Digital Commons Network^™

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 …

Fluorescent-Based Approaches For Quantifying Bacterial Transcription Initiation Kinetics, Drake Jensen

Arts & Sciences Graduate Student Theses and Dissertations

All cellular life depends on the precise regulation of its genome to adapt to environmental changes. This thesis focuses on exploring gene expression mechanisms at the level of transcription. Transcription is the process in which the enzyme RNA polymerase (RNAP) uses DNA as a template to generate nascent RNA. RNAP first binds to a regulatory sequence within the DNA called a promoter. The combined processes that occur at the promoter define transcription initiation, including promoter binding, promoter opening around the transcription start site, and initial synthesis of short RNA transcripts. Once RNAP escapes the promoter, it elongates the initial RNA …

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

Arts & Sciences Graduate Student Theses and Dissertations

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

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)5 years). We compared somatic mutations, …

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

Faculty, Staff and Students Publications

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

Sleep Duration Is Associated With Caudate Volume And Executive Function, Nicole Jones

Honors Theses

The ineligible role of the caudate nucleus in sleep has been implicated throughout multiple scientific studies. Previous literature has shown that greater caudate volume is associated with longer habitual sleep duration in older adults- ranging from 55 years of age and up. However, the association between sleep duration and caudate volume remains unknown in the younger population. In this study, we examined the caudate volume in youth to older adults (10 to 85 years old) with a greater sample size (N=464) to increase statistical power. The volumetric size of the caudate nucleus showed significantly positive association with habitual sleep duration, …

An Analysis Of The Sensory Characteristics And Microbial Constituents Of Kefir, Katherine Quay Robinson

Honors Theses

Kefir is a fermented beverage produced using sugar water or milk, kefir grains, either water kefir grains or milk kefir grains, respectively, and microbial aggregates consisting of diverse bacteria and yeasts. As kefir and fermented beverages in general are increasing in popularity, research related to optimal sensory characteristics and consumer-approval is vital. Desirable sensory characteristics for kefir beverages include low sour taste/aroma, high sweetness, carbonation, and high viscosity (Surja et al., 2019; Margareth et al., 2020). Production methods of kefir can alter sensory characteristics, but sensory characteristics are likely strongly influenced by the microbial composition of the grains/product. Thus, an …

Population Dynamics And Habitat Use By Gray Bats In An Anthropogenically Altered Landscape, Haley Price

Electronic Theses & Dissertations

Habitat loss resulting from land use change is among the greatest threats to biodiversity. Yet, in some cases, imperiled wildlife species may benefit from anthropogenic disturbance. The expansion of urbanization, agriculture, renewable energy, and mining practices impact conservation efforts for threatened and endangered bat species, and particularly species that are affected by white nose syndrome (WNS). The federally endangered gray bat (Myotis grisescens) is a cavernicolous species that is susceptible to WNS. Due to their unique roosting and foraging requirements, gray bats inhabit a small portion of the accessible caves within their geographic range. As habitat loss persists, …

The Effect Of Shrub Cover On Conifer Water-Use Patterns, Growth, And Response To Climate Change In The Southern Sierra Nevada, Marissa Goodwin

Biology ETDs

As wildfires increase in size and severity, large areas of forest are undergoing substantial increases in shrub cover. In forests where water is the limiting resource, the partitioning of soil water between shrubs and trees may determine how shrubs affect tree growth and water-stress. We analyzed the δ²H and δ¹⁸O values of xylem water for two conifer species (Abies concolor and Pinus jeffreyi) and two shrub species (Arctostaphylos patula and Ceanothus cordulatus) to assess how shrub cover affects the water-uptake patterns of conifers in the southern Sierra Nevada. We found that growing …

Structure Of A Eukaryotic Cholinephosphotransferase-1 Reveals Mechanisms Of Substrate Recognition And Catalysis, Lie Wang, Ming Zhou

Faculty, Staff and Students Publications

Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic cell membranes. In eukaryotes, two highly homologous enzymes, cholinephosphotransferase-1 (CHPT1) and choline/ethanolamine phosphotransferase-1 (CEPT1) catalyze the final step of de novo PC synthesis. CHPT1/CEPT1 joins two substrates, cytidine diphosphate-choline (CDP-choline) and diacylglycerol (DAG), to produce PC, and Mg2+ is required for the reaction. However, mechanisms of substrate recognition and catalysis remain unresolved. Here we report structures of a CHPT1 from Xenopus laevis (xlCHPT1) determined by cryo-electron microscopy to an overall resolution of ~3.2 Å. xlCHPT1 forms a homodimer, and each protomer has 10 transmembrane helices (TMs). The first 6 TMs carve …

Assessment Of Natural Roost Availability And Artificial Roost Preference By Indiana Bats In Scott County, Kentucky, Shannon Kerry Howe

