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Recombinant Expression Of Preptin Analogs For Alanine Scanning Mutagenesis Of Residues 27-29, Tehgan N. Anguilm

Theses and Dissertations

The novel peptide preptin consists of 34 amino acid residues corresponding to Asp⁶⁹-Leu¹⁰² of proinsulin-like growth factor E-peptide. Preptin has been isolated from pancreatic beta cells, and it has been found to exhibit both metabolic and mitogenic activities. This makes preptin an attractive candidate to treat insulin-independent diabetes and osteoporosis. Alanine scanning mutagenesis was utilized to substitute an alanine for residues Trp²⁷, Arg²⁸, and Gln²⁹ of preptin in order to ultimately study the structure-activity relationship of these residues to preptin’s metabolic activity.

Characterization Of Beryllium Ion Complexation In The Presence Of Biological Buffers Using Isothermal Titration Calorimetry, Guillermo Alexander Ramirez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Be2+ ion is a biologically active metal that is capable of binding to proteins and has been shown to affect various cellular processes. When treated with Be2+, certain cancer cells display cytostatic effects. GSK3β is a regulatory kinase involved in the β-catenin pathway that may be involved in producing these cytostatic effects when Be2+ binds to it. In order to determine binding parameters between Be2+ and GSK3β, isothermal titration calorimetry (ITC) can be utilized. However, titrations at physiological pH cannot be carried out due to Be2+ unique speciation at neutral pH ranges. Significant precipitation occurs at pH 6 and higher …

Geochemical Tracers Of Arctic Ocean Processes: A Study Of Gallium, Barium, And Vanadium, Laura M. Whitmore

Dissertations

The Arctic Ocean is linked to the global oceans and climate through its connectivity with the North Atlantic Ocean and the regional thermohaline deep water formation sites. It’s also a region undergoing rapid environmental change. To inform the community of potential changes in geochemical and biogeochemical cycles, this dissertation addresses three dissolved geochemical tracers (gallium, barium, and vanadium) as indicators of Arctic Ocean processes. Gallium is tested as a replacement for nutrient-type tracers in an effort to deconvolve Pacific and Atlantic derived waters in the Arctic Ocean basins. These water masses carry different heat and salt content and can influence …

Molecular Dynamics Simulations Of Apolipoprotein A1 In Ionic Liquids, Benjamin Smith

Honors Theses

High-density lipoprotein function is essential for the healthy processing of fats in the blood. The function of these proteins is determined by their conformational structure of chains of amino acids. Certain ionic liquids have been shown to interact with individual amino acids to affect the tertiary shape of the protein. These interactions can disrupt the native hydrogen bonds between amino acids which can either promote folding or denaturing of the protein. Our work focused on apoA-1, a high-density lipoprotein that binds to cholesterol for efflux from the body. We studied this protein in different ion-based liquids with sodium, chloride, and …

Identification And Quantification Of Classic, Prescription, And Synthetic Opioids In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc/Ms/Ms), Natalia A. Platosz

Student Theses

The current use and misuse of synthetic and prescription opioids in the US has reached epidemic status. According to the US Department of Health and Human Services, every day more than 130 people in the US die after overdosing on opioids, and 2.1 million had an opioid use disorder in 2016. Hair is becoming an alternative matrix of increasing interest in forensic toxicology to investigate drug use and abuse patterns due to its long window of detection. The focus of this project was to develop and validate a method that simultaneously detects and quantifies 27 classic, prescription and synthetic opioids …

Toxicity Analysis Of 2’-Deoxyguanosine-N2-6-Aminopyrene And 2’-Deoxyguanosine-N2-8-Aminopyrene In Escherichia Coli, Emily Janeiro

Honors Scholar Theses

Cancer is a disease that stems from genomic errors that are not corrected properly by cellular repair mechanisms. Errors are more likely to form when organisms are subjected to DNA damage by mutagenic compounds. 1-Nitropyrene, a nitrated polycyclic aromatic hydrocarbon (nitro-PAH), has been shown to be a potent mutagen that causes cancer. Nitro-PAHs can arise from diesel exhaust products in the environment. Out of all nitro-PAHs, 1-nitropyrene is found in largest quantities in the environment. This poses a great need to study its effects biochemically in order to address its toxicity in DNA. Other nitropyrene derivatives, including 1,6-dinitropyrene and 1,8-dinitropyrene, …

Computational Quantum Study Of Intermediates Formed During The Partial Oxidation Of Melatonin, Oladun Oladiran

