Physical Sciences and Mathematics Commons^™

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 …

The Metabolic Change Of Lipid Species In Stam Mice With Hepatocellular Carcinoma, Devin J. Peart

UNLV Theses, Dissertations, Professional Papers, and Capstones

Primary liver cancer hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. In the US, primary liver cancer is the most rapidly increasing type of cancer due to increases in hepatitis B and C and the continued trend of greater and greater percentages of the population suffering from obesity, diabetes mellitus and metabolic syndrome. The prognosis for this disease is poor, with a 5-year survival rate of 26% as compared to only 2% when the cancer is metastatic. Unfortunately, current strategies for early detection of HCC, including routine CT imaging or alpha-fetoprotein biomarker, are suboptimal and tend …

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 …

Nitric Oxide Is Involved In Heavy Ion-Induced Non-Targeted Effects In Human Fibroblasts, Megumi Hada, Premkumar B. Saganti, Francis A. Cucinotta

Health Physics & Diagnostic Sciences Faculty Publications

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the …

An Unexpected Rhenium(Iv)–Rhenium(Vii) Salt: [Co(Nh3)6]3[Reviio4][Reivf6]46h2o, James Louis_Jean, Samudee Mariappan Balasekaran, Adelheid Hagenbach, Frederic Poineau

Chemistry and Biochemistry Faculty Research

The title hydrated salt, tris[hexaamminecobalt(III)] tetraoxidorhenate(VII) tetrakis[hexafluoridorhenate(IV)] hexahydrate, arose unexpectedly due to possible contamination of the K2ReF6 starting material with KReO4. It consists of octahedral [Co(NH3)6] 3+ cation (Co1 site symmetry 1), tetrahedral [ReVIIO4] anions (Re site symmetry 1) and octahedral [ReIVF6] 2 anions (Re site symmetries 1and 3). The [ReF6] 2 octahedral anions (mean Re—F = 1.834 A˚ ), [Co(NH3)6] 3+ octahedral cations (mean Co—N = 1.962 A˚ ), and the [ReO4] tetrahedral anion (mean Re—O = 1.719 A˚ ) are slightly distorted. A network of N—HF hydrogen bonds consolidates the structure. The crystal studied was refined as a …

Aligning Best Practices In Student Success And Career Preparedness: An Exploratory Study To Establish Pathways To Stem Careers For Undergraduate Minority Students, Kimberly D. Kendricks, Anthony A. Arment, K. V. Nedunuri, Cadance A. Lowell

Journal of Research in Technical Careers

Undergraduate minority retention and graduation rates in STEM disciplines is a nationally recognized challenge for workforce growth and diversification. The Benjamin Banneker Scholars Program (BBSP) was a five-year undergraduate study developed to increase minority student retention and graduation rates at an HBCU. The program structure utilized a family model as a vehicle to orient students to the demands of college. Program activities integrated best K-12 practices and workforce skillsets to increase academic preparedness and career readiness. Findings revealed that a familial atmosphere improved academic performance, increased undergraduate research, and generated positive perceptions of faculty mentoring. Retention rates among BBSP participants …

Ultrafast Laser Filament-Induced Fluorescence Spectroscopy Of Uranyl Fluoride, P. J. Skrodzki, M. Burger, L. A. Finney, F. Poineau, S. M. Balasekaran, J. Nees, K. R. Czerwinski, I. Jovanovic

Chemistry and Biochemistry Faculty Research

Uranyl fluoride (UO2F2) is a compound which forms in the reaction between water and uranium hexafluoride, a uranium containing gas widely used for uranium enrichment. Uranyl fluoride exhibits negligible natural background in atmosphere; as a result, its observation implies the presence and active operation of nearby enrichment facilities and could be used as a tracer for treaty verification technologies. Additionally, detection of UO2F2 has a potential application in guiding remediation efforts around enrichment facilities. Laser-induced fluorescence (LIF) has been proposed in the past as a viable technique for the detection and tracking of UO2F2. We demonstrate that ultrafast laser filamentation …

The San1 Ubiquitin Ligase Functions Preferentially With Ubiquitin-Conjugating Enzyme Ubc1 During Protein Quality Control, Rebeca Lea Ibarra

