived Macrophages (Bmdm), Quinn Harker

Undergraduate Theses and Capstone Projects

RAW 264.7 cells are an immortalized line of mouse cells that are commonly used in immunological research. They will be used to compare against murine bone marrow-derived macrophages (BMDM) to see if the two lines of cells are experimentally comparable in basic inflammatory testing. A standard method of measuring cell activity is through the analysis of nitric oxide production, which can be accomplished using a Griess reaction. Cell counts will be standardized to account for differing growth rates between the two cell lines. A similar output of nitric oxide concentration as an indicator of cellular activity between the RAW 264.7 …

Understanding The Effects Of Therapeutic Horseback Riding On Functional And Behavioral Outcome In Autistic Children And Adolescents, Leigh-Anne Mccormick

Undergraduate Theses and Capstone Projects

Equine-assisted services (EAS) have been shown to provide a stimulatory environment that can improve functional motor skills and emotional well-being in individuals with autism spectrum disorder (ASD).

Effects Of Exercise On Fear Behavior In Zebrafish, Tyler Kuni

Undergraduate Theses and Capstone Projects

The experiment focuses on the behaviors of zebrafish when they are exposed to an environment that causes anxiety or fear behavior and how controlled amounts of exercise will affect the behaviors of the fish. Fearful behavior was measured by the activity level and area of the swimming during the fear conditioning process. We investigated whether the changes in activity level, areas of swimming in the tank, and depth of swimming in the tank were significant as well as if there was an interaction effect between the fear conditioning and our dependent variables. Zebrafish were randomly assigned to three groups: the …

Exploring Crypsis In Dolomedes, Joshua Nichols

Undergraduate Theses and Capstone Projects

Cryptic coloration and background matching are highly effective for some riparian spiders’ camouflage against detection by the human eye. Fishing spiders (genus Dolomedes, family Pisauridae), which are known to be cryptids, present anecdotal evidence of substrate specialization which suggest that these species may be adapted to specific microhabitats in riparian zones. Some of the semi-aquatic species of fishing spider utilize similar coloration to their riparian habitat and microhabitat choice has been previously documented. These characteristics increase effectiveness of their crypsis and could be explained by microhabitat specialization between two species. This project addresses which colors these spiders use, and explores …

An Observational Retrospective Study Of Adverse Events And Behavioral Outcomes During Pediatric Dental Sedation, Muhammad F Walji

Faculty, Staff and Student Publications

Purpose: The purpose of this study was to examine a university-based dental electronic health records (EHR) database to identify sedation-related adverse events (AEs) and assess patients' behavioral outcomes during routine pediatric dental sedations (PDSs) in a dental school clinic.

Methods: A database was screened for patients younger than 18 years old who had received dental sedation in 2019. The qualifying EHRs were then accessed and sedations were reviewed for AEs, which were categorized using a 12-point classification system and the Tracking and Reporting Outcomes of Procedural Sedation Tool. Patient behaviors were assessed using provider progress notes and categorized as presence/ …

Mechanisms Of Voltage-Gated Sodium Channel (Nav1.5) Regulation By Intracellular Fgfs, Paweorn Angsutararux

McKelvey School of Engineering Graduate Student Theses & Dissertations

Voltage-gated sodium channels (NaV) conduct the inward current responsible for the initiation and propagation of the electrical signals in myocytes and neurons, known as action potentials (AP). Precise regulation of cardiac NaV1.5 opening and closing is essential for maintaining a normal heart beat. A disruption of NaV1.5 function, especially of its inactivation after opening, results in inherited cardiac arrhythmias such as Long QT Type 3 (LQT3) syndrome. This pathology is caused by an increase in the late INa that enters myocytes later in the AP and prolongs its duration. Late INa is also enhanced in acquired diseases such as heart …

Validation, Categorizing, And Prediction Of Upper Limb Outcomes After Stroke, Jessica Barth

