Life Sciences Commons^™

Identification Of Prostate Cancer-Associated Genomic Alterations By Analyzing Variant Frequencies, Functional Effects, And Protein Interactions, Bofei Wang

Open Access Theses & Dissertations

With the ever-increasing varieties of sequencing techniques, the volume and scope of genomic data are explosively expanded, offering unparalleled opportunities for researchers to study gene-disease associations, identify biomarkers, and thus develop more effective diagnostic and therapeutic strategies. In this project, I have developed a computational workflow and a new scoring scheme, which combine statistical frequency-based analyses with two well-established functional effect prediction tools FATHMM and PROVEAN, to evaluate nonsynonymous GSVs and identify potential cancer-related protein-coding genes for downstream enrichment and protein-protein interaction (PPI) studies.

This method has been applied to process a collection of 503 whole exome sequencing datasets for …

In Vitro Investigation Of Tumor Selective Piperidones As Therapeutic Agents Against Leukemia Cancer Cells, Lisett Contreras

Open Access Theses & Dissertations

Cancer is a continuous global health issue. It is the second leading cause of death behind heart disease. Disparities across the emergence of cancer and resulting fatalities raise the importance of researching the disease. Treatments are available for certain types of cancers. However, these are typically accompanied by residual problems including side effects and the possibility for relapse. Some treatments attack all cells, leading to unwarranted side effects that make the possibility of living a comfortable life nearly impossible. Other treatments are specific to certain genetic alterations, making them only useful for a small percentage of patients. Not one treatment …

Transgenerational Differences Between Two Culturally Distinct Prairie Vole Populations, Richard Joaquin Ortiz

Open Access Theses & Dissertations

Culture can be described as a system of environmental beliefs, values, and social practices within one’s environment. This system is passed on from generation to generation and provides a basis for an individual’s behaviors and cognitive perceptions. Cultural neuroscience is an emerging field that intertwines domains of anthropology, psychology, neuroscience, and genetics to help understand the underlying processes, neural mechanisms and genomic factors that vary across cultures. Similar to humans, the socially monogamous prairie vole (Microtus ochrogaster) display populational differences in prosocial behavior and aggression based upon region-specific cultural upbringing and parental lineage. Prairie voles originating from Kansas (KS) display …

Analyzing Genetic Variation Of The Tussock Cottongrass Among Ecotypes Along A Latitudinal Gradient Through Transcriptomics, Carmen Webster

Open Access Theses & Dissertations

The Arctic is seeing some of the most extreme effects of climate change that induce environmental pressures, including warmer temperatures and longer growing seasons. Due to this, taxa may need to adapt or migrate in order to survive. The long-lived tussock cottongrass, Eriophorum vaginatum, is a foundation species in the Arctic, and little is currently known about the genetic constraints that could be playing a role in how this species will respond to the changing climate. Specific gene families that play an important role in signaling genetic pathways related to plant phenology and response to environmental stress are likely to …

Articulating The Importance Of Broader Relevance In Cures: From Definition To Actualization, Nikki T. Donegan

Open Access Theses & Dissertations

Course-based undergraduate research experiences (CUREs) have emerged as a means to foster student' scientific reasoning, promote positive attitudes and motivations toward research, and increase persistence in the science, technology, engineering, and mathematics (STEM) fields. In contrast to prescriptive laboratories, students enrolled in CUREs employ techniques and skills to collaboratively and iteratively address novel questions of broad relevance to audiences beyond the scope of the course itself. While many of the core components of CUREs are perceived to be relatively straightforward, definitionally-speaking, this latter dimension of broader relevance has, in contrast, remained largely ill-defined. In the series of studies presented herein, …

Pacific Black Duck Ecology And Habitat Assessment In Aunu'u, American Samoa, And Their Relationship To Other Mallard-Like Ducks Of Oceania, Greater Indonesia, And The Philippines, Marissa Kaminski

Open Access Theses & Dissertations

Determining a species’ ecological needs, assessing the quality of their habitat, and determining genetic differentiation and connectivity among populations is essential to their conservation. My dissertation focuses on obtaining such a holistic view for a population of Pacific Black Ducks recently established on the Island of Aunu’u, American Samoa. Specifically, I present the first evaluation of the ecology and habitat of a recently established population of Pacific Black Ducks on the Island of Aunu’u, American Samoa, in Chapter 1, while I assess the genetic connectivity and relationship of this population to other Mallard-like ducks found in Greater Indonesia, Oceania, and …

In The Search For Novel Treatments For Chagas' Disease Using Cutting-Edge Imaging Technology, Karsten Dieter Amezcua Winter

Open Access Theses & Dissertations

Chagas disease (ChD) is caused by Trypanosoma cruzi (T. cruzi), an intracellular protozoan parasite. ChD has a global mortality of 15,000 annual deaths, and approximately, 8-10 million people are infected. There is growing concern in the United States as autochthonous cases of ChD have been reported in the southern region. The two available treatments are only partially effective and highly toxic. N-aroyl derivatives and α, β-unsaturated ketones have been previously tested against Leishmania, a closely related parasite, demonstrating selective toxicity towards the microorganism. The objective of this study is to evaluate a drug library consisting of 21 α, β-unsaturated ketones …

