Cell and Developmental Biology Commons^™

Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap

Graduate Theses and Dissertations

Introduction: Muscle atrophy results from a dysfunction in protein turnover that leads to loss of mass and function and occurs concurrently with multiple pathologies such as cancer and extended bed rest. Atrophy reduces overall quality of life while increasing morbidity and mortality. Currently, efficacious therapeutic interventions to treat and prevent muscle wasting in all its forms are lacking, however if conserved mechanisms can be identified between wasting conditions, this would aid in the development of multipurpose therapeutics to ameliorate this pathology. Purpose: To examine circulating factors present across atrophic pathologies. Methods: 35 male C57BL/6J mice were assigned to hindlimb unloading …

Exploring The Role Of Ptn1 In Ustilago Maydis., Lalu Murali Krishna Vijayakrishna Pillai

Electronic Theses and Dissertations

Signal transduction is a key aspect of biological life. Cell signaling involves a series of biochemical and molecular steps that regulate the normal cellular functions, and any disruption at any of these steps is likely to have substantial impacts on cell physiology. The current study was aimed at the characterization of ptn1 of Ustilago maydis, a basidiomycete fungus. When the U. maydis, ptn1 gene was either deleted or overexpressed, it was found that the deletion of this gene lead to reduced virulence, spore production, and germination rate; effects of the overexpression were more subtle or not discernable. Previous studies …

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 …

An Oxanthroquinone Derivative Disrupts Ras Plasma Membrane Localization And Function By Inhibition Of Acylpeptide Hydrolase And Perturbation Of Sphingomyelin Metabolism, Lingxiao Tan

Dissertations and Theses (Open Access)

Oncogenic RAS proteins are commonly expressed in human cancer. To be functional, RAS proteins must undergo post-translational modification and localize to the plasma membrane (PM). Therefore, compounds that prevent RAS PM targeting have potential as putative RAS inhibitors. Here we examined the mechanism of action of oxanthroquinone G01 (G01), a recently described inhibitor of KRAS PM localization. We show that G01 mislocalized HRAS and KRAS from the PM with similar potency and disrupted the spatial organization of RAS proteins remaining on the PM. G01 also inhibited recycling of epidermal growth factor receptor and transferrin receptor, but did not impair internalization …

Embryonic Lethality Of Cranial Neural Crest Deletion Of Cdc73, Lilia Shen

Honors Scholar Theses

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a disease characterized by parathyroid tumors, renal cysts or tumors, uterine tumors, and ossifying jaw fibromas. The cause of this syndrome is linked to a tumor suppressor gene called Cdc73, which encodes the protein product parafibromin. The loss of proper expression of Cdc73/parafibromin is implicated in the development of the tumors typical of HPT-JT, although the exact mechanisms of tumorigenesis are unclear. In particular, not much is understood about the development of ossifying fibromas (OF) of the jaw in this syndrome. OF is a benign bone neoplasm that can affect the mandible and …

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

Honors Scholar Theses

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I …

Spatial Reorganization Of Histone-Like Nucleoid Structuring Proteins Caused By Silver Nanoparticles, Meaad Alqahtany

Graduate Theses and Dissertations

Silver nanoparticles (AgNPs) and ions (Ag+) can be the new generation of antibiotics due to their antimicrobial effects against bacteria and other microbes. Many studies have shown that AgNPs and suppress the growth of bacteria and damage the cell walls of the microbes; therefore, treating bacterial cells with AgNPs may be a promising method to terminate multi-resistant bacteria. In this work, the effect of AgNPs with two different surface coatings on the spatial reorganization of histone-like nucleoid structuring (H-NS) proteins in Escherichia coli bacteria was investigated using quantitative super-resolution fluorescence microscopy to understand the toxicity and antimicrobial mechanism of AgNPs. …

Do Enallagma Exsulans From Streams And Lakes Show Patterns Of Divergence?, Savannah Rae Graham

Graduate Theses and Dissertations

Divergent selection across heterogenous environments could lead to adaptive divergence in populations resulting in potential local adaption. These populations have phenotypic differences that are fitness related and make native individuals more fit than non-native individuals. My research focuses on a species of damselfly, Enallagma exsulans, to explore local adaptation and morphological differences as a result of divergent selection or plasticity. My first study explored potential local adaptation of wild caught stream and lake E. exsulans using a reciprocal transplant design, a classic approach for this objective. The stream and lake sites chosen were on a small spatial scale allowing for …

Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening

Graduate Theses and Dissertations

Colorectal cancer is the 4th most common and 2nd deadliest cancer. Problems exist with predicting which patients will respond best to certain therapy regimens. Diffuse reflectance spectroscopy has been suggested as a candidate to optically monitor a patient’s early response to therapy and has been received favorably in experimentally managing other cancers such as breast and skin. In this dissertation, two diffuse reflectance spectroscopy probes were designed: one with a combined high-resolution microendoscopy modality, and one that was optimized for acquiring data from subcutaneous murine tumors. For both probes, percent errors for estimating tissue optical properties (reduced scattering coefficient and …

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation …

The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy

Dissertations, Theses, and Capstone Projects

Cellular homeostasis is achieved by the dynamic flux in gene expression. Post-transcriptional regulation of coding and non-coding RNA offers a fast method of adapting to a changing cellular environment, including deadenylation, microRNA (miRNA) pathway, and alternative polyadenylation (APA). In this dissertation, I explored some of the mechanisms involved in the post-transcriptional regulation of gene expression. The main hypothesis in these studies is that a single APA event after DNA damage is governed by specific conditions and factors outside of current known regulators of APA, and that the resultant transcript has a role in the DNA damage response (DDR). My aims …

Context Dependent Roles Of Mdmx (Mdm4) And Mdm2 In Breast Cancer Proliferation And Circulating Tumor Cells, Chong Gao

Dissertations, Theses, and Capstone Projects

Many human breast cancers overexpress the E3 ubiquitin ligase MDM2 and its homolog MDMX. Expression of MDM2 and MDMX occurs in both estrogen receptor α positive (ER+) and triple negative breast cancer (TNBC). We and others have reported that estrogen activated MDM2 strongly promotes proliferation in ER+ T47D breast cancer cells in a p53-independent manner. Whether MDM2 elicits in vivo p53-independent proliferative functions in T47D breast cancer cells has not been determined. Furthermore it has been shown that ectopic expression of MDM2 targets E-Cadherin for degradation thus leading to increased cell migration and invasion. Therefore we assessed the in vivo …

The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud

Dissertations, Theses, and Capstone Projects

Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer

Dissertations and Theses (Open Access)

Stem cells are integral for tissue maintenance and fertility. Therefore, understanding how stem cells are regulated under stress is imperative. When confronted with acute starvation, stem cells must conserve energy and metabolites to cope with the lack of an external source. Caenorhabditis elegans germline stem cells (GSCs) are an excellent model for studying stem cell properties and regulation as they can divide throughout the life of the organism. While GSCs are an adult stem cell population, their cell cycle structure more closely mimics mouse and human embryonic stem cells with short G1 and long S phases. In this thesis, I …

Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy

Dissertations and Theses (Open Access)

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. All of these thiol-modifiers have been demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of thiol stress toxicity responsible for these outcomes are largely unknown. Furthermore, I hypothesize proteins identified as redox-active are prone to misfolding and aggregation by thiol-specific …

Il-6/Jak1 Drives Pd-L1 Phosphorylation And Glycosylation To Promote Cancer Immune Evasion, Li-Chuan Chan

Dissertations and Theses (Open Access)

Glycosylation of immune receptors and ligands, such as T-cell receptor (TCR), major histocompatibility complex (MHC), and co-inhibitory molecules, regulates immune signaling activation, antigen presentation, and immune surveillance. Recent studies revealed that the glycan structures of co-inhibitory molecules are required for receptor-ligand interaction, a critical feature for activating cancer immune evasion. However, it is unclear how oncogenic signaling initiates glycosylation of co-inhibitory molecules to induce immunosuppression. Here we show interleukin (IL)-6-activated Janus kinase 1 (JAK1) phosphorylates programmed death-ligand 1 (PD-L1)-Tyr112, leading to the recruitment of endoplasmic reticulum (ER)-associated N-glycosyltransferase, STT3A, which catalyzes the glycosylation of PD-L1, contributing to its stability. A …

