Biochemistry, Biophysics, and Structural Biology Commons^™

Targeting Protein Synthesis In Clostridioides Difficile To Develop Antimicrobial Candidate, Elvira L. Alanis

Theses and Dissertations

Clostridioides difficile is a gram positive, spore forming, obligate anaerobic bacterium that causes Clostridioides difficile infection (CDI) which can result in pseudomembranous colitis and toxic megacolon. In the case of this research a focus on Protein synthesis is made since it is an essential metabolic process and is a validated target for antibiotics. Protein synthesis begins with Initiation which includes the three translation initiation factors. Through the NMR chemical shift assignments, the IF1 structure was determined, and it was found to be composed of a short α helix and five β helixes. A peptide was designed after the short α …

Nanostructured Materials For Biomedical Applications, Silverio Lopez

Theses and Dissertations

Nanotechnology has been used in an increasing number of applications in biochemistry and molecular biology. Compared to bulk materials, nanoscale materials offer a variety of advantages in applications due to an increased surface-to-volume ratio of the reactants. The unique properties of nanostructured materials and their properties such as stability, reactivity, magnetic response, pressure discharge performance and biocompatibility depend on particle size and shape. This work focuses on a nanoenergetic material composed of Aluminum (Al), Copper II oxide (CuO), and Iodine (I) pentoxide (I2O5), and the biomedical application of nanoscale dextran-coated magnetite (Fe3O4), which was produced using microfluidics to tune particle …

Assessing The Effects Of Levonorgestrel (Lng) On Neural Differentiation In The Developing Hypothalamus Using The Zebrafish (Danio Rerio) As A Model, Gabriella Hinojosa

Theses and Dissertations

Neurogenesis is a critical component of fetal neurodevelopment consisting of: migration, proliferation and differentiation. Health concerns from anxiety to reproductive issues have been linked to alterations of neurogenesis processes. Endocrine disrupting chemicals (EDCs) can mimic hormones vital to this process, potentially adversely affecting the susceptible fetal brain. One EDC, Levonorgestrel (LNG), is a testosterone-like progestin used in birth control methods that has a high bioavailability and long half-life. Using zebrafish embryos as a model, this lab previously discovered that an environmentally relevant LNG dose (5 ng/L) significantly increased anxiety behaviors. The hypothalamus is responsible for the development …

Exploring Dna Compaction Via Bacillus Subtilis Parb Protein By Single Molecule Investigation, Miranda L. Molina

Theses and Dissertations

Faithful chromosome segregation involves ParB, a DNA-binding and compacting protein that specifically recognizes parS DNA sites near the replication origin. ParB spreads 10-20 kb from parS sites, which recruitments additional ParB molecules to neighboring DNA, forming higher-order nucleoprotein complexes. ParB is also a novel CTPase enzyme and hydrolyses CTP to self-dimerization and create a clamp that slides along DNA. To understand the roles of CTP in Bacillus subtilis ParB (BsParB), we purified wild type ParB (BsParB (WT)) and recombinant ParB (BsParB(R80A)) mutant. BsParB(R80A) was known to prevent CTP binding and not compact DNA. Proteins N- and C-terminally appended with a …

Structures And Regulations Of Translation Initiation Factors In Pseudomonas Aeruginosa Protein Biosynthesis To Develop New Potential Antimicrobial Agents, Nicolette Valdez

Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative, multidrug resistant bacterium that has been recognized as the prominent cause of nosocomial infections. Untreated acute and chronic infections associated with P. aeruginosa can develop into other diseases such as pneumonia, otitis externa, and osteomyelitis. P. aeruginosa infections commonly affect immunocompromised individuals such as cystic fibrosis, cancer, and burn patients. The misuse and overuse of antibiotics has contributed to the increased antibiotic resistance in P. aeruginosa and thus has led to an unmet need for discovery of novel antibiotic candidates. Protein biosynthesis is an essential metabolic process occurring in all bacteria and a validated target …

Contemporary Biomarker Strategies For Patients With Chest Pain, Stephen Boone, W Frank Peacock

Faculty, Staff and Students Publications

This review focuses on the strengths and limitations of conventional and high-sensitivity troponin in the evaluation of patients with suspected acute coronary syndromes. High-sensitivity troponin (hsTn) assays represent a significant innovation over prior generation troponin assays. Owing to superior analytical precision, hsTn permits more rapid "rule-in" and "rule-out" of myocardial infarction. Furthermore, hsTn assays, in properly implemented clinical pathways, permit a reduction in the portion of patients requiring extended observation and testing.

