Biochemistry Commons^™

From Resistance To Host Response: An Integrative Study Of C. Difficile Infections, Amber Consul

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridioides difficile infection (CDI) is a major healthcare challenge, causing severe gastrointestinal illness and significant mortality. Understanding the mechanisms of antibiotic resistance, epidemiology, and immune response in CDI is critical for developing effective treatments and prevention strategies.

This dissertation encompasses three complementary studies. The first study investigates the genetic mechanisms underlying cephalosporin resistance in C. difficile strain 630 through differential gene expression analysis. The second study provides a descriptive epidemiological analysis of C. difficile ribotypes in a Las Vegas patient population, highlighting differences between healthcare-associated (HA-CDI) and community-associated (CA-CDI) cases. The third study integrates serum analyte profiling and transcriptomic analysis …

Student Comprehension Of Biochemistry In A Flipped Classroom Format, Ed Harris, Evan A. Schroder, Teryn J. Berks

Department of Biochemistry: Faculty Publications

Concept-heavy courses such as Biochemistry in life and physical science curricula are challenging for many college-aged students. It is easy for students to disengage in a lecture and not learn the subject matter while in class. To improve student learning and participation, we employed a flipped format for the first half of the course and compared learning outcomes and attitudes with the traditional lecture in the second half of the course. The experimental course was an upper-level biochemistry course taken primarily by juniors (49%), seniors (40%), and some graduate students (10%) at the college level. Our results indicate that lower-performing …

Assessing The Bioactivity Of Salvia Phytochemicals Against Breast Cancers, Allison C. Portaro, Jared L. Scott, David J. Schultz

The Cardinal Edge

Breast cancer is one of the most common cancers diagnosed in adults, with 2.3 million new cases worldwide in 2020. Plants have been used in traditional medicine and are a potential source of pharmaceuticals. One example is the large Lamiaceae (mint) family. The Salvia genus, commonly known as the sages, is the largest genus in Lamiaceae with almost 900 known species. Different species of salvia are found in parts of the US, and some have a history in traditional medicine to treat cancers and other ailments. Preliminary research on three salvia species (S. lyrata, S. lyrata var. Purple …

Dysfunction Of Polyamine Metabolism In Down Syndrome Related To Cellular Senescence And Β-Amyloid Production, Andres D. Sola

Electronic Theses and Dissertations

Polyamines (PA) are ubiquitous in cells and highly involved in several important cellular functions and thus the dysregulation of their biosynthetic pathway is potentially associated with the progression of age-related diseases like Alzheimer’s’ disease (AD). Though there is research describing how PA content changes in organisms as they age or in those experiencing rapid aging from increased rates of senescence, as in Down syndrome (DS), it is not clear how this connection occurs and whether modulating this pathway may reveal downstream effects on related disease progression. This study examines how the modulation of the PA biosynthetic pathway by inhibition of …

Investigating The Role Of Tetherin Protein In Multivesicular Bodies Fusions In Lung Cancer Cells, Md. Rakib Miah

Electronic Theses and Dissertations

Cells rely on the secretion of exosomes to communicate with one another and this process is potentially mediated by a protein called tetherin, which anchors exosomes to the cell surface to limit their spread. Tetherin protein has attracted a lot of attention because of its capacity to hinder the propagation of viruses by attaching virions to the surface of host cells. Treatment with interferon-alpha (IFNα) increases the production of tetherin, although it is not known how this affects tetherin localization and exosome-mediated communication. This thesis looks at how the expression of tetherin, which IFNα boosts, affects the dynamics of intercellular …

Viral Genome Delivery Across Bacterial Cell Surfaces, Stephano M. Iglesias, Fenglin Li, Federica Briani, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

In 1952, Hershey and Chase used bacteriophage T2 genome delivery inside Escherichia coli to demonstrate that DNA, not protein, is the genetic material. Over 70 years later, our understanding of bacteriophage structure has grown dramatically, mainly thanks to the cryogenic electron microscopy revolution. In stark contrast, phage genome delivery in prokaryotes remains poorly understood, mainly due to the inherent challenge of studying such a transient and complex process. Here, we review the current literature on viral genome delivery across bacterial cell surfaces. We focus on icosahedral bacterial viruses that we arbitrarily sort into three groups based on the presence and …

Engineering The Coherent Phonon Transport In Polar Ferromagnetic Oxide Superlattices, In Hyeok Choi, Seung Gyo Jeong, Do-Gyeom Jeong, Ambrose Seo, Woo Seok Choi, Jong Seok Lee

