Biochemistry, Biophysics, and Structural Biology Commons^™

Simulating The Effects Of Co2 Gas Influx On The Thermodynamic Conditions Inside A Marine Riser Filled With Oil Based Mud, Hassan Al Dawood

Honors Capstones

No abstract provided.

Engineering Of Two-Color Atp-Binding Cassette Biosensor Proteins For Discovery Of Novel Substrates And Modulators, Bremansu Osa-Andrews

Electronic Theses and Dissertations

ATP-binding cassette (ABC) transporter proteins are a vast, ubiquitous superfamily of proteins most of which unlock the energy from ATP-binding and hydrolysis to influx or efflux a wide spectrum of structurally dissimilar substrates across cell membranes. All eukaryotic ABC transporters including P-gp and MRP1 only exist as efflux pumps whose prominent expression in cells is associated with multidrug resistance of antiretrovirals, antiepileptics, antimalarials and anticancer agents. P-gp and MRP1 reduce the bioavailability and efficacy of chemotherapeutic drugs by actively pumping out these drugs, thereby, leading to poor clinical outcomes during chemotherapy. Due to their clinical importance, profiling of the interaction …

The Contributions Of Fc Gamma Receptors And Macropinocytosis To The Internalization, Sorting And Clearance Of Antibody Coated Nanovesicles In Macrophages, George Opoku-Kusi Jr.

Electronic Theses and Dissertations

Macrophages are tissue-resident phagocytes that play critical roles in immune response and tissue homeostasis. They have a tremendous capacity to internalize objects of various sizes ranging from nanoscale viral particles to micron sized bacteria and tumor cells. This phenomenon, termed phagocytosis for the uptake of large particles, or endocytosis for the uptake of small particles, is integral to the immune response in multicellular organisms. Macrophages express FcγRs, which are tyrosine kinase receptors that bind IgG on an opsonized target. Binding of IgG Fc domain to the extracellular domain of an FcγR triggers signaling cascades that coordinate internalization of the opsonized …

Proteogenomic Study Of Nitrogen-Fixing Cyanobacterium Anabaena Cylindrica, Yeyan Qiu

Electronic Theses and Dissertations

Cyanobacteria are gram-negative photosynthetic bacteria. In some filamentous cyanobacteria such as Anabaena cylindrica, every 10^th to 20^th vegetative cells can differentiate into nitrogen fixing heterocysts. Heterocyst can induce the neighboring cells developing into spore-like akinetes. The specialized cell functions and resourceful networks have contributed to the prosperity of cyanobacteria for over 2 billion years, but the genetic mechanisms for multi-cellular differentiation are barely known, especially for akinete formation. The heterocysts, akinetes and vegetative cells of Anabaena cylindrica were isolated for proteomic study. This study identified a total of 1395 proteins, including 664 proteins from akinetes, 751 proteins from …

Study Of Anti-Proliferative Activity Of Cucurbitacins Inspired Estrone Analogs On Hepatocellular Carcinoma, Sara Elgazwi

Electronic Theses and Dissertations

Hepatocellular carcinoma (HCC) is considered the third leading cause of death from cancer. Overall survival rate is significantly low, due to the emerging resistance to chemotherapeutic agents and lack of selectivity. Recent studies have demonstrated that epidermal growth factor receptor (EGFR) is a promising molecular target for cancer therapy, especially HCC. Current studies showed that cucurbitacins are potent anticancer compounds which target EGFR. This prompted us to investigate the antiproliferative activity of novel cucurbitacins inspired estrone analogs (CIEA) against sensitive and resistant HepG2 cell lines. Anti-proliferation activity of 20 CIEA analogs were examined against HepG2 using MTT assay and showed …

Structural Features And Domain Movements Controlling Substrate Binding And Cofactor Specificity In Class Ii Hmg-Coa Reductase, Bradley R. Miller, Yan Kung

Chemistry Faculty Research and Scholarship

The key mevalonate pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) uses the cofactor NAD(P)H to reduce HMG-CoA to mevalonate in the production of countless metabolites and natural products. Although inhibition of HMGR by statin drugs is well-understood, several mechanistic details of HMGR catalysis remain unresolved, and the structural basis for the wide range of cofactor specificity for either NADH or NADPH among HMGRs from different organisms is also unknown. Here, we present crystal structures of HMGR from Streptococcus pneumoniae (SpHMGR) alongside kinetic data of the enzyme’s cofactor preferences. Our structure of SpHMGR bound with its kinetically preferred NADPH cofactor …

