Digital Commons Network^™

Crystal Structures Of Escherichia Coli Glucokinase And Insights Into Phosphate Binding, Joseph Andrews, Joshua Sakon, Chenguang Fan

Chemistry & Biochemistry Faculty Publications and Presentations

Here, we report the crystal structure of Escherichia coli glucokinase (GLK), which has phosphate bound in the cleft between the alpha and beta domains adjacent to the active site. A ternary complex consisting of GLK, glucose and phosphate is also reported in this work. Diffraction data were collected at 2.63 angstrom resolution for the phospate-bound form (R-work/R-free = 0.191/0.230) and at 2.54 angstrom resolution for the ternary complex (R-work/R-free = 0.202/0.258), both at 297 K. A B-factor analysis of the phosphate-bound GLK structure revealed consistently lower values for phosphate-interacting basic residues in the alpha 4, alpha 5 and alpha 9 …

The Role Of Androgen Receptor And B2/Alu Sine Rna Interaction In Hippocampal Dendritic Development, Troy A. Richter

Graduate Doctoral Dissertations

Once dismissed as “junk”, transposable elements have recently gained recognition for their regulatory roles, especially in the brain. During development, circulating androgens promote proper morphological development of hippocampal neurons. We and others have shown that murine B2 SINE RNA is a regulator in the rodent hippocampus. It is unknown, however, if B2 is necessary for the proper development of hippocampal neurons. This dissertation investigates the role of murine B2 in the development of primary hippocampal neurons in combination with androgen treatment. We first examined the role of ALU SINE and androgen receptor in a prostate cancer cell model and found …

Tradeoffs Between Elemental Homeostasis And Growth Govern Freshwater Phytoplankton Responses To Salinization, Samuel A.T. Dias, Clay Prater, Adriana Diaz-Delgado, Natalie A. Clay, Sally A. Entrekin, Michelle A. Evans-White

Entomology and Plant Pathology Faculty Publications and Presentations

Anthropogenic salinization resulting from road salt application can degrade aquatic environments by altering the structure and function of phytoplankton communities, ultimately reducing flows of resources through aquatic food webs. However, physiological mechanisms underlying taxon-specific responses to salinization are often poorly linked to higher-order ecosystem dynamics, limiting our ability to predict community responses to salinization. To this end, we tested hypotheses derived from Subsidy-Stress and Ecological Stoichiometry theory by growing two cosmopolitan genera, Dolichospermum (prokaryotic, cyanobacteria) and Scenedesmus (eukaryotic, green algae), across NaCl gradients and contrasting differences in their growth rates, degree of Na homeostasis, and cellular C : N : …

Exploring Fisheries Species Distribution Shifts In Response To Freshwater Inflow Through The Bonnet Carré Spillway Using Species Distribution Models, David T. May

Master's Theses

The Bonnet Carre Spillway (BCS) is a flood control structure on the Mississippi River (MR) ~52 km upstream of New Orleans. The BCS protects downstream communities from MR flooding by diverting floodwaters into Lake Pontchartrain when the MR exceeds 5.18m flood stage. Diverted waters flow east into the Mississippi Sound (MSS), introducing turbid, nutrient rich freshwater to the estuary before draining into the Gulf of Mexico. BCS openings have become much more frequent in the last decade, though little work has been done to explore the impact of the BCS on nektonic fisheries species. Here, a series of seasonal Maximum …

Assessment Of A Muscadine Grape (Vitis Rotundifolia) Mapping Population For Tolerance To Pierce’S Disease Pathogen Xylella Fastidiosa And Resistance To Black Rot Disease Pathogen Guignardia Bidwellii, Anushka Tennakoon

Master's Theses

Pierce’s disease (PD) and black rot disease cause severe economic losses for grape production under humid and warm conditions. Identifying resistance genes is crucial for controlling these disease by developing resistant cultivars. Muscadine grape (Vitis rotundifolia) cultivar ‘Pam’ has been identified to possess a high level of resistance to diseases. To elucidate the genetic basis of the resistance to the causal pathogens Xylella fastidiosa and Guignardia bidwellii in this cultivar, parents and 141 F1 individuals developed from open pollinated ‘Pam’ were evaluated for two seasons under natural disease pressure. The mapping population was genotyped using genotyping-by-sequencing (GBS) and …

Development Of A Machine Learning Framework For An Irrigation Decision Support System, Eric Wilkening, Derek M. Heeren, Yeyin Shi, Laila A. Puntel, Guillermo R. Balboa, Abia Katimbo, Kuan Zhang, Precious Nneka Amori, Bruno Lena

