Biochemistry Commons^™

Interactions Of Amyloid Peptides With Lipid Membranes, Yanxing Yang

Dissertations

The aggregation of amyloid proteins into fibrils is a hallmark of several diseases including Alzheimer’s (AD), Parkinson’s, and Type II diabetes. This aggregation process involves the formation of small size oligomers preceding the formation of insoluble fibrils. Recent studies have shown that these oligomers are more likely to be responsible for cell toxicity than fibrils. A possible mechanism of toxicity involves the interaction of oligomers with the cell membrane compromising its integrity. In particular, oligomers may form pore-like structures in the cell membrane affecting its permeability or they may induce lipid loss via a detergent-like effect. This dissertation aims to …

Angiogenic Supports For Microvascular Engineering, Zain Siddiqui

Dissertations

Ischemic tissue disease is caused by a lack of circulation / blood supply to tissue. This can be treated by introducing a number of angiogenic (pro-blood vessel forming) factors into the tissue. This work presents strategies for ischemic tissue treatment utilizing a novel proangiogenic self-assembling peptide hydrogel platform. To demonstrate the utility of this platform, its use alone as an angiogenic therapeutic (both alone as a self-assembling hydrogel and with two-component systems), and its ability to vascularize implants is explored. Due to these angiogenic scaffolds demonstrating efficacy to regenerate microvasculature, this work evaluates diseases that can be treated by the …

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

The Role Of Parkin In Mitochondrial Dna, Eliezer Lichter

Theses & Dissertations

Mitochondria are at the center of biological phenomena such as aging and diseases, especially neurodegenerative diseases. While the discovery of mitochondria only came approximately 200 years after the cell was discovered, a lot of progress has been made since. The mitochondrial genome encodes proteins vital for mitochondrial function. These proteins are only a subset of the proteins present in mitochondria; the rest are nuclear encoded. The nucleus also encodes cytosolic proteins vital for mitochondrial maintenance. One of these is Parkin, an E3 ubiquitin ligase that ubiquitinates mitochondrial proteins as mitochondria become depolarized. Its activity has been shown to be involved …

Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen

Theses & Dissertations

Cholesterol is essential for life. It is particularly important in the brain as it relies on de novo synthesis of cholesterol following the formation of the blood brain barrier (BBB). As such, disrupting sterol biosynthesis during neurodevelopment can have devastating outcomes. The most common post-lanosterol sterol biosynthesis disorder, Smith-Lemli-Opitz Syndrome, arises from a faulty DHCR7 enzyme. DHCR7 has also been shown to be inhibited by several psychotropic medications. Here we assess six beta-blockers and their effects on sterol biosynthesis in vitro. Two beta-blockers, metoprolol and nebivolol strongly inhibit DHCR7 in four separate in vitro models of both mouse and …

A Universal Mechanism Of G Protein Inhibition, Tyson Daniel Todd

Arts & Sciences Electronic Theses and Dissertations

G protein coupled receptors transduce a truly staggering number of diverse extracellular signals including chemical messengers, physical force, and even photons into specific cellular responses through their coupling to heterotrimeric G proteins. G proteins amplify the originating signal through their binding to downstream effectors, activating a complex network of overlapping responses that allow the cell to respond perfectly to that specific stimulus. It is critical to the cell that this process is carried out faithfully in order to respond to the myriad environmental cues and avoid injury, exhaustion, and death for the individual cell or the development of pathology if …

A Structural Perspective On Neutralizing Antibodies To Flaviviruses And Coronaviruses, John Michael Errico

Arts & Sciences Electronic Theses and Dissertations

The presence of neutralizing antibodies typically correlates strongly with protection from infection, particularly for RNA viruses; elicitation of neutralizing antibody responses is thus the primary goal of most vaccines, and monoclonal antibodies (mAbs) can be leveraged as potent therapeutics. Thus, understanding the properties of individual antibodies that comprise polyclonal antibody responses and their epitopes is essential for countermeasure design. In this dissertation, I explore the epitopes and functional properties of monoclonal antibodies targeting the structural proteins of two families of RNA viruses, flaviviruses and coronaviruses.