Tocilizumab In Patients Hospitalised With Covid-19 Pneumonia: Efficacy, Safety, Viral Clearance, And Antibody Response From A Randomised Controlled Trial (Covacta), Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Atul Malhotra, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Sinisa Savic, Ivor S Douglas, Julia Garcia-Diaz, Mariam S Aziz, Nichola Cooper, Taryn Youngstein, Lorenzo Del Sorbo, David J De La Zerda, Andrew Ustianowski, Antonio Cubillo Gracian, Kevin G Blyth, Jordi Carratalà, Bruno François, Thomas Benfield, Derrick Haslem, Paolo Bonfanti, Cor H Van Der Leest, Nidhi Rohatgi, Lothar Wiese, Charles Edouard Luyt, Rebecca N Bauer, Fang Cai, Ivan T Lee, Balpreet Matharu, Louis Metcalf, Steffen Wildum, Emily Graham, Larry Tsai, Min Bao

Faculty, Staff and Students Publications

BACKGROUND: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated.

METHODS: Adults in Europe and North America hospitalised with COVID-19 (

FINDINGS: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted …

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair

Dissertations and Theses (Open Access)

KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS have led to limited success resulting in a need to identify new mechanisms to targeting KRAS. The interaction of KRAS with its regulators, effectors, and the membrane present one such avenue. In this study, we investigated how post-translational covalent and environmental modifications could modulate these interactions of KRAS. Using computational molecular dynamics simulations, nuclear magnetic resonance spectroscopy …

Tissue-Specific Matrix Control Of Cell Cohesion And Migration Signaling Complexes, Tristen Tellman

Dissertations and Theses (Open Access)

The extracellular matrix (ECM) is a complex, interconnected network of three major constituents: collagens, glycoproteins, and proteoglycans, along with their enzyme modifiers. Within this network and beyond the structural role, each ECM molecule contributes a context-specific signal that influences cellular fate and behavior. Among these behaviors, cellular migration provides an essential function in developing tissues, wound healing, and cancer cell metastasis. Using two glandular organs, the normal salivary gland and the cancerous prostate, this dissertation describes the tissue-specific composition of two ECM signaling complexes (type I hemidesmosomes and the perlecan-semaphorin 3A-plexin A1-neuropilin-1 (PSPN) complex) and translates this knowledge into viable …

Plant Homeodomain Finger Protein 20 (Phf20) And Its Homolog Phf20 Like 1 (Phf20l1) Define Two Distinct Non-Specific Lethal (Nsl) Complexes, Hieu Van, Hieu T. Van

Dissertations and Theses (Open Access)

Plant Homeodomain Finger Protein 20 (PHF20) and its homolog PHF20 Like 1 (PHF20L1) are known subunits of the Non-Specific Lethal (NSL) complex, which acetylates lysine residues on histone H4 and regulates gene expression. The current model assumes that PHF20 and PHF20L1 are present together in the NSL complex, although it has never been tested. Performing extensive biochemical analysis, we observed that PHF20 and PHF20L1 were exclusively and independently associated with the NSL complex. Our protein domain analysis showed that the C-termini of PHF20 and PHF20L1 are crucial for their interactions with the respective complexes. Furthermore, enrichment sites of PHF20 and …

Utah Tick Surveillance An Animated Public Service Announcement, Keith Wilson

Undergraduate Honors Capstone Projects

As the United States’ population grows, we develop more land into housing and recreate farther into wilderness areas, consequentially encountering ticks with increasing frequency. As the climate continues to change, tick population distributions are also changing, influencing our population’s exposure to tick-borne diseases. Lyme disease, a tick-borne disease named after Lyme, Connecticut, is one of the fastest growing emerging diseases in North America, and the most prevalent vector-borne infection in the United States. There are two species of tick in North America, Ixodes scapularis and Ixodes pacificus, known to be carriers of the causative agent of Lyme disease, a …

Floating Treatment Wetlands For Brackish Waters: Plant Selection And Nutrient Uptake Potential., Andrea Landaverde

All Theses

Brackish water bodies in coastal regions provide critical ecosystem services that support human and environmental health. Anthropogenic activities such as agricultural and industrial activities, construction, urban settlements, and tourism contribute to increased inputs of nitrogen (N) and phosphorus (P) in brackish coastal ecosystems. Excess nutrients can lead to impaired water quality and affect marine organisms. Floating treatment wetlands (FTWs) are a vegetated-base technology used to remove contaminants from water column, that has been mainly studied and applied in freshwater systems. Application of FTWs in brackish systems requires further investigation, as high salinity in brackish waters could result in toxicity to …

Optimization Of Modular, Long-Range, Ultra-Fast Optical Tweezers With Fluorescence Capabilities For Single-Molecule And Single-Cell Based Biophysical Measurements, Subash C. Godar

