Biochemistry, Biophysics, and Structural Biology Commons^™

Effects Of Cations And Dipicolinic Acid On B. Anthracis Spore Physiology And Cytotoxicity, Chandler P. Hassan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Inhalation of Bacillus anthracis spores leads to the most severe form of anthrax. Following phagocytosis by alveolar macrophages, spores germinate inside the phagolysosome. The mechanism used by the newly germinated B. anthracis cells to survive within macrophages is not completely understood.B. anthracis spores contain large concentrations of calcium in complex with dipicolinic acid (Ca-DPA). Upon germination, the cell excretes the large depot of Ca-DPA. DPA is an amphipathic molecule that could act as a buffer and modulate phagolysosome acidification. Intracellular calcium overload can disrupt signaling pathways required for normal macrophage function and trigger cell death. We hypothesized the release of …

Differential Expression Of Cellular And Exosomal Microrna Isolated From Oral Cancer Cells And Their Resistance To Chemotherapy, Brady Petersen

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: MicroRNAs are abundant small non-coding RNA with a variety of known functions, including transcriptional activation and inhibition. Recent evidence has suggested that microRNA expression may influence the responsiveness of some cancers to chemotherapy, including liver and lung cancers. Some evidence has now suggested that specific microRNAs, such as miR-21, miR-155, and miR-375, may influence oral cancer responsiveness to chemotherapy – although much remains to be discovered.

Objective: Based upon the lack of evidence in this area, the primary objective of this study was to evaluate microRNA expression and responsiveness among oral cancers.

Methods: Five commercially available oral cancer cell …

Xrcc4 And Mre11 Roles And Transcriptional Response To Repair Of Talen-Induced Double-Strand Dna Breaks, Ronald Benjamin, Atoshi Banerjee, Xiaogang Wu, Corey Geurink, Lindsay Buczek, Danielle Eames, Sara G. Trimidal, Janice M. Pluth, Martin R. Schiller

Health Physics & Diagnostic Sciences Faculty Publications

Double-strand breaks (DSB) are one of the most lethal forms of DNA damage that, if left unrepaired, can lead to genomic instability, cellular transformation, and cell death. In this work, we examined how repair of transcription activator-like effector nuclease (TALEN)-induced DNA damage was altered when knocking out, or inhibiting a function of, two DNA repair proteins, XRCC4 and MRE11, respectively. We developed a fluorescent reporter assay that uses TALENs to introduce DSB and detected repair by the presence of GFP fluorescence. We observed repair of TALEN-induced breaks in the XRCC4 knockout cells treated with mirin (a pharmacological inhibitor of MRE11 …

Dual Activities Of Acc Synthase: Novel Clues Regarding The Molecular Evolution Of Acs Genes, Chang Xu, Bowei Hao, Gongling Sun, Yuanyuan Mei, Lifang Sun, Yunmei Sun, Yibo Wang, Yongyan Zhang, Wei Zhang, Mengyuan Zhang, Yue Zhang, Dan Wang, Zihe Rao, Xin Li, Jeffery Shen, Ning Ning Wang

Life Sciences Faculty Research

Ethylene plays profound roles in plant development. The rate-limiting enzyme of ethylene biosynthesis is 1-aminocyclopropane-1-carboxylate (ACC) synthase (ACS), which is generally believed to be a single-activity enzyme evolving from aspartate aminotransferases. Here, we demonstrate that, in addition to catalyzing the conversion of S-adenosyl-methionine to the ethylene precursor ACC, genuine ACSs widely have Cβ-S lyase activity. Two N-terminal motifs, including a glutamine residue, are essential for conferring ACS activity to ACS-like proteins. Motif and activity analyses of ACS-like proteins from plants at different evolutionary stages suggest that the ACC-dependent pathway is uniquely developed in seed plants. A putative catalytic mechanism for …

Functional Coordination Of Bet Family Proteins Underlies Altered Transcription Associated With Memory Impairment In Fragile X Syndrome, Seung Kyoon Kim, Xihui Liu, Jongmin Park, Dahun Um, Gokhul Kilaru, Cheng Ming Chiang, Mingon Kang, Kimberly M. Huber, Keunsoo Kang, Tae Kyung Kim