Electronic Theses and Dissertations

Melatonin is a neurohormone produced by the pineal gland in the brain. It functions as an antioxidant to scavenge free radicals. Free radicals are reactive species; they often oxidize the cells leading to oxidative stress which may lead to severe health complications. Reaction of melatonin with free radicals is known to be stepwise, as such the stability of the intermediates can be examined. Thus, the possibility of using melatonin as an in vivo spin trap can be determined. Spin traps allow characterization of unstable radical species using electron spin resonance spectroscopy. In this research, ab initio quantum chemistry techniques were …

X-Panding Halogen Bonding Interactions: Hybrid Cocrystals Composed Of Ionic Halides, Iodine And Organoiodines, Khadijatul Kobra

All Dissertations

Halogen bonding referred to as an attractive, noncovalent interaction between an electrophilic region of a halogen atom X (acts as Lewis acid) and a nucleophilic region of a molecule Y (acts as Lewis base). Such interactions and the resulting polymeric networks play an important role in many fields related to crystal engineering, including for example, the fabrication of liquid crystals and novel drug design. The application of halogen bonding has particular promise in biological systems by increasing the lipophilicity of drugs to improve penetration through lipid membranes and tissues, enabling better intracellular delivery.

Based on this concept, my research at …

Effect Of Charged Lipids On The Ionization Behavior Of Glutamic Acid Containing Transmembrane Helices, Brooke Nunn

Chemistry & Biochemistry Undergraduate Honors Theses

Transmembrane proteins make up critical components of living cells. Protein function can be greatly impacted by the charged state of its respective components, the side chains of amino acid residues. Thus far, in the lipid membrane, little is known about the properties of residues such as glutamic acid. To explore these properties, I have included glutamic acid in a suitable model peptide-lipid system for fundamental biophysical experiments. Within the system, I have placed a glutamic acid residue instead of leucine in the L14 position of the helical hydrophobic peptide GWALP23 (acetyl-GGALWLALALALAL¹⁴ALALWLAGA-amide). Substitutions of glutamine and aspartic acid serve …

Computational Study Of Novel Fxbn Spin Trap Analogs With Hydroxyl Radicals, Alexis Harvey

Undergraduate Honors Theses

Free radicals are reactive molecules, which makes them difficult to study. Learning more about free radicals is necessary since they are implicated in many diseases and conditions such as Alzheimer’s disease and aging. Spin traps are molecules that can be used to stabilize free radicals to allow time for the free radicals to be characterized. The purpose of this research was to examine four novel spin traps that combine the properties of existing spin traps to possibly create more effective spin traps. The four novel molecules in question were designed by taking the 4-methylfuroxanyl ring from the α(Z)-(3-methylfuroxan-4-yl)-N-t-butylnitrone spin trap …

Heteroatom-Doped Chemical Vapor Deposition Carbon Ultramicroelectrodes, Alexis Sanwick

Undergraduate Honors Theses

Metal nanoparticles have been a primary focus in areas of catalysis and electrocatalysis applications as a result of their large surface area-to-volume ratios. While there is an increased interest in understanding the properties and behaviors of metal nanoparticles, they can become expensive over time. Recent research has incorporated the idea of using heteroatom-doped materials as a cheaper catalytic alternative to metal nanoparticles. In this study nitrogen-doping and phosphorous-doping techniques were applied to chemical vapor-deposited carbon ultramicroelectrodes in order to study the electrocatalytic properties toward the oxygen reduction reaction and the enhanced affinity for the deposition of gold nanoparticles onto the …

Raman Spectroscopic And Quantum Chemical Investigation Of The Effects Of Tri-Methylamine N-Oxide (Tmao) On Hydrated Urea, Hydrated Guanidinium, And Hydrogen Bonded Networks, Genevieve Verville

Honors Theses

Trimethylamine N-Oxide (TMAO), guanidinium, and urea are three important

osmolytes with their main significance to the biophysical field being in how they

uniquely interact with proteins. TMAO is known to stabilize and counteract the

destabilizing effects of both urea and guanidinium. The exact mechanisms by which