UNLV Theses, Dissertations, Professional Papers, and Capstones

Protein quality control (PQC) is a critical process wherein misfolded or damaged proteins are cleared from the cell to maintain protein homeostasis. In eukaryotic cells, the removal of misfolded proteins is primarily accomplished by the ubiquitin-proteasome system (UPS). In the UPS, ubiquitin-conjugating enzymes and ubiquitin ligases append poly-ubiquitin chains onto misfolded protein substrates signaling for their degradation. The kinetics of protein ubiquitylation are paramount since a balance must be achieved between the rapid removal of misfolded proteins versus providing sufficient time for protein chaperones to attempt refolding. To uncover the molecular basis for how PQC substrate ubiquitylation rates are controlled, …

The Presence Of Clostridium Difficile On Environmental Surfaces In Healthcare Facilities Pre- And Post-Decontamination Of Patient Rooms, Theresa Trice

UNLV Theses, Dissertations, Professional Papers, and Capstones

Healthcare-associated infections (HAIs) are infections related to receiving medical care. HAIs are responsible for an excess of morbidity and mortality among hospitalized patients. Though most HAIs rates are on the decline, Clostridium difficile infection rates are at an all-time high, primarily due to the persistence of C. difficile spores in the environment. In the United States, Clostridium difficile-related mortality rates per million have increased from 5.7 in 1999 to 23.7 in 2004, with an estimated 26,642 deaths due to Clostridium difficile infections (CDIs). Clostridium difficile is transmitted via the fecal-oral route or aerosolized endospores, but it can also be transmitted …

Beryllium Is A Potent And Unique Gsk-3Β Inhibitor With Potential To Differentially Regulate Glycogen Synthase And Β-Catenin, Ata Ur Rahman Mohammed Abdul

UNLV Theses, Dissertations, Professional Papers, and Capstones

Glycogen Synthase Kinase-3β (GSK-3β) is an important serine/threonine kinase that phosphorylates/regulates diverse and metabolically important proteins. Some of the important substrates of GSK-3β are glycogen synthase, tau, β-catenin, cyclin D1, axin, c-jun, c-myc, Heat Shock Factor–1, BCL-3, CREB, Histone H1.5, mdm2, p21 (CIP1), pyruvate dehydrogenase and many more. De-regulation of GSK-3β has been implicated in diseases like cancer, Alzheimer’s disease, bipolar disorder and type 2 diabetes mellitus. Currently, GSK-3β is one of the most widely studied proteins and there is a great interest in developing potent and efficient GSK-3β-inhibitors for research as well as therapeutic purposes. We demonstrate that beryllium …

Synthesis And Characterization Of Novel Platinum(Ii) And Platinum(Iv) Complexes Containing 4,4′--Disubstituted--2,2′--Bipyridine Ligands For The Treatment Of Cancer, Van Vo

UNLV Theses, Dissertations, Professional Papers, and Capstones

Three series of platinum(II) and platinum(IV) complexes containing 4,4′-disubstituted-2,2′-bipyridine ligands have been synthesized and characterized by 1H NMR, 13C NMR spectroscopy, elemental analysis, mass spectroscopy, and differential scanning calorimetry measurements. The MTS cell proliferation assay was used to examine the in vitro anti-proliferative activities of these complexes in various human breast, lung, and prostate cancer cells. The cell's response to the complexes varies between different cell lines; however, the low EC₅₀ values determined from the MTS data indicate that several of the complexes are much more potent than cisplatin.

Flow cytometric analysis of selected compounds revealed induction of apoptosis …

Initial Characterization Of A Conserved Active Site Residue For The Cdc34 Ubiquitin Conjugating Enzyme, Arvin Akoopie

Honors College Theses

Ubiquitin-conjugating enzymes (E2s) covalently modify protein substrates with ubiquitins. The active site cysteine residues on E2s are essential for catalyzing the transfer of ubiquitin from the E2 active site onto the protein substrate, however there is a limited amount of information available concerning additional active site residues for E2s that may also participate in catalysis. Cdc34 is an essential E2 that has merited the lion’s share of attention for biochemical analysis of the E2 family. Previous phylogenetic analysis of Cdc34 amino acid sequences has identified an invariably conserved histidine residue close to the active site cysteine in the primary structure, …

What Can Biochemistry Students Learn About Protein Translation? Using Variation Theory To Explore The Space Of Learning Created By Some Common External Representations, Thomas J. Bussey

UNLV Theses, Dissertations, Professional Papers, and Capstones

Biochemistry education relies heavily on students' ability to visualize abstract cellular and molecular processes, mechanisms, and components. As such, biochemistry educators often turn to external representations to provide tangible, working models from which students' internal representations (mental models) can be constructed, evaluated, and revised. However, prior research has shown that, while potentially beneficial, external representations can also lead to alternative student conceptions.