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Currently used irrigation scheduling techniques often require significant human intervention and are time consuming, particularly for variable rate irrigation. This research aimed to develop a conceptual framework that incorporates disparate data sources leveraging both mechanistic and machine learning (ML) approaches. The overarching objective is to utilize the growing availability of data and technology to manage irrigation more precisely, which will minimize negative impacts of irrigation on our water resources. An initial irrigation machine learning model was proposed and tested in this study as a key component of an edge-cloud computing and federated learning decision-making framework. The specific objectives were (1) …

Activation And Suppression Mechanisms Of The Nrg1 Helper Nlrs, Yu-Ru Wang, Ruize Zhang, Daowen Wang, Yong Wang, Zheng Qing Fu

Faculty Publications

No abstract provided.

Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy

Electronic Theses, Projects, and Dissertations

Hematopoietic stem and progenitor cells (HSPCs) quiescence is vital for the success of bone marrow transplantation, as it preserves long term self- renewal and prevents premature exhaustion (Takubo et al., 2013; Wilson et al., 2008). However, bone marrow transplant (BMT) failure remains a clinical challenge, often due to lack of long-term engraftment and insufficient stress reliance. Both of these characteristics are tightly linked to disrupted stem cell quiescence and metabolic imbalance (Anso et al., 2017; Vannini et al., 2016). One key player is S-phase kinase protein (SKP2), an E3 ubiquitin ligase that targets cell cycle inhibitors, like p27, for proteosome …

Multicenter Span Trial Of Fasudil In Ischemic Stroke, Takahiko Imai, Andreia Lopes De Morais, Xuyan Jin, Tao Qin, Jessica Lamb, Karisma A Nagarkatti, Mu-Hsun Chen, Ligia S B Boisserand, Rakesh B Patel, Mariia Kumskova, Anjali Chauhan, Krishnan M Dhandapani, Mohammad B Khan, Pradip K Kamat, Yanrong Shi, Suyi Cao, Basavaraju G Sanganahalli, Joseph B Mandeville, Patrick D Lyden, David C Hess, Enrique C Leira, Anil K Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Raymond C Koehler, Lauren H Sansing, Márcio A Diniz, Cenk Ayata

Children’s Nutrition Research Center Staff Publications

Background: The SPAN (Stroke Preclinical Assessment Network) is a confirmatory multicenter trial network to test cerebroprotective interventions in experimental acute stroke. In a first-of-its-kind trial, SPAN tested 6 interventions in a rodent model of transient focal ischemic stroke. Here, we report the efficacy of fasudil, an isoform-nonselective rho-associated kinase inhibitor, on primary and secondary outcomes in the SPAN trial.

Methods: Fasudil was administered at 10 mg/kg intraperitoneally every 12 hours for 6 doses starting 5 minutes before reperfusion in a 60-minute endovascular filament middle cerebral artery occlusion model. The active treatment arm (n=345) was compared with the pooled intraperitoneal and …

The Role Of The Jnk Gene In Ovarian Cancer Inflammatory Pathways, Tashoy D. Campbell

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Ovarian cancer, one of the leading causes of cancer-related deaths in women globally, presents a significant challenge due to its common late-stage diagnosis and chemoresistance (inability of the tumor to respond to drugs). The c-Jun N-terminal kinase (JNK) signaling pathway plays a crucial role in ovarian cancer progression, contributing to inflammation, tumor survival, metastasis, and chemotherapy resistance. This literature review examines the role of the JNK signaling pathway in ovarian cancer, with a focus on its role in inflammation, metastasis, and chemoresistance. JNK regulates key inflammatory cytokines, such as TNF-α and IL-6, which promote tumor growth and immune evasion. Moreover, …

Use Of Infrared Spectroscopy In Animal Studies: Aspects Of Health Science, Brian Manzanares

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Non-invasive imaging technologies, such as infrared thermography (IRT), near-infrared spectroscopy (NIRS), and fourier-transform infrared spectroscopy (FTIR) are revolutionizing the field of animal research by enabling real-time, stress-free assessment of physiological conditions. Such methods like these are align with the ethical standards of the 3Rs, replacement, reduction, and refinement-by reducing the need of invasive procedures while enhancing data quality and animal welfare. These methods can also provide critical insight into animal health, behavior, and stress responses without the need for invasive procedures or restraint, thereby minimizing harm and distress. This literature review will explore the practical applications of IRT, NIRS, and …

