Molecular Biology Commons^™

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …

Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff

Honors Scholar Theses

Mechanotransduction is the process by which a mechanical stimulus is converted to a cellular signal. This process is heavily influential of cell morphology, differentiation, and behavior. However, altered levels of mechanical stimuli are also found in many pathological contexts. For example, cancerous cells have stiffer surrounding tissue than healthy cells, and research suggests that this alters cell behavior and promotes metastasis. Despite these findings, the cellular processes behind these signaling alterations remain widely unknown. Understanding these cascades is critical, as involved proteins can give us a deeper understanding of the role of mechanotransduction, and certain proteins can potentially be targeted …

Dissecting Regulation Mechanism Of Interdomain Electron Transfer In Nitric Oxide Synthases, Huayu Zheng

Chemistry and Chemical Biology ETDs

Nitric oxide (NO) is generated by one of the three isoforms of mammalian NO synthases (NOSs), neuronal, endothelial and inducible NOS (nNOS, eNOS, and iNOS, respectively). Dysregulated NOS is implicated in pathologies of numerous severe diseases including Alzheimer and Parkinson’s diseases. Molecular mechanisms of NOS regulation, once fully understood, are potentially key targets for development of selective new pharmaceuticals for treating these diseases that currently lack effective treatments.

Despite recent developments, there are significant gaps in current understanding of the regulation mechanism of the FMN-heme interdomain electron transfer (IET), an essential step in NOS, by its key regulators such as …

Impact Of Cd82 Expression On Acute Myeloid Leukemia Chemosensitivity And Quiescence, Muskan Floren

Biomedical Sciences ETDs

Acute Myeloid Leukemia (AML) patients respond favorably to induction chemotherapy, however, long-term outcomes remain poor due to a high rate of chemoresistance and bone marrow minimal residual disease. To improve long-term patient outcomes, it’s critical to identify regulators of chemotherapy resistance in AML and develop therapies that are directed towards bone marrow resident AML cells. In Chapter 2, we uncover the impact of CD82 expression in AML response to chemotherapeutic treatment and the contribution of Protein Kinase C α (PKCα) and β1 integrin signaling in promoting p38 MAPK activation to support CD82-mediated AML cell survival. In Chapter 3, we …

Fluorescence Spectroscopic And Molecular Modelling Studies On The Molecular Interaction Mechanism Of Bromodeoxyuridine With Human Serum Albumin, Amira Adlin Roslan

Student Works (2020-2029)

The interaction of a nucleoside analogue, bromodeoxyuridine (BrdU) with human serum albumin (HSA) was studied to investigate the binding phenomenon and analyze the protein conformation upon BrdU binding. Multiple spectroscopic techniques, viz. intrinsic and three-dimensional (3-D) fluorescence, ultraviolet-visible (UV-Vis) absorption and circular dichroism (CD) spectroscopy along with molecular docking were used. A decrease in the Stern-Volmer constant (Ksv) with the increase in temperature suggested BrdU-induced quenching of protein fluorescence as static quenching and thus implied BrdU−HSA complex formation. This was also supported by UV-Vis absorption spectral results, showing hyperchromism in the absorption spectrum of HSA upon BrdU addition. Intermediate binding …

Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark

Publications and Research

The fungal cell wall serves as the interface between the cell and the environment. Fungal cell walls are composed largely of polysaccharides, primarily glucans and chitin, though in many fungi stress-resistant cell types elaborate additional cell wall structures. Here, we use solid-state nuclear magnetic resonance spectroscopy to compare the architecture of cell wall fractions isolated from Saccharomyces cerevisiae spores and Cryptococcus neoformans melanized cells. The specialized cell walls of these two divergent fungi are highly similar in composition. Both use chitosan, the deacetylated derivative of chitin, as a scaffold on which a polyaromatic polymer, dityrosine and melanin, respectively, is assembled. …

Implications Of Lysine Acetylation On The Enzymes Of The Tca Cycle, Sumana Venkat

Graduate Theses and Dissertations

The tricarboxylic acid (TCA) cycle is a central route for the energy production via oxidative phosphorylation and is ubiquitous throughout nature. Apart from playing a major role in energy provision, it is also essential for a wide range of physiological functions in any organism. Although an increasing emphasis is laid on the interlinking role of the cycle, its regulation and control are less very less understood. As the field progresses, the consequences of TCA cycle anomalies are shown to be tied to various cancers and other disorders. The matter becomes more complex when considering the varying functions of the isozymes …