Computer Science Faculty Research

Bromodomain and extraterminal proteins (BET) are epigenetic readers that play critical roles in gene regulation. Pharmacologic inhibition of the bromodomain present in all BET family members is a promising therapeutic strategy for various diseases, but its impact on individual family members has not been well understood. Using a transcriptional induction paradigm in neurons, we have systematically demonstrated that three major BET family proteins (BRD2/3/4) participated in transcription with different recruitment kinetics, interdependency, and sensitivity to a bromodomain inhibitor, JQ1. In a mouse model of fragile X syndrome (FXS), BRD2/3 and BRD4 showed oppositely altered expression and chromatin binding, correlating with …

The Role Of Nutrition And Hormone Signaling In Extended Larval Development And Obesity In Starvation-Selected Drosophila Melanogaster, Jennifer M. Clark

UNLV Theses, Dissertations, Professional Papers, and Capstones

Brief periods of starvation are a common stressor that most animals encounter in the wild and must be able to survive in order to maximize their fitness. Starvation resistance of the adult fruit fly, Drosophila melanogaster, is thought to be primarily conferred by adult fat stores, body size, metabolic rate, behavior, and activity levels. Additionally, flies selected for starvation resistance also often show delayed pupariation, which is usually indicative of altered hormone signaling. How starvation selection extends development and if it contributes to adult starvation resistance remains incompletely studied. Identifying the targets of starvation selection that cause extended development and …

Understanding The Role Of Ano1 In Oral Cancer, Mallary Forrest

UNLV Theses, Dissertations, Professional Papers, and Capstones

In 2008, the gene ANO1 was discovered to encode a calcium activated chloride channel. This gene is located on the 11q13 locus, a locus that is commonly amplified in many cancers including cancer of the head and neck. ANO1 is situated in close proximity to genes associated with growth and apoptosis. As rapid proliferation and lack of apoptosis are hallmark characteristics of cancer, growth factors and apoptosis mediators are expected to be altered in cancer. But what does a calcium activated chloride channel have to contribute to cancer’s pathogenesis? Is it an active gene in cancer progression or is it …

Effects Of Curcumin And Its Different Formulations In Preclinical And Clinical Studies Of Peripheral Neuropathic And Postoperative Pain: A Comprehensive Review, Paramita Basu, Camelia Maier, Arpita Basu

Kinesiology and Nutrition Sciences Faculty Publications

Lesion or disease of the somatosensory system leads to the development of neuropathic pain. Peripheral neuropathic pain encompasses damage or injury of the peripheral nervous system. On the other hand, 10–15% of individuals suffer from acute postoperative pain followed by persistent pain after undergoing surgeries. Antidepressants, anticonvulsants, baclofen, and clonidine are used to treat peripheral neuropathy, whereas opioids are used to treat postoperative pain. The negative effects associated with these drugs emphasize the search for alternative therapeutics with better efficacy and fewer side effects. Curcumin, a polyphenol isolated from the roots of Curcuma longa, possesses antibacterial, antioxidant, and anti-inflammatory properties. …

Vitamin D3 Induces Mesenchymal-To-Endothelial Transition And Promotes A Proangiogenic Niche Through Igf-1 Signaling, Lei Chen, Anweshan Samanta, Lin Zhao, Nathaniel R. Dudley, Tanner Buehler, Robert J. Vincent, Jeryl Hauptman, Magdy Girgis, Buddhadeb Dawn

School of Medicine Faculty Publications

Biological Sciences; Physiology; Molecular Biology; Cell Biology

Rasagiline Effects On Glucose Metabolism, Cognition, And Tau In Alzheimer’S Dementia, Dawn C. Matthews, Aaron Ritter, Ronald G. Thomas, Randolph D. Andrews, Ana S. Lukic, Carolyn Revta, Jefferson W. Kinney, Babak Tousi, James B. Leverenz, Howard Fillit, Kate Zhong, Howard H. Feldman, Jeffrey Cummings