Genetic Counselor Utilization And Interpretation Of Somatic Tumor Testing In Evaluation For Lynch Syndrome, Danielle Williams

Dissertations and Theses (Open Access)

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome characterized by increased risk for colorectal and uterine cancers. Individuals with pathogenic variants in the mismatch repair (MMR) genes (MLH1, MSH2/EPCAM, MSH6, PMS2) are diagnosed with LS and subsequently recommended to proceed with high risk screening protocols to increase prevention and early detection of LS-related cancers. Various tumor studies can help identify those at high risk for LS, but sometimes create uncertainty with discordant screening and germline results, leading to unexplained mismatch repair deficiency (UMMRD). Somatic testing of the MMR genes has created opportunities for resolving …

The Role Of Gene Expression Noise In Mammalian Cell Survival, Kevin Farquhar

Dissertations and Theses (Open Access)

Drug resistance and metastasis remain obstacles to effective cancer treatment. A major challenge contributing to this problem is cellular heterogeneity. Even in the same environment, cells with identical genomes can display cell-to-cell differences in gene expression, also known as gene expression noise. Gene expression noise can vary in magnitude in a population or in fluctuation time scales, which is influenced by gene regulatory networks.

Currently, it is unclear how gene expression noise from gene regulatory networks contributes to drug survival outcomes in mammalian cells. An isogenic cell line with a noise-modulating genetic system tuned to the same mean is required. …

Cross-Presentation Is A Source Of Tumor Antigens For Multiple Myeloma Immunotherapy, Alexander A. Perakis

Dissertations and Theses (Open Access)

Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here …

John's "Embryonic Stem Cell Research: Re-Explored Considering Scientific, Philosophical And Theological Understanding Of Human Life" (Book Review), Joseph Baumstarck Jr.

The Christian Librarian

No abstract provided.

Evaluating The Potential Of Repurposing Commercially Available Drugs For The Treatment Of Viral Infections, Brennan Connor Mcewan

Undergraduate Honors Capstone Projects

Viral infections that are often overlooked as common seasonal illnesses such as influenza can rapidly become a public threat. They threaten society as new, more dangerous strains of these common viruses emerge and as strains develop resistance to current vaccines and antiviral treatments (Kochanek, Murphy, Xu, & Tejada-Vera, 2014). To combat this, the development of antiviral treatments with novel mechanisms of action is essential. Repurposing drugs instead of developing new drugs can save years of development time and hundreds of millions of dollars (DiMasi, Hansen, & Grabowski, 2003). To support the effort to discover drugs with unique mechanisms of action, …

Cellular Localization Of Rad51d Mutant Proteins And The Application Of Art To Increase Scientific Literacy In America, Claire L. Chabot

Senior Theses

Ovarian cancers are the leading cause of death from cancer of the female reproductive system. Approximately 50% of ovarian cancers have defects in the homologous recombination (HR) DNA repair pathway that is required for the repair of DNA double-stranded breaks. The status of HR genes, such as BRCA1, BRCA2, and the RAD51 family, contributes to ovarian cancer development as well as treatment decisions regarding chemotherapy, radiation, and immunotherapy. The overarching goal of this project is to identify new insights into HR that can integrate with Precision Medicine Initiatives and align with the goals of the Cancer Moonshot 2020 Program. I …

Analysis Of Spheno-Occipital Synchondrosis (Sos) Fusion In A Contemporary Southern Nevada Subadult Hispanic Population Using Archival Cone-Beam Computerized Tomography (Cbct) Images, Megan Baker

UNLV Theses, Dissertations, Professional Papers, and Capstones

This study employs the three-dimensional visualization capability of cone-beam computed tomography (CBCT) to investigate the relationship between chronological age and timing of fusion of the spheno-occipital synchondrosis in a male/female subadult Hispanic population of Southern Nevada. The sample includes cross-sectional data of 374 orthodontic patients (166 males and 208 females) aged 8-20 years. The SOS is scored by a four-stage scoring system as completely open (stage 0), less than half fused (stage 1), more than half fused (stage 2), or completely fused (stage 3) as visualized in the midsagittal plane in the CBCT image. The relationship between SOS fusion stage …

