Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer,
2023
University of Texas at El Paso
Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya
Open Access Theses & Dissertations
Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …
Overexpression Of Ubtf Correlates With Aggressive Phenotypes Of Prostate Cancer Cells,
2023
The University of Texas Rio Grande Valley
Overexpression Of Ubtf Correlates With Aggressive Phenotypes Of Prostate Cancer Cells, Guillermo Andres Saldana
Theses and Dissertations
Prostate cancer (PrCa) is one of the most common malignancies in men globally and the second leading cause of cancer associated deaths in developed countries. Accumulating evidence have demonstrated involvement of various molecular and cellular factors in the development, progression and chemoresistance of PrCa and many of them were successfully established as potential molecular targets for therapy. Despite these advancements, the underlying mechanisms of PrCa occurrence is still unclear, which limits the diagnosis and therapy. Therefore, it is an urgent need to discover potential molecular targets which can be used in rational design of new strategies for the prevention and …
Synthesis Of Bacterial Glycerophospholipids For Biomembrane Model Studies: A Means To Advanced Biofuels,
2023
East Tennessee State University
Synthesis Of Bacterial Glycerophospholipids For Biomembrane Model Studies: A Means To Advanced Biofuels, Felix Adulley
Electronic Theses and Dissertations
To reduce reliance on fossil fuels, sustainable biofuels are being pursued, especially advanced biofuels like 1-butanol that have higher energy content and greater compatibility with existing infrastructure than ethanol. A persistent challenge is the yield-limiting toxicity of biofuels and process solvents, such as tetrahydrofuran, to the microbes that ferment biomass into biofuel. The cell membrane is a focal point of toxicity, and understanding how it interacts with fuels and solvents is key to improving yield. Phospholipid bilayers are the core of biomembranes, and model biomembranes of defined composition provide the ideal platform for biophysical studies. To this end, glycerophospholipids characteristic …
Intestinal Microbiome, Fecal Fermentation Profile, And Health Indices In Hiv Infected Men Versus Non-Infected Controls,
2023
East Tennessee State University
Intestinal Microbiome, Fecal Fermentation Profile, And Health Indices In Hiv Infected Men Versus Non-Infected Controls, Mary Andreae, Mary C. Andreae Mrs
Electronic Theses and Dissertations
Many HIV-positive (HIV+) males on Highly Active Anti-Retroviral Therapy (HAART) experience metabolic abnormalities, including Non-Alcoholic Fatty Liver Disease (NAFLD) and lipodystrophy. The intestinal microbiota and short chain fatty acids (SCFA), participate in bidirectional communication with their host. Dysbiosis in HIV+ males on HAART demonstrate a Prevotella-rich enterotype shaped by multiple factors including, medications, adiposity, diet, intestinal permeability, and lifestyle; our objective was to investigate these factors. 19 HIV+ and 21 HIV- males were enrolled. BMI and hip-to-waist ratio (H:W) were obtained, and FibroScan for liver health. Intestinal permeability markers Claudin-21, flagellin, and intestinal fatty acid binding protein (IFABP) in …
Cyclin D1 Extensively Reprograms Metabolism To Support Biosynthetic Pathways In Hepatocytes,
2023
University of Minnesota
Cyclin D1 Extensively Reprograms Metabolism To Support Biosynthetic Pathways In Hepatocytes, Heng Wu, Betsy T. Kren, Andrew N. Lane, Teresa A. Cassel, Richard M. Higashi, Teresa Whei-Mei Fan, George S. Scaria, Laurie L. Shekels, Mark A. Klein, Jeffrey H. Albrecht
Markey Cancer Center Faculty Publications
Cell proliferation requires metabolic reprogramming to accommodate biosynthesis of new cell components, and similar alterations occur in cancer cells. However, the mechanisms linking the cell cycle machinery to metabolism are not well defined. Cyclin D1, along with its main partner cyclindependent kinase 4 (Cdk4), is a pivotal cell cycle regulator and driver oncogene that is overexpressed in many cancers. Here, we examine hepatocyte proliferation to define novel effects of cyclin D1 on biosynthetic metabolism. Metabolomic studies reveal that cyclin D1 broadly promotes biosynthetic pathways including glycolysis, the pentose phosphate pathway, and the purine and pyrimidine nucleotide synthesis in hepatocytes. Proteomic …
Md_Harmonize: A Python Package For Atom-Level Harmonization Of Public Metabolic Databases,
2023
University of Kentucky
Md_Harmonize: A Python Package For Atom-Level Harmonization Of Public Metabolic Databases, Huan Jin, Hunter N. B. Moseley
Markey Cancer Center Faculty Publications