The Role Of Nicotine In Treating Neurodegenerative Diseases, Jacquelyn T. Deaton

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Neurodegenerative diseases have emerged as a critical medical challenge because they cause progressive neuronal death alongside structural or functional deterioration. Families, healthcare institutions, and affected individuals face significant challenges due to neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases, which impair both cognitive function and motor abilities. Researchers have found that nicotine in tobacco products is a compound with therapeutic potential. This literature review explores how nicotine interacts with neurodegenerative mechanisms, such as oxidative stress and inflammation, and assesses its potential neuroprotective effects in conditions like Alzheimer's and Parkinson's diseases. In the central nervous system, nicotine binds to the …

Computational Frameworks To Unravel The Immune Landscape, Shan He

Dissertations and Theses (Open Access)

Recent advances in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy, face challenges such as resistance and immune-related adverse events, partly due to our limited understanding of the immune signaling pathways. While high- throughput genomic data provide unprecedented resolution into these immune pathways, their full potential is limited by the lack of well-annotated, context-specific immune gene sets. To address this need, I developed a workflow to construct immune gene sets by integrating RNA- seq datasets and performing decomposition. Using this approach, I constructed 28 immune- specific gene sets from 83 bulk RNA-seq datasets and 12 Natural Killer (NK) …

Resolving Intra-Tumoral Heterogeneity Of Breast Cancer Using Single-Cell Multi-Omics, Yun Yan

Dissertations and Theses (Open Access)

Breast cancer is a highly heterogeneous disease characterized by diverse genetic, transcriptional, and epigenetic landscapes. Understanding how intra-tumoral heterogeneity (ITH) influences therapeutic response and drives tumor evolution remains a central challenge in cancer biology. Here, we leverage single-cell multi-omics technologies to dissect the cell states and gene expression programs underlying breast cancer heterogeneity, with a focus on triple-negative breast cancer (TNBC) and estrogen receptor-positive (ER+) breast cancer.

In the first part, we applied single-cell RNA sequencing and spatial transcriptomics to profile over 400,000 cells from 101 treatment-naïve TNBC patients. We identified 4 archetypes at the patient level and 13 metaprograms …

Use Of The Protein Misfolding Cyclic Amplification For Food Safety And Drug Discovery, Maria R. Benavente Garcia-Huidobro

Dissertations and Theses (Open Access)

Prion diseases are fatal neurodegenerative disorders caused by the misfolding of the normal prion protein (PrP^C) into its infectious form (PrP^Sc). While the zoonotic potential of chronic wasting disease (CWD) remains uncertain, the presence of prions in food products raises public health concerns. Additionally, therapeutic strategies for prion diseases remain limited. This thesis presents a methodological exploration of the Protein Misfolding Cyclic Amplification (PMCA) technique to address these challenges in two key areas: (1) detecting CWD prions in processed meats subjected to common cooking procedures, and (2) identifying potential anti-prion compounds through a high-throughput PMCA adaptation. …

Predicting Genetic Interactions Using Functional Interaction Networks, Iulia Veronica Gheorghe

Dissertations and Theses (Open Access)

Mapping genetic interactions is central to understanding cellular systems and identifying therapeutic vulnerabilities, particularly in the context of cancer. Among these interactions, synthetic lethality, where simultaneous loss of two genes is lethal but loss of either alone is tolerated, offers a powerful framework for selectively targeting tumor-specific dependencies. In model organisms like S. cerevisiae, comprehensive double-knockout screens have revealed detailed genetic interaction maps, enabling systems-level insights into pathway structure, gene function, and cellular organization. Replicating this achievement in human cells, however, is complicated by the scale and complexity of the human genome. Recent advances in genome-wide CRISPR knockout screening have …

Structural Functional Investigation Of Hap40, Amanda M. Solbach

Dissertations and Theses (Open Access)

STRUCTURAL FUNCTIONAL INVESTIGATION OF HAP40

Amanda Marie Solbach

Dissertation Advisor: Sheng Zhang, Ph.D.

Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene, resulting in a mutant huntingtin (mHTT) protein with an elongated polyglutamine tract. While the genetic basis of HD is well established, the mechanisms underlying mHTT toxicity and its impact on cellular function remain incompletely understood. Recent discoveries implicate Huntingtin-associated protein 40 (HAP40) as a critical regulator of HTT stability and intracellular function. However, the physiological and pathological significance of this interaction has not been fully explored.