Considering the breadth of biochemical phenomena, protein translation has been identified as an essential biochemical process and can subsequently be considered a fundamental concept for biochemistry students to learn. External representations of translation range from static diagrams to …

Anti-Germinants As A New Strategy To Prevent Clostridium Difficile Infections, Amber Janece Howerton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridium difficileinfections (CDI) have emerged as a leading cause of hospital-associated complications. CDI is the major cause of antibiotic-related cases of diarrhea and nearly all cases of pseudomembranous colitis. The infective form of C. difficileis the spore, a dormant and hardy structure that forms under stress. Germination of C. difficile spores into toxin producing bacteria in the GI tract of susceptible patients is the first step in CDI establishment. Patient susceptibility occurs with a disruption of the natural gut microbiota by broad-spectrum antibiotics. Antibiotic treatments usually resolve CDI but refractory cases are on the rise. Of great concern is the …

Secondary Structure, A Missing Component Of Sequence- Based Minimotif Definitions, David P. Sargeant, Michael R. Gryk, Mark W. Maciejewsk, Vishal Thapar, Vamsi Kundeti, Sanguthevar Rajasekaran, Pedro Romero, Keith Dunker, Shun-Cheng Li, Tomonori Kaneko, Martin Schiller

Life Sciences Faculty Research

Minimotifs are short contiguous segments of proteins that have a known biological function. The hundreds of thousands of minimotifs discovered thus far are an important part of the theoretical understanding of the specificity of protein-protein interactions, posttranslational modifications, and signal transduction that occur in cells. However, a longstanding problem is that the different abstractions of the sequence definitions do not accurately capture the specificity, despite decades of effort by many labs. We present evidence that structure is an essential component of minimotif specificity, yet is not used in minimotif definitions. Our analysis of several known minimotifs as case studies, analysis …

Achieving High Accuracy Prediction Of Minimotifs, Tian Mi, Sanguthevar Rajasekaran, Jerlin Camilus Merlin, Michael R. Gryk, Martin Schiller

Life Sciences Faculty Research

The low complexity of minimotif patterns results in a high false-positive prediction rate, hampering protein function prediction. A multi-filter algorithm, trained and tested on a linear regression model, support vector machine model, and neural network model, using a large dataset of verified minimotifs, vastly improves minimotif prediction accuracy while generating few false positives. An optimal threshold for the best accuracy reaches an overall accuracy above 90%, while a stringent threshold for the best specificity generates less than 1% false positives or even no false positives and still produces more than 90% true positives for the linear regression and neural network …

Cell Migration Dynamics After Alteration Of Cell-Cell Contacts In Fibrosarcoma And Glioblastoma Cell Lines, Hassan S. Rizvi, Ronald K. Gary

Undergraduate Research Opportunities Program (UROP)

Cell migration is a vital component of metastasis. In this study, our intent was to study cell migration by alteration of the Wnt/GSK-3 Pathway. Since BeSO4 is a known GSK-3 kinase inhibitor, we hypothesized that this agent would cause cell migration to decrease as a result of β-catenin stabilization. Two human cell lines, HT-1080 (fibrosarcoma) and A172 (glioblastoma), were used to observe migration levels in the presence and absence of BeSO4. Our results show that cell migration is diminished for cells that were pre-treated with BeSO4, in comparison to the untreated (control) cells.

Novel Thermophilic Cellulolytic Isolates Belonging To The Phylum Chloroflexi, Maryknoll Palisoc, Jessica K. Guy, Joseph P. Peacock, Duy C. Trinh, Jeremy A. Dodsworth, Brian P. Hedlund

Undergraduate Research Opportunities Program (UROP)

Current biofuel technologies utilize valuable foodstuffs, such as corn kernels and cane sugar, as sources of easily metabolized sugars. Microbes are used to ferment these sugars into bioethanol, a first-generation biofuel. However, in order to avoid diverting foodstuffs from the food supply, the development of second-generation biofuels technology is necessary. Second-generation biofuels are produced by converting structurally complex lignocellulosic biomass, such as agricultural and municipal wastes, to fermentable sugars or directly to biofuels.