All Dissertations

An Optical tweezer is a tightly focused laser beam that applies and senses precise and localized optical force to a dielectric microsphere and offers a unique and effective tool for manipulating the single cell or cell components, including nucleotides and dynein motor proteins. Here, I used highly stabilized optomechanical components and ultra-sensitive detection modules to significantly improve the measurement capabilities over a wide range of temporal and spatial scales. I combined the optical tweezer-based force spectroscopy technique with fluorescence microscopy to develop an integrated high-resolution force-fluorescence system capable of measuring displacements at sub-nanometer, forces at sub-piconewton over a temporal range …

Supertertiary Structural Dynamics Modulate Function In Postsynaptic Density Protein 95, George L. Hamilton Iii

All Dissertations

Proteins, RNA, and DNA serve as the primary sub-cellular machinery that give rise to the necessary functions of life. The long-standing paradigm has been that the structures of biomolecules, or the arrangement of the subunits that make up a biomolecule, determine biological function. However, biomolecules are not static objects. Instead, they often undergo structural rearrangements that are crucial to enabling and regulating their functions. In my thesis I present several studies of the interplay between the structures, dynamics, and functions of biomolecules that combine experimental fluorescence spectroscopy and computational methods to probe these systems at the single-molecule level. In particular, …

Preparation Of Proteins And Peptides From Heat-Stabilized Defatted Rice Bran Via Solid State Fermentation And Investigating For Skin Health, Ali A. Bisly

Graduate Theses and Dissertations

Heat-stabilized defatted rice bran (HDRB) is an abundant and inexpensive agro-industrial by-product of rice milling and rice oil extraction process. Furthermore, HDRB is a potential source of proteins. However, the direct protein extraction has low yield of protein due to the impact of heat stabilization and oil extraction process which made the HDRB proteins bound and interact with other components. This research is based on using solid-state fermentation (SSF), which is a natural and cost-effective approach to facilitate protein extraction from HDRB using Bacillus subtilis (natto) Takahashi as a microorganism.

Response surface methodology (RSM) analysis was used with Box-Behnken design …

Diffusive Dynamics Of Biological Macromolecules In The Cytoplasm Of Live Bacteria, Asmaa Ali Sadoon

Graduate Theses and Dissertations

Bacteria are small organisms that play important roles in our bodies and in maintaining our surrounding environment. However, bacterial infections are considered as one of the health diseases that threatens the lives of humans. Resistance of bacteria to antibiotics has made treating bacterial infections more challenging. With the emergence of many developed optical techniques, it has become possible to study various biological mechanisms of molecules inside these small organisms with high resolution and precise localization. In this research, single particle tracking photoactivation localization microscopy (sptPALM) technique was used to investigate the dynamics of fluorescent histonelike nucleoid-structuring proteins (H-NS) in live …

Study Of Adaptive Radiation Effects On Sprint Performance In Anolis Ecomorphs, Alexander J. Bergeson

Honors Thesis

Anolis lizards have become model organisms for the study of adaptive radiation and convergent evolution due to repeated patterns of specialization that allow them to live in different environmental niches within the habitats they occur. As part of a suite of adaptations for living in specific habitats, many species have repeatedly evolved specific changes in anatomy and physiology that make them better able to perform and survive in their surroundings. These specialized forms are referred to as “ecomorphs” based on their preferred habitats and have been well documented among Caribbean anoles. Mainland species, on the other hand, are less studied. …

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert

Animal Science Undergraduate Honors Theses

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 …

Transcriptome-Wide Identification Of Rna-Binding Protein Binding Sites Using Seclip-Seq, Steven M Blue, Brian A Yee, Gabriel A Pratt, Jasmine R Mueller, Samuel S Park, Alexander A Shishkin, Anne C Starner, Eric L Van Nostrand, Gene W Yeo

Faculty, Staff and Students Publications

Discovery of interaction sites between RNA-binding proteins (RBPs) and their RNA targets plays a critical role in enabling our understanding of how these RBPs control RNA processing and regulation. Cross-linking and immunoprecipitation (CLIP) provides a generalizable, transcriptome-wide method by which RBP/RNA complexes are purified and sequenced to identify sites of intermolecular contact. By simplifying technical challenges in prior CLIP methods and incorporating the generation of and quantitative comparison against size-matched input controls, the single-end enhanced CLIP (seCLIP) protocol allows for the profiling of these interactions with high resolution, efficiency and scalability. Here, we present a step-by-step guide to the seCLIP …

Internal Medicine Residents' Perceptions Of Virtual Morning Report: A Multicenter Survey, Tyler J Albert, Joel Bradley, Helene Starks, Jeff Redinger, Cherinne Arundel, Albertine Beard, Laura Caputo, Jonathan Chun, Craig G Gunderson, Dan Heppe, Anand Jagannath, Kyle Kent, Michael Krug, James Laudate, Vignesh Palaniappan, Amanda Pensiero, Zaven Sargsyan, Emily Sladek, Matthew Tuck, Paul B Cornia

Faculty, Staff and Students Publications

IMPORTANCE: The COVID-19 pandemic disrupted graduate medical education, compelling training programs to abruptly transition to virtual educational formats despite minimal experience or proficiency. We surveyed residents from a national sample of internal medicine (IM) residency programs to describe their experiences with the transition to virtual morning report (MR), a highly valued core educational conference.