Arts & Sciences Graduate Student Theses and Dissertations

The incidence and costs of stroke in the United States are projected to rise over the next decade because of the aging population. Declining stroke mortality over the past few decades means that more people survive stroke and live with physical, cognitive, and emotional disability. Stroke remains one of the leading causes of disability in the United States because very few survivors experience a full recovery of their upper limb. Upper limb recovery after stroke is critical to performing activities of daily living and physical and occupational therapies are one of the only treatment options to address these challenges. The …

Progress In Research On Site-Specific Nutrient Management For Smallholder Farmers In Sub-Saharan Africa, P. Chivenge, S. Zingore, K. S. Ezui, S. Njoroge, M. A. Bunquin, A. Dobermann, K. Saito

All Peer-Reviewed Publications

Increasing fertilizer access and use is an essential component for improving crop production and food security in sub-Saharan Africa (SSA). However, given the heterogeneous nature of smallholder farms, fertilizer application needs to be tailored to specific farming conditions to increase yield, profitability, and nutrient use efficiency. The site-specific nutrient management (SSNM) approach initially developed in the 1990 s for generating field-specific fertilizer recommendations for rice in Asia, has also been introduced to rice, maize and cassava cropping systems in SSA. The SSNM approach has been shown to increase yield, profitability, and nutrient use efficiency. Yield gains of rice and maize …

Lintul-Cassava-Npk: A Simulation Model For Nutrient-Limited Cassava Growth, J. G. Adiele, A. G.T. Schut, K. S. Ezui, K. E. Giller

All Peer-Reviewed Publications

A solid understanding of the dynamics of plant nutrient requirements and uptake from the soil is needed to provide robust fertilizer recommendations, timing of applications and nutrient use efficiency. Our objective was to develop and test the ability of the crop model LINTUL-Cassava-NPK to simulate biomass growth and yield of cassava under nutrient-limited conditions. We used experimental data from six fields located in three different agro-ecologies in Nigeria: Rainforest Zone– Ogoja and Ikom (Cross River), Rainforest Transition Zone – Ekpoma (Edo) and Guinea Savanna Zone – Otukpo (Benue) over two consecutive growing seasons from 2016 to 2018. Nutrient stress in …

Combining Computer Simulations And Deep Learning To Understand And Predict Protein Structural Dynamics, Michael D. Ward

Arts & Sciences Graduate Student Theses and Dissertations

Molecular dynamics simulations provide a means to characterize the ensemble of structures that a protein adopts in solution. These structural ensembles provide crucial information about how proteins function, and these ensembles also reveal potential drug binding sites that are not observable from static protein structures (i.e. cryptic pockets). However, analyzing these high- dimensional datasets to understand protein function remains challenging. Additionally, finding cryptic pockets using simulation data is slow and expensive, which makes the appeal of computationally screening for cryptic pockets limited to a narrow set of circumstances. In this thesis, I develop deep learning based methods to overcome these …

Functional And Anatomical Characterization Of Descending Periaqueductal Gray (Pag) Projections And Their Role In Pain Modulation, Jose Gabriel Grajales

Arts & Sciences Graduate Student Theses and Dissertations

Endogenous analgesic pathways embody a potential target for the development for chronic pain therapies. Previous studies have demonstrated the role of the ventrolateral periaqueductal gray (vlPAG) in descending pain modulation. It has been proposed that tonic GABAergic neurotransmission at the level of the vlPAG serves to inhibit efferent excitatory projections that mediate descending analgesia. Disinhibition of these projection neurons allows subsequent activation of rostral ventromedial medulla (RVM) neurons that inhibit nociception at the level of the spinal cord. However, lack of cell-type specificity in these studies has prevented the determination of the role of specific subsets of vlPAG neurons in …