Measurement & Analysis Of The Temporal Discrimination Threshold Applied To Cervical Dystonia, Rebecca B. Beck, Eavan M. Mcgovern, John Butler, Dorina Birsanu, Brendan Quinlivan, Ines Beiser, Shrut Narasimham, Sean O'Riordan, Michael Hutchinson, Richard B. Reilly

Other resources

The temporal discrimination threshold (TDT) is the shortest time interval at which an observer can discriminate two sequential stimuli as being asynchronous (typically 30-50 ms). It has been shown to be abnormal (prolonged) in neurological disorders, including cervical dystonia, a phenotype of adult onset idiopathic isolated focal dystonia. The TDT is a quantitative measure of the ability to perceive rapid changes in the environment and is considered indicative of the behavior of the visual neurons in the superior colliculus, a key node in covert attentional orienting. This article sets out methods for measuring the TDT (including two hardware options and …

Steroid-Coa Ligases, Fadd17a1 And Fadd19a1, And Their Role In Cholesterol Side-Chain Degradation In Mycobacterium Tuberculosis, Johnathan Salim Abou-Fadel

Open Access Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is a serious health issue arising from the increasing incidence of multi-drug resistant (MDR-TB) strains that are becoming more prevalent in high-risk countries, especially here in the Texas/Mexico border. Confirmed cases and outbreaks in schools and hospitals are more frequent in this region due to the high-volume pedestrian traffic between the two cities, and the lack of a modernized health system in Mexico. Identification of new Mtb metabolic pathways for development of novel antitubercular drugs is urgently needed. The goal of this current work investigates two Mtb fatty acyl-CoA ligase enzymes' (FadD17A1 and FadD19A1) to explore whether …

Coordination Of Different Ligands To Copper(Ii) And Cobalt(Iii) Metal Centers Enhances Zika Virus And Dengue Virus Loads In Both Arthropod Cells And Human Keratinocytes, Shovan Dutta, Michael J. Celestine, Supreet Khanal, Alexis Huddleston, Colin Simms, Jessa Faye Arca, Amlam Mitra, Loree Heller, Piotr Kraj, Michael Ledizet, John F. Anderson, Girish Neelakanta, Alvin A. Holder, Hameeda Sultana

Biological Sciences Faculty Publications

Trace elements such as copper and cobalt have been associated with virus-host interactions. However, studies to show the effect of conjugation of copper(II) or cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food additives or mosquito repellent such as 2-acetylethiazole or citral, respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections have not been explored. In this study, we show that four compounds comprising of thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a copper(II) complex with acetylethTSC as a ligand (compound 2), a thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III) complex …

Rack1 Is A Critical Component In Ires-Mediated Translation, Ethan Asher Lafontaine

Legacy Theses & Dissertations (2009 - 2024)

Due to its sheer number of interacting partners, core ribosomal protein RACK1 is a key player in many cellular processes and has been shown to play a vital role of translation initiation of the Hepatitis C virus RNA. The HCV 5′ untranslated region contains an internal ribosome entry site. IRES-mediated translation is a process employed in eukaryotes by select viruses and some cellular mRNAs by which translation initiation bypasses the canonical mRNA cap-dependent pathway by means of an RNA secondary structure (the IRES). While cap-dependent translation requires the recruitment of a suite of initiation factors, IRES-mediated translation requires few to …

Technology Development For Detection Of Circulating Disease Biomarkers From Liquid Biopsies Using Multifunctional Nanomaterials, Mustafa Balcioglu

Legacy Theses & Dissertations (2009 - 2024)

Despite the advance health care, devastating health conditions such as cancer and infectious diseases that affect populations worldwide are too often not diagnosed until morbid symptoms become apparent in the late phase. Obtaining an early and accurate diagnosis that reveal a hidden lethal threat before the disease becomes complicated may dramatically reduce the severity of its impact on the patient’s life and increase the probability of survival. For example, in the case of ovarian cancer, which is the fifth most common malignancy and the fifth leading cause of cancer mortality in women in the US, the 5-year relative survival is …

Cyclic Adenosine Monophosphate Signaling In Mycobacterium Tuberculosis : New Insights Into A Universal Second Messenger, Richard Mcpherson Johnson

Legacy Theses & Dissertations (2009 - 2024)

Despite being the focus of intense research for many years Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the deadliest bacterial pathogen plaguing mankind today. Humans are the sole host and reservoir for Mtb, and Mtb has coevolved closely with its human host for thousands of years. Mtb currently infects over two billion people worldwide and over 1.5 million people die from TB each year, arguably making Mtb the most successful bacterial pathogen on the planet.