Flaviviruses are globally distributed arthropod-borne positive-sense RNA viruses transmitted primarily by either mosquitos or ticks. …

Nanoparticle Conjugated Photosensitizer For Targeted Photodynamic Inactivation Of Cancer Cells, Symone D. Crowder

Honors College Theses

Photodynamic therapy (PDT) is considered to be a potential replacement for traditional methods of chemotherapy. It includes the administration of photosensitizing agents (PS), which generate reactive oxygen species (ROS) upon excitation at a specific wavelength. With new outlooks and techniques, cancer research is advancing each day. It has allowed the progress of several theranostic drug delivery systems (DDS) exploring the area of nanomedicine.2 In the present work, a Rhodamine derivative, Rhodamine 6G (R6G) was used as the PS. In general, rhodamine compounds undergo cytotoxic reactions on photoexcitation by electron transfer reactions with folic acid within cells, making them a favorable …

Bis-Indolyl Compounds And The Induction Of Apoptosis In T98g Glioblastoma Multiforme Cells, Margot C. Brown

Seton Hall University Dissertations and Theses (ETDs)

1,1-bis(3’idolyl)-1(aryl)methane compounds (BIM compounds) have been shown to have anti-cancer properties in colon cancer, bladder cancer, and leukemia cells. The purpose of this work was to determine if BIM compounds could be an effective treatment of glioblastoma multiforme. Sulforhodamine B (SRB) assays showed that 20µM of the BIM compounds could inhibit cellular proliferation of the T98G glioblastoma multiforme cell line over 72 hours. Then immunoblotting was used to analyze the molecular pathway induced by BIM compounds. An increase in the expression of both BAX and cleaved caspase 3 suggest BIM compounds activate programmed cell death, or apoptosis in glioblastoma cells. …

Dynamics Of Redox-Driven Molecular Processes In Local And Systemic Plant Immunity, Philip Berg

Theses and Dissertations

The work here presents two main parts. In the first part, chapters 1 – 3 focus on dynamical systems modeling in plant immunity, whereas chapters 4 – 6 describe contributions to computational modeling and analysis of proteomics and genomics data. Chapter 1 investigates dynamical and biochemical patterns of reversibly oxidized cysteines (RevOxCys) during effector-triggered immunity (ETI) in Arabidopsis, examines the regulatory patterns associated with Arabidopsis thimet oligopeptidase 1 and 2’s (TOP1 and TOP2), roles in the RevOxCys events during ETI, and analyzes the redox phenotype of the top1top2 mutant. The second chapter investigates the peptidome dynamics during ETI …

Molecular Basis Of Viroid Rna-Templated Transcription, Shachinthaka D. Dissanayaka Mudiyanselage

Theses and Dissertations

Transcription is a fundamental process catalyzed by DNA-dependent RNA polymerases (DdRPs). Interestingly, some DdRPs can use both DNA and RNA as templates for transcription. This RNA-dependent RNA polymerase (RdRP) activity of DdRPs is used by RNA-based pathogens such as viroids and hepatitis delta virus for replication. In addition, RdRP activity of DdRPs widely occurs in various organisms to regulate gene transcription. Despite the importance of this intrinsic RdRP activity of DdRPs, associated factors and mechanisms are in their infancy stage. We employed potato spindle tuber viroid (PSTVd) as a model to study RNA-templated transcription. Here, we present evidence showing that …

Screening Anti-Pd-L2 Peptides As Antitumor Ligands Using Phage Display, Chien Tran Phuoc

Honors Projects

Cancer still remains one of the top leading causes of death in America. Recently, programmed cell death protein 1 (PD-1) blockades have been demonstrated to be highly effective against various types of cancer. By blocking PD-1 from binding with their ligands (PD-L1 and PD-L2), the “off” signal to the immune system is inhibited, hence reinvigorating the immune cells to kill tumor cells. To date, despite PD-L1 and PD-L2 both interacting with PD-1, research efforts have only been focused on developing anti-PD-L1 inhibitors. Therefore, the work of this honor project has focused on finding anti-PD-L2 peptides by phage display, with the …

Chemical Control And Understanding Of Horizontal Gene Transfers, Drug-Resistance Development, And Filament And Biofilm Formation, Yuchen Jin