Chemical and Materials Engineering Faculty Publications

Artificial superlattices composed of perovskite oxides serves as an essential platform for engineering coherent phonon transport by redefining the lattice periodicity, which strongly influences the lattice-coupled phase transitions in charge and spin degrees of freedom. However, previous methods of manipulating phonons have been limited to controlling the periodicity of superlattice, rather than utilizing complex mutual interactions that are prominent in transition metal oxides. In this study on oxide superlattices composed of ferromagnetic metallic SrRuO3 and quantum paraelectric SrTiO3 , phonon modulation by controlling the geometry of superlattice in atomic-scale precision is realized, demonstrating the coherent phonon engineering using structural and …

The Effect Of Nerolidol On The Renal Dysfunction Following Bilateral Ureteral Obstruction In The Rat, Harun Rashed Toumi

Theses

This thesis addressed nerolidol’s potential therapeutic and protective effects on bilateral ureteral obstruction-induced uropathy in rats. Obstructive uropathy stands as a notable contributor to acute kidney injury (AKI), accounting for 5-10% of all AKI cases worldwide, with a particularly high prevalence among the elderly, constituting 22% of AKI cases in this age group. Urinary tract obstruction, often attributed to factors such as kidney stones, urinary tract deformities and benign/malignant growths such as benign prostatic hyperplasia (BPH) in older men can lead to detrimental outcomes if left untreated, potentially progressing to kidney failure and even mortality. The severity of the kidney …

Diverse Pathways In Gpcr-Mediated Activation Of Ca2+ Mobilization In Hek293 Cells, Francesco De Pascali, Asuka Inoue, Jeffrey L. Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

G protein-coupled receptors transduce extracellular stimuli into intracellular signaling. Ca²⁺ is a well-known second messenger that can be induced by G protein-coupled receptor activation through the primary canonical pathways involving Gα_q- and Gβγ-mediated activation of phospholipase C-β (PLCβ). While some G_s-coupled receptors are shown to trigger Ca²⁺ mobilization, underlying mechanisms remain elusive. Here, we evaluated whether G_s-coupled receptors including the β₂-adrenergic receptor (β₂AR) and the prostaglandin EP₂ and EP₄ receptors (EP₂R and EP₄R) that are endogenously expressed in human embryonic kidney 293 …

Noncontact Diffuse Reflectance Spectroscopy Of Synovial Fluid Samples For Rapid Identification Of Infections, Erin E. Drewke, Robert L. Brand, Caroline G. Geels, Hanna K. Jensen, Kevin Wong, Jarret D. Sanders, Narasimhan Rajaram

Biomedical Engineering Faculty Publications and Presentations

Severe joint infections, such as septic arthritis, require rapid diagnostic testing of the synovial fluid aspirated from joints level so that a surgical team can be assembled quickly. We present a diffuse reflectance spectroscopy (DRS) system for noncontact determination of infection. Using a light-tight syringe holder and fiber optic probe, diffusely reflected light from 475 to 655 nm was acquired from 18 patient samples through the wall of a syringe in a noncontact and sterile manner. We determined the reflectance ratios at two different wavelengths—R ₄₉₀/R ₆₀₀ and R ₅₈₀/R ₆₀₀ and found statistically significant …

The Divergent Responses Of Salinity Generalists To Hyposaline Stress Provide Insights Into The Colonisation Of Freshwaters By Diatoms, Kathryn J. Judy, Eveline Pinseel, Kala M. Downey, Jeffrey A. Lewis, Andrew J. Alverson

Biological Sciences Faculty Publications and Presentations

Environmental transitions, such as the salinity divide separating marine and fresh waters, shape biodiversity over both shallow and deep timescales, opening up new niches and creating opportunities for accelerated speciation and adaptive radiation. Understanding the genetics of environmental adaptation is central to understanding how organisms colonise and subsequently diversify in new habitats. We used time-resolved transcriptomics to contrast the hyposalinity stress responses of two diatoms. Skeletonema marinoi has deep marine ancestry but has recently invaded brackish waters. Cyclotella cryptica has deep freshwater ancestry and can withstand a much broader salinity range. Skeletonema marinoi is less adept at mitigating even mild …