Integrated Health Sciences Faculty Publications

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer's disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose–positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points. Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to …

Transcriptional Control Of Virulence Genes In The Bacterial Pathogen Shigella Flexneri, Joy Asami Mckenna

UNLV Theses, Dissertations, Professional Papers, and Capstones

Shigella species, the causal agents of bacillary dysentery, use a type III secretion system (T3SS) to inject two waves of virulence proteins, known as effectors, into the human colonic epithelium to subvert host cell machinery. Transcriptional regulation of these virulence genes is controlled by the three-tiered VirF/VirB/MxiE signaling cascade. Of these, VirB has the largest regulon (~50 genes); however, VirB regulatory properties are poorly understood. To date, VirB is known to function to counter or 'anti-silence' transcriptional silencing mediated by the histone-like nucleoid structuring protein H-NS. To better understand VirB regulation, my colleagues and I chose to better define the …

In Vivo Biosynthesis Of Inorganic Nanomaterials Using Eukaryotes - A Review, Ashiqur Rahman, Julia Lin, Francisco E. Jaramillo, Dennis A. Bazylinski, Clayton Jeffryes, Si Amar Dahoumane

Life Sciences Faculty Research

Bionanotechnology, the use of biological resources to produce novel, valuable nanomaterials, has witnessed tremendous developments over the past two decades. This eco-friendly and sustainable approach enables the synthesis of numerous, diverse types of useful nanomaterials for many medical, commercial, and scientific applications. Countless reviews describing the biosynthesis of nanomaterials have been published. However, to the best of our knowledge, no review has been exclusively focused on the in vivo biosynthesis of inorganic nanomaterials. Therefore, the present review is dedicated to filling this gap by describing the many different facets of the in vivo biosynthesis of nanoparticles (NPs) using living eukaryotic …

Rapid Evolution Of Starvation Resistance In Drosophila: Physiological And Molecular Mechanisms, Austin Joseph Mckenna

UNLV Theses, Dissertations, Professional Papers, and Capstones

The Gibbs lab has maintained starvation-selected Drosophila melanogaster for >130 generations. These starvation-selected flies evolved an obese phenotype with a suite of physiological differences compared to control-fed flies. Previous studies have shown that long-term starvation-selected Drosophila contain more lipids, have lower metabolic rates and develop more slowly than controls. This dissertation encompasses 1) Examining the molecular mechanisms contributing to starvation resistance, 2) Functional validation of the candidate plin1 allele, and 3) Rapid physiological and genomic evolution in starvation-selected Drosophila.

Starvation-selected Drosophila survive starvation conditions much longer than control-fed flies. This study took a simple approach to identify possible differences in …

The Perplexing Paradox Of Clostridioides (Clostridium) Difficile Infection (Cdi) - Analysis Of Anti-Germinants As Part Of Cdi Prophylaxis, Christopher Yip

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridioides (Clostridium) difficile infections (CDI) have become the leading cause of nosocomial antibiotic-associated diarrhea worldwide. Under normal circumstances, bacteria found in the gastrointestinal tract provide a barrier against C. difficile colonization. Upon antibiotic therapy, the protective barrier is lost as the microbial community becomes depleted thus providing the opportunity for C. difficile to colonize the human gut. Exposure to taurocholate, a bile acid produced within the mammalian gastrointestinal tract, causes C. difficile spores to begin their transition, a process known as germination, from metabolically dormant structures to toxin-producing cells. As germination is required for the onset of CDI, anti-germination compounds …

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 …

Delineation Of Events In Centripetal Migration During Drosophila Oogenesis, Travis Tait Parsons

UNLV Theses, Dissertations, Professional Papers, and Capstones

All multicellular organisms initially start out as a single cell. This cell must use the genetic information encoded in its DNA to multiply in number and build itself into a complex multicellular organism. How this process occurs is the focus of developmental biology, a field that seeks to understand how a combination of genetic information and environmental conditions shape a cell from its beginnings as a zygote all the way to maturity. A fundamental part of this process is the ability of cells to work together in order to build complex tissues and organs. Cells achieve this coordination by using …