A major challenge to integrating public metabolic resources is the use of different nomenclatures by individual databases. This paper presents md_harmonize, an open-source Python package for harmonizing compounds and metabolic reactions across various metabolic databases. The md_harmonize package utilizes a neighborhood-specific graph coloring method for generating a unique identifier for each compound via atom identifiers based on a compound’s chemical structure. The resulting harmonized compounds and reactions can be used for various downstream analyses, including the construction of atom-resolved metabolic networks and models for metabolic flux analysis. Parts of the md_harmonize package have been optimized using a variety of computational …
Design And Characterization Of A Novel Eef2k Degrader With Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer,
2023
Central South University; Hunan Provincial Engineering Research Centre of Translational Medicine and Innovative Drug
Design And Characterization Of A Novel Eef2k Degrader With Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer, Changxin Zhong, Rongfeng Zhu, Ting Jiang, Sheng Tian, Xiaobao Zhao, Xiaoya Wan, Shilong Jiang, Zonglin Chen, Rong Gong, Linhao He, Jin-Ming Yang, Na Ye, Yan Cheng
Markey Cancer Center Faculty Publications
Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the …
Flavonol Glucosylation: A Structural Investigation Of The Flavonol Specific 3-O Glucosyltransferase Cp3gt,
2023
East Tennessee State University
Flavonol Glucosylation: A Structural Investigation Of The Flavonol Specific 3-O Glucosyltransferase Cp3gt, Aaron S. Birchfield
Electronic Theses and Dissertations
Flavonoid glycosyltransferases (GTs), enzymes integral to plant ecological responses and human pharmacology, necessitate rigorous structural elucidation to decipher their mechanistic function and substrate specificity, particularly given their role in the biotransformation of diverse pharmacological agents and natural products. This investigation delved into a comprehensive exploration of the flavonol 3-O GT from Citrus paradisi (Cp3GT), scrutinizing the impact of a c-terminal c-myc/6x histidine tag on its enzymatic activity and substrate specificity, and successfully achieving its purification to apparent homogeneity. This established a strong foundation for potential future crystallographic and other structure/function analyses. Through the strategic implementation of site-directed mutagenesis, a thrombin …
Elucidation Of The Role Of Avocado Wri1 And Wri2 And Their Ability To Affect Oil Content And Composition When Co-Expressed With Pdat1 And Dgat1,
2023
East Tennessee State University
Elucidation Of The Role Of Avocado Wri1 And Wri2 And Their Ability To Affect Oil Content And Composition When Co-Expressed With Pdat1 And Dgat1, Jyoti Ranjan Behera
Electronic Theses and Dissertations
Plants synthesize and store oil, mostly as triacylglycerols (TAG), in seeds that is transcriptionally controlled by WRINKLED1 (WRI1), an APETALA2 (AP2) transcription factor. Among the four Arabidopsis WRI paralogs, WRI2 is nonfunctional, while the others are expressed in a tissue-specific manner. Additionally, two rate-limiting enzymes, diacylglycerol acyltransferase (DGAT) and phospholipid diacylglycerol acyltransferase (PDAT) catalyze the terminal step in TAG assembly and contribute to oil accumulation. Avocado (Persea americana) mesocarp, a non-seed tissue, accumulates significant amounts of TAG (~70% by dry weight) enriched with heart-healthy oleic acid. The oil accumulation stages in mesocarp coincide with the high expression of …
The Interplay Between Lung Adenocarcinoma, Nutrient Availability, And The Microbiome.,
2023
University of Louisville
The Interplay Between Lung Adenocarcinoma, Nutrient Availability, And The Microbiome., Alexis A. Vega
Electronic Theses and Dissertations
Lung cancer is one of the most common forms of cancer diagnosed, and has the highest lethality rate across all other forms of cancer in the U.S. While current therapeutic options include chemo-, immuno-, and radio-therapy, the benefits of caloric or nutrient restriction on cancer cells has also been investigated. Due to the many biological functions associated with methionine, many have proposed a methionine restricted diet would lead to favorable outcomes when combating cancer. Although our cells are incapable of synthesizing methionine, the bacteria found in our microbiome can. Furthermore, recent discoveries suggest an independent microbiome found within tumors that …
Doxorubicin-Induced Changes To The Tgf-Β Signaling Pathway And Autophagic Flux In Fibroblasts: Implications For Cardiotoxicity,
2023
Boise State University
