Molecular Biology Commons^™

Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo

Legacy Theses & Dissertations (2009 - 2024)

The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …

Artificial Intron Technology To Generate Conditional Knock-Out Mice, Amber N. Thomas-Gordon

Dissertations and Theses (Open Access)

Genetic engineering has been re-shaped by the invention of new tools in modern biotechnology in a way that offers precision and efficiency in modifying the genome at a single nucleotide level and/or allowing precise control of gene expression. Such gene manipulation brings about significant findings and revelations in comprehending more about embryonic development, cellular and physiological functions, and disease pathology. Current methods used to produce conditional knockouts have limitations on conditional allele placement and modification varies among genes in different organisms. Thus, a system for generating conditional alleles with fidelity remains a challenge. My goal was to examine an approach …

Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency, Deborah C. Ehie

Graduate Theses/Dissertations

Gene therapy is a very challenging field, especially with new emerging genetic disorders. Chitosan (CS), due to chitosan’s flexibility, biocompatibility, and biodegradability, has been of interest in the world of gene therapy especially as researchers are gravitating towards non-viral vectors due to the problems caused by viral vectors. Nevertheless, there are still issues regarding solubility, cellular uptake of cargos being transported in vitro or in vivo, increased cytotoxicity levels, as well as many other things that prevent chitosan from being an efficient gene delivery agent. Here I present five derivatives of chitosan, which were all modified with either triethylphosphonium …

In Ovo Administration Of Defined Lactic Acid Bacteria Previously Isolated From Adult Hens Induced Variations In The Cecae Microbiota Structure And Enterobacteriaceae Colonization On A Virulent Escherichia Coli Horizontal Infection Model In Broiler Chickens, Margarita A. Arreguin-Nava, Brittany D. Graham, Bishnu Adhikari, Melissa Agnello, Callie M. Selby, Xochitl Hernandez-Velasco, Christine N. Vuong, Bruno Solis-Cruz, Daniel Hernandez-Patlan, Juan David Latorre, Guillermo Tellez Jr., Billy M. Hargis, Guillermo Tellez-Isaias

Poultry Science Faculty Publications and Presentations

The effects of in ovo administration of a defined lactic acid microbiota (LAM), previously isolated from adult hens, in the cecae microbiota structure and Enterobacteriaceae colonization after exposure to virulent Escherichia coli during the hatching phase of broiler chickens were evaluated. Embryos inoculated with LAM showed a significant (P < 0.05) reduction of Enterobacteriaceae colonization at day-of-hatch (DOH) and day (d) 7. Furthermore, there was a significant increase in total lactic acid bacteria on DOH, body weight (BW) DOH, BW d7, and d0–d7 BW gain and reduced mortality d0–d7 was observed in the LAM group compared with that in phosphate-buffered saline (PBS) control. …

Investigating The Role Of Quaking In Antigen Uptake And Cross-Presentation By Dendritic Cells, Yating Li

Dissertations and Theses (Open Access)

Dendritic cells (DCs) are considered the most potent antigen presenting cells (APC) due to their superior capability of cross-presenting exogenous antigens to CD8⁺ T cell for strong adaptive immune responses. They internalize foreign antigens by phagocytosis, endocytosis or macropinocytosis, which are then processed in endosomal compartments and loaded onto MHC Class I molecules. However, the molecular mechanisms regulating exogenous antigen uptake and cross-presentation by DCs are not fully understood.

In this study, we discovered that an RNA-binding protein, Quaking (QKI) plays a pivotal role in antigen uptake by DCs. Our previous studies in neural stem cells and microglia have …

Elevated Cochlear Adenosine Causes Hearing Loss Via Adora2b Signaling, Jeanne Manalo

Dissertations and Theses (Open Access)

Over 538 million people in the world have been diagnosed with hearing loss (HL). Current treatments for the most common type of HL, sensorineural HL, are limited to hearing aids and cochlear implants with no FDA-drugs available. The hearing process demands an abundance of ATP and HL is often attributed to a disruption in this metabolic energy currency. Patients who lack adenosine deaminase (ADA), the enzyme that irreversibly metabolizes adenosine, have high levels of adenosine that yield severe health problems, including HL; however, the pathogenic mechanisms behind HL and adenosine remain elusive. Our lab has found a HL phenotype in …

Using Novel Mouse Knockout Models To Study The Roles Of Asm (Acid Sphingomyelinase) In The Regulation Of Multiple Stem Cell Compartments In Vivo, Amro Abdalla

