Digital Commons Network^™

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were …

Genetic Resistance To The Downy Mildew Pathogen And Breeding Towards Durable Disease Management In Spinach, Bazgha Zia

Graduate Theses and Dissertations

Spinach (Spinacia oleracea) is a self-pollinated, dioecious winter crop. Prevalent challenges to the production of spinach include disease pressure imposed by downy mildew, which is caused by Peronospora effusa (=P. farinosa f. sp. spinaciae [Pfs]). A total of 19 new races of P. effusa have emerged, imposing serious challenges to the disease management in spinach production. Accordingly, this study was designed to explore the genetic components for establishing the basis of durable disease resistance development against the downy mildew pathogen (P. effusa 13) in spinach, through the use of various genome engineering approaches.

Our results have led (Chapter 2) to …

Physiological And Molecular Responses Of Eurythermal And Stenothermal Populations Of Zostera Marina L (Eelgrass) To Climate Change, Carmen C. Zayas-Santiago

OES Theses and Dissertations

As CO₂ levels in Earth’s atmosphere and oceans steadily rise, varying organismal responses may produce ecological losers and winners. Increased ocean CO₂ can enhance seagrass productivity and thermal tolerance, providing some compensation for climate warming. However, the consistency of this CO₂ effect across populations of cosmopolitan species such as Zostera marina L. (eelgrass) remains largely unknown. This study analyzed whole-plant performance metabolic profiles and gene expression patterns of distinct eelgrass populations in response to CO₂ enrichment. Populations were transplanted from Nisqually Landing and Dumas Bay, two cold water environments in Puget Sound, WA (USA) that rarely …

Elucidating The Evolution And Function Of Srnas That Facilitate Bacterial Stress Tolerance, Madeline Claire Krieger

Dissertations and Theses

Non-coding small RNAs (sRNAs) are ubiquitous post-transcriptional regulators found in both gram-negative and gram-positive bacteria. Despite their integral role in many regulatory pathways, including those that facilitate stress-tolerance, little is known about the evolutionary forces that drive the emergence of novel sRNAs, how prevalent sRNAs are within bacterial species, or the functions of a majority of these transcripts. In this work, I first describe the evolution of OxyS, a well-characterized sRNA in gram-negative Enterobacteriaceae that is involved in coordinating the bacterial response to oxidative stress. Next, I identify novel sRNAs differentially produced by the gram-positive oral pathogen Streptococcus mutans in …

The Role Of Med31 And Med12 In Directing Adipogenesis Of Human Adult-Derived Mesenchymal Stem Cells, Joseph Straub

Master's Theses

Selective gene expression is crucial in maintaining the self-renewing and multipotent properties of stem cells. Mediator is a large, evolutionarily conserved, multisubunit protein complex that modulates gene expression by relaying signals from cell type-specific transcription factors to RNA polymerase II. In humans, this complex consists of 30 subunits arranged in four modules: head, middle, tail, and kinase. In our introduction, we show the state of the field of Mediator study with a focus on the critical kinase module. In the following chapters, we used siRNA knockdowns to investigate the roles of the highly-conserved core subunit MED31 and the kinase module …

Differential Gene Expression In Starvation Selected Drosophila Melanogaster, Katherine Schultz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Fruit flies that have been selected for starvation resistance can be used in experimental studies to study physiological processes. Both their genomes and their phenotypes, especially metabolism, change significantly as a result of artificial selection. Starvation selected flies develop slower and are larger due to higher lipid content as adults. We used RNAseq to study gene expression in third instar larval fat body tissue from selected and control lines at the same chronological time point, when the fed control (“FC”) lines were wandering, and the starvation selected (“SS”) lines were in the third larval instar but not yet wandering due …

The Role Of Med31 And Med12 In Directing Adipogenesis Of Human Adult-Derived Mesenchymal Stem Cells, Joseph Straub

Doctoral Dissertations

Selective gene expression is crucial in maintaining the self-renewing and multipotent properties of stem cells. Mediator is a large, evolutionarily conserved, multisubunit protein complex that modulates gene expression by relaying signals from cell type-specific transcription factors to RNA polymerase II. In humans, this complex consists of 30 subunits arranged in four modules: head, middle, tail, and kinase. In our introduction, we show the state of the field of Mediator study with a focus on the critical kinase module. In the following chapters, we used siRNA knockdowns to investigate the roles of the highly-conserved core subunit MED31 and the kinase module …

Identification Of Ires Activity In Cellular Mrnas And Viral Rna Using A Circular Rna Construct, Priyanka Sehta

Legacy Theses & Dissertations (2009 - 2024)