Post-Transcriptional Methylation Of Mitochondrial-Trna Differentially Contributes To Mitochondrial Pathology, Sunita Maharjan, Howard Gamper, Yuka Yamaki, Thomas W. Christian, Robert Y. Henley, Nan-Sheng Li, Takeo Suzuki, Tsutomu Suzuki, Joseph A. Piccirilli, Meni Wanunu, Erin L. Seifert, Douglas C. Wallace, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Human mitochondrial tRNAs (mt-tRNAs), critical for mitochondrial biogenesis, are frequently associated with pathogenic mutations. These mt-tRNAs have unusual sequence motifs and require post-transcriptional modifications to stabilize their fragile structures. However, whether a modification that stabilizes a wild-type (WT) mt-tRNA would also stabilize its pathogenic variants is unknown. Here we show that the N¹-methylation of guanosine at position 9 (m¹G9) of mt-Leu(UAA), while stabilizing the WT tRNA, has a destabilizing effect on variants associated with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). This differential effect is further demonstrated, as removal of the m¹G9 …

Characterizing The Influence Of Metabolism On Steady State Water Exchange In Yeast As A Potential Mri Diagnostic Biomarker, Samantha Mumford

Dissertations and Theses

Under conditions of ionic equilibrium with the environment a cell maintains a constant volume yet rapidly exchanges water molecules with the extracellular space. The rate constant for steady state water efflux, k_io, can be measured using contrast enhanced magnetic resonance (CE-MR). The active water cycling (AWC) hypothesis is puts forward that k_io is primarily influenced by cellular ATP levels and H⁺ ATPase activity at the cell membrane. Due to the correlation between k_io and ATP levels, k_io is thought to be a probable MRI biomarker for metabolic diseases such as cancer. Yet, the molecular …

Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios

PANDION: The Osprey Journal of Research and Ideas

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing …

Cryo-Em Analysis Of Pseudomonas Phage Pa193 Structural Components, Stephano M. Iglesias, Chun-Feng Hou, Johnny Reid, Evan Schauer, Renae Geier, Angela Soriaga, Lucy Sim, Lucy Gao, Julian Whitelegge, Pierre Kyme, Deborah Birx, Sebastien Lemire, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193. We used bioinformatics, proteomics, and cryogenic electron microscopy single particle analysis to identify, annotate, and build atomic models for 21 distinct structural polypeptide chains forming the icosahedral capsid, neck, contractile tail, and baseplate. We identified a putative scaffolding protein stabilizing the interior of the capsid 5-fold …

Examination Of Photoinduced Radicals In Two Crystal Forms Of Triphenylamine Bis-Urea Macrocycles, Md Faizul Islam, Gamage Isuri P. Wijesekera, Anmon J. Sindt, Mark D. Smith, Linda S. Shimizu

Faculty Publications

This study probes two solvates of triphenylamine (TPA) bis-urea macrocycle 1 and their activated structures to evaluate their maximum photoinduced radicals (PIRs), the subsequent decay of the radicals, and their regeneration. The hierarchical assembly of TPAs shows promise in stabilizing less substituted derivatives, potentially expanding the utility of TPAs that lack stabilizing para-substituents. Single crystal structure analysis reveals that host 1 adopts a planar conformation with the two ureas pointing in opposite directions when dimethoxyethane (DME) is encapsulated within the channel. Whereas previously, 1 adopted a bowl-shaped conformation with the two ureas pointing in the same direction (syn …

Examination Of Photoinduced Radicals In Two Crystal Forms Of Triphenylamine Bis-Urea Macrocycles, Md Faizul Islam, Gamage Isuri P. Wijesekera, Ammon J. Sindt, Mark D. Smith, Linda S. Shimizu

Faculty Publications

This study probes two solvates of triphenylamine (TPA) bis-urea macrocycle 1 and their activated structures to evaluate their maximum photoinduced radicals (PIRs), the subsequent decay of the radicals, and their regeneration. The hierarchical assembly of TPAs shows promise in stabilizing less substituted derivatives, potentially expanding the utility of TPAs that lack stabilizing para-substituents. Single crystal structure analysis reveals that host 1 adopts a planar conformation with the two ureas pointing in opposite directions when dimethoxyethane (DME) is encapsulated within the channel. Whereas previously, 1 adopted a bowl-shaped conformation with the two ureas pointing in the same direction (syn …

Water Quality Of Silver Creek, A Buried Urban Stream, Nick Bultje, Valerie Krause, Rebecca Nulty

Student Papers and Reports

There are many sources of pollution that can affect a watershed. These pollutants can impact the water's pH, temperature, conductivity, and dissolved solids. Escherichia coli is a specific pollutant that comes from waste products of humans and animals. High levels of E. coli cause serious health problems. This study examines Silver Creek, a tributary within the Plaster Creek watershed. Silver Creek runs mostly underground and has storm drainage systems that flow into the creek. The goal was to explore the effects of the underground section of Silver Creek on water quality and E. coli levels. The water quality and levels …

Characterizing Substituted Imidazolidinetriones As A Novel Class Of Pyruvate Carboxylase Inhibitors, Nicholas O. Schneider

Dissertations (1934 -)

Pyruvate carboxylase (PC) is implicated in a variety of diseases, including type-2 diabetes, cancer, and bacterial/viral infections. However, there are currently no molecular tools capable of precisely manipulating PC activity both in vitro and in vivo. This dissertation describes the identification and characterization of 1,3-disubstituted imidazolidinetriones as a novel class of potent, selective, and permeable allosteric inhibitors of Staphylococcus aureus PC. Based on kinetic, structural, and biophysical data, this class of inhibitors is hypothesized to bind at the noncatalytic “exo binding” site on PC. This exo binding site is reportedly important for catalysis, but it had not previously been considered …

The Anaerobic Rose Chamber (Arc): Novel Applications For Probing Clostridioides Difficile Dynamics, Tatiana Zvonareva

Chemistry & Biochemistry Theses & Dissertations

Clostridioides difficile infection (CDI) is an urgent public health threat with a high rate of recurrence and limited treatment options. Caused by the anaerobic intestinal pathogen C. difficile, this disease affects up to 500,000 Americans annually. Despite progress in our understanding of CDI pathophysiology, the lack of effective and accessible experimental platforms compatible with obligate anaerobe physiology hinders the advancement of treatment therapy. The application of in vivo models has been indispensable in understanding CDI pathophysiology, probing the complexity of the host response to the microbe, and establishing treatment protocols, and it continues to be essential in preclinical testing. …

Synthesis Of Drug-Like Molecules And Investigation Of Their Biological Activity, Duyen Nguyen '25, Sunny Nguyen '26, Jeffery A. Hansen

Annual Student Research Poster Session

This study examines the products derived from the ring-opening reactions of two novel epoxides—chlorobenzene epoxide and furan epoxide—highlighting their notable biological activity, particularly in the context of potential anticancer agents. One key finding: a synthesized stereoisomer of a hexylamine-derived β-amino alcohol exhibited a remarkably low LC50 value of 6.6 ppm in the Brine Shrimp Lethality Assay, significantly outperforming the other isomer compound’s LC50 value, at 13 ppm. This discovery underscores the critical role of stereochemistry in enhancing bioactivity, as evidenced by the distinct physical and chemical properties of the two hexylamine-derived isomers, including differences in appearance and solubility. Building on …

E-Textbook For Better Learning In Chemistry 120, Anh Vu '27, Jeffery A. Hansen

Annual Student Research Poster Session

Organic chemistry is a highly visual subject since organic compounds are 3D objects. For this reason, in order to fully understand the composition, properties, and chemistry of these compounds, it is essential to understand and visualize their 3D structures. Nevertheless, there is a frequent necessity to depict organic substances on 2D surfaces, such as paper, a computer screen, or a whiteboard. As a result, one of the biggest obstacles we will face is learning these molecules in a 2D format while maintaining an accurate understanding of 3D nature. The purpose of this e-textbook is to fully utilize the digital medium …

Designing An Attachment Assay For Epidermal Cell-To-Cell Attachment, Tiala Ortega '26, Colleen L. Doçi

Annual Student Research Poster Session

Cell adhesion includes various processes and is essential in cell communication and regulation. The mechanical interactions between a cell and its extracellular matrix control the behavior and function of a cell. In this project, we are studying cell attachment in different ways. The epidermal monostrato layer is a vertical and horizontal interaction and is not accounted for in usual assay protocols so I wanted to investigate this by creating an assay including multiple cell layers, a monolayer and an attached layer, to further develop a protocol for optimal cell-to-cell attachment. I hypothesized that the number of cell attachments to the …

Comparison Of Two Disaccharides And Their Saccharide Components In Aot Reverse Micelles: Impacts Of D-Trehalose And D-Sucrose, Delaney Collier '25, Bridget L. Gourley, Nancy E. Levinger