UNLV Theses, Dissertations, Professional Papers, and Capstones

Acid Sphingomyelinase (ASM) is a lipid-modifying enzyme that breaks down sphingomyelin lipids into ceramide and phosphorylcholine. Genetic mutations in the human ASM gene leads to Niemann pick diseases (NPD) type A & B. In NPD type A, patients die between 1-2 years old due to severe neurological complications, while NPD type B patients live to adulthood but suffer from severe visceral organ complications. Type A is usually associated with complete inactivation of the ASM gene. The hallmark of NPD is Purkinje neuron (PN) death. PNs, the major neurons in the cerebellum part of the brain, regulate the balance and fine …

Dimerization Of The Notch Intracellular Domain Results In Distinct Signaling Activity, Jacob Jeffery Crow

Boise State University Theses and Dissertations

The Notch signaling pathway is a core component of multicellularity; enabling cells to directly communicate with both their neighbors and the surrounding microenvironment. These signals are translated directly through the Notch proteins, where a fragment of Notch transitions into the nucleus to act as a co-transcription factor, setting into motion a host of physiological responses. Commonly involved in pathways that define a cell’s identity and fate decisions, what appears to be a simplistic pathway instead exists in a state of high-tunability and strict control. Missteps in this pathway are generally embryonically lethal or lead to a suite of congenital disorders …

Transcriptional Control Of Virulence Genes In The Bacterial Pathogen Shigella Flexneri, Joy Asami Mckenna

UNLV Theses, Dissertations, Professional Papers, and Capstones

Shigella species, the causal agents of bacillary dysentery, use a type III secretion system (T3SS) to inject two waves of virulence proteins, known as effectors, into the human colonic epithelium to subvert host cell machinery. Transcriptional regulation of these virulence genes is controlled by the three-tiered VirF/VirB/MxiE signaling cascade. Of these, VirB has the largest regulon (~50 genes); however, VirB regulatory properties are poorly understood. To date, VirB is known to function to counter or 'anti-silence' transcriptional silencing mediated by the histone-like nucleoid structuring protein H-NS. To better understand VirB regulation, my colleagues and I chose to better define the …

A Novel Serpinb1 Single-Nucleotide Polymorphism Associated With Glycemic Control And Β-Cell Function In Egyptian Type 2 Diabetic Patients, Dina H. Kassem, Aya Adel, Ghada H. Sayed, Mohamed M. Kamal

Pharmacy

Aims: Serine protease inhibitor B1 (SerpinB1) is a neutrophil elastase inhibitor that has been proved to be associated with type 2 diabetes mellitus and pancreatic β-cell proliferation. In this study, we investigated 2 SERPINB1 SNPs, rs114597282 and rs15286, regarding their association with diabetes risk and various anthropometric and biochemical parameters in Egyptian type 2 diabetic patients.

Materials and Methods: A total of 160 subjects (62 control and 98 type 2 diabetic patients) participated in this study. Various anthropometric and biochemical parameters were assessed. Genotyping assay for the two SNPs was done using TaqMan genotyping assays. The association of rs15286 variants …

The Shape Of Metabolism: Mitochondrial Dynamics, Remodeling, And Bioenergetic Reprogramming In Disease, Carl Decker

KGI Theses and Dissertations

Mitochondria are dynamic, double-membrane bound hubs of bioenergetics, cell signaling, and redox balance that exist as an oscillating network of fused superstructures and smaller, single organelles. Importantly, their position at the junction of catabolic and anabolic metabolism connects these morphological fluctuations to larger cellular metabolic programs, which in turn have implicated mitochondrial dynamics in a number of disease states and a varied set of cell phenomena. For example, differentiation of memory t-cells is dependent on mitochondrial network morphology, and in particular on remodeling dynamics that yield fused mitochondrial assemblies favoring oxidative phosphorylation-driven metabolism. In contrast, many cancers have been shown …

Characterization Of The Overexpression Of The Native H+-Pumping Pyrophosphatase In The Microalga Picochlorum Soloecismus, Kimberly T. Wright

Biology ETDs

Microalgae are of interest for the creation of sustainable and cost competitive alternatives to petroleum-based fuels and chemicals. However, cultivation, extraction and processing of algal biomass requires improved yields to achieve economic feasibility. The advancement of microalgal biotechnology and various genetic engineering techniques allow the improvement of microalgae biomass for this purpose. Here, the characterization of the overexpression of the native vacuolar H+ pumping pyrophosphate (AVP1) in Picochlorum soloecismus was examined. AVP1 overexpression causes biomass increase in relevant plant crops. When overexpressed in this microalga it increases carbon storage in the form of starch in a closed laboratory photobioreactor. However, …

Novel Long Non-Coding Rna Cdlinc Promotes Nsclc Progression, Christina J. Moss

USF Tampa Graduate Theses and Dissertations

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide with a low 5-year survival rate of only around 21%. This low 5-year survival rate is due to two main reasons. First, NSCLC is often diagnosed at the later stages when it has already metastasized. Second, NSCLC is an incredibly diverse, heterogenous disease making it very hard to target the true molecular oncogenic drivers. New targets for personalized therapeutics are needed based on the expression status of each individual lung cancer tumor.

