Life Sciences Commons^™

Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi

Graduate Theses and Dissertations

Nature achieves molecular self-assembly through the ordered growth of nanoscale building blocks with high efficiency to fabricate macromolecular architectures. One example of self- assembly is peptides folding onto protein is one of the most astounding biological self-assembly processes. When proteins aggregate to form amyloid fibers, the secondary structure of the protein converts from its native state to a cross-beta-sheet. Fibroblast growth factors (FGFs) possess an essential role in neuronal survival during development. In addition, they are involved in neural stem cell (NSC) proliferation. Fibroblast growth factors (FGFs) are well known to be synthesized in the central nervous system (CNS) and …

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 …

University Of Arkansas, Chemistry And Biochemistry Department Graduate Student Publications, 2018- November 2023. 39p., Jeremy Smith, Lutishoor Salisbury

University Libraries Faculty Publications and Presentations

This report provides a compilation of the research publications by the Chemistry and Biochemistry (CHBC) Graduate students for the period: 2018-November 2023. It includes publications by the CHBC graduates and those where a CHBC faculty was the main advisor. It includes a summary of the research. The listing is organized according to type of publications within specific years.

University Of Arkansas, Chemistry And Biochemistry Department Research Publications, 2014- November 2023. 107p., Jeremy Smith, Lutishoor Salisbury

University Libraries Faculty Publications and Presentations

This report provides a compilation of the research publications by the Chemistry and Biochemistry faculty for the period: 2014 - November 2023. The information was gathered from major databases in science and technology including Web of Science, SciFinder, Reaxys, PubMed, IEEE Explore and Engineering Index. At least one author in each of the publications has the CHBC department as its affiliation. It includes a table summarizing the research. The listing is organized according to type of publications within specific years.

Phenotypic And Transcriptomic Characterization Of Rice Snrk1 Mutants Developed By Crispr/Cas9 Mutagenesis, Maria Clara Faria Chaves

Graduate Theses and Dissertations

SnRK1 is a heterotrimeric protein kinase that is composed of a catalytic subunit (α) and two regulatory subunits (β and βγ), and it has a main role in regulating energy homeostasis in the plant by modulating anabolic and catabolic process. SnRK1 phosphorylates and alters the activities of enzymes involved in metabolism and regulates gene expression by altering the activity of chromatin-remodeling enzymes or the transcription factors. Rice contains three functional paralogs of SnRK1α: SnRK1αa (LOC_Os03g17980), SnRK1αb (LOC_Os08g37800), and SnRK1αc (LOC_Os05g45420). This study focused on the function of these SnRK1 paralogs by evaluating the phenotypic and transcriptomic characteristics and the disease …

Studying The Phosphorylation Of Isocitrate Dehydrogenase In Humans, Hannah Smith

Chemistry & Biochemistry Undergraduate Honors Theses

Isocitrate dehydrogenase is an important enzyme in the citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. While there are three isoforms of isocitrate dehydrogenase (IDH1, IDH2, and IDH3), this research will focus on IDH1. The phosphorylation of isocitrate dehydrogenase is a process that has been linked to the formation of both luminal-like and basal-like breast cancer. Despite these correlations, the mechanisms that cause breast cancer development are unknown. To examine this, an enzyme activity assay for each phosphorylation variant and crystallization were conducted. The results of these indicate that phosphorylation at each site (IDH1-T77, IDH1-S188, …

Differential Electrostatic Interaction Patterns In Sars-Cov-1 And Sars-Cov-2 Variants: A Molecular Dynamics Simulation Study, Ugochi Hope Isu

Graduate Theses and Dissertations

The SARS-related coronavirus (SARS-rCoV) is a highly contagious virus that has raised significant worldwide health concerns. It caused outbreaks in 2002-2003 and more recently in 2019-2020 with SARS-CoV-2. SARS-CoV-2 is responsible for the COVID-19 pandemic, which has resulted in a significant global impact on health and the economy. The spike protein of the virus plays a critical role in its infectivity and transmission, and the receptor-binding domain (RBD) within the spike protein is of particular interest, as it is responsible for binding to the human angiotensin-converting enzyme 2 (ACE2) receptor. In this study, we used Molecular dynamics (MD) simulations to …

Expression, Purification, And Characterization Of Fibroblast Growth Factor 19, Elizabeth Ford

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast growth factors (FGFs) are a family of signaling proteins with diverse biological functions. Fibroblast growth factor 19 (FGF19) regulates several vital physiological processes, including bile acid, glucose, and lipid homeostasis. However, its therapeutic potential is limited by its structural instability. The purpose of this study is to express, purify, and characterize recombinant FGF19 to build the foundation for the creation of stable mutants, which can be used to treat a variety of common diseases including type 2 diabetes, atherosclerosis, and nonalcoholic fatty liver disease. The parameters for overexpression in Escherichia coli were optimized according to optical density, inducer concentration, …