Annual Student Research Poster Session

Reverse micelles, featuring an AOT surfactant with a polar head group and nonpolar tail, encapsulate a polar phase at the nanoscale. With water as the polar phase, the nanoconfined water pool interactions and water-interface interactions mimic biological nanoconfinement. Thus, we investigated the impact of osmolytes on AOT reverse micelles to explore the role they play in biological systems. We investigated two disaccharides, D-trehalose and D-sucrose, and their monosaccharide components, glucose+glucose and glucose+fructose. We chose these molecules for their biological significance and to allow us to investigate whether subtle structural changes in the osmolyte impacts the intermolecular interactions in confinement as …

A Comparative Analysis Of Urea Vs. Acetamide In Aot Reverse Micelles, Kate Walsh '26, Bridget Gourley, Nancy E. Levinger

Annual Student Research Poster Session

In our exploration of the interactions between water and amide osmolytes, we focused on the effects of urea and acetamide on the stability of reverse micelles (RMs) formed with Sodium Bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane. Water, with its unique polarity and its ability to facilitate hydrogen and proton transfer, played a crucial role in our study, as we aimed to uncover how these amides would influence micellar behaviour. Our results revealed a compelling contrast between urea and acetamide. Acetamide, with its lower polarity due to a methyl group substitution, demonstrated superior solubility and significantly reduced precipitate formation compared to urea. This …

Enzyme Encapsulation Within The Hk97 Virus-Like Particle: An Investigation Of Substrate Inhibition Kinetics Within A Confined And Crowded Environment, Joseph B. Lively

Chemistry Theses

Substrate inhibition is a paradoxical phenomenon observed in enzyme kinetics where increasing substrate concentrations lead to a marked decrease in the rates of enzyme-catalyzed reactions. Affecting an estimated 20% of studied enzymes, substrate inhibition poses significant challenges to the understanding of their function in essential biological processes and to their exploitation in industrial and therapeutic contexts. Studies show substrate inhibition to be a real limitation in vitro and rational conclusions have been drawn to explain the relevance of substrate inhibition in the self-regulation of biological pathways. However, there is currently no consensus on what role substrate inhibition plays in vivo …

Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee

Dartmouth College Ph.D Dissertations

Cholesterol dysregulation is implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Niemann-Pick type C disease (NPCD). This study focused on evaluating the potent ACAT1 inhibitor, F26, as a therapeutic strategy for NPCD. F26 demonstrated superior ACAT1 inhibition and efficacy compared to the previously studied inhibitor, F12511, both in vitro and in vivo. Notably, F26 exhibited enhanced pharmacokinetic properties, including prolonged duration of action and better brain retention, making it a more promising candidate for treating neurodegenerative diseases.

F26 was encapsulated in a liposome-based nanoparticle system, DSPE-PEG2000 with phosphatidylcholine (PC), for enhancing its …

Considerations For Widespread Implementation Of Blood-Based Biomarkers Of Alzheimer's Disease, Michelle Mielke, Matthew Anderson, Wesson Ashford, Andreas Jeromin, Pei-Jung Lin, Allyson Rosen, Jamie Tyrone, Lawren Vandevrede, Deanna Willis, Zul Merali

Brain and Mind Institute

Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimer's Disease BBM Workgroup convened to address these challenges …

Crystal Archer: Profile Of The Newest Chbc Faculty Member, Danna Jaimes-Fajardo, Jeremy J. Smith, Lutishoor Salisbury

University Libraries Faculty Publications and Presentations

Presents the research profile of Crystal Archer, Assistant Professor, Chemistry and Biochemistry department. It highlights her research interests, education, and impact of her research.

Investigating Neurite Outgrowth Influenced By Breast Cancer Progression Using In Vitro Models Of Collagen I Hydrogels, Emma Waskom '27, Nikolas Ala-Kokko, Younghye Song

Annual Student Research Poster Session

Through the use of vitro modeling of tumor progression, using collagen I hydrogels and progressing cell lines, a demonstration of the interactions between breast cancer cells and nerve cells can be investigated. With these models, our goal is to compare the measurement of outgrowth of nerve cells through the use of supplemented NGF and co cultures of breast cancer cells. Human MCF-CA1a.cl1, -AneoT, and -10A, adipose-derived stem cells (ASCs), and rat PC-12 cells, were all passaged from 2D cultures and cultured in a collagen I hydrogen at a cell density of 250,000 cells/ml of media. Collagen hydrogels were then made …