Biochemistry, Biophysics, and Structural Biology Commons^™

Using Nmr Chemical Shift Perturbations To Map Interactions Between Acyl-Acyl Carrier Proteins And Acyl Homoserine Lactone Synthases, Madison N. Rizzo

Boise State University Theses and Dissertations

A pandemic of antibiotic resistance is underway and affecting multiple industries, including veterinary, agricultural, and healthcare. High bacterial population density is a major form of defense for bacterial cells against drugs, contributes to antibiotic resistance, and is one of the requirements for the formation of biofilms. Quorum sensing is a form of cell-to-cell communication that both gram-negative and gram-positive bacteria use to account for density behavior. When the population density of bacteria reaches a certain level (a “quorum”), there is an observed coordinated shift in gene expression that leads to optimized growth or virulence. Acyl carrier proteins (ACP) and the …

Serum Amyloid A Augments The Atherogenic Effects Of Cholesteryl Ester Transfer Protein, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Preetha Shridas

Saha Cardiovascular Research Center Faculty Publications

Serum amyloid A (SAA) is predictive of CVD in humans and causes atherosclerosis in mice. SAA has many proatherogenic effects in vitro. However, HDL, the major carrier of SAA in the circulation, masks these effects. The remodeling of HDL by cholesteryl ester transfer protein (CETP) liberates SAA restoring its proinflammatory activity. Here, we investigated whether deficiency of SAA suppresses the previously described proatherogenic effect of CETP. ApoE¡/¡ mice and apoE¡/¡ mice deficient in the three acute-phase isoforms of SAA (SAA1.1, SAA2.1, and SAA3; “apoE¡/¡ SAA-TKO”) with and without adeno-associated virus-mediated expression of CETP were studied. There was no effect of …

Spatial Metabolomics Reveals Glycogen As An Actionable Target For Pulmonary Fibrosis, Lindsey R. Conroy, Harrison A. Clarke, Derek B. Allison, Samuel Santos Valenca, Qi Sun, Tara R. Hawkinson, Lyndsay E. A. Young, Juanita E. Ferreira, Autumn V. Hammonds, Jaclyn B. Dunne, Robert J. Mcdonald, Kimberly J. Absher, Brittany Dong, Ronald C. Bruntz, Kia H. Markussen, Jelena A. Juras, Warren J. Alilain, Jinze Liu, Matthew S. Gentry, Peggi M. Angel, Christopher M. Waters, Ramon C. Sun

Saha Cardiovascular Research Center Faculty Publications

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high- dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed …

College Of Natural Sciences Newsletter, March - May 2023, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 4, Issue 2

Page 1 Dean's Message
Page 2-7 Awards and Recognition
Page 8 March 3rd Corothers Seminar
Page 9 54th Geography Convention
Page 10 Spring 2023 Day of Scholars
Page 11 2023 URSCAD Snaps
Page 12-14 Media Coverage of CNS
Page 15 Open PRAIRIE Data

Shortening Of Telomeres Caused By Bacterial Lipopolysaccharides In Hiv-1 Exposed Human Oral Keratinocytes, Daphne Alcala Zúñiga

Theses and Dissertations

The Human Immunodeficiency Virus-1 (HIV-1) continues to affect many individuals around the globe. Although people with HIV (PWH) have longer life expectancies because of modern treatments, they continue to exhibit comorbidities that are signs of premature aging compared to healthy individuals. The significance of the oral microbiome during HIV-1 infection has become of interest as chronic inflammatory conditions, such as periodontitis, have shed light on the detrimental effects of chronic inflammation. HIV-1 infection can promote dysbiosis, an imbalance of the oral microbiota, which in turn promotes the growth of opportunistic microorganisms such as P. gingivalis. This overpopulation enhances pathogenicity through …

Analysis Of The Electrostatic Characteristics Of The Zika Virus Capsid Using Computational Methods, Cassandra Guadalupe Del Rio De Avila

Open Access Theses & Dissertations

Zika virus (ZIKV) is a flavivirus that is usually transmitted through the bite of infected mosquitoes. This virus can cause a variety of neurological disorders, the most common being Guillain-Barré syndrome in adults. Moreover, it is of great concern in pregnant women, since can cause deformities in the brain and other organs of newborns.Studying the structural characteristics of the virus during its mature and infectious phase can provide crucial information on the mechanisms by which it enters and replicates within host cells, as well as its evolution, transmission, and interaction with other living organisms. The symmetric pattern present in the …