Dissertations - ALL

Biofilms formed by microbes on surfaces are the sources for persistent infectious diseases and environmental problems. The mechanism and details of how antibiotics promote biofilm formation is largely unknown. For instance, it not clear what stages of biofilm growth are promoted to proceed faster than without antibiotics, what phenotypes of bacteria form in an antibiotic-promoted biofilm, and what different biofilm compositions and structures are caused by the presence of antibiotics. Among other effects, antibiotics can cause bacteria to form filaments of living bacteria. Here, we conduct a real-time study of the adherence of bacteria and antibiotic-induced filamentous bacteria on surfaces …

The Role Of Fatty Acid Metabolism In The Pathogenesis Of Trypanosoma Brucei, Nava Poudyal

All Dissertations

Trypanosoma brucei is the protozoan parasite that causes African Sleeping Sickness in humans and nagana, a wasting disease in cattle. T. brucei completes its life cycle in two hosts, mammals and the tsetse fly insect vector. Due to the geographical restriction of the tsetse fly, the disease is endemic in sub-Saharan Africa. Both the insect and mammalian forms of the parasite need fatty acids to anchor their surface proteins. We worked on three projects on fatty acid metabolism and its role in immune evasion strategies of T. brucei. First, we assessed the role of T. brucei surface proteins in …

Synthesis And Biological Testing Of Small-Molecule Mitochondrial Complex I Inhibitors, Willough Sloan

Undergraduate Honors Theses

This thesis delineates two main projects: the first outlines the structure elucidation efforts toward a Diels-Alder adduct of a novel reaction for the synthesis of chimaphilin, a naphthoquinone-based natural product with apoptotic or antiproliferative activity in certain cancer cells^1,2. The structure elucidation extends to derivatives of chimaphilin synthesized by the same cyclization reaction. While Diels-Alder reactions are usually regioselective, ¹H-NMR and ¹³C-NMR of the adducts was inconclusive and indicated the possibility of regioisomer presence, with one regioisomer being chimaphilin (or derivatives). A multitude of crystallization methods were carried out in order to be able to analyze …

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …

Functional Characterization Of The Newly Discovered Type V Crispr-Cas Protein Cas12a2, Dylan J. Keiser

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Similarly to people, bacteria are under the treat of infection by viruses. To circumvent these threats, bacteria evolve complex immune systems. Our understanding of some of these immune systems has led to many advancements in the field of Biotechnology including tools that made expressing proteins for study in a lab easier, tools that revolutionized the feasibility of gene editing, and tools that could change the way we think about viral diagnostics and cancer therapeutics. A certain type of immune system that bacteria use to fight virus is called a CRISPR system. Presented here is work to understand the function of …

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 …

Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam

Dissertations & Theses (Open Access)

ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …

Characterization Of The Isothermal Titration Calorimetry Single Injection Method Using T4 Polynucleotide Kinase As A Model System For Kinases, Rebecca Chaehee Lim

UNLV Theses, Dissertations, Professional Papers, and Capstones

Kinases are an important class of enzymes involved in the regulation of different cellular processes. The dysfunctional activity, either hyperactivity or inactivity, of kinases has been associated with many types of diseases, making kinases a major therapeutic target. As of 2020, more than 80 kinase inhibitors have been FDA-approved and have revolutionized the treatment for progressive disorders such as cancers and Alzheimer's diseases. However, there is always the possibility of developing severe side effects or resistance to drugs so the search for new therapeutics must continue with efficiency and accuracy.Isothermal titration calorimetry (ITC) is a state-of-the-art technique specialized in detecting …

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 …

Characterizing And Epitope Mapping Single-Domain Antibodies On Borrelia Burgdorferi Protein Ospa, Saiful Basir

Legacy Theses & Dissertations (2009 - 2024)

Epitope mapping a protein that enables pathogenesis is crucial for the development of therapies and prophylactics that can inhibit the pathogen’s function and its transmission of disease. The lipoprotein OspA enables Lyme Disease etiologic pathogen, Borrelia burgdorferi, to inhabit the tick midgut until transmission occurs. Anti-OspA mAbs and their smaller VHH counterparts are highly specific and tailored to bind proteins such as OspA, reproducibly, at established binding sites or epitopes. Previous studies found an array of mAbs that successfully bound OspA and have already been used in epitope mapping. To our knowledge, this is the first use of VHHs in …