Purification Of Anginex: An Inhibitor Of Tumor Metastasis Using Rdrd Tag, Suraj Kolluru

Inquiry: The University of Arkansas Undergraduate Research Journal

Anginex is a cytokine-like β-sheet forming peptide of 33 amino acids with potent anti-angiogenic activity.Anginex is essential in inhibiting abnormal processes caused by angiogenesis, such as tumor growth and blood vessel formation. However, Anginex has limitations, including poor stability, short half-life, complicated synthesis, and low purity. Rubredoxin dimer (RdRd) is used as a protein tag to improve stability and detection of Anginex during purification for the first time. A plasmid was designed to contain the RdRd-Anginex fusion protein. RdRd-Anginex plasmid was transformed and expressed in E. coli BL21star cells. The results show RdRd-Anginex has been purified using a Nickel Sepharose …

Molecular Characterization Of Nitrogenase Regulation In Methanosarcina Acetivorans, Melissa Chanderban

Graduate Theses and Dissertations

Nitrogenase is the metalloenzyme only found in bacteria and archaea that is essential for biological nitrogen fixation (diazotrophy), but it can also serve as a catalyst in biofuel production. All diazotrophs contain a molybdenum (Mo) nitrogenase, while some species contain additional alternative nitrogenases where either vanadium (V) or iron (Fe) replace Mo in the active site cofactor. Nitrogen fixation by bacteria has been extensively studied. The limited investigation of nitrogen fixation in methanogenic archaea (methanogens) indicates production of nitrogenase is simpler than in bacteria and methanogen nitrogenase has different biochemical properties. Thus, methanogen nitrogenases provide a promising alternative for genetic …

The Binding Of The Micronutrient Transition Metals To The Alkylation Products Of Chemical Warfare Agent, Sulfur Mustard, And Thiols, Potentially Giving New Understanding To Physiological Effects Of Exposure And Increased Toxicity, Colin O'Donnell

Graduate Theses and Dissertations

Model compounds, 3,6,9-trithaiundecane-1,11-dicarboxylic acid (TTDPA), 2,5,8-trithianonane-1,9-dicarboxylic acid (TTDAA), and 1,11-diamide-3,6,9-trithiaundecane (TTDAce), closely related to the adducts formed by cysteine alkylation of the chemical weapon, sulfur mustard, were synthesized. It is shown that TTDPA forms complexes with key metal micronutrients: copper, nickel, cobalt, manganese, and zinc. Though the strength of binding to TTDPA varies, the complexes in many cases precipitate from solution. All metals produced a visible precipitate upon interaction with TTDPA under the conditions tested, however only Cu2+, Mn2+, and Zn2+ produced enough to be measured. The mass of formed precipitate seemed to peak at an equimolar ratio of TTDPA …

Using Molecular Dynamics Simulations To Decipher Mechanistic Details Of Biomolecular Processes Of Biology And Biotechnology Oriented Applications, Adithya Polasa

Graduate Theses and Dissertations

Researchers in chemistry and biology often utilize computer simulations, in conjunction with experimental data, to model and predict the structures, energies, kinetics, processes, and functions of the systems that are their focus of study, ranging from single molecules to whole viruses. Here, we use molecular dynamics (MD) techniques to gain a deeper understanding of biomolecular processes in biology and biotechnology-oriented applications. Using a mixture of equilibrium and non-equilibrium MD simulations, this work describes the insertion process of YidC at the atomic level. In order to better comprehend the insertion process, several docking models of YidC-Pf3 in the lipid bilayer were …

Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson

Chemistry & Biochemistry Undergraduate Honors Theses

Known to cause gas gangrene, Hathewaya histolytica secretes two sister collagenases, collagenase G (Col G) and collagenase H (Col H), to degrade the triple helical structure of collagen to further infection in a host. Individual domains of Col H have been crystalized in previous studies, but methods in x-ray crystallization of full-length Col H have been unsuccessful. Using Small Angle X-Ray Scattering (SAXS) data, atomistic modeling was used to generate multiple conformations of Col H while accounting for flexibility between domains. Full-length Col H was found to adopt a two-state conformational model exhibiting a majority compact and a minority elongated …

Habitability, And Evolution Of Microorganisms Under Extreme Conditions, Azarin Yazdani