The Hybridizing Ions Treatment (Hit) Method Development And Computational Study On Sars-Cov-2 E Protein., Shengjie Sun

Open Access Theses & Dissertations

Fast and accurate calculations of the electrostatic features for highly charged biomolecules such as DNA, RNA, highly charged proteins, are crucial but challenging tasks. Traditional implicit solvent methods calculate the electrostatic features fast, but they are not able to balance the high net charges in the biomolecules effectively. Explicit solvent methods add unbalanced ions to neutralize the highly charged biomolecules in molecular dynamic simulations, which require more expensive computing resources. Here we developed a novel method, the Hybridizing Ions Treatment (HIT) method, which hybridizes the implicit solvent method with the explicit method to realistically calculate the electrostatic potential for highly …

Strike-Induced Chemosensory Searching, Kleptoparasitism, And The Possibility Of Chemical Crypsis In Rattlesnakes, Mark Scott Teshera

Open Access Theses & Dissertations

Predator-prey interactions shape the natural histories of both species as each tries to adapt and counter-adapt to the tactics of the other. This important evolutionary dynamic is crucial for ecosystem formation and stability. Predation is a fundamental aspect of life for most organisms, and many venomous reptiles, particularly ambush-foraging viperids, have evolved a prey-acquisition strategy that is highly effective in immobilizing prey, while minimizing possible counterattacks. Best studied in rattlesnakes, this remarkable behavioral sequence is known as strike-induced chemosensory searching (SICS). Throughout decades of research, the body of SICS literature on venomous reptiles has become fairly robust, particularly in rattlesnakes. …

Chanism Of G-Βγ-Dependent Regulation Of Neuronal Differentiation And Neurodegeneration, Diana Olivas

Open Access Theses & Dissertations

Neurodegeneration is a pathological condition associated with a progressive loss of neurons, and occurs in many neurological disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Lou Gehrig’s disease (ALS). It is the most common cause of dementia among people 65 and older. With the increasing of life expectancy, the prevalence of neurodegenerative diseases is also increasing rapidly. However, the cause of this disorder is largely unknown, and no effective drugs are available to treat the disease process. Therefore, it is crucial to identify new target(s) and strategies for therapeutic interventions. Cytoskeletal defects followed by dysfunction is a major characteristic …

Development And Characterization Of The Next Generation Drug For The Direct Targeting Of The Fkbp52 Co-Chaperone For The Treatment Of Castration Resistant Prostate Cancer, Ashley Nichole Payan

Open Access Theses & Dissertations

Prostate cancer is the most common cancer among American men, the third highest mortality rate. Current treatment options consist of androgen deprivation therapies, actual or chemical castration, and the use of androgen blockers called anti-androgens. Ultimately the disease advances to a hormone-independent state known as castration-resistant prostate cancer (CRPC). The folding, activation, and nuclear translocation of steroid hormone receptors requires the sequential action and cooperation of at least twelve proteins that make up four distinct complexes. At least one of these proteins, the FKBP52 cochaperone, is a promising therapeutic target for disrupting several mechanisms important in prostate cancer (PCa). FKBP52 …

Characterization Of Gabaergic Horizontal Cells In The Mouse Retina, Zulema Uresti

Open Access Theses & Dissertations

The inner nuclear layer of the mammalian retina contains the cell bodies of the amacrine, bipolar and horizontal neurons. About 90% of the amacrine neurons are glycinergic and GABAergic and marked by the expression of the vesicular inhibitory amino acid transporter, VIAAT. By contrast, the phenotype in horizontal inhibitory neurons vary among different mammals. In the primate retina, experimental evidence suggests the absence of VIAAT and hypothesizing that GABA could be released by efflux through the GABA transporters. On the other hand, in rodents, the horizontal cells express the VIAAT and carry out vesicle-dependent GABA release. Although the retina cells …

Evaluation Of The Cytotoxyc Effects Of Lmdf5-7 On A Human T-Cell Leukemia Cell Line, Andrea F. Ibarra Chacon

Open Access Theses & Dissertations

According to World Health Organization (WHO), cancer is the second leading cause of death worldwide, with 9.6 million deaths in 2018 . In the United States, an estimated 434,982 people were living with cancer during 2017 . Leukemia is the most common blood cancer in children from birth to 14 years old . In particular, Hispanic children in the United States experience a higher incidence rate of leukemia . Therefore, the discovery of novel cancer therapies is necessary to help those affected survive the disease. A new compound, LMDF5-7 was investigated and found to have anticancer properties that can help …

Pyronaridine, A Good Candidate For A Repurposed Anticancer Drug, Paulina Villanueva

Open Access Theses & Dissertations

The antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cell lines to PND, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations. PND elicited phosphatidylserine externalization, mitochondrial depolarization, and DNA fragmentation in both the triple-negative MDA-MB-231 breast cancer and HL-60 leukemia cell lines. In addition, PND treatment altered cell cycle progression in both cancer cells. Subsequent DNA mobility-shift assays, UV-Visible spectroscopic titrations, and circular dichroism (CD) experiments revealed that PND intercalates with DNA. Furthermore, transcriptome signatures findings suggested that PND might act …