The major technological hurdle limiting the mass production of second-generation biofuels is the difficulty in efficiently converting structurally complex lignocellulosic materials to fermentable sugars or directly to …

Synthesis Of A Chemical Probe For Identification Of Ger Receptor Proteins Of Bacillus Anthracis, Hyelee Lee

UNLV Theses, Dissertations, Professional Papers, and Capstones

Bacillus anthracis,a gram positive, endospore-forming, rod-shaped, aerobic bacterium, is the causative agent of anthrax. A key step in the pathogenic cycle is the spore germination, where the dormant spore transforms into a metabolically active cell. This allows B. anthracis to proliferate and secrete toxins. It is believed that spore germination is triggered when small molecules, known as germinants, are recognized by germination (Ger) receptor proteins located in the inner membrane of spores. Most Ger proteins are encoded by tricistronic operons, resulting in three distinct products, the A-, B-, C-subunits. Genomic sequencing showed that B. anthracis has seven ger receptor …

Accumulation Of Polonium-210 In Different Species Of Fish In Lake Mead, Suraj Ghevarghese John, Shungmugam Nallaperumal, Vernon Hodge

Festival of Communities: UG Symposium (Posters)

Discovered by Pierre Curie and Marie Skłodowska-Curie in 1898, polonium is a chemical element with an atomic number of 84. This rare naturally occurring radioactive element is chemically similar to bismuth and tellurium, and forms in uranium ores. Polonium-210 is an naturally occurring radioactive element with a half-life of 138.376 days(1). This element is found in trace amounts in most organisms. Our research is focused on the accumulation of polonium-210 in fish that occupy in Lake Mead.

The sample species is chosen based on varying lake stratification (layers of the lake). This gives us a good idea of the difference …

Characterization Of Ips Pini Ipsdienol Dehydrogenase (Idol Dh), Heidi Pak, Claus Tittiger, William Welch

Festival of Communities: UG Symposium (Posters)

Ipsdienol is an important pheromone component for pine engraver beetle, Ips pini. Ipsdienol is a ten carbon monoterpenoid secondary alcohol and ipsdienone is the corresponding ketone. We are characterizing the activity of recombinant IDOL DH produced in Sf9 (insect) cells. The enzyme has a high stereospecificity: (-) ipsdienol was found to be a substrate while (+)-ipsdienol was neither a substrate nor inhibitor. Closely related monoterpenoids, such as nerol, geraniol, and citral, were neither substrates nor inhibitors. Smaller compounds, such as 2-propanol, also failed to act as an inhibitor or substrate. This indicates the binding site of this enzyme is highly …

Scireader Enables Reading Of Medical Content With Instantaneous Definitions, Patrick R. Gradie, Megan Litster, Rinu Thomas, Jay Vyas, Martin Schiller

Life Sciences Faculty Research

Background

A major problem patients encounter when reading about health related issues is document interpretation, which limits reading comprehension and therefore negatively impacts health care. Currently, searching for medical definitions from an external source is time consuming, distracting, and negatively impacts reading comprehension and memory of the material.

Methods

SciReader was built as a Java application with a Flex-based front-end client. The dictionary used bySciReader was built by consolidating data from several sources and generating new definitions with a standardized syntax. The application was evaluated by measuring the percentage of words defined in different documents. A survey was used …

Antimicrobial Activity Of D-Lenolate®, Andy Phui

UNLV Theses, Dissertations, Professional Papers, and Capstones

Olive trees are one of the most important fruit trees in the Mediterranean. Although not validated by research, olive leaves are traditionally believed to fight off fever and infections. It has been shown that olive leaf extracts possess antimicrobial activity. Olive leaf extracts contain polyphenols. One of the major phenolic compounds is oleuropein. Oleuropein and other polyphenols have been shown to exhibit antimicrobial activity. East Park Research (EPR) developed an extraction process that they claim does not alter the chemical composition of the olive leaves. The extract is known by the commercial name d-lenolate®. Studies have provided evidence that d-lenolate®, …

Bacillus Cereus And Bacillus Anthracis Germination Kinetics: A Michaelis-Menten Approach, Helen Luu

UNLV Theses, Dissertations, Professional Papers, and Capstones

Bacillus species are rod-shaped, gram-positive bacteria that are capable of producing endospores. In this dormant stage, the endospores can persist in hostile physical and chemical environments. Once conditions become favorable, the spores germinate into actively dividing cells, vegetative cells. Germination is a crucial step for the pathogenicity of the Bacilli in affecting a host organism.

Our study applies mathematical approaches to spore germination to determine whether the binding of one germinant will affect the binding of another germinant. We pursued this approach with two different species, B. cereus and B. anthracis, both pathogenic organisms. B. cereus is a widely known …

Partitioning Of Minimotifs Based On Function With Improved Prediction Accuracy, Sanguthevar Rajasekaran, Tian Mi, Jerlin Camilus Merlin, Aaron Oommen, Patrick R. Gradie, Martin R. Schiller

Life Sciences Faculty Research

Background

Minimotifs are short contiguous peptide sequences in proteins that are known to have a function in at least one other protein. One of the principal limitations in minimotif prediction is that false positives limit the usefulness of this approach. As a step toward resolving this problem we have built, implemented, and tested a new data-driven algorithm that reduces false-positive predictions.