Graduate Theses and Dissertations

The choice of a solvent determines the possible biochemistry of life. Life on Earth is based on carbon biochemistry and has evolved in an environment with water as a solvent. As a polar solvent abundant on Earth, water has unique physical properties, including a large range of liquidity and low viscosity, making it a very good solvent for terrestrial life. Liquids other than water are abundant in the universe, and the chemical nature of these liquids might lead to different chemistries of life. In the first chapter, we review the main characteristics of a good solvent, and then we use …

Characterization Of The Influence Of A Small Molecule Inhibitor On Ras-Related Proteins Interactions, Emilio Duverna

Graduate Theses and Dissertations

The Ras superfamily of small G proteins are involved in cell-signaling processes that, if not regulated, may lead to cell multiplication, apoptosis inhibition, and tumorigenesis. They function as molecular switches, which through GTP/GDP exchange cycle, switch on or off cellular activities. Overexpression and/or hyperactivity of these proteins have been linked to many diseases including various cancers. CDC42, a member of the Rho subfamily of the Ras superfamily of small G proteins, participates in the regulation of many cellular processes including cell adhesion, mitosis, and cytoskeletal rearrangements. CDC42 binds to and activates many effector proteins including CDC42-activated kinase (ACK). Abnormal activities …

Characterization Of Fgf1/Fgf2 Heterodimer With Mutation R136e, Brett Haley

Biological Sciences Undergraduate Honors Theses

Fibroblast growth factors are a family of heparin binding proteins that are involved in a broad spectrum of physiological functions, such as angiogenesis, cell proliferation, cell differentiation, and wound healing. Fibroblast growth factor 1 (FGF-1) is a member of the FGF superfamily and can bind universally to fibroblast growth factor receptors. Fibroblast growth factor 2 (FGF-2) is similar in structure to FGF-1 but has been shown to have a potent effect on angiogenesis. A physiologically stable dimerization of these two growth factors could prove to induce desirable effects in the instance of wound healing. In this study, we have designed …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

Characterization Of A Protein-Small Molecule Interaction Between Microtubules And Novel Ruthenium-Polypyridyl Complexes, Chloe Hutchison

Chemistry & Biochemistry Undergraduate Honors Theses

Microtubules are cytoskeletal filaments that play a role in essential functions within the cell such as cell motility, intracellular transport, structural support and chromosome segregation. Tubulin is a heterodimeric protein that exhibits GTP dependent polymerization and self- assembles into polar microtubule filaments. Microtubules are dynamic polymers corresponding to their role in separation of duplicated chromosomes during mitosis. As the polymers cycle through rounds of polymerization and depolymerization based on their nucleotide state, the chromosomes are pulled towards the poles in the mitotic cell. Their normal function and dynamics can be disrupted in highly proliferative cells that interrupt cell cycle progression …

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

Studying The Lysine Acetylation Of Aconitase Isozymes In E. Coli, Sara Ottinger

Chemistry & Biochemistry Undergraduate Honors Theses

The contents of this thesis have been modified from the publication “Araujo J, Ottinger S, Venkat S, Gan Q and Fan C (2022) Studying Acetylation of Aconitase Isozymes by Genetic Code Expansion. Front. Chem. 10:862483”. Though studies have found multiple lysine sites in which acetylation takes place in Escherichia Coli aconitase, acetylation’s effects on the enzyme’s activity have yet to be studied. Aconitase is the dehydratase-hydratase found in the citric acid and glyoxylate cycles responsible for the reversible isomerization of citrate to isocitrate via cis-aconitate intermediate. There are two isoforms of aconitase in E. coli: AcnA and AcnB. In …

Studying Acetylation Of Aconitase Isozymes By Genetic Code Expansion, Jessica Araujo

Graduate Theses and Dissertations

The tricarboxylic acid (TCA) cycle is a very important, centrally located, energy-producing pathway that connects numerous other metabolic and regulatory pathways. Enzymes of this cycle have been more recently implicated in various cancers and neurometabolic disorders, however, the exact mechanism by which this happens becomes quite complex when considering the potential modification of these enzymes and the presence of multiple forms of the enzymes and therefore there is much to be studied in this area.

Aconitase has become a recent enzyme of interest as its substrate, citrate, has been found to play a major role in many vital processes within …

Preparation Of Proteins And Peptides From Heat-Stabilized Defatted Rice Bran Via Solid State Fermentation And Investigating For Skin Health, Ali A. Bisly

Graduate Theses and Dissertations

Heat-stabilized defatted rice bran (HDRB) is an abundant and inexpensive agro-industrial by-product of rice milling and rice oil extraction process. Furthermore, HDRB is a potential source of proteins. However, the direct protein extraction has low yield of protein due to the impact of heat stabilization and oil extraction process which made the HDRB proteins bound and interact with other components. This research is based on using solid-state fermentation (SSF), which is a natural and cost-effective approach to facilitate protein extraction from HDRB using Bacillus subtilis (natto) Takahashi as a microorganism.