Doxorubicin-Induced Changes To The Tgf-Β Signaling Pathway And Autophagic Flux In Fibroblasts: Implications For Cardiotoxicity, Conner Patricelli
Boise State University Theses and Dissertations
Doxorubicin is a commonly used chemotherapeutic used to treat many different types of cancer. However, its clinical use is limited due to its cardiotoxic adverse effects. While multiple mechanisms have been shown to be responsible for doxorubicin-induced cardiotoxicity, it is generally accepted that the principle mechanism is oxidative stress induction through the production of reactive oxygen species and free radicals in the myocardium. However, efforts to reduce/prevent doxorubicin toxicity using antioxidants have largely failed in pre-clinical and clinical trials. The targeted approach using a liposome delivery of doxorubicin significantly reduced the risk of cardiotoxicity; however, this approach is limited to …
Development Of Novel Methods To Study Host-Microbe Interactions In The Larval Zebrafish Gastrointestinal Tract,
2023
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Development Of Novel Methods To Study Host-Microbe Interactions In The Larval Zebrafish Gastrointestinal Tract, Anh K. Trinh Nguyen
Dissertations and Theses (Open Access)
The dynamic nature and inaccessible location of the intestine pose significant challenges to the study of intestinal physiology and pathology. Zebrafish larvae, possessing optical transparency and genetic tractability, offer an accessible and clinically relevant model for investigating dynamic events in the intestine via time-lapse imaging. In the first part of this work, I discuss our efforts to optimize the parameters of a foodborne infection assay using paramecia as a vehicle. This method provides an effective, high-throughput alternative to infection via immersion or oral gavage, and replicates the most common route of transmission of gastrointestinal (GI) infection in humans. The foodborne …
A Signal To Divide: Apoptotic Extracellular Vesicles As Carriers Of Mitogenic And Immunogenic Signals,
2023
The Texas Medical Center Library
A Signal To Divide: Apoptotic Extracellular Vesicles As Carriers Of Mitogenic And Immunogenic Signals, Safia Essien, Safia Essien
Dissertations and Theses (Open Access)
Efficient replacement of dead cells in epithelial tissue is crucial for maintaining barrier function and tissue homeostasis. Apoptotic cells can signal to neighboring cells to stimulate proliferation and compensate for cell loss and maintain overall cell numbers in normal physiology and cancer. While dying cells can transmit instructive cues to neighboring cells, the molecular mechanisms that induce cell division are not well understood. Recent evidence suggests that apoptotic bodies (ABs) or apoptotic extracellular vesicles (AEVs) mediate cell-to-cell communication and carry diverse biologically active cellular cargo which can influence cell proliferation. This dissertation visualizes and characterizes AEVs in larval zebrafish and …
Biochemical And Kinetic Analysis Of Phosphofructokinase In The Eukaryotic Human Pathogen Entamoeba Histolytica,
2023
Clemson University
Biochemical And Kinetic Analysis Of Phosphofructokinase In The Eukaryotic Human Pathogen Entamoeba Histolytica, Jin Cho
All Dissertations
Entamoeba histolytica is a water- and food-borne intestinal parasite that causes amoebiasis and liver abscess in ~100 million people each year leading to ~100,000 deaths. This amitochondriate parasite lacks many metabolic pathways including the tricarboxylic acid cycle and oxidative phosphorylation, and cannot synthesize purines, pyrimidines, or most amino acids. As a result, E. histolytica is presumed to rely on its modified pyrophosphate (PPi)-dependent glycolytic pathway for ATP production during growth on glucose. This pathway relies on a PPi-dependent rather than ATP-dependent phosphofructokinase (PFK) and thus has a net production of three ATP per glucose. However, in …
Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy,
2023
Clemson University
Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy, Zhao Zhang
All Dissertations
Cardiomyopathy, a disease of the heart muscle, is characterized by structural and functional abnormalities of the myocardium, in the absence of coronary artery disease, hypertension, valvular disease or congenital heart disease. In 2020, there were approximately 6.11 million prevalent cases of cardiomyopathy and myocarditis, and 0.37 million related deaths worldwide. Many affected individuals are asymptomatic, and chronically treated patients are at risk of heart failure. Within the myocardium, cardiomyocytes reside in a complex and dynamic extracellular matrix (ECM), consisting of basement membrane and interstitial matrix. The interactions between cardiomyocytes and myocardial ECM play a critical role in maintaining cardiac geometry …