This …

Investigating The Role Of The Lysine-Specific Demethylase 4c In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen

Dissertations and Theses (Open Access)

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell-like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared to non-neoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomics analyses revealed that loss of KDM4C in both human …

Long-Chain Fatty Acids Promote Candida Albicans Gut Colonization By Restructuring The Fungal Cell Surface, Musfirat Shubaita

Dissertations and Theses (Open Access)

Long-chain fatty acids promote Candida albicans gut colonization by restructuring the fungal cell surface

Musfirat Shubaita, BS

Advisory Professor: J. Christian Perez, Ph.D.

The yeast Candida albicans is a facultative anaerobe residing in the human digestive tract. Although fungal genetic determinants of mammalian host colonization have been identified, little is known about signals and molecules in the intestinal environment that influence C. albicans proliferation. Previously unpublished data from the Perez lab showed that oleic acid, one of the most abundant long-chain fatty acids in nature, promotes C. albicans colonization of the murine intestine. The goal of this research is to …

Studies Of The Mechanisms Of Reverse Signaling By Cd40l, Barbara M. Nassif Rausseo

Dissertations and Theses (Open Access)

CD40 ligand (CD40L) is a transmembrane protein expressed on activated CD4 T cells, traditionally known for its role in forward signaling by engaging CD40 on antigen- presenting cells to promote immune activation. While this pathway is well characterized, there is evidence that CD40L also mediates reverse signaling, acting as a signaling receptor on T cells which enhances T cell function. However, the extent, consequences, and mechanism of CD40L-mediated reverse signaling in CD4 T cells remain poorly defined. This dissertation investigates the mechanisms and effects of CD40L reverse signaling on T cell function using both primary human T cells and the …

Microbial Metabolite Regulation Of Microglial Ahr Signaling In Alzheimer’S Disease, Ghalya E. Alrousan

Dissertations and Theses (Open Access)

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaque accumulation, neuroinflammation, and cognitive decline. Recent evidence suggests that systemic factors, particularly the gut microbiota and its metabolites, play a significant role in shaping brain immune responses, including microglial activation. However, the mechanisms linking gut dysbiosis to microglial dysfunction in AD are poorly understood. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor responsive to tryptophan metabolites, has recently gained attention as a key regulator of neuroinflammation and microglial function. I hypothesize that the loss of beneficial microbial AHR ligands, specifically indole derivatives, during aging and AD …

Ecomorphological Diversification Of Tooth Complexity In The Oral Jaws Of Marine Teleostean Fishes, Keiffer L. Williams

All Dissertations

Teeth are essential biological tools that function as a direct interface between predator and prey, thus providing essential insights into the evolutionary history and ecological diversity of vertebrates. Historically, studies on vertebrate dentitions have been qualitative and focused on mammals. More recently, quantitative methods have been developed that can reliably measure tooth surface complexity. These methods have been applied across both mammals and saurian reptiles to test for correlations with diet, leading to the conclusion that herbivorous species generally possess higher overall tooth complexity than any other dietary group. Surprisingly, the relationship between tooth complexity and diet in the most …

From Cities To Ranches: Assessing Public Support For Jaguar (Panthera Onca) Conservation And Livestock Predation In Colombia, Luz Angelica Solano

All Dissertations

Jaguars are among the most emblematic large carnivores worldwide. Nonetheless, the species has declined by 25% in less than 25 years and their range has been reduced by 55%, approximately, primarily due to habitat loss from increasing agricultural development, retaliatory killings from human-jaguar conflict, and overhunting of their natural prey. Given the anthropogenic nature of these threats, developing effective coexistence strategies and public support for jaguar conservation are increasingly urgent for the continued persistence of this species. I conducted a scoping review to assess trends and gaps in the existing peer-reviewed literature, grey literature, and news articles related to human-jaguar …

Interactions Of Biorational And Synthetic Dmi Fungicides For Control Of Fruit Diseases, Johanna Wesche

All Dissertations

Biological fungicides are increasingly investigated as sustainable alternatives to synthetic fungicides in fruit crop protection. This dissertation examines the interactions between two commercial biological fungicides, Bacillus subtilis AFS032321 (Theia) and metabolites of Pseudomonas chlororaphis AFS009 (Howler EVO); and demethylation inhibitor (DMI) fungicides, with a focus on compatibility, synergistic potential, and resistance implications. In vitro assays revealed that commonly used DMI fungicides difenoconazole, metconazole, tebuconazole, and propiconazole inhibited vegetative growth of B. subtilis at concentrations above 50 µg/ml, whereas mefentrifluconazole promoted colony expansion. Under controlled conditions, lesion development on detached fruit was inhibited synergistically when Theia was combined with the growth-promoting …