Candida Species And Bacterial Strains In The Vaginal Microbiome, Brett Tortelli

Arts & Sciences Graduate Student Theses and Dissertations

The vaginal environment is a dynamic ecosystem, hosting various microbial species from diverse taxa including bacteria, fungi and viruses. The composition of bacteria within the vaginal microbiome has gained a lot of recent attention and has been associated with reproductive health and disease. The vaginal microbiome of healthy reproductive-aged women is frequently dominated by Lactobacillus species and has low species diversity when compared to other anatomic sites. The composition of the bacterial community is often described in terms of five common community types. Four of the five community types are dominated by a single Lactobacillus species (L. crispatus, L. iners, …

Macrophage Proliferation Machinery Drives Immunosuppression And Pdac Progression (巨噬细胞增值机制抑制肿瘤免疫促进胰腺癌发展), Chong Zuo

Arts & Sciences Graduate Student Theses and Dissertations

Tumor-associated macrophages (TAMs) are abundant in near all solid tumors and are involved in many aspects of cancer progression. The presence of TAMs is negative prognostic indicator in several cancer types including pancreatic cancer. Attempts to target this population by limiting their number in PDAC tumors have not achieved promising results, as compensatory resistance pathways have already been defined. The heterogeneity of TAMs puts another barrier into this targeting strategy, given macrophage subsets are important in maintaining tissue homeostasis and some in performing anti-tumor functions. Previous studies have shown that TAMs in PDAC tumors have dual origins – HSC-derived and …

Molecular Characterization Of Integrase-Rna Interactions And Their Role In The Replication Of Hiv-1 And Other Retroviruses, Christian Shema Mugisha

Arts & Sciences Graduate Student Theses and Dissertations

HIV-1 integrase (IN) enzyme has an emerging non-catalytic role in particle maturation, whichinvolves its binding to the viral genome in virions. Allosteric integrase inhibitors (ALLINIs) and class II integrase substitutions inhibit the binding of IN to the viral genome and cause formation of eccentric non-infectious HIV-1 particles. These viruses are characterized by the mislocalization of the viral ribonucleoprotein complexes between the translucent conical CA lattice and the viral lipid envelope. We have previously demonstrated that IN binding to the viral genome is mediated by basic residues within the C-terminal domain of IN. In the first chapter, we show how basic …

Characterizing The Role Of Interferons In Host-Microbe Interactions In Disseminated Murine Norovirus Infection And Steady-State Hematopoiesis, Forrest Walker

Arts & Sciences Graduate Student Theses and Dissertations

Interferons are critical cytokines responsible for regulating host-microbe interactions in the context of infectious disease as well as homeostatic interactions with the host’s native microbiota. Although significant knowledge regarding the role of interferons in these interactions has been gained in the past sixty years, the diversity of microbes with which the host interacts and the plethora of interferons (with over twenty distinct cytokines organized into three types, based on their receptor utilization) which the host uses in these responses leads to a significant number of interactions which remain to be characterized. Here, we further dissect the role of interferons in …

Antigen Presentation In Central Nervous System Antitumor Immunity, Jay Aaron Bowman-Kirigin

Arts & Sciences Graduate Student Theses and Dissertations

Glioblastoma multiforme (GBM) patients face limited treatment options and poor outcomes. The median survival is less than two years, and there are no FDA approved immune therapies. Although GBM itself is an immune-suppressive, heterogeneous tumor, the lack of FDA approved immune therapies might be in part because the cancer immunity cycle is less well understood for GBM than for other tumor types. My studies focused on developing mouse models of malignant glioma that more faithfully recapitulate human GBM from an immunologic perspective, and on defining the role of the conventional dendritic cell 1 subset (cDC1) and lymphatic drainage in central …

Regulation And Function Of Integrin Β3 In Bone-Metastatic Breast Cancer Cells In The Therapeutic Setting, Gregory Chandler Fox