Online Theses and Dissertations

In addition to using natural roosts, Indiana bats (Myotis sodalis) form maternity colonies in artificial roosts such as rocket boxes and bark-mimic structures. However, few Indiana bat study systems contain multiple artificial roost types alongside natural roosting options. I sought to analyze roost use on a landscape with multiple roost types and determine the effects of reproductive condition on roost type and canopy closure selection. I also characterized the forest overstory composition and determined the quantity and quality of Indiana bat roosting habitat across the landscape. My field site was Veterans Memorial Wildlife Management Area (VMWMA) in Scott County, Kentucky, …

Role Of Fungal Arv-1 Protein In Sterol Metabolism And Pathogenicity Of The Chestnut Blight Fungus Cryphonectria Parasitica, Soumyadip Kundu

Theses and Dissertations

Intracellular sterol redistribution is an important step in the lipid homeostasis of organisms, a process directly linked to the organizational arrangement in the plasma membrane (PM) of cells. Previous studies in the budding yeast Saccharomyces cerevisiae have demonstrated that the ARV1 (ACAT-related enzyme-2 required for viability 1) protein is a major regulator of sterol transport from the endoplasmic reticulum to the plasma membrane, contributing to the structural organization of the PM, rendering it resistant to anti-fungal compounds as well as maintaining ER integrity. This study assessed the significance of ARV1 in the plant pathogenic fungus Cryphonectria parasitica (Cparv1) …

An Investigation Into Transcription Fidelity And Its Effects On C. Elegans And S. Cerevisiae Health And Longevity, Olivia S. Dinep-Schneider

Theses and Dissertations

mRNA molecules form an intermediate in the transfer of sequences from DNA to ribosomes in order to guide protein production. Errors can be introduced into mRNA, producing aberrant proteins which place a strain on cellular regulatory machinery, causing increased risks of apoptosis, cancer, and decreased fitness. These errors may be introduced due to decreased transcriptional proofreading capabilities, exposure to chemicals, or mistakes in RNA editing machinery. It is important to investigate these causes of transcription errors to better understand the long-neglected area of mRNA fidelity which has such significant impacts on our cellular functions. In this paper, it was determined …

Host-Acquired Virus Genes Support An Ancient Antiviral Role Of The Pirna Pathway In Dipterans, Rebecca Christian

Theses and Dissertations

Endogenous viral elements (EVEs) have been recently investigated as a source of transgenerational immune memory. These “viral fossils” are abundant in Aedes mosquitoes and partner with the host’s primary antiviral defense system, the RNA interference (RNAi) pathways. This partnership appears unique to mosquitoes, which encode an expansion of the Piwi endoribonucleases. To interrogate EVE-Piwi partnerships and their role in antiviral defense, I performed a comparative small RNA analysis of two naturally occurring EVE-virus pairs – one in the mosquito Aedes albopictus, and one in the midge Chaoborus americanus. Both express an EVE related to the nucleoprotein of their …

Locomotion And Life History In A Leaping Primate: Mechanics And Energetics Of Movement Throughout The Propithecus Lifespan, Nicholas Heslep

Masters Theses, 2020-current

Arboreal primates are typically altricial, exhibit long juvenile periods, and use dynamic locomotor behaviors that can be challenging and risky. Sifaka (Propithecus verreauxi) have particularly slow life histories for their size, with long juvenile periods, protracted reproductive careers, and long life spans. Slow somatic growth poses potential mechanical challenges for juvenile sifaka who use thigh-powered vertical clinging and leaping to follow group members during travel. I examined mechanical and energetic costs of movement in developing sifaka. I instrumented 8 wild sifaka (3 yearlings, 3 subadults, 2 adults) in 4 social groups with inertial sensors measuring tri-axial acceleration for …

The Response Of Microcystis And The Microbiome To Exogenous Hydrogen Peroxide, Bryan A. Puma

Masters Theses, 2020-current

Microcystis spp. produce prolific annual blooms in freshwater systems worldwide. The success of these blooms depends heavily on the Microcystis spp. overcoming environmental factors such as oxidative stress caused by reactive oxygen species (ROS) like hydrogen peroxide. Most Microcystis genomes do not contain many genes for responding to oxidative stress, including those that encode the enzyme catalase. Other cyanobacteria such as Prochlorococcus that also lack hydrogen peroxide degrading enzymes have been shown to benefit from partnerships with heterotrophic bacteria. Microcystis spp. may also receive similar benefits from heterotrophic bacteria in the phycosphere. To test this hypothesis, we examined the …

Characterizing The Effects Of Light On The Early Onset Photoreceptor Function Loss In Mucolipidosis Type Iv, Rebecca Cistulli