Improved Rumen Microbiome Interpretation Via Empirical Filtration Derived From Known Mock Microbiomes, Wesley A. Tom

School of Biological Sciences: Dissertations, Theses, and Student Research

The rumen microbiome plays a critical role in ruminant health and performance. As a consequence, many studies investigate microbial community composition using 16S rDNA based sequencing. As such, data quality and data filtering are critical to accurately identify microbial community composition. In this study we use mock communities to empirically select data filtering parameters to reduce artifact populations and compared the effect of filtering using different bioinformatic pipelines using rumen bacterial community data. The filtering parameters identified provides consistent estimates of rumen microbial diversity, regardless of bioinformatic pipeline utilized and provides a more accurate view of microbiome structure and composition. …

The Effects Of Off-Season Evidence-Based Training Block Periodization Program On The Performance Of Soccer Athletes In A Di School: An Exploratory Study, Ibrahim F. Almughathawi

Electronic Theses and Dissertations

The investigators explored the effects of a two-year evidence-based block periodization strength training program on performance outcomes in NCAA Division I male soccer athletes. The investigators aimed to examine longitudinal changes in body composition, explosive strength, and match-play physical demands, as well as the associations between field-based performance assessment and GPS-derived metrics. Using a retrospective design, data were drawn from a research data repository for athletes who participated in a long-term sport science monitoring program under the same head coach and training conditions. Performance measures included vertical jump assessments (static and counter movement jumps under bodyweight and external load), isometric …

Orchestrated Architecture Dismantling: Borrelia Burgdorferi’S Coordinated Destruction Of Adaptive Immune Responses, Craig A. Land

Electronic Theses and Dissertations

Borrelia burgdorferi represents the most prevalent vector-borne bacteria in North America, affecting ~476,000 Americans annually yet persisting despite robust immune responses. This project reveals spirochetes target adaptive immunity through coordinated lymphatic colonization and precision immune dysregulation.

Using comparative host models (C57BL/6 vs. reservoir Peromyscus leucopus), we demonstrate lymph node colonization within 48-hours, with spirochetes exploiting LYVE-1-positive lymphatic structures as dissemination highways while avoiding the interior of follicular regions. Critically, we identify targeted CD4+ T-cell elimination in germinal center border zones at 21-DPI, precisely when these cells should be coordinating protective immunity. Concurrent upregulation of inhibitory receptor CD32b creates molecular …

Molecular And Clinical Insights Into Role Of Gper In Hepatocellular Carcinoma (Hcc), Hossain Ahmed

Theses and Dissertations

Metabolic dysfunction–associated steatotic liver disease (MASLD), encompassing stages from steatosis (MASLD) to steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma (HCC), is the most prevalent chronic liver disease worldwide, yet molecular markers of progression remain limited. The G protein–coupled estrogen receptor (GPER), a non-genomic estrogen receptor with metabolic and anti-inflammatory roles, emerges as a candidate regulator in hepatic pathophysiology. In this Dissertation thesis, we have delineated for the first time clinicopathological assessment of liver biopsies across MASLD stages revealing a robust inverse correlation between GPER expression and disease severity. Higher GPER levels in early MASLD associated with favorable metabolic and biochemical profiles, …

Yizhi Sun: Profile Of The Newest Chbc Faculty Member., Danna Jaimes-Fajardo, Jeremy J. Smith, Lutishoor Salisbury

University Libraries Faculty Publications and Presentations

Presents the research profile of Yizhi Sun, Assistant Professor, Chemistry and Biochemistry department. It highlights his research interests, education, and impact of his research.

Using Livestreaming Technology To Answer Novel Questions About The Behavior And Physiological Ecology Of The Prairie Rattlesnake (Crotalus Viridis), Max C. Roberts

Master's Theses

Recent advances in remote monitoring technology are opening up new opportunities for developing innovative natural history and biological research methodologies. In particular, the emergence of livestreaming camera technology has made recording remote video of wild and secretive animals much easier and made it possible to collect data at extremely fine temporal resolutions. In 2024, Project RattleCam launched a livestreaming camera at a Prairie Rattlesnake (Crotalus viridis) den in Colorado. The goal of this work was to study Prairie Rattlesnake behavior 24-7 throughout the species’ active season with minimal human disturbance. Additionally, I used this system to study the …