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A Cancer-Specific Study On The Differentially Expressed Protein-Protein Interactions Of Fumarate Hydratase, Sydney Lac 2023 The Texas Medical Center Library

A Cancer-Specific Study On The Differentially Expressed Protein-Protein Interactions Of Fumarate Hydratase, Sydney Lac

Dissertations and Theses (Open Access)

Fumarate hydratase (FH) is an enzyme used in the Krebs Cycle to convert fumarate to malate, and it is controlled by the FH gene. In this paper, we will investigate its role in Uterine Corpus Endometrial Carcinoma (UCEC) and how FH-deficient cells affect tumorigenesis. It is well-established that FH has been extensively studied in connection with renal cell carcinoma, skin and uterine leiomyomas, pheochromocytoma, and paraganglioma. However, we aim to construct an interaction network of significant genes related to the FH gene under conditions of FH deficiency in the Kreb Cycle. Creating an interactive network that illustrates the interconnectedness of …


Growth, Yield, And Photosynthetic Dry Matter Remobilization Response Of Barley To Plant Growth Promoting Rhizobacteria (Pgpr) And Nitrogen, Abazar Abbasi, Shahram Mehri, Hossein Solimanzadeh, Saeid Alipour 2023 Department of Agronomy and Plant Breeding, Parsabad Moghan Branch, Islamic Azad University, Parsabad Moghan, Iran

Growth, Yield, And Photosynthetic Dry Matter Remobilization Response Of Barley To Plant Growth Promoting Rhizobacteria (Pgpr) And Nitrogen, Abazar Abbasi, Shahram Mehri, Hossein Solimanzadeh, Saeid Alipour

The Philippine Agricultural Scientist

A two-year factorial experiment based on a randomized complete block design with three replicates was carried out on barley cultivar LB-IRAN at the research farm of the Islamic Azad University, Ardabil, Iran, during the cropping years of 2019–2021, in order to survey the impact of plant growth-promoting rhizobacteria (PGPR) and nitrogen fertilizer on growth, yield, and remobilization of photosynthetic dry matter in barley. The first factor included five nitrogen levels: 0 (control), 25, 50, 75, 100 kg/ha net nitrogen; the second factor contained grain inoculations with four bacteria: no inoculation (control), Azotobacter chroococcum race 5, Azospirillum lipoferum race of, and …


Synthesis Of Bacterial Glycerophospholipids For Biomembrane Model Studies: A Means To Advanced Biofuels, Felix Adulley 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, Mary Andreae, Mary C. Andreae Mrs 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, 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 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, Huan Jin, Hunter N. B. Moseley 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, 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 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, Aaron S. Birchfield 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, Jyoti Ranjan Behera 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 …


Biochemical And Kinetic Analysis Of Phosphofructokinase In The Eukaryotic Human Pathogen Entamoeba Histolytica, Jin Cho 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 …


Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman 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 …


Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman 2023 University of Arkansas, Fayetteville

Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman

Chemistry & Biochemistry Undergraduate Honors Theses

The FGF-1 subfamily, composed of FGF-1 and FGF-2, assists in broad health-related processes such as cell proliferation and angiogenesis respectively.1,2 The subfamily shows promising signs as a therapeutic, however, the inherent thermal instability leads to a low half-life in vivo.3 To assist in improving the stability, FGF-1 and FGF-2 were connected via a 12-residue glycine linker ultimately producing a heterodimer. This heterodimer was further examined to discover its novel properties. Inspiration for this project was drawn from previous research which performed five mutations on FGF-1 ultimately improving stability in the protein complex. In addition to these five …


Interfacial Interactions Between Engineered Nanoplastics And Biological Systems: Towards An Atomic And Molecular Understanding Of Plastics- Driven Cellular Dyshomeostasis, Afroz Karim 2023 University of Texas at El Paso

Interfacial Interactions Between Engineered Nanoplastics And Biological Systems: Towards An Atomic And Molecular Understanding Of Plastics- Driven Cellular Dyshomeostasis, Afroz Karim

Open Access Theses & Dissertations

The persistent presence of micro (nano) plastics in our environment has raised concerns regarding potential health risks associated with human exposure. With the extensive use of plastic materials and the widespread consumption of plastic-contaminated food items, two types of microplastics, polystyrene (PS) and polymethylmethacrylate (PMMA), have attracted increased attention. While the adverse effects of microplastics on animals and marine life have been extensively studied, their potential impact on human health remains largely unexplored. Specifically, the interaction between microplastics and biomolecules within the human body and their effect on human health have yet to be comprehensively investigated. This dissertation study focuses …


Structural Studies Of The Human Hsp60 And Bacteriophage Phiel Chaperonins, Daniel Han von Salzen 2023 University of Texas at El Paso

Structural Studies Of The Human Hsp60 And Bacteriophage Phiel Chaperonins, Daniel Han Von Salzen

Open Access Theses & Dissertations

Chaperonins are large protein complexes responsible for the refolding of misfoldedsubstrate. Many mechanisms of the folding process have not been completely elucidated. Here we perform biochemical and structural analysis on two chaperonins, the human mitochondrial Hsp60 and the bacteriophage EL encoded PhiEL, to better understand key structural components and their purpose to the chaperonin function. Hsp60 plays an essential role in maintaining protein within the mitochondrial matrix. Despite its importance, the detailed mechanism of ATP hydrolysis and the role of the C-terminal tail remains unresolved. Here we show that the C-terminal tail not only acts as a sensor for the …