Carbon Quantum Dots' Effects On The Structure And Function Of Neurodegenerative And Non-Neurodegenerative Associated Proteins, Shima Masoudi Asil

Open Access Theses & Dissertations

Protein folding is an important physical process in which the sequences of polypeptides fold into a three-dimensional biological active structure. Misfolding is the conversion of a protein molecule into a structure unlike the native form, and therefore misfolded proteins have a strong tendency to aggregate and make fibrils. Amyloid aggregation is constituted by misfolded amyloidogenic proteins. Neurodegenerative diseases, such as Alzheimer’s Disease (AD), stem from the abnormal accumulation of harmful proteins, including Amyloid-ß peptides, tau protein, and the presynaptic protein α-synuclein in the nervous system. Alzheimer's disease is the most common neurodegenerative disorder that causes memory and learning deficits and …

Developing And Applying Computational Methods On Biomolecules, Shengjie Sun

Open Access Theses & Dissertations

Computational biophysics is an interdisciplinary subject that uses numerical algorithms to study the physical principles underlying biological phenomena and processes. Electrostatic interactions play an important role in computational molecular biophysics and their potential impact on disease mechanisms. At distances larger than several Angstroms, electrostatic interactions dominate all other forces, while the alteration of short-range electrostatic pairwise interactions can also have significant effects. The dual nature of electrostatic interactions, being dominant at long-range and specific at short-range, underscores their profound implications for wild-type structure and function. Any disruption of the complex electrostatic network of interactions may abolish wild-type functionality and could …

Microscopic And Spectroscopic Analysis Of Nordihydroguaiaretic Acid Effect On Astrocytes, Lizbeth Vanessa Martinez Lopez

Open Access Theses & Dissertations

Astrocytes, one of the most abundant cell components in the central nervous system (CNS), have been a research target in the last few years. Several studies have found that astrocytes are not only mere supporters of neurons but also of essential processes developed in the CNS. Their malfunction could induce neurodegenerative diseases and brain tumors. Thus, further understanding of astrocytes and their role is of high interest to develop possible new treatments and methods of disease diagnosis, especially in brain cancer. The plant Larrea tridentata (La Gobernadora in Mexico or Creosote bush in the United States) is known to have …

Quantum Chemistry–Machine Learning Approach For Predicting Properties Of Lewis Acid–Lewis Base Adducts, Hieu Huynh, Thomas J. Kelly, Linh Vu, Tung Hoang, Phuc An Nguyen, Tu C. Le, Emily Jarvis, Hung Phan

Chemistry and Biochemistry Faculty Works

Synthetic design allowing predictive control of charge transfer and other optoelectronic properties of Lewis acid adducts remains elusive. This challenge must be addressed through complementary methods combining experimental with computational insights from first principles. Ab initio calculations for optoelectronic properties can be computationally expensive and less straightforward than those sufficient for simple ground-state properties, especially for adducts of large conjugated molecules and Lewis acids. In this contribution, we show that machine learning (ML) can accurately predict density functional theory (DFT)-calculated charge transfer and even properties associated with excited states of adducts from readily obtained molecular descriptors. Seven ML models, built …

Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel

Honors Scholar Theses

Among structural biology techniques, Nuclear Magnetic Resonance (NMR) provides a holistic view of structure that is close to protein structure in situ. Namely, NMR imaging allows for the solution state of the protein to be observed, derived from Nuclear Overhauser Effect restraints (NOEs). NOEs are a distance range in which hydrogen pairs are observed to stay within range of, and therefore experimental data which computational models can be compared against. To that end, we investigated the effects of adding the NOE restraints as distance restraints in Molecular Dynamics (MD) simulations on the 24 residue HP24stab derived villin headpiece subdomain to …

Dopamine Dysregulation In Antiretroviral Drugs Treated Neuronal Cells, Andrea S. Bustos

Theses and Dissertations

According to the world health organization (WHO), 37.7 million people worldwide in 2020 were living with the human immunodeficiency virus (HIV-1). In the US, combination antiretroviral therapy (cART) drugs have shown effectiveness in combating HIV-1 infection. As a result, cART has prolonged the lifespan of people with HIV aiding these patients to age with the virus. Clinical evidence has established the long-term effects of cART in the aging population causing neuropsychiatric disorders such as depression. However, the underline molecular mechanism that cART induces depression-related neurodegeneration has not been established. This study will pursue a dopamine (DA) dysregulation marker in cART …