Masters Theses, 2020-current

Retinal degenerative diseases (RDD’s) are a diverse group of retinal disorders that cause visual impairment. While RDD prevalence is high, little is known about the molecular mechanisms underlying the pathogenesis within some of these disorders. Here we are trying to elucidate the molecular mechanisms that drive early onset photoreceptor function loss in the RDD, Mucolipidosis type IV (MLIV). MLIV is a lysosomal storage disorder that results from loss of function mutations in the MCOLN1 gene and leads to a disruption of autophagy. The MCOLN1 gene encodes a lysosomal cation channel called Trpml1. Based on previous data from our lab, we …

Understanding Context Dependent Responses To Climate Change In Arizona Tiger Salamanders (Ambystoma Mavortium Nebulosum), Kentrell Richardson

Masters Theses, 2020-current

Future emissions scenarios project climate change to increase average global temperatures by at least two ℃ in the next 50 years resulting in changes in local climate and causing increased variability within microclimates. Ectotherms are especially sensitive to climate change due to their dependence on environmental temperatures to regulate physiological functions. Changes in temperature are likely to impact thermally cued processes within amphibians and result in changes in variable magnitudes and directions within local populations.

Salamanders were placed in cups and partially submerged in a water bath and heated at a rate of ~0.27℃/ minute. Once salamanders were unable to …

Energy Homeostasis In An Extreme Vertebrate: Relationships Between Life-History Status And The Molecular Stress Response In Red-Sided Garter Snakes, Rysa Thomas

Masters Theses, 2020-current

Vertebrates experience diverse and unique life-history events, many of which are annual and energetically taxing. Energy is a limited resource and thus its careful budgeting is critical for successful transitions between life-history states and across the lifetime of a species. Glucocorticoids (GCs) regulate vertebrate energetics via partitioning of energy use and storage in metabolic tissues (liver, fat, muscle) and exert their effects through activation of two main receptor types, the glucocorticoid receptor (GR), responsible for mobilization of energy from storage tissues, and the mineralocorticoid receptor (MR), responsible for ion balance and osmotic homeostasis. Species adapted to extreme environments carefully balance …

Microglia Refine Early Multisensory Circuits In The Lateral Cortex Of The Inferior Colliculus In A Complement-Dependent Manner, Shaida Hamidi

Masters Theses, 2020-current

Microglia cells (MGCs), the resident macrophage of the brain, play a pivotal role in synaptic pruning of newly established circuits during early critical periods. Classical complement cascade signaling enables MGCs to identify unnecessary or underutilized contacts and specifically target them for removal and subsequent degradation. Such recognition and engulfment behaviors require receptor-ligand interactions, whereby “eat me” tags (complement component 3, C3) bind their cognate receptor (complement receptor 3, CR3) expressed on MGCs. Compromised complement signaling in certain systems results in under-pruning or unrefined map configurations, and is thought perhaps to underlie certain autism-related behavioral phenotypes (e.g. sensory hypersensitivities, decreased social …

Classic Iga-Vasculitis With Nephrotic Range Proteinuria - Rare Presentation In An Adult, Ella Teplitsky, Maryam Zafar, Abubakar Tauseef, Marissa Varghese, Joseph Thirumalareddy, Sunil Nair, Akshat Sood, Mohsin Mirza

Journal of Community Hospital Internal Medicine Perspectives

IgA vasculitis formerly known as Henoch-Schonlein Purpura is characterized by leukocytoclastic vasculitis and IgA immune complex in small vessels of the affected organ. IgA vasculitis can involve any organ system depending upon the deposition of the IgA immune complex. IgA vasculitis is a clinical diagnosis which manifest with abdominal pain, arthralgia/arthritis, palpable purpura, and kidney involvement. Occasionally, serum IgA levels or skin or kidney biopsy can help in confirming the diagnosis. Treatment is usually supportive, but studies have proved that prednisone or immunosuppressive agents can help in the prevention or progression of the disease. Hereby we present a case of …

A Deeper Understanding Of Noise Effects On Cetaceans, Jason N. Bruck

Faculty Publications

Recent research with cetaceans under human care is illuminating just how dolphins are affected by human-made noise both in terms of their ability to cooperate as well as their ability to habituate to such noise. This research is providing granular detail to regulators assessing the problems associated with anthropogenic effects and is highlighting a role for behavior/cognition research in conservation.