TMAO stabilizes and both guanidinium and urea destabilize folded proteins continue

to be debated in the literature. Some studies suggest that solvent interactions do not

play a large role in TMAO’s stabilizing effects and therefore advocate direct

stabilization, whereas others suggest that TMAO counteracts denaturation primarily

through an indirect effect of strong solvent interactions. …

Synthesis Of Amide And Sulfonamides As Pde11 Inhibitors, Noor Abouchakra

Theses, Dissertations and Culminating Projects

With increasing age, individuals begin to experience cognitive decline, especially memory deficits. Given the lack of effective treatments for memory loss, a new promising approach includes targeting second messenger systems that play a critical role in cognitive processes by inhibiting phosphodiesterases (PDEs), specifically PDE11A since its expression is restricted to the brain. PDE11A is responsible for regulating levels of second messengers, such as cyclic AMP and cyclic GMP, which participate in several biochemical processes relating to long term memory function. Since these signaling cascades are controlled by PDEs that result in turning off the signaling pathway, inhibiting phosphodiesterases will lead …

Dose Response Effect Of Mycobacterium Smegmatis-Derived Lipomannan In Raw 264.7 Murine Macrophages, Cassandra Robertson

Undergraduate Theses and Capstone Projects

Tuberculosis is a debilitating respiratory disease caused by the bacterial species Mycobacterium tuberculosis, which acts by infecting the host’s macrophages and evading their immune responses. The purpose of the study was to determine if RAW 264.7 murine macrophage activity could be facilitated and intensified by stimulation with LAM from M. smegmatis. Stimulation with bacterial LAM, and lipopolysaccharide (LPS) as a positive control, yields functional endpoints: nitric oxide (NO) production measured by nitrites (NO2) in the culture supernatant and expression of proteins, such as tumor necrosis factor-α and inducible nitric oxide synthase (iNOS). RAW 264.7 cells were stimulated dose-responsively with LAM …

Development Of Capillary-Channeled Polymer (C-Cp) Fiber As Stationary Phase For Biological Sample Application, Lei Wang

All Dissertations

Capillary-channeled polymer (C-CP) fibers as an alternative support/stationary phase for biomacromolecule separations on analytical and preparative scales have been developed by Marcus research group. The combination of the fiber micro- and macro-structures and in-column orientation allows operation at comparably high linear velocities (~100 mm s-1) without excessive system backpressure. The ability to move fluid efficiently through the structure is complemented by the fact that the fiber physical structure is effectively nonporous with respect to the size of proteins, therefor there is no significant intrafiber diffusion. Ultimately, these factors combine for protein separations that are devoid of appreciable van Deemter C-term …

Resolution Of Portable Raman Spectrometers And Its Effect On The Analysis Of Biological Specimens, Jalissa Thomas

Chemistry

Body fluid traces are a common and a major form of evidence that can be found at a crime scene, as it is a good source of DNA. As such, it is vital that body fluid evidence is properly detected and identified. Issues with the current methods of identifying body fluids and the large backlog of evidence in most forensic labs call for more accurate on-scene (in situ) body fluid identification. Past research has demonstrated that Raman spectroscopy is an advantageous tool for accurately and quickly identifying body fluids, namely in the laboratory. Portable Raman instruments have been …

Analysis Of Fatty Acids In Chukchi Sea Sediments, Damilola Ajadi

Theses and Dissertations

The Arctic Ocean and its marginal seas are key areas for understanding the global climate system. Climate change causes increased terrigenous materials to be carried into the ocean as well as higher production of marine organic matter in the ocean. This study determined the concentrations, distribution, and sources of fatty acids in core sediments from four locations: Stations H32, H30, BarC5 and H24 in the Chukchi Sea, which are in the Arctic Ocean. Fatty acids are valuable tracers of marine or terrigenous inputs and may give evidence to the extent of climate change. Fatty acids were analyzed, characterized using GC-MS …

Comparison Of Three Analytical Techniques For General Characterisation Of Selected Algae And Cyanobacteria, Mohamed Iqbal Suhaina Nashath

Student Works (2020-2029)

Algae and cyanobacteria maintain the oxygenation of earth, and are utilised as biofuels, biofertilizers and nutrition feed. The characterisation of algae and cyanobacteria through conventional methods require technical expertise, laborious sample preparation, and moderately expensive instruments and reagents. Hence, in this study, selected bioanalytical techniques with minimal sample preparation were incorporated, to simplify the characterisation of algae and cyanobacteria. The objectives of this research were to study the phylogenetic relationship of the selected algae and cyanobacteria via the 23S plastid ribosomal ribonucleic acid (rRNA) and 18S rRNA biomarkers; to validate the presence of the microcystin synthetase (mcy) gene cluster encoding …

Synthesis And Characterization Of Carbon Monoxide Producers Bipyridine Flavonolate Palladium(Ii) And Platinum(Ii) Complexes: Potential Anti-Cancer Agents, Sarah Whitfield