Functional And Physiological Role Of Extra-Hypothalamic Corticotropin Releasing Hormone Neurons In The Nucleus Of The Hippocampal Commissure In Regulation Of Stress Response, Hakeem Kadhim

Graduate Theses and Dissertations

Corticotropin releasing hormone (CRH) neurons located within the paraventricular nucleus (PVN) are known to be involved in regulation of stress responses. Recently, CRH neurons were identified above the PVN within the nucleus of the hippocampal commissure (NHpC) that located in the septum. We hypothesized that CRH neurons in the NHpC play a critical role in the stress response due to their rapid activation and could be a part of the traditional hypothalamo-pituitary-adrenal (HPA) axis. The dissertation addresses the role of 1) CRH expressing neurons in the NHpC compared with those within the PVN utilizing two different stressors, food deprivation (FD) …

The Effect Of Epa And Dha On Skeletal Muscle Physiology And Energy Balance, Saeed Jebor Ghnaimawi

Graduate Theses and Dissertations

Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) supplementation commonly suggested during pregnancy confers many health benefits on offspring and more recently improves fetal BAT development and induces myoblast trans-differentiation into adiopocytes through activating PPARs expression. Embryonic myoblast is a highly flexible cell showing great capacity to change its phenotype into adipocyte in response to EPA and DHA supplementation in many in vitro models. However, a little is known about the identity of derived adipocytes, whether, they change into brown or white adipocyte, and in vivo evidence is still missing. Given that the myogeneis process is initiated at the mid of …

Comprehensive Survey Of The Litter Bacterial Communities In Commercial Turkey Farms, Bishnu Adhikari, Guillermo Tellez-Isaias, Tieshan Jiang, Brian Wooming, Young Min Kwon

Poultry Science Faculty Publications and Presentations

The importance of microbiota in the health and diseases of farm animals has been well-documented for diverse animal species. However, studies on microbiotas in turkey and turkey farms are relatively limited as compared to other farm animal species. In this study, we performed a comprehensive survey of the litter microbiotas in 5 commercial turkey farms in the Northwest Arkansas (H, M, V, K, and R farms) including one farm with positive incidence of cellulitis (R farm). Altogether 246 boot swabs were used for 16S rRNA gene profiling of bacterial communities. At phylum level, 11 major bacterial phyla (≥0.01%) were recovered. …

Population Structure Of A Federally Endangered Plant (Astragalus Jaegerianus Munz, Fabaceae) With Limited Range Using Microsatellites, Sueann Neal

Electronic Theses, Projects, and Dissertations

Studies on population genetics examine the relationship and effects of population structure, migration, gene flow and demographic history, and are therefore important in the conservation of endangered species. Astragalus jaegerianus, a critically federally endangered species found in a geographically restricted range is investigated to determine population structure and genetic variation. Previous research on A. jaegerianus focused on DNA sequence data for cpDNA and nrDNA showed no variation. Further research on A. jaegerianus utilizing AFLP’s on the whole genome indicated substantial gene diversity and population structure consistent with geographically widespread species. AFLP research is a cost-effective process to identify levels …

Calcium Dyshomeostasis In Neurodegeneration, Nicholas Emanuel Karagas

Dissertations and Theses (Open Access)

Neurodegenerative diseases, despite constituting a major and growing cause of mortality globally, have few effective treatments. In order to develop novel therapeutics to combat neurodegeneration, a better understanding of the molecular mechanisms underlying these diseases is needed. Neurons rely on Ca²⁺ to mediate many of their unique functions, and aberrant Ca²⁺ signaling has been broadly implicated in neurodegeneration. The goal of this dissertation is to delineate specific examples of Ca²⁺ dyshomeostasis that I have uncovered in Drosophila models of neurodegeneration.