The Effects Of Vascular Endothelial Growth Factor On The Characteristics Of Pluripotent Dental Pulp Stem Cells, Cale Forgues

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many believe that stem cells hold the key to regenerative medicine. Therefore, research with stem cells has become increasingly popular over the years. Three specific groups of study have become present in literature. The first group has focused much of their research on harvesting and cultivating stem cell lines to retain their pluripotent ability. Stem cells can be tricky to cultivate and preserve over time as they will often differentiate or die. Another group examines the specific characteristics that a pluripotent stem cell has and how to retain, or even create, a cell with pluripotent potential. Lastly, the third group …

Characterization Of Microtubule Organizing Centers In The Genus Protostelium, Including Evolutionary Implications, Ethan Taylor Ozment

Graduate Theses and Dissertations

Microtubule organizing centers (MTOCs) are cellular regions of microtubule nucleation. The best known MTOCs are those associated with the centrosome, but several non-centrosomal MTOCs are known in eukaryotes, especially in land plants. MTOCs are poorly characterized across the breadth of amoebozoan diversity, but are well-known in certain amoebozoan lineages, including the genus of protosteloid slime molds Protostelium. The structure of the MTOC is known for two non-ciliated species, P. nocturnum and P. mycophaga, as well as P. aurantium, which can reversibly become ciliated under appropriate conditions. P. nocturnum and P. mycophaga have acentriolar centrosomal MTOCs while P. aurantium has a …

Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu

Graduate Theses and Dissertations

Ipomoeassin F is a flagship congener of a resin glycoside family that inhibits growth of many tumor cell lines with only single-digital nanomolar IC50 values. However, biological and pharmacological mechanisms of ipomoeassin F have been undefined. To facilitate exploration of the biological and pharmacological properties, we performed sophisticate SAR (Structure–activity relationship) studies of ipomoeassin F to understand its pharmacophore and structure properties so that we can design favorable probes for further biological investigation. By applying appropriate deviates that possess fluorescent groups and similar bio-activity, the target protein was found to be localized in endoplasmic reticulum (ER). Through biotin affinity pull …

Delineation Of Events In Centripetal Migration During Drosophila Oogenesis, Travis Tait Parsons

UNLV Theses, Dissertations, Professional Papers, and Capstones

All multicellular organisms initially start out as a single cell. This cell must use the genetic information encoded in its DNA to multiply in number and build itself into a complex multicellular organism. How this process occurs is the focus of developmental biology, a field that seeks to understand how a combination of genetic information and environmental conditions shape a cell from its beginnings as a zygote all the way to maturity. A fundamental part of this process is the ability of cells to work together in order to build complex tissues and organs. Cells achieve this coordination by using …

Hormone Signaling, Gene Expression, And Mitochondrial Hormone Receptor Expression In Avian Muscle (Cells), Kentu Rushadd Lassiter

Graduate Theses and Dissertations

Mitochondria are vital to the proper growth and function of muscle cells since they’re responsible for the majority of ATP production used for cellular energy. Previous studies have investigated how differences in mitochondrial function affects feed efficiency (FE) in broilers phenotyped for High and Low FE. Low FE broilers have been shown to have increased levels of reactive oxygen species (ROS), thus contributing to higher levels of oxidative stress and damage seen in these birds. Global gene and protein expression studies conducted on breast muscle of the High FE and Low FE phenotypes have suggested that differences in mitochondrial function …

Immunogenicity Of Tumor Initiating Stem Cells: Potential Applications In Novel Anticancer Therapy, Durga Khandekar, Suneetha Amara, Venkataswarup Tiriveedhi

Biology Faculty Research

Tumor initiating stem cells (TISCs) are a subset of tumor cells, which are implicated in cancer relapse and resistance to chemotherapy. The metabolic programs that drive TISC functions are exquisitely unique and finely-tuned by various oncogene-driven transcription factors to facilitate pro-cancerous adaptive challenges. While this change in TISC metabolic machinery allows for the identification of associated molecular targets with diagnostic and prognostic value, these molecules also have a potential immunological application. Recent studies have shown that these TISC-associated molecules have strong antigenic properties enabling naïve CD8+T lymphocytes to differentiate into cytotoxic effector phenotype with anticancer potential. In spite of the …