OBJECTIVE: Assess resident views about virtual MR content and teaching strategies during the COVID-19 pandemic.

DESIGN: Anonymous, web-based survey.

PARTICIPANTS: Residents from 14 academically affiliated IM residency programs.

MAIN MEASURES: The 25-item survey on virtual MR included questions on demographics; frequency and reason for attending; opinions …

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 …

The Role Of Ccaat Binding Factor In The Regulation Of Catalase Gene Expression In Candida Albicans, Zahra Al-Rumaih

Graduate Theses and Dissertations

Candida albicans is a fungal opportunistic human pathogen. Its infections range from surficial infections like skin rash to fatal systemic infections. Filamentation growth mode is associated with C. albicans virulence because it helps penetration of the host’s epithelial cells. The CCAAT-binding factor (CBF) is a conserved heterooligomeric transcription factor found in 30% of eukaryotes genes. In C. albicans it is composed of 4 major subunits, including Hap2, Hap3, Hap4, and Hap5. Hap2 and Hap5 are essential for DNA binding and function. Hap4 has 3 homologous subunits: Hap41 and Hap42 are putative subunits of CBP. Hap43 is the only Hap4 subunit …

The Effect Of Age On The Mating Call Of The Tungara Frog, Zaizhen Xu

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

A Proteomic Analysis To Identify Changes In Bacterial Protein Expression Following Overexpression Of A Spider Silk Protein, Jamie (Ju Yeon) Park, Jaeyoung (Kate) Lee, David Chanyang Eum, Minji Jung, Sungkyung Lee

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Proteomic Analysis Of The Expression Of Masp1 Dragline Silk Protein In E. Coli, Sophie Rae Pazzo, Rajan Amit Patel, Kamrin Athwal, Edward Kim

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

The Role Of Npun_F0875 In Hormogonium Development And Motility, Daniel Sepulvida, Austin Wong

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Extracting Dna From Embalmed Tissue To Study Genetic Predisposition To Degenerative Disc Disease, Conner Lynn

Undergraduate Theses

INTRODUCTION. According to a prominent study, 80-90% of people will show some evidence of degenerative disc disease (DDD) by age 50. Researchers have proposed that a Q326W substitution in the COL9A2 gene increases susceptibility to DDD. The role of collagen IX in intervertebral discs is not completely known, but due to its increased flexibility compared to other types of collagens, it is thought to connect collagen II with other components of the cartilage which are important to the integrity of the disc. Collagen II can be found within the nucleus pulposus and the inner portion of the annulus fibrosis. Researchers …

Computational Investigations Into Binding Dynamics Of Tau Protein Antibodies: Using Machine Learning And Biophysical Models To Build A Better Reality, Katherine Lee

University Scholar Projects

Misregulation of post-translational modifications of microtubule-associated protein tau is implicated in several neurodegenerative diseases including Alzheimer’s disease. Hyperphosphorylation of tau promotes aggregation of tau monomers into filaments which are common in tau-associated pathologies. Therefore, tau is a promising target for therapeutics and diagnostics. Recently, high-affinity, high-specificity single-chain variable fragment (scFv) antibodies against pThr-231 tau were generated and the most promising variant (scFv 3.24) displayed 20-fold increased binding affinity to pThr-231 tau compared to the wild-type. The scFv 3.24 variant contained five point mutations, and intriguingly none were in the tau binding site. The increased affinity was hypothesized to occur due …

Design, Synthesis, And Analysis Of Paired Coiled-Coil Peptidic Molecular Building Blocks Used For Linearly Controlled Self-Assembly Of Α-Helical Coiled-Coil Heterodimer Peptide Pairs, Jason Distefano

Chemistry Theses

Molecular building blocks are fundamental to biological synthesis and processes and have been utilized in advanced materials, drugs and drug delivery systems, and biotechnology. Proteins have been used as molecular building blocks for the construction of complex, well-ordered structures. Coiled-coil protein domains are essential subunits used for the oligomerization of protein complexes, gene expression, and structural elements of biological materials. The synthesis and assembly of proteins utilizing coiled-coil motifs are of great scientific interest due to their potential applications in disease treatment, biomechanical motors, nanoscale delivery systems, etc. However, assembling protein complexes with specific morphology is still challenging because …