I first define the role a neurodegeneration-associated mutation plays in perturbing presynaptic [Ca²⁺], which is …

Regulation Of In Vitro And In Vivo Hepatic Stellate Cell Activation By The Ayrl Hydrocarbon Receptor, Shivakumar Rayavara Veerabhadraiah

Boise State University Theses and Dissertations

Liver fibrosis is a pathological condition characterized by the excessive deposition of extracellular matrix material by activated hepatic stellate cells (HSCs). We recently reported that activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases HSC activation in vitro and in mouse models of experimental liver fibrosis. The goal of this project was to determine the mechanism by which AhR activation impacts HSC activation and the subsequent development of liver fibrosis. It is possible that HSCs are direct cellular targets for TCDD. Alternatively, TCDD could increase HSC activation indirectly by exacerbating hepatocyte damage …

Drivers Of Rickettsial Pathogen Transmission And Spillover In Local Tick Populations In Southeastern Virginia, Alexandra Cumbie

Biomedical Sciences Theses & Dissertations

Cases of spotted fever group rickettsiosis are becoming more prevalent in the United States. In Virginia, there are three human-biting ticks which are largely responsible for the spread of rickettsial pathogens and the increase in disease cases. These species include Dermacentor variabilis, Amblyomma americanum, and Amblyomma maculatum; all of which are vectors of rickettsial agents to vertebrate hosts. These species are sympatric as adults and have the potential to share large and small mammal hosts. Their interactions on and off host and their associated rickettsiae were the focus of this dissertation work. Amblyomma americanum is the vector …

Not Too Hot, Not Too Cold, But Moderately Variable: The Influence Of Environmental Variability On Coral Thermal Tolerance, Courtney Nicole Klepac

Biological Sciences Theses & Dissertations

Anthropogenic climate change is causing an increase in the frequency and severity of marine heat waves, resulting in declining health of coral reef ecosystems worldwide. Coral bleaching events – the breakdown in symbiosis between the coral host and their intracellular photosynthetic algae – are increasingly common in recent years and contribute to widespread losses in coral cover. However, bleaching and heat stress responses vary across spatial scales both within and among coral species. Coral populations native to highly variable environments can have greater bleaching resistance than corals from more stable habitats and corals transplanted into these variable reef sites can …

Prevention Of Chronic Inflammation By Targeting Macrophage Integrin Adb2, Cady Forgey

Electronic Theses and Dissertations

Macrophage integrin a_Db₂ promotes macrophage retention and accumulation within inflamed tissue, a key event in development of chronic inflammation. Recently, the P5 peptide was identified as a specific inhibitor for integrin a_Db₂ interaction with 2-(ω-carboxyethyl) pyrole (CEP), a ligand at inflammatory sites. This thesis aims to identify integrin a_D I-domain amino acids involved in binding P5 peptide and likewise to CEP. We propose that non-conserved, basic amino acids of the integrin a_Db₂ I-domain are responsible for binding to P5 peptide and likewise to CEP. Eight amino acids were analyzed by …

A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a very poor patient prognosis (5-year survival of ≤ 7%). While transcriptional profiling has aided in the classification of this disease into at least two broader subtypes, this alone has so far been insufficient to inform on more nuanced patterns of oncogenic dependency. We hypothesized that a more comprehensive and granular characterization of PDAC disease diversity is required to establish relevant context for targeted therapy. To this end, we sought to establish an integrated platform to: i) more comprehensively characterize differential oncogenic signaling across our tumor models, and ii) establish …

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations and Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

Sine Oculis Homeobox Homolog 1 (Six1) Plays A Critical Role In The Progression Of Pulmonary Fibrosis., Cory Wilson

Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia with a median survival time of 2-4 years after diagnosis. The alarming mortality rate is due to the lack of effective treatments. IPF is a chronic disease that is characterized by alveolar destruction due to increasing extracellular matrix deposition that leads to poor lung compliance, impaired gas exchange, and ultimately respiratory failure. Repetitive alveolar epithelial injury is a central process to the underlying pathology with injury to the type II alveolar epithelial cells (AT2) specifically being a key player in the pathogenesis of IPF. Recent studies have shown that …

Ionic Mechanism Of Lysosomal Function And Cell Metabolism, Jian Xiong

Dissertations and Theses (Open Access)

Two Pore Channels (TPCs) are endolysosomal ion channels that are permeable to sodium and calcium. Defects in TPCs have been implicated to impair vesicle trafficking, autophagy and cell metabolism control; however, the detailed mechanism remains largely unknown. In this study, I show that TPCs are critical for appropriate cargo delivery to the lysosomes and deletion of either TPC1 or TPC2 leads to delayed clearance of autophagosomes, resulting in enlarged lysosomes and accumulated contents inside the lysosomes. Cells with both TPC deleted also exhibit 50% reduction in lysosomal amino acids under normal culture conditions, leading to reduced homeostatic mTORC1 activation.

Glutamine …