Regulated Transcriptional Silencing Promotes Germline Stem Cell Differentiation In Drosophila Melanogaster, Pooja Flora

Legacy Theses & Dissertations (2009 - 2024)

Germ cells are the only cell in an organism that have the capacity to give rise to a new organism and are passed from one generation to the next. Therefore, to maintain this unique ability of totipotency and immortality, germ cells execute specific functions, such as, repression of a somatic program and contour a germ line-specific pre- and post-transcriptional gene regulatory landscape. In many sexually reproducing organisms, germ cells are formed during the earliest stages of embryogenesis and undergoes several stages of development to eventually get encapsulated by the somatic cells of the gonad. Once, in the gonad, the germ …

Dna Functionalized Nanoparticles In Nanobiosensor And Sensor Array Development For Molecular Diagnostics And In Vitro Identification Of Biomolecules, Mustafa Salih Hizir

Legacy Theses & Dissertations (2009 - 2024)

Nucleic acid technology along with vast variety of nanomaterials has demonstrated a great potential in many applications from biosensing studies to molecular diagnostics, from biomedical and bioanalytical research to environmental analysis. Especially short single stranded (ss) DNA molecules, called oligonucleotides, are extraordinary biopolymers featuring diverse functionality on the nanoparticles thanks to their high degree of programmability, target-specific binding or cleavage, molecular recognition ability, structure-switching capability, and unique interactions at the bio-nano interfaces. Among those, there have been many biosensing applications utilizing ss DNAs and numerous nanomaterials through various detection techniques such as fluorometric, colorimetric or electrochemical methods. Although many groundbreaking …

Chromatin-Signaling Axis Orchestrates The Formation Of Germline Stem Cell Differentiation Niche In Drosophila, Maitreyi Upadhyay

Legacy Theses & Dissertations (2009 - 2024)

Stem cells have the unique capability of self-renewing into stem cells and differentiating into several terminal cell types. Loss of either of these processes can lead to aging, progression towards degenerative diseases and cancers. Insight into how self-renewal and differentiation are regulated will have tremendous therapeutic impact. Drosophila is an excellent model system for stem cell study due to the availability of various mutants, markers and RNAi technology. In order to study stem cell biology, we use female Drosophila gonads, whose stem cell population – the germline stem cells (GSCs) gives rise to gametes.

The Dissemination, Regulatory Role, And Evolution Of Mycobacterial Inteins, Danielle Skye Kelley

Legacy Theses & Dissertations (2009 - 2024)

Inteins are intervening protein elements, capable of coordinating escape from a host protein through a self-catalyzed mechanism, called protein splicing. This results in free intein and a mature host protein product. Inteins are also mobile elements and many contain homing endonucleases that enable the targeting to ectopic sites and invasion of novel niches. Inteins have been found across all three domains of life and are often present in replication, recombination, and repair proteins. However, it is unclear if the observed distribution is simply a factor of endonuclease preference or if inteins have been selectively maintained due to an adaptation that …

Evaluating The Effects Of Vitamin D And Hyaluronic Acid On The Radiation Response Of Normal Mammary Epithelial Cells And Breast Cancer Cells, Lauren Rose-Boehnlein

Legacy Theses & Dissertations (2009 - 2024)

Each year over 200,000 American women are diagnosed with breast cancer. Nearly 25% of them are told they have triple negative breast cancer (TNBC), the most aggressive and lethal form, with few targeted treatment options beyond the standard regimen of surgery, chemotherapy, and radiotherapy. Over 40% of TNBC cases overexpress hyaluronan synthase 2 (HAS2), a cell membrane enzyme that synthesizes the extracellular matrix (ECM) polysaccharide hyaluronic acid (HA). HA binds to and activates the cell surface receptor CD44, which is highly enriched on the cell surface of cancer stem cells (CSCs) and has been associated with epithelial to mesenchymal transition …

Circular Rna : A Review Of History, Diseases, And Diagnostic Potential, Daniel Conley

Legacy Theses & Dissertations (2009 - 2024)

Abstract

Heteromeric Assemblies Of Glua3 Flip And Flop Shows Differences In Their Channel Opening Kinetics, Nicholas Karl

Legacy Theses & Dissertations (2009 - 2024)

Prior studies of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, including that of GluA3 AMPA receptor subunit, have shown that alternative mRNA splicing, which generates flip and flop variants with different amino acid sequences, gives rise to functional differences between the two variants. The goal of this MS thesis is to investigate the basic gating properties of the heteromeric complex channels formed from GluA2R/GluA3 AMPA receptor subunits and the different variants between the two subunits. The hypothesis to be tested is whether different GluA3 variants affect the channel gating properties when each of the variants is in a complex with the Q/R-site edited …

Functional Modulation Of Ampa Receptors By R/G Editing And Auxiliary Subunits, Wei Wen

Legacy Theses & Dissertations (2009 - 2024)

The propagation of information in the central nervous system is, in essence, the flow of ions. Neurons connect with each other to form neural circuits that perform distinct functions, and these connections are formed through synapses. Excitatory and inhibitory synapses determine the excitability of a neuron, which further dictates the firing of action potentials. The major ion channels that mediate the transmission at the excitatory synapses are ionotropic glutamate receptors, among which AMPA receptors are responsible for the fast excitatory transmission. Therefore, the functionalities of AMPA receptors substantially affect the information flow, and dysfunction of them could potentially cause many …

The Development Of Bioaffinity-Based Concepts For On-Site Forensic Analyses : Blood, Sweat, And ... Fingerprints?, Crystal Huynh

Legacy Theses & Dissertations (2009 - 2024)

There have been many advances in forensic science over the recent years, but a majority of the tests currently preformed are still heavily reliant upon laboratory-based processes. This means that valuable pieces of information are left unexamined until a crime scene has been completely processed and evidence is moved to a crime lab. In some cases, the evidence may even be left in a queue due to backlogs from previous cases. The delay resulting from the time necessary for crime scene processing and transportation, as well as additional time spent waiting on lab equipment availability, hinders an investigator’s ability to …

Retinoic Acid Receptor Isoform-Specific Control Of Mouse Salivary Gland Development And Regeneration, Kara Desantis

Legacy Theses & Dissertations (2009 - 2024)

Controlled expansion and differentiation of progenitor cell populations is essential for organogenesis followed by continued maintenance of the population into and through adulthood. As the K5+ basal cell population is regulated by retinoic acid signaling, we interrogated the contribution of specific RAR isoforms to the regulation of these cells during submandibular salivary gland (SMG) organogenesis and regeneration. Retinoic acid has previously been shown to be involved in the development of the salivary gland, and recently, lack of retinoid signaling has been shown to impact the K5+ population of basal progenitor cells. Since retinoic acid is known to exert stimulatory effects …

Genetically Engineered Polypeptides As Biomimetic Light Harvesting Optical Antenna, Jason P. Seeley

Legacy Theses & Dissertations (2009 - 2024)

Natural resources useful for the generation of energy are limited. The development of efficient materials capable of utilizing the abundant free solar radiation is of considerable interest. Utilization of otherwise wasted energy sources, including solar radiation, is a progressive step in the quest for sustainable energy. Solar radiation incident upon the earth’s surface exceeds current energy requirements and motivates scientists to investigate and develop functional devices and nanomaterials including light harvesting complexes (LHC) capable of capturing solar radiation for energy conversion and storage.

Complete Genome Sequence Of Moraxella Bovis Strain Epp-63 (300), An Etiologic Agent Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Aaron M. Dickey, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

We report here the complete closed genome sequence of Moraxella bovis strain Epp-63 (300) (Epp63). This strain was isolated from an infectious bovine keratoconjunctivitis (IBK) case in 1963. Since then, Epp63 has been used extensively for IBK research. Consequently, the genome sequence of Epp63 should help elucidate IBK host-pathogen interactions.

Methionine Sulfoximine: A Novel Anti Inflammatory Agent, Tyler Peters

Wayne State University Dissertations

ABSTRACT

METHIONINE SULFOXIMINE: A NOVEL ANTI-INFLAMMATORY AGENT

by

TYLER J. PETERS

October 2018

Advisor: William Brusilow

Major: Biochemistry and Molecular Biology

Degree: Doctor of Philosophy

The glutamine synthetase inhibitor methionine sulfoximine (MSO), shown previously to prevent death caused by an inflammatory liver response in mice, was tested on in vitro production of cytokines by mouse peritoneal macrophages triggered with lipopolysaccharide (LPS). MSO significantly reduced the production of Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha (TNFα) at 4 and 6 hours after LPS-treatment. This reduction did not result from decreased transcription of IL-6 and TNFα genes, and therefore appeared to …

Computational Design Of Levansucrase For Production Of Tailor-Made Length Levan-Type Fructo-Oligosaccharides, Pongsakorn Kanjanatanin

Chulalongkorn University Theses and Dissertations (Chula ETD)

Levansucrase (LS) is an exocellular fructosyltransferase catalyzing the hydrolysis of sucrose and polymerization of levan and levan-type fructo-oligosaccharides (LFOs) that have various potentials in pharmaceutical and biological applications such as prebiotics and anticancer agents. LFOs with the chain length of 5 (LFO5 or GF4) showed inhibition activity against the SW480 colorectal cell lines up to about 83%. Although LFO5 has beneficial properties, the ability to produce LFO5 in large quantity is still limited. This study aimed to explore conformational diversity and elucidate the structural and molecular properties of LFO5, LFO10 and LFO15 as well as to redesign the active site …

Crispr/Cas9-Induced Genetic Disruption And Characterization Of Udp-Galactopyranose Mutase In Trypanosoma Cruzi, Claudia Manriquez

Open Access Theses & Dissertations

The protozoan parasite, Trypanosoma cruzi, is the causative agent of Chagas disease (ChD), or American trypanosomiasis, which affects 6-8 million people in Latin America. It is estimated that 2-3 million people will develop severe lifelong cardiac and/or digestive disorders. ChD has become a life threat not only to endemic regions but most recently also to nonendemic regions, including the United States, owing to extensive worldwide migration in recent years. The lack of a vaccine and the limited efficacy of the two drug treatments available make it urgent to develop novel therapies to treat such a threatening disease. UDP-Galactopyranose mutase (UGM) …

Geant4 Study Of A Gamma Ray Collimator For Proton Therapy, Selim Romero

Open Access Theses & Dissertations

This Thesis presents the results of an investigation of the use of collimators in proton therapy. The problem to solve is that in the proton therapy, we do not have the certainty if the target-tumor is receiving all the energy to destroy it or if we are really shooting at this one, so the remaining question is: where the beam is hitting? How to know it? to answer those questions our work has the propose of study proton therapy to determine where the proton interactions occur, these kinds of interactions usually produce gamma rays, and we simulated in GEANT4 the …

Algae Biofuel Triacylglyceride Transesterification Optimization, Erik Ferenczy

Senior Honors Theses

Algae biofuels may hold the key to solving the problem of fossil fuel consumption by being comparable in content, renewable, and carbon-neutral. Many biofuel researchers and corporations have undertaken to increase the production rate or capacity of triacylglycerides (TAG), the fat precursor to biodiesel fuel produced by algae, in algae cultures and published articles documenting their findings. This research is devoted to evaluating the effect of water that may be present in samples on the conversion efficiency of TAG into fatty acid methyl esters (FAME), commonly referred to as biodiesel. Therefore, that efficiency was studied to find the water content …

Studies On E2 Conjugation Enzyme Partners Of Mulan E3 Ubiquitin Ligase, Rebekah J. Fitzpatrick

Honors Undergraduate Theses

Mulan is an E3 ubiquitin ligase embedded in the outer mitochondria membrane. Mulan’s participation in the ubiquitination process is conducted through its cytosol exposed RING finger domain, and its ability to modulate protein ubiquitination makes it a key player in mitochondrial and cellular homeostasis. Mulan is known to be involved in mitochondrial fission, fusion, mitochondrial stress, apoptosis, and Parkin-independent mitophagy. Dysregulation of Mulan in mice has been shown to correlate with human neurodegenerative disorders and heart disease. Accumulation of Mulan is predicted to be responsible for the motor neuron degeneration 2 (mnd2) phenotype in mutant mice through the deregulation of …