Electronic Theses and Dissertations

Novel designed metal ligand complexes as prodrugs are useful in the effort to find more effective and selective anti-cancer treatments. Carbon monoxide, CO, is known to induce mitochondrial collapse in cancer cells. Herein is described the synthesis of seven novel bipyridine flavonolate palladium(II) and platinum(II) complexes with the property of releasing carbon monoxide, and their characterization with FTIR, UV-Vis, fluorescence, NMR, and ESI mass spectra. Their ability to release carbon monoxide was investigated through oxygenation reaction under various conditions of temperature and light irradiation. The nitroxygenation reaction of the palladium complexes was also studied with nitrosyl hydride, HNO, generated in …

Spectroscopic And Computational Studies Of The Agricultural Active Ingredient Dicamba, James Johnson

Honors Theses

3,6-dichloro-2-methoxy benzoic acid, more commonly known as Dicamba, is the active ingredient in an array of pesticides used on farmlands across the globe. Dicamba’s mode of action works by mimicking the plant hormone auxin, which is synonymous to growth hormones in mammals. The mimicking of auxin results in excessive elongation and growing, which is eventually fatal for plants when the rate of growth can no longer be sustained. Dicamba has risen in prominence in recent years due to drift damage as a result of Dicamba’s high volatility. Having the ability to identify Dicamba is crucial for the agricultural industry. The …

Assessing Amino Acid Racemization In Avian Eggshells Through Reverse Phase Liquid Chromatography, Nikitha Nelapudi

Honors Theses

The extent of amino acid racemization (AAR) observed in organic material offers insight into geochronology. Within the scope of AAR research, Avian eggshells are reliable sources of data due to retention of indigenous amino acids through calcification. This project develops a robust quantification methodology for up to 9 D/L amino acids using reverse-phase HPLC (RP-HPLC) with precolumn derivatization. Reliable quantitation is established via statistical assessment of detectability and calibration curves. Progress has focused on obtaining adequate enantioseparation and reproducible data of single D/L amino acids.

Design Of A Novel Isoxazoline Class Drug For The Suppressive Treatment Of Malaria, Peyton Ware

Honors Theses

Design of a novel isoxazoline class drug for the suppressive treatment of erythrocytic malaria through the inhibition of Plasmodium Falciparum Gylceraldehyde-3-phosphate Dehydrogenase (PfGAPDH) gave rise to creation of a synthetic plan for the proposed target molecule α-amino- 3-bromo-4,5-dihydroisoxazol-5-yl propionic acid. A literature-based analysis of the moieties targeting the PfGADPH active site led to the design of the target molecule. Subsequently, an exploration of the literature yielded a possible bifold synthetic plan. Attempts at a model epoxidation reaction using mCPBA and further efforts towards the synthesis of a 3- bromoisoxazoline were shown to be successful using GCMS analysis.

A Game-Theoretic Approach To Deciphering The Dynamics Of Amyloid-Beta Aggregation Along Competing Pathways, Preetam Ghosh, Pratip Rana, Vijayaraghavan Rangachari, Jhinuk Saha, Edward Steen, Ashwin Vaidya

Faculty Publications

Aggregation of amyloid-β (Aβ) peptides is a significant event that underpins Alzheimer's disease (AD). Aβ aggregates, especially the low-molecular weight oligomers, are the primary toxic agents in AD pathogenesis. Therefore, there is increasing interest in understanding their formation and behaviour. In this paper, we use our previously established results on heterotypic interactions between Aβ and fatty acids (FAs) to investigate off-pathway aggregation under the control of FA concentrations to develop a mathematical framework that captures the mechanism. Our framework to define and simulate the competing on- and off-pathways of Aβ aggregation is based on the principles of game theory. Together …

Co Sense And Release Flavonols: Progress Toward The Development Of An Analyte Replacement Photocorm For Use In Living Cells, Marina Popova, Tatiana Soboleva, Abby D. Benninghoff, Lisa M. Berreau

Chemistry and Biochemistry Faculty Publications

Carbon monoxide (CO) is a signaling molecule in humans. Prior research suggests that therapeutic levels of CO can have beneficial effects in treating a variety of physiological and pathological conditions. To facilitate understanding of the role of CO in biology, molecules that enable fluorescence detection of CO in living systems have emerged as an important class of chemical tools. A key unmet challenge in this field is the development of fluorescent analyte replacement probes that replenish the CO that is consumed during detection. Herein, we report the first examples of CO sense and release molecules that involve combining a common …