Translation initiation is a critical step in the process of protein synthesis. The canonical way of translation initiation involves ribosomes being recruited to the 7-methyl guanosine cap present at the 5’end of the untranslated region (5’ UTR) of the RNAs. However, viral RNAs and some cellular mRNAs lack this 5’ cap structure and thus deploy an alternate non-canonical translation initiation mechanism. In non-canonical translation initiation, ribosome recruitment is facilitated by the RNA secondary structures called Internal Ribosome Entry Site (IRES) present most often in the 5’ UTR. To measure IRES-mediated translation, the dual luciferase assay has been the gold standard. …

Mapping Genetic Variants Associated With Dynamic Protein Abundance In Haploid Yeast, Tanner Thuet-Davenport

WWU Graduate School Collection

As organisms respond to changes in their environment genetic variation between individuals can directly affect organismal trait phenotypes by altering gene expression. Historically, studies have focused on the effect of genetic variation on mRNA synthesis (transcription) and decay rates. Relatively few studies have probed the relationship between DNA variants and protein-specific regulation of individual genes, despite the plethora of evidence that RNA levels are often poor proxies for protein levels. No study to date has mapped genetic variation associated with dynamic protein levels. In this study we investigated the location and identity of genetic variants acting on protein expression dynamics …

Molecular Studies On The Interactions Between Biomphalaria Snails And Schistosoma Mansoni, Lijun Lu

Biology ETDs

Biomphalaria snails serve as vectors for Schistosoma mansoni, a trematode causing human schistosomiasis. Control of Schistosoma mansoni involves chemotherapy of affected people, but new control methods built on improved understanding of schistosome-snail interactions are needed. My dissertation applies molecular and bioinformatics approaches to understand such interactions. Chapter 1 shows that significant differences exist among Biomphalaria species in Africa with respect to their ability to support schistosome development. Chapters 2 and 3 reveal the transcriptional responses of Biomphalaria glabrata susceptible (SUS) or resistant (RES) to Schistosoma mansoni. Chapter 2 identifies a new family of snail immune factors, the AIG …

Functional Investigations Of Proteins And Enzymatic Toxins From Full-Length-Enriched Cdna Of Timber Rattlesnake (Crotalus Horridus), Joshua Osula

Theses

Snake Venom is a highly modified form of saliva, contains hundreds of zootoxins, necrotoxins, cytotoxins, neurotoxins, and mytotoxins, all of which are primarily made up of mostly proteins, polypeptides, and other components such as enzymes, lipids, and carbohydrates. Although snake venom is known for its harmful effects, it has also had a positive impact in scientific discovery and medicine. Some toxins from snakes function to inhibit pain, and this means they can be very effective analgesics. For instance, crotalphine is considered a 14-amino-acid-peptide that has a disulfide bond and shows analgesic properties through TRPA1 desensitization. This …

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) …

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

A Gene Expression Profile Associated With Successful Cns Axon Regeneration In Xenopus Laevis, Jamie L. Belrose

Legacy Theses & Dissertations (2009 - 2024)

Background: The South African claw-toed frog, Xenopus laevis, is uniquely suited for studying differences between regenerative and non-regenerative responses to CNS injury within the same organism, because some CNS neurons (e.g., retinal ganglion cells after optic nerve crush (ONC)) regenerate axons throughout life, whereas others (e.g., hindbrain neurons after spinal cord injury (SCI)) lose this capacity as tadpoles metamorphose into frogs. Tissues from these CNS regions (frog ONC eye, tadpole SCI hindbrain, frog SCI hindbrain) were used in a three-way RNA-seq study of axotomized CNS axons to identify potential core gene expression programs for successful CNS axon regeneration.

Environmental Influences On Expression Of Virulence- And Survival-Associated Genes And Epigenetic Modifications Of Dna In Vibrio Vulnificus, James W. Conrad

USF Tampa Graduate Theses and Dissertations

Vibrio vulnificus is an autochthonous inhabitant of warm, brackish coastal waters and is an opportunistic pathogen that causes the highest mortality of all seafood-related illnesses (1). These fatal infections are generally caused by the clinically-associated vcgC/16S rRNA type B genotypes within the biotype I group (2–5). However, the reasons for the heightened infectiousness of the clinically-associated strains over environmentally-associated ones remains elusive, as no unique clinically-associated virulence genes have been identified through genomic sequencing or other strategies. DNA methylation may contribute to regulation of virulence by affecting gene transcription, and was investigated in the highly virulent V. vulnificus strain CMCP6. …

Degradation Of Transcriptional Repressor Atf4 During Late-Phase Long-Term Potentiation, Spencer Smith