Biochemical Analyses Of Udgx-A Crosslinking Uracil-Dna Glycosylase, Chuan Liang 2023 Clemson University

Biochemical Analyses Of Udgx-A Crosslinking Uracil-Dna Glycosylase, Chuan Liang

All Dissertations

DNA base damage is common due to exposure to various endogenous and exogenous factors. To repair the base lesions, such as uracil from cytosine deamination, enzymes from the uracil-DNA glycosylase (UDG) superfamily are critical, which can recognize the damaged base and initiate the base excision repair (BER) pathway. There used to be six families of proteins identified in the UDG superfamily until a new member, UDGX, was found in Mycobacterium smegmatis, which is a unique DNA-crosslinking UDG. In this dissertation work, a series of biochemical analyses of the newly found UDGX are performed, including the analyses of structures, functions, …


Delineating The Impact Of Vascular Smooth Muscle Cell Abca1/G1 And Mir-33a Expression On Atherosclerosis, Olanrewaju Oladosu 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 Human Fibroblast Growth Factor 2 Variant To Determine Effects On Structure, Stability, And Cell Proliferation, Ryan Layes 2023 University of Arkansas, Fayetteville

Characterization Of Human Fibroblast Growth Factor 2 Variant To Determine Effects On Structure, Stability, And Cell Proliferation, Ryan Layes

Graduate Theses and Dissertations

Fibroblast growth factors (FGFs) are a family of cell signaling proteins conserved across multiple species. Each individual FGF elicits different cellular functions including, but not limited to, proliferation, migration, differentiation, angiogenesis, and wound healing. One of the most studied members, fibroblast growth factor 2 (FGF2), has demonstrated substantial wound healing capacity in a wide range of tissues including skeletal, muscular, neural, respiratory, epithelial, and cardiovascular. This ability makes FGF2 a potential therapeutic for a wide range of conditions and injuries. However, due to a short half-life at room temperature, therapeutic use of FGF2 is limited. It has been demonstrated that …


Quantifying The Role Of Water Quality On Nitrogen Cycling In A Trophic Estuary, Kayla Gonzalez-Boy 2023 Kennesaw State University

Quantifying The Role Of Water Quality On Nitrogen Cycling In A Trophic Estuary, Kayla Gonzalez-Boy

Symposium of Student Scholars

Jobos Bay Estuary is an intertidal, tropical estuary located in southern Puerto Rico. The estuary covers about 12 km2 and has a variety of habitats, such as seagrass beds, mangroves, mud flats, and coral reefs, which play important roles in sediment trapping and water quality maintenance. Seagrasses also serve as nursery and feeding grounds and provide shelter for macrofauna. Currently, the role of seagrasses and water quality on nitrogen (N) cycling in trophic estuaries is not well constrained. Understanding variations in sediment-based effects on N cycling rates and transformations, and how they are associated with water quality, is an …


Chemical Composition, Mineral Profile, Anti-Bacterial, And Wound Healing Properties Of Snail Slime Of Helix Aspersa Müller, Marouane Aouji, Amine Rkhaila, Bouchra Bouhaddioui, Malak Zirari, Hala Harifi, Youness Taboz, Lalla Aicha Lrhorfi, Rachid Bengueddour 2023 Laboratory of Natural Resources and Sustainable Development, Department of Biology, Faculty of Sciences, Ibn Tofail University, BP 133, Kenitra 14000, Morocco

Chemical Composition, Mineral Profile, Anti-Bacterial, And Wound Healing Properties Of Snail Slime Of Helix Aspersa Müller, Marouane Aouji, Amine Rkhaila, Bouchra Bouhaddioui, Malak Zirari, Hala Harifi, Youness Taboz, Lalla Aicha Lrhorfi, Rachid Bengueddour

BioMedicine

Mucus is a substance made by snails that serves a variety of purposes and is increasingly employed in the medical and cosmetic industries. It includes bioactive compounds with a range of biological characteristics that could be useful in the treatment of particular issues. This study assessed the wound-healing efficiency, antibacterial activity, chemical and mineral composition of Helix aspersa Müller slime. Inductively Coupled Argon Plasma Atomic Emission Spectrometry (ICP-OES) was used for mineral analysis, while Gas chromatography coupled to mass spectrometry (GC-MS) analysis was used for chemical characterization. The findings showed that the H. aspersa Müller slime had inhibitory activity on …


Integration Of Algae And Biomass Processes To Synthesize Renewable Bioproducts For The Circular Economy, Jessica Martin 2023 University of South Florida

Integration Of Algae And Biomass Processes To Synthesize Renewable Bioproducts For The Circular Economy, Jessica Martin

USF Tampa Graduate Theses and Dissertations

Rapid population growth and global industrialization have substantially heightened the demand for fossil-based fuels and products in various sectors of the global economy, including energy production, transportation fuels, and as raw materials for petrochemicals. The intense consumption of fossil fuels has caused immense environmental impacts, especially pertaining to carbon dioxide emissions. Shifting to renewable feedstocks (raw materials) is expected to reduce these emissions by lowering the carbon footprint of fuels and products compared to traditional fossil-derived alternatives. This transition aligns with the goal of creating a sustainable and circular economy, emphasizing efficient resource use, and reducing waste generation through recycling …


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