Methodology/Principal Findings

Certain domains and minimotifs are known to be strongly associated with a known cellular process or molecular function. Therefore, we hypothesized that by restricting minimotif predictions to those where the minimotif containing protein and target protein have …

Venn, A Tool For Titrating Sequence Conservation Onto Protein Structures, Jay Vyas, Michael R. Gryk, Martin R. Schiller

Life Sciences Faculty Research

Residue conservation is an important, established method for inferring protein function, modularity and specificity. It is important to recognize that it is the 3D spatial orientation of residues that drives sequence conservation. Considering this, we have built a new computational tool, VENN that allows researchers to interactively and graphically titrate sequence homology onto surface representations of protein structures. Our proposed titration strategies reveal critical details that are not readily identified using other existing tools. Analyses of a bZIP transcription factor and receptor recognition of Fibroblast Growth Factor using VENN revealed key specificity determinants. Weblink: http://sbtools.uchc.edu/venn/.

A Proposed Syntax For Minimotif Semantics, Version 1., Jay Vyas, Ronald J. Nowling, Mark W. Maciejewski, Sanguthevar Rajasekaran, Michael R. Gryk, Martin R. Schiller

Life Sciences Faculty Research

BACKGROUND:

One of the most important developments in bioinformatics over the past few decades has been the observation that short linear peptide sequences (minimotifs) mediate many classes of cellular functions such as protein-protein interactions, molecular trafficking and post-translational modifications. As both the creators and curators of a database which catalogues minimotifs, Minimotif Miner, the authors have a unique perspective on the commonalities of the many functional roles of minimotifs. There is an obvious usefulness in standardizing functional annotations both in allowing for the facile exchange of data between various bioinformatics resources, as well as the internal clustering of sets of …

Identifying Biomarkers For Resistance To Novel Cisplatin Analogues In Human Lung, Breast And Prostate Cancers, Becky Michelle Hess

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cisplatin is a common therapeutic agent used in cancer treatment. Unfortunately, resistance to cisplatin in addition to severe side effects limits its use in cancer treatment. Two novel cisplatin analogues, 4DB and 4TB were shown to have varying cytotoxicity in lung, breast and prostate cancer cells. The hypothesis for this study states that the differences in 4DB and 4TB cytotoxicity among different tissue types is due to the type and efficiency of DNA repair mechanisms involved in response to these drugs.

To test the hypothesis, proteins involved in the rate limiting step of nucleotide excision repair (NER) and mismatch repair …

Minimotif Miner 2nd Release: A Database And Web System For Motif Search, Sanguthevar Rajasekaran, Sudha Balla, Patrick R. Gradie, Michael R. Gryk, Krishna Kadaveru, Vamsi Kundeti, Mark W. Maciejewski, Tian Mi, Nicholas Rubino, Jay Vyas, Martin R. Schiller

Life Sciences Faculty Research

Minimotif Miner (MnM) consists of a minimotif database and a web-based application that enables prediction of motif-based functions in user-supplied protein queries. We have revised MnM by expanding the database more than 10-fold to approximately 5000 motifs and standardized the motif function definitions. The web-application user interface has been redeveloped with new features including improved navigation, screencast-driven help, support for alias names and expanded SNP analysis. A sample analysis of prion shows how MnM 2 can be used.

Comparison Of Water Quality, Zooplankton Density, And Cover In Razorback Sucker (Xyrauchen Texanus [Abbott]) Spawning Areas Of Lake Mead And Lake Mohave, Michael E. Golden, Paul B. Holden, Southern Nevada Water Authority

Publications (WR)

Las Vegas Bay and Echo Bay in Lake Mead have small, self-sustaining populations of razorback sucker (Xyrauchen texanus [Abbot]). Increased productivity and cover have been hypothesized as reasons for successful recruitment of razorback sucker in Lake Mead. Conversely, reproduction has been documented on Lake Mohave, another lower Colorado River reservoir, but no recruitment has been observed. In 2000, BIO-WEST, Inc. was contracted by the Southern Nevada Water Authority to design and implement a study to examine nutrient levels, zooplankton density, and cover in areas with and without razorback sucker recruitment success. We sampled Echo Bay, Las Vegas Bay, and …