Biology Theses

Maintenance of long-term synaptic plasticity requires gene expression mediated by cAMP-responsive element binding protein (CREB). Gene expression driven by CREB can commence only if the inhibition by a transcriptional repressor ATF4 (activating transcription factor 4; aka CREB2) is relieved. Previous research showed that the removal of ATF4 occurs through ubiquitin-proteasome-mediated proteolysis. Using chemically induced hippocampal long-term potentiation (cLTP) as a model system, we investigated the mechanisms that control ATF4 degradation. We observed that ATF4 phosphorylated at Serine-219 increases upon induction of cLTP and decreases by about 30 min thereafter. Proteasome inhibitor β-lactone prevents the decrease in ATF4. We found that …

Exploring The Connection Between Acid Exposure And Virulence In Listeria Monocytogenes, Minghao Li

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Listeria monocytogenes is a gram-positive food-borne pathogen that is widely dispersed in the environment and can cause listeriosis with high fatality rates when consumed in contaminated food products. They are capable of growing over a wide range condition. Listeria is also able to tolerate adverse conditions which allows the bacterium to survive in unfavorable environments. The ubiquitous nature of L. monocytogenes makes it difficult to eliminate from food systems. One major problem in the food industry is the survival of L. monocytogenes under sublethal low pH-environment since organic acids are widely used as food decontaminants. Prior research has suggested that …

Changes In Gene Expression Profiles In Müller Glia Following Exposure To An Α7 Nicotinic Acetylcholine Receptor Agonist, Megan L. Stanchfield

Masters Theses

Previous studies from this lab have determined that dedifferentiation of Müller glia (MG) occurs after application of an α7 nicotinic acetylcholine receptor agonist, PNU-282987 (PNU), to retinal pigment epithelial (RPE) cells in adult rodents. This study was designed to explore the role of the HB-EGF/Ascl1/Lin28a signaling pathway in MG dedifferentiation to retinal progenitor cells. RNAseq was performed on MG following contact with RPE-J cells treated with PNU-282987. Up- or down-regulated genes were compared with published literature of MG dedifferentiation that occurs in lower vertebrate regeneration or with transcript profiles during early mammalian development. Between 8-12 hours, up-regulation was observed in …

Transcriptome Studies On The Toxicity Of Silica Nanoparticles, Shih-Yi Hsu

USF Tampa Graduate Theses and Dissertations

Nanotechnology enables more precise harmony in health condition via reducing the dosage amount, improving the delivery of hydrophobic drugs, more specific targeting to the cancerous sites, and so on. Nevertheless, issues regarding the toxicity of nanotechnology have begun to call for attention several decades later after the innovation of nanotechnology. Tools about risk management of nanotechnology have been developed, but recently not much evidence recognizes the toxicity of nanoparticles (NPs) except for some animal studies, which demonstrated organ damage after the exposure to NPs. Toxicogenomic approach refers to the method utilizing gene expression to evaluate the chemical toxicity. Databases as …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

Comparative Genomics Of Human Mesenchymal Stem Cells And Human Mesenchymal Stem Cells Derived Vascular Smooth Muscle Cells, Samia Ismail

Biomedical Engineering Undergraduate Honors Theses

As of 2017, vascular diseases contributed to 23.1% of all deaths in America. To address the need for more effective and sustainable treatment options for these ailments, stem cell differentiation and implantation has emerged as a viable alternative to standard bypass and graft insertions. A completely autologous treatment can be achieved by extracting adult stem cells, differentiating them into vascular smooth muscle cells (VSMCs), and then reimplanting these cells at the affected tissue site. This study aims to investigate the efficiency of the VSMC differentiation from human mesenchymal stem cells (hMSCs) by comparing 4 cell lines of untreated hMSCs with …

Developmental Regulation Of Sirtuin Genes In Broiler Chicks, Heather L. Winter

Chancellor’s Honors Program Projects

No abstract provided.

Investigating The Toxicology Of Intramuscular Injected Cnt-Ab In Mice Followed By Microwave Hyperthermia., Conner Clark

Honors College Theses

The advent of carbon nanotubes (CNTs) has led to a wide range of research in various fields including cancer therapy for targeting specific localized and site-specific treatment. Carbon nanotubes bound to tumor specific antibodies (Ab) offers specific treatment for cancer cells without affecting surrounding tissue. This treatment makes use of infrared absorptive properties of nanotubes to incinerate both the nanotube and its associated tumor in vivo. We seek to affirm the initial results of CNT in cancer therapy by investigating the toxicological effect in mice injected with CNT-Ab followed by microwave hypothermia. After 1-week post-injection, mice were sacrificed followed …

Pthr1/Sox9 And Idh1/Idh2 Relative Expression In Primary Chondrocyte And Chondrosarcoma Cells Under The Synergistic Influence Of Inducible Hypoxia And Extracellular Acidosis, Kostika Vangjeli