Understanding The Developmental Regulation Of Opa1 Processing In C2c12 Myoblasts, Harpreet Kaur

Theses and Dissertations

Mitochondria is an energy-producing organelle in the cell that accept electrons from the Krebs cycle to generate energy in the form of ATP by oxidative phosphorylation. Two mitochondrial aspects, bioenergetics and dynamics are critical for energy balance and cellular stress responses. Mitochondrial dynamics refers to the balance between mitochondrial fusion (mitochondrial biogenesis) and mitochondrial fission (mitochondrial fragmentation). Cellular stress conditions that lead to dissipation of transmembrane potential (Δψm) trigger the activation of an IMM protein, OMA1, a metalloprotease that leads to processing of another IMM protein, optic atrophy-1 (OPA1) that mediates IMM fusion. Persistent stress primes the mitochondria to mitophagy …

Biological Optimization Of Polymer-Based Antiretroviral Drug Towards The Gut-Associated Lymphoid Tissue (Galt), Arkajyoti Paul

Theses and Dissertations

Background: Combination antiretroviral therapy (cART) has significantly decreased the disease mortality associated with HIV-1 but does not efficiently reach the HIV reservoir organs such as GALT. In this regard, the present study determined the efficacy of the polymer-based nanoformulations using F127 alone and in combination with L61 to encapsulate three clinically available cART drugs such as Emtricitabine (FTC), Tenofovir Disoproxil Fumarate (TDF), and Dolutegravir (DTG) in in vitro and in vivo system. Methods: The selected formulations were studied for their biological and chemical characterization towards human cell line viz. Caco-2 and Human peripheral blood mononuclear cells (PBMC) and in vivo …

Structural And Functional Insight Of Helicobacter Pylori Translation Initiation Factor If1 (Hpif1) In Protein Biosynthesis And Rational Design Of New Antimicrobial Candidates, Asif Shahriar

Theses and Dissertations

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human gastric mucosa and is associated with peptic ulcer disease and gastric cancer. Bacterial protein synthesis is a fundamental metabolic process occurring in all bacteria and is a validated target of antibiotics; however, the precise structural mechanism of H. pylori protein biosynthesis remains unknown. Protein synthesis contains four stages, and translational initiation is the most important and highly regulated critical step, involving three initiation factors (IF1, IF2, IF3) and other key components. IF1 plays a vital role in regulating this step by binding to the 30S ribosomal subunit cooperatively …

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 …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations and Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Elucidating The Direct Role Of M6a In The Human Transcriptome, Lana Al Hasani

Dissertations and Theses (Open Access)

The best characterized and most abundant internal RNA modification is the methylation of adenosine at position 6 to give N6-methyladenosine (m6A). m6A modification on cellular RNAs was discovered in the 1970s. The past decade has witnessed major progress that illustrated important roles of this mark in various aspects of gene control. Due to its pleiotropic roles, the direct effect of m6A regulation of gene expression has remained incompletely understood. Traditional methods of understanding protein function, like CRISPR/Cas9 and RNA interference, have many limitations and have halted the process of fully understanding the direct functions of m6A. Here, we attempt alternative …

Regulation And Function Of Zeb1 Acetylation In Lung Adenocarcinoma Progression And Metastasis, Mabel Perez-Oquendo

Dissertations and Theses (Open Access)

Lung cancer metastasis is leading the causes of cancer-related mortality in the United States and worldwide. Epithelial-to-mesenchymal transition (EMT) is a model for metastasis that results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. Zinc finger E-box-binding homeobox 1 (ZEB1) recognizes and binds to E-boxes of epithelial gene promoters to repress its transcription. ZEB1 has inconsistent molecular weights, which have been attributed to post-translational modifications (PTMs). In the presented dissertation, I specifically addressed the gap in the molecular mechanisms by which PTMs of ZEB1 regulate its ability to induce EMT and how its activity might …