Delineating The Impact Of Vascular Smooth Muscle Cell Abca1/G1 And Mir-33a Expression On Atherosclerosis,
2023
Clemson University
Delineating The Impact Of Vascular Smooth Muscle Cell Abca1/G1 And Mir-33a Expression On Atherosclerosis, Olanrewaju Oladosu
All Dissertations
Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide due to being the predominant factor in heart attack and stroke deaths. Atherosclerotic cardiovascular disease is caused by cholesterol accumulating in arteries. It is historically thought that the cell type most responsible for causing atherosclerosis via excessive cholesterol accumulation is intimal monocyte-derived macrophages. However, macrophage-like cells (MLC) of vascular smooth muscle cell (VSMC) origin have now been proposed as another cell type to trigger atherosclerosis, since VSMC cholesterol accumulation results in these cells to trans-differentiate into a MLC phenotype. Three major genes involved in cholesterol metabolism are ABCA1, ABCG1, and …
Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei,
2023
Clemson University
Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman
All Dissertations
The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …
Mechanical Properties Of Natural Osmia Lignaria Silk And Recombinant Expression Of The Silk Proteins,
2023
Utah State University
Mechanical Properties Of Natural Osmia Lignaria Silk And Recombinant Expression Of The Silk Proteins, Jackson Morley
Undergraduate Honors Capstone Projects
The use of petroleum-based plastic and the subsequent waste has led researchers to explore alternatives in the form of biopolymers. Spider silk and hagfish intermediate filaments show the potential to be advantageously utilized in textile and biomedical industries. Bee silk is a sparsely studied biopolymer that has shown potential to be added to these other impressive biopolymers. Osmia lignaria, is a solitary bee native to the western United States. Silk from these bees can be isolated while the larvae are spinning their silk. The silk from these bees has been mechanically tested for strength, stress, strain, and elasticity. Cocoon …
Effect Of Plant Genotype On Plant-Microbe Interactions And Multi-Generation Ecosystem Selection Of Microbial Communities Associated With Plant Biomass In Arabidopsis Thaliana,
2023
University of Massachusetts Boston
Effect Of Plant Genotype On Plant-Microbe Interactions And Multi-Generation Ecosystem Selection Of Microbial Communities Associated With Plant Biomass In Arabidopsis Thaliana, Nachiket Shankar
Graduate Doctoral Dissertations
The microbiome's role in shaping host phenotypes is a critical area of investigation, with implications for ecology, evolution, and host health. Dynamic plant-microbe interactions are influenced by factors like soil type, environment, and genotype. Understanding their impact on microbial communities is key for tailored plant benefits. An artificial ecosystem selection experiment was done for eight generations with Arabidopsis thaliana Ler and Cvi. This revealed distinct microbial communities shaped by genotypes and biomass treatments. Initially, environment dominated, but over time, genotype and biomass gained influence, explaining ~40% of the variation. Moreover, genotype-specific rhizobacterial associations were observed, enhancing understanding of community dynamics …
Evaluation Of Potential Role Of R-Loop And G-Quadruplex Dna In The Fragility Of C-Myc During Chromosomal Translocation Associated With Burkitt's Lymphoma,
2023
The Texas Medical Center Library
Evaluation Of Potential Role Of R-Loop And G-Quadruplex Dna In The Fragility Of C-Myc During Chromosomal Translocation Associated With Burkitt's Lymphoma, Nitu Kumari, Kohal Das, Shivangi Sharma, Sumedha Dahal, Sagar Sanjiv Desai, Urbi Roy, Anju Sharma, Meghana Manjunath, Vidya Gopalakrishnan, S T Retheesh, Saniya M Javadekar, Bibha Choudhary, Sathees C Raghavan
Faculty, Staff and Student Publications
t(8;14) translocation is the hallmark of Burkitt's lymphoma and results in c-MYC deregulation. During the translocation, c-MYC gene on chromosome 8 gets juxtaposed to the Ig switch regions on chromosome 14. Although the promoter of c-MYC has been investigated for its mechanism of fragility, little is known about other c-MYC breakpoint regions. We have analyzed the translocation break points at the exon 1/intron 1 of c-MYC locus from patients with Burkitt's lymphoma. Results showed that the breakpoint region, when present on a plasmid, could fold into an R-loop confirmation in a transcription-dependent manner. Sodium bisulfite modification assay revealed significant single-strandedness …