Response surface methodology (RSM) analysis was used with Box-Behnken design …

Regulation Of The Reaction Between Cytochrome C And Cytochrome C Oxidase In The Mitochondria, Anders Nowell

Biological Sciences Undergraduate Honors Theses

Cytochrome c (Cc) is a multifunction protein that has important life and death functions in the cell. In the electron transport chain (ETC), Cc transfers electrons from cytochrome bc₁ to cytochrome c oxidase (CcO), which helps build the electrochemical gradient that drives ATP synthase. The reaction of Cc with CcO is very important in ETC regulatory processes. Previous research shows phosphorylation sites in Cc that affect the binding with CcO, with measurable effects on k_d, k_f, and K_D. These effects result in changes in mitochondrial membrane potentials, respiration, and reactive oxygen species (ROS) …

Site-Specific Effects Of Lysine Acetylation On Aminoacyl-Trna Synthetase, Hao Chen

Graduate Theses and Dissertations

Aminoacyl-tRNA synthetases (AARSs) are an ancient and highly conserved family of enzymes which can catalyze a two-steps aminoacylation reaction to charge tRNAs with their cognate amino acids, thus playing crucial roles in ribosomal protein synthesis. Naturally, the accurate amino acids and tRNA recognition of these synthetases are essential to the fidelity of translation process. To assure the correct recognition, some of these synthetases have evolved with an editing function to help remove the mischarged tRNAs. In addition to these functions, AARSs are also involved in various biological processes ranging from transcription to translation. Currently, a series of proteomic studies have …

Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder

Graduate Theses and Dissertations

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …

Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays, Mamello Mohale

Graduate Theses and Dissertations

Human fibroblast growth factor one (hFGF1) belongs to a family of 22 FGF members produced by fibroblast cells. Cell signaling during physiological processes of angiogenesis and wound healing occurs when hFGF1 binds to its receptor (FGFR). However, when heterogenous homeostasis is not maintained, fibroblast cells exhibit excessive proliferation which can lead to a myriad of cancers. smFRET is an ultrasensitive distant dependent (1-10 nm) technique capable of resolving such heterogeneity in structural dynamics and binding affinities (Kd). Therefore, we successfully designed and characterized fluorescently labeled hFGF1 tracers which span the visible light region of the electromagnetic spectrum for use in …

Enzymatic Degradation Of Microcystin-Lr By Microcystinase (Mlra), Faisal Alqhtani

Graduate Theses and Dissertations

Microcystin-LR (MC-LR) is affecting the water supply worldwide. Hence, a way to eliminate this toxin is an essential target. In this study, successful cloning of the mlrA gene and producing MlrA enzyme that can degrade the cyclic MC-LR to linearized MC-LR was done. MlrA protein was expressed in Escherichia coli BL-21 (E. coli). Also, enhancing the MlrA yield by adding nickel to LB media was a success in producing more MlrA enzyme from the same volume. Even though the enzyme showed no activity after adding Ni, the enzyme was expressed at a higher yield. Furthermore, it was to investigate adding …

Investigating Effects Of Microenvironmental Stress On Cell Metabolism Using Multiphoton Imaging, Lisa Rebello

Graduate Theses and Dissertations

Resistance to therapy in cancer is a major cause of poor prognosis in patients. Tumor hypoxia plays an active role in mediating treatment resistance and has been linked to metastases and metastatic potential in cancer. Our research focused on three objectives: i) To understand metabolic effects of chronic and intermittent hypoxia in murine breast cancer cells and its affiliation with metastatic potential ii) To identify the metabolic changes associated with radiation therapy in a panel of radiosensitive and radioresistant human head and neck cancer cells and iii) to monitor the changes in cell metabolism associated with gain of treatment resistance. …

Evaluating Bioenergetics And Mitochondrial Dynamics In Patient Fibroblasts With Pathogenic Mitochondrial Dna Mutations Causing Leigh Syndrome, Ajibola Bakare

Graduate Theses and Dissertations

Leigh syndrome (LS) is a rare fatal mitochondrial disorder of infants caused by pathogenic mutations in the nuclear (nDNA) or mitochondrial DNA (mtDNA) leading to mitochondrial dysfunction. The extent to which pathogenic mtDNA variants regulate disease severity in LS is not well understood. The heterogeneous nature of this disorder, based in part by complex mitochondrial genetics, and the nuclear and mitochondrial cross-talk has made it particularly challenging to investigate and develop therapies for treating LS . While the prognosis is poor, several studies are underway to understand the pathophysiology of LS. This dissertation provides a comprehensive structural and functional analysis …

Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza

Graduate Theses and Dissertations

The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …