Biochemistry Commons^™

Haloferax Volcanii For Carotenoid Production, Erika Smith

Honors Theses

Carotenoids are used as natural colorants and have been shown to have numerous health benefits, making these molecules highly desirable in the aquaculture, pharmaceutical, and nutraceutical markets. There is increasing consumer demand for the natural synthesis of carotenoids, but current methods are limited by the cost and difficulty of extraction from organisms. The halophilic archaeon Haloferax volcanii is amenable to extraction and has an endogenous carotenoid biosynthetic pathway that culminates in the accumulation of the carotenoid bacterioruberin; however, H. volcanii also synthesizes important precursors that can be converted into more highly-desired carotenoids, such as β-carotene and astaxanthin, in the presence …

The Biogeochemical Cycling Of Iron, Copper, Nickel, Cadmium, Manganese, Cobalt, Lead, And Scandium In A California Current Experimental Study, Travis Mellett, Matthew T. Brown, P. Dreux Chappell, Carolyn Duckham, Jessica N. Fitzsimmons, Claire P. Till, Robert M. Sherrell, Maria T. Maldonado, Kristen N. Buck

OES Faculty Publications

A 3-day shipboard incubation experiment was conducted in the California Current System in July 2014 to investigate the cycling of iron (Fe), copper (Cu), nickel (Ni), cadmium (Cd), manganese (Mn), cobalt (Co), lead (Pb), and scandium (Sc) under a range of light and particle conditions. Filtered (< 0.2 μm) and unfiltered treatments were incubated under the following light conditions: Dark, light (“UV”), and light without the ultraviolet (UV) wavelengths (“noUV”). The experiment was sampled for carbon and Fe uptake rates, dissolved trace metal concentrations (Fe, Cu, Ni, Cd, Mn, Co, Pb, Sc), Fe and Cu speciation, size-fractionated concentrations of Cd and Fe, and diatom community composition from DNA sequencing. Exposure to UV light increased phytoplankton Fe uptake in the first 24 h of the incubation relative to the noUV treatment, suggesting that a fraction of the ambient ligand-bound Fe was photoreactive. Fe-binding organic ligand production was observed in the unfiltered light treatments in association with increasing chlorophyll a, and evidence for Cu-binding ligand production in these treatments was also observed. Biological uptake of Cd and Co was observed along with scavenging of dissolved Pb. Manganese appeared to be rapidly oxidized by Mn-oxidizing bacteria with concomitant drawdown of dissolved Ni. Scandium displayed similar trends to Fe, reinforcing the limited observations …

Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt

Theses and Dissertations

Acute myeloid leukemia (AML) is the second most common type of leukemia and accounts for 80% of adult acute leukemia cases and is characterized by the accumulation of poorly or undifferentiated myeloid blast cells. Standard treatment includes chemotherapy, which if unsuccessful, is followed by more rigorous chemotherapy as well as stem cell transplantation. Considering most patients are over the age of 45, these more rigorous therapies are not always possible, and as such, new therapies must be developed. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) that results in the expression of an MLL fusion protein …

Synergistic Effect Of Smac-Mimetic And Poly (I:C) On Apoptosis Of Cholangiocarcinoma Cells, Thanpisit Lomphithak

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cholangiocarcinoma (CCA), a malignancy transformed from cholangiocytes in the bile ducts is more common in Asia and has the highest incidence rate in Thailand. CCA is an aggressive malignancy which has high mortality, high recurrence rate and poor prognosis due to late diagnosis and lack of effective treatment, therefore identification of novel therapeutic targets could lead to the development of more efficient therapy. CCA is associated with chronic inflammation that could upregulate Toll-like receptor 3 (TLR3) in CCA cells. TLR3 agonist, poly(I:C) has been reported to directly induce apoptosis in selected cancers and also activates anti-tumor immunity. However, in some …

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 …

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 …

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 …

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 …

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 …

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 …

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.

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 …

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 …

Split Deoxyribozyme Probe For Efficient Detection Of Highly Structured Rna Targets, Sheila Raquel Solarez

Honors Undergraduate Theses

Transfer RNAs (tRNAs) are known for their role as adaptors during translation of the genetic information and as regulators for gene expression; uncharged tRNAs regulate global gene expression in response to changes in amino acid pools in the cell. Aminoacylated tRNAs play a role in non-ribosomal peptide bond formation, post-translational protein labeling, modification of phospholipids in the cell membrane, and antibiotic biosynthesis. ^[1] tRNAs have a highly stable structure that can present a challenge for their detection using conventional techniques. ^[2] To enable signal amplification and lower detection limits, a split probe - split deoxyribozyme (sDz or BiDz) probe, which …

Discovery Of Novel Muraymycin Antibiotics And Insight Into The Biosynthetic Pathway, Zheng Cui

Theses and Dissertations--Pharmacy

New antibiotics with novel targets or mechanisms of action are needed to counter the steady emergence of bacterial pathogens that are resistant to antibiotics used in the clinic. MraY, a promising novel target for antibiotic development, initiates the lipid cycle for the biosynthesis of peptidoglycan cell wall, which is essential for the survival of most, if-not-all, bacteria. MraY is an enzyme that catalyzes the transfer and attachment of phospho-MurNAc-pentapeptide to a lipid carrier, undecaprenylphosphate. Muraymycins are recently discovered lipopeptidyl nucleoside antibiotics that exhibit remarkable antibiotic activity against Gram-positive as well as Gram-negative bacteria by inhibiting MraY. We conducted a thorough …

Morphological, Genetic And Biochemical Characterization Of The Anti-Malarial Herb, Artemisia Annua Germplasm Collection At West Virginia University, Delini K. Samarasinghe

Graduate Theses, Dissertations, and Problem Reports (ETD)

Malaria is one of the deadliest diseases in human history. Nearly half of the world’s population, is at the risk in 106 countries. Only in 2016, this disease killed about 445,000 people, 72% of them being children under age five. It also accounts for US $12 billion dollars of direct costs in Africa alone. Five different species of Plasmodium cause malaria but P. falciparum is the most detrimental one, causing 50% of all malaria cases and is considered as the deadliest parasite in humans. Artemisinin (ART), a 15 C sesquiterpenoid is currently the only precursor to the most effective anti-malarial …

Surface And Structural Modification Of Carbon Electrodes For Electroanalysis And Electrochemical Conversion, Yan Zhang

Theses and Dissertations--Chemistry

Electrocatalysis is key to both sensitive electrochemical sensing and efficient electrochemical energy conversion. Despite high catalytic activity, traditional metal catalysts have poor stability, low selectivity, and high cost. Metal-free, carbon-based materials are emerging as alternatives to metal-based catalysts because of their attractive features including natural abundance, environmental friendliness, high electrical conductivity, and large surface area. Altering surface functionalities and heteroatom doping are effective ways to promote catalytic performance of carbon-based catalysts. The first chapter of this dissertation focuses on developing electrode modification methods for electrochemical sensing of biomolecules. After electrochemical pretreatment, glassy carbon demonstrates impressive figures-of-merit in detecting small, redox-active …

Comparative Toxicology Of Nio And Ni(Oh)₂ Nanoparticles, Melissa Hope Cambre

Masters Theses

“Understanding the potential toxicity of nanoparticles (NPs) is important to ensure that these new products do not impose harmful effects to human and environmental health. Paper I is a literature review in which we discuss characteristics of nanomaterials, with an emphasis on transition metal oxide nanoparticles that influence cytotoxicity. Identification of those properties may lead to the design of more efficient and safer nanosized products for various industrial purposes and provide guidance for assessment of human and environmental health risk. We then investigate biochemical and molecular mechanisms of cytotoxicity that include oxidative stress-induced cellular events and alteration of the pathways …

Enhanced Hot Electron Lifetimes In Quantum Wells With Inhibited Phonon Coupling, Hamidreza Esmaielpour, Vincent R. Whiteside, Herath P. Piyathilaka, Sangeetha Vijeyaragunathan, Bin Wang, Echo Adcock-Smith, Kenneth P. Roberts, Tetsuya D. Mishima, Michael B. Santos, Alan D. Bristow, Ian R. Sellers