One way of looking for these new therapeutics is to begin by identifying the oncogenotype …

A Health Evaluation Of Gulf Of Mexico Golden Tilefish (Lopholatilus Chamaeleonticeps) And Red Snapper (Lutjanus Campechanus) Following The Deepwater Horizon Oil Spill, Kristina Leigh Deak

USF Tampa Graduate Theses and Dissertations

A lack of baseline heath indices for offshore Gulf of Mexico (GoM) teleosts complicated impact assessments of the Deepwater Horizon (DWH) oil spill. While measurement of contaminant levels in fish after a pollution event can document exposure, such data fail to provide meaningful information about how this contact affects an animal's physiology. Controlled exposure studies have highlighted the utility of biomarkers that may indicate deleterious, long-lasting effects of pollutant exposure on various life stages of fish, however, their extrapolation to wild-caught, non-model species is challenging. In an increasingly chemically-saturated environment, it can also be difficult to separate the influence of …

Dissecting The Cellular Control Of Septin Organization In A Global Cereal Killer, Nawaraj Dulal

Graduate Theses and Dissertations

Rice blast disease, caused by the filamentous fungus Magnaporthe oryzae, destroys sufficient rice each year to feed 60 million people, and is a serious threat to global food security. A wheat-adapted lineage of M. oryzae now poses threat to global wheat production. Rice blast disease is currently controlled using limited fungicides, and the emergence of fungicide resistance within M. oryzae populations is a growing concern. There is a pressing need to identify new classes of fungicides to control the disease, which requires better understanding of the basic biology of the pathogen. To establish disease, M. oryzae forms a specialized dome …

Investigation Of Multiphasic 3d-Bioplotted Scaffolds For Site-Specific Chondrogenic And Osteogenic Differentiation Of Human Adipose-Derived Stem Cells For Osteochondral Tissue Engineering Applications, Julia T. Oxford

Biomedical Research Institute Publications and Presentations

Osteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site-specific osteogenic and chondrogenic differentiation of human adipose-derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using …

Secretion Of Proteins And Antibody Fragments From Transiently Transfected Endothelial Progenitor Cells, Loree Heller, Reynald Thinard, Melanie Chevalier, Sezgi Arpag, Yu Jing, Ruth Greferath, Richard Heller, Claude Nicolau

Bioelectrics Publications

In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis, neuroinflammation can lead to blood-brain barrier (BBB) breakdown. After intravenous or intra-arterial injection into mice, endothelial progenitor cells (EPCs) home to the damaged BBB to promote neurovascular repair. Autologous EPCs transfected to express specific therapeutic proteins offer an innovative therapeutic option. Here, we demonstrate that EPC transfection by electroporation with plasmids encoding the reporter protein GFP or an anti-beta-amyloid antibody fragment (Fab) leads to secretion of each protein. We also demonstrate the secreted anti-beta-amyloid Fab protein functions in beta-amyloid aggregate solubilization.

Taxonomic And Genetic Diversity, And Pathogenicity Of Diaporthe Species Associated With Soybean, Fakhir Eraheem Hameed Al Shuwaili

Graduate Theses and Dissertations

Diaporthe species (anamorph: Phomopsis) are associated with a wide range of plant hosts as plant pathogens, asymptomatic endophytes, and saprobes. One of these hosts is soybean, which is one of the most important crops in U.S. agriculture. Several Diaporthe species cause important diseases on soybean in the U.S., and specifically in Arkansas. The taxonomy, genetic diversity, and pathogenicity of Diaporthe species associated with asymptomatic infection of soybean are rarely studied with accurate molecular tools. Therefore, this dissertation aimed to assess the diversity and boundaries of Diaporthe associated with soybean in Arkansas. Furthermore, pathogenicity and alternative lifestyles were assessed among Diaporthe …

Elucidating Collagen Degradation Synergy Between Col G And Col H From Hathewaya (Clostridium) Histolytica And Identifying Novel Structural Features In Hpt And Rec Domains From Vars Histidine Kinase In V. Alginolyticus, Perry Caviness

Graduate Theses and Dissertations

In this research the mechanisms by which Hathewaya (Clostridia) histolytica collagenases are secreted and work together to degrade collagens are investigated. While H. histolytica collagenases Col G and Col H have similar multi-domain structures the difference in number of and orientation of the domains hint that the two target different regions in collagen. Study small angle x-ray scattering (SAXS) was used to give a low-resolution envelope of full-length Col G and Col H and Col G/Col H non-catalytic domains bound to a collagen-like peptide (mini-collagen). SAXS derived envelopes along with structural information was used to tease out the mechanisms by …

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 …