Development Of Nucleic Acid Diagnostics For Targeted And Non-Targeted Biosensing, Christopher William Smith

Legacy Theses & Dissertations (2009 - 2024)

The field of nucleic acid technology is rapidly expanding with new impactful discoveriesbeing made each year. Starting from the discovery of the double-helix structure, cloning, gene editing, polymerase chain reaction (PCR), CRISPR technology, and even the late mRNA vaccines; nucleic acid technology is at the forefront of improving medicine. Nucleic acid technology is extremely versatile due to its easy programmability, automated cheap synthesis, and even its catalog for numerous chemical modifications that can be used to alter structure stability. For example, the number of permutations that can be made with DNA just by altering the code for adenine (A), cytosine …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

Synthesis Of Trifluoromethyl Ketones By (Diethylamino) Sulfur Trifluoride (Dast)-Mediated Nucleophilic Trifluoromethylation Of Benzoic Acids, Michael A. Vescio

Honors College Theses

Within the past few decades, the presence of fluorine containing

organic molecules has increased significantly. Many of the

current industrial production methods are not cost-effective,

practical, or inherently safe. This work describes a new methodology

for the synthesis of trifluoromethyl ketones. Our new method involves

the use of benzoic acid and trifluoromethyl trimethylsilane (TMSCF₃) as starting

materials along with diethylamino sulfur trifluoride (DAST) as a reagent

to obtain moderate to good yields of expected products in a short

reaction times.

Esterase Mediated Insecticide Resistance In The Southern House Mosquito, Culex Quinquefasciatus, Vivek Pokhrel

LSU Doctoral Dissertations

Much is known about the development of insecticide resistance associated with targeted application against insect populations. However, off-target selection by applications of insecticides in agricultural and residential sites also impacts development of insecticide resistance and is understudied. Similarly, the impact of selecting one life stage of mosquitoes on the insecticide susceptibility of different life stages is largely unknown. The first part of this study shows that susceptibility to chlorantraniliprole, which is applied in rice and sugarcane fields in LA, decreased (5.7 to12-fold) in populations of Culex quinquefasciatus collected from near these fields compared to a reference field strain. In addition, …

Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila

Dissertations

Organic synthesis has been significantly advanced with the employment of transition metal complexes. The discovery of transition metal catalysts provided the synthetic community with powerful tools for accelerating reactions and making them more selective and efficient. Many chemical reactions do not happen without a catalyst.

Iron-based catalysts have several advantages for the chemical industry because it is a non-toxic and ecologically friendly metal. Our group previously found that ferrocenium cations with a 3+ oxidation state of iron-catalyzed propargylic substitution reactions at low temperatures. The sandwich structure of ferrocenes allows substituents to be introduced on the cyclopentadienyl rings, which allows for …

The Effect Of Licogliflozin (Sglt1/2 Inhibitor) On Diabetes And Cardiac Complications, Alanoud Gharib Alblooshi

Theses

Diabetes mellitus (DM) is a chronic endocrine disease affecting millions of people worldwide. In spite of the advances made in the management of DM, poor glycemic control and diabetes complications are still very common. There is a continuous search for new and more effective drugs to treat DM. One of the drugs currently in clinical trials for the treatment of DM is licogliflozin (LIK066), a dual SGLT1/2 inhibitor, which can be used to treat obesity and diabetes. LIK066 inhibits glucose reabsorption in the kidney and small intestine, thereby reducing hyperglycemia. This study aims to investigate the efficacy of licogliflozin on …

Conformational Dynamics And Aggregation Of Thermally Stressed Proteins Studied By Hydrogen/Deuterium Exchange Mass Spectrometry, Nastaran Nosrat Tajoddin

Electronic Thesis and Dissertation Repository

Proteins perform various biological functions, e.g., as enzymes or transporters. In addition to naturally occurring proteins, the use of protein therapeutic drugs for treating cancer and other diseases is a rapidly growing area. A thorough biophysical characterization of proteins and protein therapeutics opens the door to a more comprehensive understanding of their role in health and disease. This dissertation aims to expand the capabilities of an existing technique (Hydrogen Deuterium Exchange Mass Spectrometry, HDX-MS), which is widely used for probing protein structure and dynamics. Conventionally, HDX-MS experiments are performed as a function of labelling time. Here we aim to establish …