Transcriptional Silencing And Anti-Silencing Of Virulence Genes In The Bacterial Pathogen Shigella Flexneri: Virb, Dna Supercoiling, And The Histone-Like Nucleoid Structuring Protein, Michael Adam Picker

UNLV Theses, Dissertations, Professional Papers, and Capstones

Transcriptional silencing and anti-silencing affect many aspects of bacterial physiology, including virulence in bacterial pathogens. In Shigella species, a group of gram-negative pathogens that cause bacillary dysentery in humans, the histone-like nucleoid structuring protein (H-NS) transcriptionally silences virulence genes found on the large virulence plasmid while VirB anti-silences these genes. However, the mechanistic details of their interplay are not fully understood. To elucidate their regulatory mechanisms, I use the icsP virulence locus, which shares a long intergenic region with the divergently transcribed ospZ gene (1535 bp from TSS to TSS). Prior to this work, two discrete H-NS binding regions had …

The Caspase Cascade During Hibernation In The Golden-Mantled Ground Squirrel, Spermophilus Lateralis, Michael David Treat

UNLV Theses, Dissertations, Professional Papers, and Capstones

In several human pathologies like heart attack, stroke, neurodegenerative diseases, and autoimmune disorders, widespread cell death, or apoptosis, is a major cause of organ dysfunction and death. Hibernating golden-mantled ground squirrels, Spermophilus lateralis, experience numerous conditions during the winter that are known to be pro-apoptotic in other mammal systems (e.g. extreme hypothermia, ischemia and reperfusion, acidosis, increased reactive oxygen species, bone and muscle disuse). However, studies suggest that hibernators may invoke a protective phenotype to limit widespread cell damage and loss during the hibernation season. Could regulating apoptosis provide protection against the harmful conditions experienced during the hibernation season? Could …

Complete Sequencing And Comparative Analysis Of The Genomes Of The First Magnetotactic Gammaproteobacteria Isolated In Pure Culture: Strains Bw-2 And Ss-5, Corey Geurink

UNLV Theses, Dissertations, Professional Papers, and Capstones

The genomes of the first two discovered magnetotactic bacteria (MTB) belonging to the ammaproteobacteria, strains BW-2 and SS-51, were sequenced, sealed, annotated and compared to MTB of other phylogenetic groups. Cells of both strains are rod-shaped and biomineralize cuboctahedral and elongated octahedral crystals of magnetite, respectively, that are enveloped in a protein-embedded, lipid-bilayer membrane referred to as the magnetosome membrane or vesicle. The crystals and their associated membranes are known as magnetosomes. Magnetosome crystals consist of either magnetite (Fe3O4) or greigite (Fe3S4) and, because of their specific mineral compositions, crystal morphologies and sizes, the biomineralization processes involved in magnetosome formation …

Software For Sequence Analysis Of Variants In Functional Screening Libraries And Personalized Genome Files, Jacklyn Michelle Newsome

UNLV Theses, Dissertations, Professional Papers, and Capstones

Detailed knowledge of protein function is critical for both the study of protein interactions and the development of drugs which target specific proteins. Currently, there are few techniques that directly examine protein function. The techniques that are available are time consuming and can only address one variant of a protein at a time. Our laboratory has designed 3 high throughput protein function screens. We hypothesize that these will address this shortfall.

The first screen is the Chimeric Minimotif Decoy (CMD) Assay. For this screen, we constructed red fluorescent proteins with one or more C-terminal minimotifs. Minimotifs are short, contiguous amino …

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 …

Determining The Presence Of Carbapenem Antibiotic Resistance In Clinical Isolates, Fidelis Uzoma Enyinnaya

UNLV Theses, Dissertations, Professional Papers, and Capstones

Carbapenems are β-lactam antibiotics reserved for the treatment of severe microbial infections, especially those targeting the Enterobacteriaceae. Introduced in the 1980s, carbapenems have been used successfully in hospitals, and in the 1990s resistance was discovered. Carbapenem resistance is conferred through the production of carbapenemases. In the U.S., the most common carbapenemase is Klebsiella pneumoniae carbapenemase (KPC). In 2012, the National Healthcare Safety Network reported a carbapenem resistance rate of 13.0% among Klebsiella pneumoniae infections, and indicated that the mortality rate associated with carbapenem resistant Enterobacteriaceae (CRE) infections ranged from 48.0-71.9%. According to the Food and Drug Administration (FDA), carbapenem resistance …