Long-Range Regulation By The Shigella Virulence Gene Regulator, Virb, Cody Cris

UNLV Theses, Dissertations, Professional Papers, and Capstones

Nucleoid-structuring proteins (NSPs) in bacterial cells can exert gene regulatory effects over great distances on DNA. This contrasts with the traditional view of bacterial transcriptional regulation, where transcription factors bind cis-acting regulatory sites proximal (<250 bp) to promoters to influence gene expression. In Shigella species, the histone-like nucleoid-structuring protein (H-NS) transcriptionally silences many genes on the large (~220 kb) virulence plasmid. During host colonization, however, silencing by H-NS is alleviated by the anti-silencer protein, VirB, which remodels the H-NS:DNA complex. This transcriptional anti-silencing is mediated by VirB:DNA interactions and the modulation of DNA supercoiling, which lead to the up-regulation of virulence genes. VirB is a central regulator of Shigella virulence, but the mechanistic basis for transcriptional regulation is incompletely characterized. Here, I focus on the potential for VirB to regulate transcription from remotely located DNA binding sites. Employing complementary in vivo approaches, I assessed the spatial stringency of the VirB binding site and elucidated how varying cellular VirB levels impacts regulation over different distances. I also evaluated how a molecular roadblock on DNA influences remote regulation by VirB. Additionally, I developed control tools to validate the ability of VirB to spread along DNA, an activity of VirB that putatively drives transcriptional regulation. These data are consistent with transcriptional anti-silencing being driven by VirB spreading along DNA. Overall, these findings highlight how VirB is not a conventional transcriptional regulator and broaden our perspective on transcriptional control in bacteria. Furthermore, this work contributes to our understanding of long-range gene regulatory effects, which are frequently overlooked and poorly characterized in bacteria.

Microorganisms In Extreme Environmental Conditions, Khanh Mai Nguyen

Graduate Theses and Dissertations

Organisms are known to be able to prosper under normal and extreme environmental conditions, which are classified as mesophile and extremophile, respectively. Extremophiles can thrive under a large array of conditions, from pressures, temperatures, salinity, and pH to a combination of them. For example, to survive on the ocean floor, marine biomass must have its biomolecular machinery adapted to the high pressures and high salinity environment. Moreover, around the hydrothermal vents, aside from pressure and salinity, the microbes that live there also need to adjust to the temperature as well as the pH level. Aside from high temperatures, researchers also …

Neuronal Or Intestinal Knockdown Of C. Elegans Nadk-1 Decreases Oxygen Consumption And Reactive Oxygen Species, Jake Regan

Electronic Theses and Dissertations

Reactive oxygen species (ROS) such as H2O2 can damage cellular components and are formed as a byproduct of mitochondrial oxidative metabolism. Studies using the nematode C. elegans have found that increasing ROS during development or early adulthood can extend lifespan, while increasing ROS during later adulthood normally decreases lifespan. NADPH provides the reducing power for several cellular antioxidants and is synthesized in a two-step reaction from NAD+ with the first step being catalyzed by NAD kinase (NADK). In this study, the effects of knocking down C. elegans cytoplasmic NADK, nadk-1 globally or in a neuron or intestine-specific manner starting from …

Determination Of Cadmium Uptake In Crassostrea Virginica Shell Under Controlled Conditions, Joseph John Pavelites Ii

Graduate Theses and Dissertations (2019 - present)

The objective of this thesis was to meet growing demand for the development of environmental biomonitors that protect ecosystems and public health. To do this, I determined the potential of oyster shell as a bioindicator of cadmium (Cd) in the environment by determining the mode of Cd uptake and relationships between Cd concentrations in the environment, shell, and soft tissues of juvenile eastern oysters (Crassostrea virginica Gmelin). I performed a review of the literature on the ability of oyster shell to retain metal contaminants and the factors that could affect this process (Chapter 2). I then reared C. virginica …

Cyclic-Di-Gmp Regulates Salmonella Typhimurium Infection Of Epithelial Cells And Macrophages, Abdulafiz Musa

Electronic Theses and Dissertations

Regulation of the bacterial second messenger cyclic-di-GMP in Salmonella Typhimurium allows it to delicately alter phenotypes to optimize invasion and survive intracellularly in epithelial cells and macrophages to become virulent and cause infection. Cyclic-di-GMP concentration is regulated by the presence of external stimuli, sensory diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), and cyclic-di-GMP binding effectors. Previous studies established that maintenance of low cyclic-di-GMP concentrations is required for survival in macrophages, and that deletion of 3 active PDEs reduces this survival. Here I showed that these 3 PDEs also influenced the infection of epithelial cells. Further studies re-established the decreased survival in …

Non-Destructive Imaging Of Phytosulfokine Trafficking In Plants Using Fiber-Optic Fluorescence Microscopy, Bernard Abakah