Biological Sciences Theses & Dissertations

Cartilage cells (Chondrocytes) grow in rather unique environmental conditions in the human body. Cartilage is avascular tissue and lacks innervation. Its main source of nutrients is derived from the synovial fluid and/or perichondrium. Consequently, these cells must survive and thrive under hypoxic and acidic stressors. Published data suggests that there are a multitude of genes affected from either one of these two stressors or both. However, these factors are frequently overlooked in cartilage research, and results are reported in either normoxia/pH=7.0 conditions, or they only account for one of the conditions. The scope of this study is to examine how …

Characterizing Adaptive Non-Coding Changes In The Regulation Of Human Gene Expression, Jason Pizzollo

Doctoral Dissertations

Differential patterns of gene expression contribute to phenotypic differences between species. Understanding evolutionary changes in gene regulatory elements can help explain traits that separate humans from closely related species. Here, in two separate studies, we investigate gene expression and gene regulatory differences between humans our closest living evolutionary relatives, chimpanzees, in the context of uniquely human traits: increased susceptibility to epithelial cancers and neural developmental and functional processes that underlie our increased cognitive capacity. Using genomic methods to study gene expression and open chromatin, we compare human and chimpanzee responses to a serum challenge, an assay that that mimics patterns …

De-Coding The Impact Of Evolved Changes In Gene Expression And Cellular Phenotype On Primate Evolution, Trisha Zintel

Doctoral Dissertations

The goal of the dissertation work outlined here was to investigate the influence of proximal processes contributing to evolutionary differences in phenotypes among primate species. There are numerous previous comparative analyses of gene expression between primate brain regions. However, primate brain tissue samples are relatively rare, and my results have contributed to the pre-existing data on more well-studied primates (i.e. humans, chimpanzees, macaques, marmosets) as well as produced information on more rarely-studied primates (i.e. patas monkey, siamang, spider monkey). Additionally, the primary visual cortex has not previously been as extensively studied at the level of gene expression as other brain …

Interspecific Gene Flow Potentiates Adaptive Evolution In A Hybrid Zone Formed Between Pinus Strobiformis And Pinus Flexilis, Mitra Menon

Theses and Dissertations

Species range margins are often characterised by high degrees of habitat fragmentation resulting in low genetic diversity and higher gene flow from populations at the core of the species range. Interspecific gene flow from a closely related species with abutting range margins can increase standing genetic diversity and generate novel allelic combinations thereby alleviating limits to adaptive evolution in range margin populations. Hybridization driven interspecific gene flow has played a key role in the demographic history of several conifer due to their life history characteristics such as weak crossability barriers and long generation times. Nevertheless, demonstrating whether introgression is adaptive …

Identification And Analysis Of Genes With Differential And Tissue-Specific Expression In Poplars, Bailey Mitchell

Masters Theses

Poplars have become one of the most frequently studied plant species for their applications in biotechnology, commercial benefits, and ecological importance. Microarray analysis is commonly used to analyze differential gene expression in many organisms. Investigations have examined differential gene expression and performed functional analyses on a single tissue or organ within poplar trees or a closely related set of tissues and organs, but usually do not broadly analyze gene expression across a large number of tissues and organs in poplar. This thesis work aims to generate data on the most differentially expressed genes for the major groups of tissues and …

Transcriptomic Profiling Of Postmortem Prefrontal Cortex And Nucleus Accumbens From Chronic Alcohol Abusers., Eric S. Vornholt

Theses and Dissertations

Alcohol use disorder (AUD) is a debilitating psychiatric illness that develops from a combination of genetic and environmental factors. While it is well documented that AUD is heritable, the shift from recreational alcohol use to abuse/dependence is poorly understood. In this dissertation, using postmortem brain tissue from individuals with alcohol dependence (AD), we profiled the genome-wide expression of circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) to better understand the impact of gene expression on the development of AUD. To achieve this, we performed two independent studies that explore transcriptome differences between AD cases and controls. The first of …

The Role Of Progesterone Receptor In The Postnatal Development Of The Dentate Gyrus And Episodic-Like Memory, Andrew James Newell

Legacy Theses & Dissertations (2009 - 2024)

The hippocampus is a critical structure for the encoding and retrieval of declarative memories in humans, including episodic-memories. In rodents the steroid hormone receptor progesterone receptor (PR) is expressed in the dentate gyrus (DG) of the hippocampus during the postnatal period, a key stage in development of DG cytoarchitecture and connectivity. During the first postnatal week, the main cortical input to the hippocampal circuit, the perforant path, innervates the molecular layer (MOL) of the DG and forms temporary initial synaptic connections with pioneer neurons. By the third postnatal week, long-term synapses have been established with granule cells, the principle neurons …