The Role Of Oswrky71 And Its Interacting Proteins In Seed Germination And Early Growth Of Cereal Grains, Margaret Ja Shin

UNLV Theses, Dissertations, Professional Papers, and Capstones

During seed germination and early seedling growth, complex molecular and physiological events occur in rice (Oryza sativa) and other cereal grains. As the seed transitions to vegetative tissue, it responds to both favorable and unfavorable environmental conditions and is vulnerable to attack by predation and disease. Although seeds are relatively small and tender in size, extensive and sophisticated molecular networks enables the immobile seed to grow, survive and adapt in its environment. One of the networks I am interested in is in the crosstalk between the gibberellin (GA) and abscisic acid (ABA) signaling pathways. These pathways are interesting because they …

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 …

Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO₄ stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO₄ is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …

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 …

A Polymerase Chain Reaction Method For The Detection Of Selenomonas Noxia, Arthuro Mehretu

UNLV Theses, Dissertations, Professional Papers, and Capstones

In recent studies, periodontal health has been linked to being overweight and/or obese. Among common oral bacteria, Selenomonas noxia has been implicated in converting periodontal health to disease. Selenomonas spp. have also been found in gastric ulcers, and were misdiagnosed as Helicobacter -like organisms, but no further studies were conducted. The increasing clinical and epidemiological importance of S. noxia necessitates the development of a rapid detection method. In this study, a TaqMan 16S rRNA based real-time Polymerase Chain Reaction (PCR) method was developed, optimized and evaluated for the rapid and specific detection of S. noxia . The 16S PCR assay …

Global And Specific Controls Of Protein Synthesis In Hibernators, Peipei Pan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Mammalian hibernation is a highly dynamic physiological process that is composed of a series of torpor bouts, wherein hibernators oscillate between periods of torpor and interbout arousal. Although normally vital to homeostasis, many energetically consumptive processes such as translation or protein synthesis are virtually ceased during hibernation. Earlier studies indicated that protein synthesis had fallen to almost negligible levels. Cap-dependent initiation of translation is well regulated by eukaryotic translation initiation factor 4E (eIF4E) and its binding partner eIF4E-binding protein 1 (4E-BP1) when hibernators cycle in and out the torpor state. Herein, I investigated well-characterized regulatory mechanisms of global and specific …

Investigating The Origin Of Coprolites From Three Great Basin Caves, Chelsey Vandrisse, Duane P. Moser, David Rhode

Undergraduate Research Opportunities Program (UROP)

The study of coprolites (mummified feces) is a relatively new endeavor, which enables investigations of the health and diet of ancient people and provides some of the oldest evidence to date for the human habitation in North America (2). In this project, 18 coprolites were examined from archeological digs at three Great Basin caves: the Bonneville Estates Rockshelter (UT), Hidden Cave (NV), and Top of the Terrace Rockshelter (UT). The main objectives were: 1) to verify human origin through the presence of mitochondrial DNA (mtDNA) and 2) assuming human origin, characterize intestinal microflora of Native Americans prior to European contact. …

Dna Secondary Structures And Their Contribution To Mutagenesis In B. Subtilis Stationary Phase Cells, Carmen Vallin, Holly Martin, Christian Ross, Ronald Yasbin, Eduardo Robleto

Undergraduate Research Opportunities Program (UROP)

It is widely known and accepted that the cause of many mutations in cells are generated during the replication process of actively dividing cells, however more recent research has shown that mutations also arise in non growing conditions, a phenomenon known as stationary phase mutagenesis. Much of what is known come from studies in eukaryotic and bacterial models. It has been proposed that in non~growing cells, the process of transcription plays an important role in mutagenesis. We test the hypothesis that DNA secondary structures, formed during transcription, promote mutagenesis. The transcription-generated structures are speculated to be prone to mutations by …