Arts & Sciences Graduate Student Theses and Dissertations

Breast cancer is the most common non-cutaneous malignancy in women, with over 250,000 patients diagnosed each year in the United States alone. The bone is the most common site of recurrence in breast cancer, affecting over two-thirds of patients with metastatic disease and presenting as the only evidence of distant spread in up to 30%. Clinically, breast cancer bone metastases manifest most often as profoundly osteolytic lesions that negatively impact survival and patient quality of life. Bone-targeted therapies such as bisphosphonates and the anti-RANKL monoclonal antibody denosumab have revolutionized the treatment of bone metastases through inhibition of osteoclast-mediated bone destruction; …

Dnmt3a Regulates Hematopoietic Stem Cells Via Dna Methylation-Independent Functions, Won Kyun Koh

Arts & Sciences Graduate Student Theses and Dissertations

Hematopoiesis is strictly regulated to sustain blood production throughout adult life. De novo DNA methyltransferase 3-alpha (DNMT3A) is one of the major epigenetic regulators found to have an essential role in hematopoietic stem cell (HSC) differentiation. DNMT3A mutations are prevalent in myeloid diseases and malignancies that include acute myeloid leukemia (AML; ~22%), myelodysplastic syndrome (MDS; ~10%), and myeloproliferative neoplasm (MPN; ~8%). Importantly, DNMT3A mutations are not only the founding events of HSC malignant transformation, but they are also occurring as pre-leukemic lesions. Therefore, it is necessary to evaluate the molecular changes that occur in DNMT3A mutant HSCs, and how those …

Unraveling Population Heterogeneity Using Single-Cell Analysis, Wenjun Kong

Arts & Sciences Graduate Student Theses and Dissertations

The human body contains approximately 100 trillion cells, encompassing distinct cell types that serve diverse functions. Understanding cell population heterogeneity is vital for uncovering different biological functions and mechanisms. In addition, cells at transition during continual processes, such as development, reprogramming, and disease, are essential for painting the entire blueprint and highlighting critical stages of the progression trajectory. For instance, cell fate engineering holds much promise for generating clinically valuable cell types from mature somatic cells. Nonetheless, current reprogramming protocols are inefficient, and charting the changes in cell identity during such processes can help design strategies to mitigate the off-target …

Techniques For Spatial Analysis Of C. Elegans Anatomy And Reporter Expression, Nicolette Marie Laird

Arts & Sciences Graduate Student Theses and Dissertations

Quantitative analysis of microscopy images is integral to investigating biological phenomena. Despite a variety of tools to aid in analyzing C. elegans images, quantitative microscopy studies are still difficult due to the flexible and deformable nature of the nematode. These differences in posture and shape must first be corrected before analysis. Manual approaches to solve these problems are time intensive and infeasible for large datasets. Additionally, current automated tools rely on high-magnification imaging using labeled nuclei as fixed markers for comparison. Labelling can be achieved either with transgenic animals or fluorescent dyes; however, both of these can be impractical for …

The Role Of Soxe Transcription Factors In Melanoma Initiation, Eva Tulchinsky Kramer

Arts & Sciences Graduate Student Theses and Dissertations

Cutaneous melanoma, a cancer of transformed melanocytes, has the highest mortality rate among skin cancers and remains difficult to treat once metastasized. Melanoma is characterized by high genetic heterogeneity, implicating epigenetic dysfunction as an additional regulator of oncogenesis. Indeed, an increasing number of epigenetic modifiers and modifications have been identified in melanoma linked to faster melanoma onset, and then targeted with therapeutics with success. Thus, identifying and mechanistically characterizing these epigenetic and transcriptional alterations in melanoma will further our understanding of their contributions to oncogenesis and enable more diverse therapeutic options. To evaluate global epigenetic and transcriptional differences between melanocytes …

T Cell Regulation Of Regenerative Environment In Acellular Nerve Allograft Repaired Peripheral Nerves, Deng Pan