Sensor-Controlled Digital Game For Heart Failure Self-Management: Protocol For A Randomized Controlled Trial, Kavita Radhakrishnan, Christine Julien, Matthew O'Hair, Rachel Tunis, Grace Lee, Angelica Rangel, James Custer, Tom Baranowski, Paul J Rathouz, Miyong T Kim

Faculty, Staff and Students Publications

BACKGROUND: Heart failure (HF) is the leading cause of hospitalization among older adults in the United States. There are substantial racial and geographic disparities in HF outcomes, with patients living in southern US states having a mortality rate 69% higher than the national average. Self-management behaviors, particularly daily weight monitoring and physical activity, are extremely important in improving HF outcomes; however, patients typically have particularly low adherence to these behaviors. With the rise of digital technologies to improve health outcomes and motivate health behaviors, sensor-controlled digital games (SCDGs) have become a promising approach. SCDGs, which leverage sensor-connected technologies, offer the …

Exrna-Eclip Intersection Analysis Reveals A Map Of Extracellular Rna Binding Proteins And Associated Rnas Across Major Human Biofluids And Carriers, Emily L Laplante, Alessandra Stürchler, Robert Fullem, David Chen, Anne C Starner, Emmanuel Esquivel, Eric Alsop, Andrew R Jackson, Ionita Ghiran, Getulio Pereira, Joel Rozowsky, Justin Chang, Mark B Gerstein, Roger P Alexander, Matthew E Roth, Jeffrey L Franklin, Robert J Coffey, Robert L Raffai, Isabelle M Mansuy, Stavros Stavrakis, Andrew J Demello, Louise C Laurent, Yi-Ting Wang, Chia-Feng Tsai, Tao Liu, Jennifer Jones, Kendall Van Keuren-Jensen, Eric Van Nostrand, Bogdan Mateescu, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small …

An Argument For The Utilization Of Amphibian Stress As An Indicator Of Wetland Condition, Andrew W. Sisson

Honors College Theses

Traditional forms of rapid wetland condition assessments focus on foliage health, nutrient enrichment, chemical contamination, and surrounding land usage, often overlooking an evaluation of the animals living in the wetland. More intense assessments include the National Wetland Condition Assessment (NWCA) and indices of biotic integrity, which focus on community composition (e.g., diversity and species richness) and abundances. These indices require expertise in species identification and do not provide information about the animal’s fitness. Animal stress physiology, which generally correlates with measures used to quantify animal fitness (e.g., survival, reproduction, and body condition), may provide a complementary rapid assessment method aimed …

Smile For The Camera: Patterns Of Mammal Abundance In Great Hill Forest Through Four Years Of Camera Trapping, Alexander Gonatas

Honors Program Theses and Projects

Snapshot USA is a nationwide camera trapping project aiming to determine biodiversity and abundance of animal populations across all 50 states. Since 2019, participants have used camera traps to document wildlife every September and October, coinciding with animal activity patterns and North American academic year starts. Understanding biodiversity through long-term monitoring is an important topic to study, because the knowledge obtained can help track populations and better understand wildlife responses to disturbances. Since Snapshot USA participants use the same methods and trapping season, the information we collect can be directly compared to other Snapshot USA locations. At Great Hill Forest …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Consolidated Chamber Design And Protocol For Olfactory Conditioning Assay With Drosophila Melanogaster, Sasha Bronovitskiy, Andres Castillo, Michael Yan, Fang Ju Lin

Journal of the South Carolina Academy of Science

The olfactory conditioning assay is widely used in Alzheimer’s disease research to quantify learning and memory in Drosophila melanogaster. The assay tests ability to recall an aversive conditioned stimulus of scent paired with electrical shock when presented a choice between shock-associated and unrelated scents. The T-maze, a commonly used apparatus for olfactory conditioning assays, employs an elevator mechanism to transfer live flies from the shock-delivering training chamber to the scent selection point. This elevator mechanism is known to cause fly casualty. T-mazes are not commercially available and often difficult to reproduce. Other existing variations of olfactory conditioning apparatuses use …

Measuring Selenoprotein Content In False Map Turtles (Graptemys Pseudogeographica) Along The Missouri River, Ruby A. Hawks

Honors Thesis

Metals and metalloids are becoming more prevalent in lakes and reservoirs of South Dakota which are toxic and hazardous in high concentrations or when biomagnified through trophic levels. Selenium is of particular concern as it can bind into the structures of proteins in place of other elements, changing protein structure and function within affected organisms. Zebra mussels (Dreissena polymorpha) are an invasive filter-feeding metal-bioaccumulating species that are rapidly spreading upstream through the Missouri River. They can take up selenium and directly transfer it to higher trophic level taxa. False map turtles (Graptemys pseudogeographica) are a common …

Sex And Environmental Effects On Chemical Signals Of Gryllus Rubens, Marion Davis Creech Iii, Marion Davis Creech Iii

Honors College Theses

Many animals communicate with one another in the context of reproduction, utilizing different modalities. In some cases, more than one modality is used by the sender and receiver. Each modality can provide different sets of information, or function in a different context. Importantly, no matter the modality, the signals should be clearly distinguishable between males and females and need to be reliable even in the face of environmental changes.

In field crickets, there are two major modes of communication. For long-range communication, the males produce acoustic signals to attract females. At short-range, chemical communication involving cuticular hydrocarbons (CHCs) in males …