Electronic Theses and Dissertations

Plants secrete peptide ligands and use receptor signaling to respond to stress and control development. Understanding these phenomena is key to improving plant health and productivity for food, fiber, and energy applications. Phytosulfokine (PSK), a sulfated peptide hormone, regulates plant cell division, growth, and stress tolerance via specific phytosulfokine receptors (PSKRs). This study uses fiber-optic fluorescence microscopy to elucidate trafficking of PSK in live plants. The microscope features two-color optics and an objective lens connected to a 1-m coherent imaging fiber mounted on either a conventional upright microscope body or 5-axis positioning system (X–Y–Z plus pitch and yaw). PSK and …

New Dna Repair And Demethylation Functions In Uracil Dna Glycosylase Superfamily, Chenyan Chang

All Dissertations

Uracil-DNA glycosylase (UDG) superfamily, which consists of several groups of enzymes that recognize the damaged DNA bases and initiate the base excision repair (BER) pathway, is most important in dealing with DNA deamination and other base modifications. Thymine DNA glycosylase (TDG), which belongs to family 2 in the UDG superfamily, is able to specifically recognize and cleave the 5-methylcytosine (mC) oxidative derivatives including 5-formylcytosine (fC), 5-carboxylcytosine (caC), 5-hydromethyluracil (hmU) caused by active demethylation or DNA damage. My dissertation work is mainly focused on the fC and caC glycosylase activity within UDG superfamily. Chapter 1 is a general introduction to the …

Acetate Metabolism In The Fungal Pathogen Cryptococcus Neoformans, Oly Ahmed

All Dissertations

Cryptococcus neoformans is an environmental basidiomycetous fungus with a worldwide distribution and a wide range of habitats. Inhalation of the desiccated yeasts or spores of C. neoformans often leads to opportunistic pulmonary infections in immunocompromised individuals, and in severe cases causes lethal meningitis following hematogenous dissemination. During infection, depending on the tissue and disease state, the invading fungi experience a range of nutrient microenvironments within the host body. As a result, rapid metabolic adaptations geared towards efficient utilization of carbon sources alternative to glucose become one of the prime determinants of survival and growth for the pathogen. Incidentally, cryptococcal infection …

E-Cadherin Force Transmission And Stiffness Sensing, Mazen Mezher

Mechanical & Aerospace Engineering Theses & Dissertations

E-cadherin is the chief mediator of cell-cell adhesion between epithelial cells and is a known mechanosensor. Force transmission and stiffness sensing are two crucial aspects of E-cadherin mechanobiology.

E-cadherin has an extracellular adhesive region, a transmembrane region and an intracellular region that binds to adhesion-associated proteins. Here, we assessed how different factors affect the level of force transmission (i) from inside the cell such as adhesion-associated proteins, (ii) on the cell membrane, such as growth factor receptors and (iii) outside the cell, such as different binding partners in adhesion. To study the level of force transmission inside the cell, we …

Nanosecond Pulsed Electric Field Modulates Electron Transport And Mitochondrial Structure And Function, Lucas Nelson Potter

Biomedical Engineering Theses & Dissertations

Pulsed power treatment has been used to induce regulated cell death (RCD) in cells or ablate tumors in animals. A subset of pulsed power as electroporation with high voltage and pulse duration of milliseconds is used for biomedical treatment to induce pores in the plasma membrane of cells. Nanosecond Pulsed Electric Fields (nsPEFs)– an extension of electroporation, uses waveforms with pulse durations on the order of 10-900 nanoseconds. nsPEF treatment has demonstrated intracellular effects for potential biomedical applications. In this work, nsPEF treatment is used to demonstrate changes that affect viability, plasma membrane permeability ROS (Reactive Oxygen Species) in the …

Gonads Without Glp-1: Silencing Glp-1 In The Male Somatic Gonad In Caenorhabditis Elegans, Matthew Titus

Undergraduate Theses

In C. elegans, the gene glp-1 encodes for a Notch receptor called GLP-1, one of two found in C. elegans’ genome. The gene has been previously implicated in the development of the hermaphroditic germline as well as playing a role in the mitosis/meiosis decision. Genetic screening has further identified it as potentially playing a role in the development of the male somatic gonad, making it an ideal candidate for a reverse genetic. We did this by silencing glp-1 and observing if any alterations to the gonad’s phenotype occur.

Normally this could be done by performing a gene knockout. …