Mycobacteriophage Morphology As A Diagnostic For Cluster Assignment, Ethan Dionne

Chemistry & Biochemistry Student Scholarship

Major: Biochemistry

Faculty Mentor: Dr. Kathleen A. Cornely, Chemistry and Biochemistry

Phages are viral bodies that infect bacterial hosts, and have shown promising applications as alternatives to antibiotics for the treatment of bacterial infections. This project examines the morphology of siphoviridae mycobacteriophage, which have long, flexible, non-contractile tails as well as the characteristic head, called a capsid. Using electron microscopy photos of sequenced phages, tail length and capsid diameter were measured and compared to further characterize morphological relationships between genetically distinct phages. The data presented has the potential to work as a diagnostic tool to classify unsequenced phages to genetically …

Towards The Development Of Low-Cost And Easily-Deployable Sensing Platforms For Phosphate, Maureen Pontarelli, Thomas Koch

Chemistry & Biochemistry Student Scholarship

Maureen Pontarelli ’20
Major: Chemistry

Thomas Koch '20
Major: Biochemistry

Faculty Mentor: Dr. John Breen, Chemistry and Biochemistry

Exploration Of K2 Mycobacteriophages With Bred​, Colby Agostino, Olivia Schmitt

Chemistry & Biochemistry Student Scholarship

Colby Agostino ’22
Major: Biochemistry and Computer Science

Olivia Schmitt ’22
Major: Biochemistry

Faculty Mentor: Dr. Kathleen A. Cornely, Chemistry and Biochemistry

ZoeJ and Marcoliusprime are mycobacteriophage capable of infecting tuberculosis causing bacteria via the lytic and lysogenic cycles. The lytic cycle is the form of viral replication that results in cell death. Lysogeny involves phage DNA being integrated with the DNA of the host cell and preserved through binary fission. However, the bacteria causing tuberculosis do not die in the lysogenic phase. This research project will involve creating mutants of ZoeJ and Marcoliusprime that will not contain the genes …

Structure Activity Relationship (Sar) Studies Of Neurotoxin Quinoline-Derivatives, Dylan Smeyne

Honors College Theses

Structure activity relationship (SAR) studies are performed in order to identify the core structure that is responsible for the biological activity of an organic molecule. Recently, we have synthesized a drug prototype which contains several functional groups, such as an alcohol, an ester, a fluorine, and an aromatic ring. While studying in vivo toxicity of this molecule in zebrafish (Danio rerio) embryo, we observed that it has a unique biological activity that causes a sudden inactivity in embryo movement. Continued investigation revealed that this molecule blocks sodium channels in neurons causing a temporary anesthesia in Danio rerio embryo. The biological …

Sequence Changes Modulate Peptoid Self-Association In Water, Amelia A. Fuller, Christian J. Jimenez, Ella K. Martinetto, Jose L. Moreno Jr., Anna L. Calkins, Kalli M. Dowell, Jonathan Huber, Kyra N. Mccomas, Alberto Ortega

Chemistry and Biochemistry

Peptoids, N-substituted glycine oligomers, are a class of diverse and sequence-specific peptidomimetics with wide-ranging applications. Advancing the functional repertoire of peptoids to emulate native peptide and protein functions requires engineering peptoids that adopt regular secondary and tertiary structures. An understanding of how changes to peptoid sequence change structural features, particularly in water-soluble systems, is underdeveloped. To address this knowledge gap, five 15-residue water-soluble peptoids that include naphthalene-functionalized side chains were designed, prepared, and subjected to a structural study using a palette of techniques. Peptoid sequence designs were based on a putative amphiphilic helix peptoid bearing structure-promoting (S)-N-(1-naphthylethyl)glycine residues whose self-association …

295— Biomimicry: Investigating The Active Site Model Of Lactate Racemase, Stephanie Podguski, Maisy Ross

GREAT Day Posters

Because of humans’ heavy impact on nature with industrialization and resource extraction, biomimetics, also known as biomimicry, is a study that has emerged. Biomimetics utilizes observations from nature to comprehend the principles of underlying mechanisms and apply concepts that may benefit science, medicine, engineering and the like. An area of biochemistry we are applying this to is the lactate racemase enzyme.This metalloenzyme is found in many prokaryotic organisms and catalyzes the interconversion between the two optical isomers of lactic acid. The structure of this enzyme consists of a square-planar nickel (II) ion coordinated by a histidine residue and a pincer …