Arts & Sciences Graduate Student Theses and Dissertations

Peripheral nerve injury (PNI) is common and has debilitating long term sequelae. Development of new therapies to improve regeneration following PNI is therefore critical. Acellular nerve allografts (ANAs) are increasingly utilized in the clinic for the repair of PNI and an improved mechanistic understanding of nerve regeneration through ANA is important for developing better therapies. Inflammation is an important aspect of regeneration, and the role of macrophage has been increasingly documented. Other aspect of inflammation has not been well-defined. In particular, there is limited understanding on the role of T cells in the regeneration of peripheral nerve. However, evidence in …

Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene

Arts & Sciences Graduate Student Theses and Dissertations

Alzheimer’s disease (AD) is the leading cause of dementia and is pathologically defined by the aggregation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Rare heritable mutations within the genes for amyloid precursor protein (APP) and presenilin 1 (PSEN1), and presenilin 2 (PSEN2) cause early onset AD and account for approximately 1% of AD cases. While the majority of AD cases are late-onset (LOAD), which is defined by a markedly more complex genetic architecture that is comprised of many genetic risk factors that influence AD through multiple cellular pathways. The advent of deep sequencing analyses have allowed for the identification …

Vcp: A Gatekeeper For Intracellular Proteopathic Seeding, Jiang Zhu

Arts & Sciences Graduate Student Theses and Dissertations

Protein inclusions such as β-amyloid, tau, α-synuclein, and TDP-43 are considered the pathologic hallmarks of many neurodegenerative diseases. These proteins are prone to misfold, aggregate, and template new aggregates. Accumulating evidence suggests that those proteins in their high-molecular-weight forms can serve as a "seed", spread through an interconnected brain network, and induce new inclusions. Therefore, it is essential to understand the mechanism of proteopathic seeding. In this dissertation, we performed a whole genomic CRISPR-Cas9 KO screening to identify gene modifiers of αS seeding. Within the screening, we found several hits of endolysosomal function and trafficking, including VCP. VCP is a …

The Role Of Fibroblast Growth Factor-9 In Influenza A Virus Pathogenesis, Bradley Edward Hiller

Arts & Sciences Graduate Student Theses and Dissertations

Influenza A virus (IAV) is a respiratory virus in the Orthomyxoviridae family which causes both seasonal epidemics and pandemics. IAV preferentially infects epithelial cells in the upper and lower respiratory tract, resulting in a range of disease severity from mild upper respiratory infections to potentially-lethal pneumonia. Ultimately, the severity of symptoms and complications from IAV infection depends on control of virus replication in the lungs, the inflammatory nature of the immune response, and the effectiveness of post-infection lung repair to regain pulmonary function. An arsenal of secreted proteins in the lung regulates these antiviral, inflammatory, and regenerative activities during infection, …

Control Of Intestinal Turnover And Cell Death Through Canonical Autophagy Pathways Within Mouse And Human Epithelia, John Steven Ekman

Arts & Sciences Graduate Student Theses and Dissertations

Regulation of epithelial turnover is essential for the maintenance of the structure and function of the intestine. The balance of intestinal epithelial turnover is known to be modulated by cell-extrinsic cytokines such as Tumor Necrosis Factor (TNF). Likewise, cell-intrinsic modulation of survival and death is afforded by a highly-conserved, multi-step pathway termed autophagy. In this body of work, I have characterized a specific and potent role for autophagy in protecting mouse intestinal epithelial cells (enterocytes) from TNF-triggered cell death. Specifically, I have found that the autophagy initiation factor Atg14 is central to mediating this protective role. Utilizing conditional loss of …

Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough

Arts & Sciences Graduate Student Theses and Dissertations

The overall goal of this dissertation is to gain a better understanding of how current Alzheimer disease pathologic progression models interact with sources of individual-level variation in pathology to influence overall disease progression in a clinically meaningful way. Many sources of variation, both internal (e.g., genetic mutations, heterogeneity of tau pathology) and external (e.g., diet and exercise, sleep quality), are known to influence disease progression and symptom onset in AD. With the advent of therapies that have shown successful reduction of amyloid load in trials and the rapid progression of anti-tau therapies, we hypothesize that a better understanding of how …