Faculty & Staff Scholarship

Hot electrons established by the absorption of high-energy photons typically thermalize on a picosecond time scale in a semiconductor, dissipating energy via various phonon-mediated relaxation pathways. Here it is shown that a strong hot carrier distribution can be produced using a type-II quantum well structure. In such systems it is shown that the dominant hot carrier thermalization process is limited by the radiative recombination lifetime of electrons with reduced wavefunction overlap with holes. It is proposed that the subsequent reabsorption of acoustic and optical phonons is facilitated by a mismatch in phonon dispersions at the InAs-AlAsSb interface and serves to …

Esope-Equivalent Pulsing Protocols For Calcium Electroporation: An In Vitro Optimization Study On 2 Cancer Cell Models, Stefania Romeo, Anna Sannino, Maria Rosaria Scarfi, P. Thomas Vernier, Ruggero Cadossi, Julie Gehl, Olga Zeni

Bioelectrics Publications

Reversible electroporation is used to increase the uptake of chemotherapeutic drugs in local tumor treatment (electrochemotherapy) by applying the pulsing protocol (8 rectangular pulses, 1000 V/cm, 100 µs) standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy multicenter trial. Currently, new electrochemotherapy strategies are under development to extend its applicability to tumors with different histology. Electrical parameters and drug type are critical factors. A possible approach is to test pulse parameters different from European Standard Operating Procedure on Electrochemotherapy but with comparable electroporation yield (European Standard Operating Procedure on Electrochemotherapy-equivalent protocols). Moreover, the use of non-toxic drugs …

Dynamic Control Of Particle Separation In Deterministic Lateral Displacement Separator With Viscoelastic Fluids, Yuke Li, Hongna Zhang, Yongyao Li, Xiaobin Li, Jian Wu, Shizhi Qian, Fengchen Li

Mechanical & Aerospace Engineering Faculty Publications

We proposed an innovative method to achieve dynamic control of particle separation by employing viscoelastic fluids in deterministic lateral displacement (DLD) arrays. The effects of shear-thinning and elasticity of working fluids on the critical separation size in DLD arrays are investigated. It is observed that each effect can lead to the variation of the critical separation size by approximately 40%. Since the elasticity strength of the fluid is related to the shear rate, the dynamic control can for the first time be easily realized through tuning the flow rate in microchannels.

Targeting The Cellular Redox Environment: A Novel Approach For The Treatment Of Hematopoietic Neoplasms, Dustin W. Carroll

Theses and Dissertations--Toxicology and Cancer Biology

Hematopoietic stem cells (HSCs) that function to maintain the hematopoietic compartment through self-renewal and differentiation capacities, as well as their downstream progeny, are susceptible to transformation resulting in the generation of the leukemic stem cell (LSC). Chief in the factors that control HSC regulation and protection of the HSC compartment is the cellular redox environment. Deregulation of the Hematopoietic Stem/Progenitor Cell (HSPC) redox environment results in loss of HSPC function and exhaustion. The characteristic developments of HSPC exhaustion via exposure to redox stress closely mirror phenotypic traits of hematopoietic malignancies, presenting the HSPC/LSC redox environment as a potential therapeutic target. …

Influence Of Dietary Ractopamine And Supranutritional Supplementation Of Vitamin E On Proteome Profile Of Postmortem Beef Longissimus Lumborum Muscle, Hyun Mok Kim

Theses and Dissertations--Animal and Food Sciences

The effects of dietary ingredients on the proteome profile of postmortem beef longissimus lumborum (LL) muscle were evaluated. In the first experiment, the influence of dietary ractopamine on the whole-muscle proteome of beef LL was examined. Five proteins were differentially abundant between ractopamine-fed (RAC) and non-ractopamine fed (CON) groups. The differentially abundant proteins were over-abundant in RAC and were related to muscle structure development (F-actin-capping protein subunit beta-2 and PDZ and LIM domain protein-3), chaperone (heat shock protein beta-1), oxygen transportation (myoglobin), and glycolysis (L-lactate dehydrogenase A chain). These findings indicated that ractopamine influences the abundance of proteins associated with …