Biochemistry, Biophysics, and Structural Biology Commons^™

Functionalized Carbon Quantum Dots: A Promising Nanomaterial For Investigating Their Potential In Neurodegenerative Disease Treatment, Sherin M. El Morsy

Open Access Theses & Dissertations

Neurodegenerative diseases such as Parkinson's Disease (PD), Alzheimer's Disease (AD), and Huntington's Disease (HD) remain incurable, despite extensive research into therapeutic development. In the United States of America, the annual cost of PD and AD in terms of patient care and lost productivity is approximately $200 billion. Consequently, there is a critical and unaddressed need for the development of innovative drugs and drug delivery systems that can decelerate, stop, or ideally reverse neurodegenerative diseases. The dissertation presented here focuses on devising strategies to target PD through multiple mechanisms, including the inhibition of protein aggregation and the reduction of oxidative stress. …

Tc-Ptp-Mediated Regulation Of P38 Mapk Pathway Promotes Uvb-Induced Apoptosis In Skin, Lindsey Susie Shim

Theses and Dissertations

T-cell protein tyrosine phosphatase (TC-PTP) is a non-receptor PTP that has been shown to have various roles in signaling pathways. Our previous studies have demonstrated that the TC-PTP deficiency in the epidermis can exacerbate hyperplastic response by inducing epidermal cell proliferation in response to tumor promoter TPA or UVB exposure. This implies that TC-PTP plays a tumor-suppressive role in the epidermis and provides protection against UVB radiation, which is well known to contribute to skin cancer development. The p38 mitogen-activated protein kinase (MAPK) is one of serine/threonine kinases that are activated through environmental stress including UVB. It has been demonstrated …

Effect Of An Anti-Hiv Polymer Based Nanoformulation On Immune Mediating Cells Within The Gut Associated Lymphoid Tissue And Its Behavioural Impacts, Blessed Ofori

Theses and Dissertations

This thesis investigates the therapeutic potential of nanoformulated antiretroviral therapy (NF cART) and its implications for HIV-associated chronic inflammation and neurobehavioral outcomes. In the first study, NF cART demonstrated enhanced efficacy in modulating inflammasome activation and reducing viral reservoirs in gut-associated lymphoid tissue (GALT) and the small intestine of HIV-infected humanized mice. Key markers of inflammation (NLRP3, Caspase-1, and IL-1β) and viral replication (LTR and p24 levels) were significantly suppressed with NF cART compared to conventional therapy, though residual LTR expression persisted in the small intestine. In the second study, nanoformulated Emtricitabine uniquely enhanced locomotor activity and reduced anxiety-like behaviors …

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Independent Evolution Of Oleate Hydratase Clades In Bacillales Reflects Molecular Convergence, Robert J. Neff, Priscilla C. Lages, Shannon K. Donworth, James D. Brien, Christopher D. Radka

Markey Cancer Center Faculty Publications

Oleate hydratase (OhyA), a flavoenzyme that catalyzes the hydration of unsaturated fatty acids, has been identified in various Bacillales organisms, including those in the Listeria, Lysinibacillus, Paenibacillus, and Staphylococcus genera. In this study, we combine structural biology with molecular and phylogenetic analyses to investigate the evolutionary dynamics of the OhyA protein family within the Bacillales order. Our evolutionary analysis reveals two distinct OhyA clades (clade I and clade II) within Bacillales that, while sharing catalytic function, exhibit significant genomic and structural differences. Our findings suggest that these OhyA clades originated from independent evolutionary processes through convergent evolution rather than gene …

Encapsulation Of Probiotics By Cellulose Nanocrystal-Alginate Composite Beads For Ph Stimuli-Responsive Delivery, Akrip Jati

Graduate Theses and Dissertations

Microencapsulation has garnered significant interest, with oral probiotics delivery systems showing enormous potential to help restore the gut microbiome. This method holds vast potential to protect and release specific microbial strains to the desired target site (i.e., colon) within the gastrointestinal tract (GIT). However, current encapsulation methodologies, utilizing either synthetic or biological materials as carriers, encounter challenges such as suboptimal encapsulation efficiency, premature probiotic release, and inadequate control over release kinetics. In this work, hydrogel microsphere (HM) composites of different cellulose nanocrystal (CNC) forms (i.e., colloidal (c), and crosslinked (x)) and alginate (ALG) were used as advanced controlled release systems …

Hemodynamic And Clinical Outcomes With Balloon-Expandable Valves Versus Self-Expanding Valves In Patients With Small Aortic Annulus Undergoing Transcatheter Aortic Valve Replacement: A Meta-Analysis Of Randomized Controlled Trials And Propensity Score Matched Studies, Mushood Ahmed, Areeba Ahsan, Shehroze Tabassum, Irra Tariq, Eeshal Zulfiqar, Mahnoor Farooq Raja, Asma Mahmood, Raheel Ahmed, Farhan Shahid, Syed Khurram M Gardezi, Mahboob Alam, Rodrigo Bagur, Mamas A Mamas

Faculty, Staff and Students Publications

Transcatheter aortic valve replacement (TAVR) is considered more effective than surgical aortic valve implantation for patients with a small aortic annulus (SAA), however, the comparative efficacy of different transcatheter heart valves (THVs) remains uncertain. A literature search was performed across databases from their inception until June 2024 to identify eligible randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Clinical outcomes were evaluated using a random-effects model to pool risk ratios (RRs) with 95 % confidence intervals (CIs). The analysis included 10 studies with 2,960 patients. BEVs were associated with a significantly smaller indexed effective orifice area (MD: -0.18, 95 …

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 …

Assessing The Temporal Role Of Mir-200 Loss In Murine Models Of Nsclc, Jared Fradette

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer related deaths in the United States, with non-small cell lung cancer (NSCLC) making up a majority of new diagnoses. Metastasis is the big killer in NSCLC and is driven by epithelial-mesenchymal transition (EMT) and immune evasion. The microRNA 200 family is a master regulator of EMT and is implicated in immune regulation. In this study we have developed a novel genetically engineered mouse model (GEMM) and derived primary cell lines from them to explore the role of microRNA-200 in early EMT and immune changes. Our model combines conditional activation of Kras^{G12D …}

Characterizing Mechanisms Of Dna Repair And Genome Stability, Joshua Turner

All Dissertations

Every day our cells are bombarded with DNA lesions that threaten the stability of our genome. To help maintain genomic integrity our cells evolved to have a network of enzymes dedicated to repairing DNA lesions. Upon encountering a site of DNA damage, a cell recruits enzymes that remodel the stalled replication fork by reannealing the newly synthesized DNA together known as fork regression. Loss of fork regression activity has been shown to promote replication stress resistance after induced DNA damage. In this thesis, I discuss the role F-Box Helicase 1 (FBH1) plays in fork regression and how FBH1 promotes the …

Soil Organic Matter Processes From The Treetops To The Clay Particle: The Role Of Climate, Minerals, And Organic Matter Chemistry In Soil Carbon Accumulation And Stability, Jessica G. Murray

All Graduate Theses and Dissertations, Fall 2023 to Present

Soils store more carbon than plants and the atmosphere, yet release ten times more carbon dioxide (CO₂) to the atmosphere than human activities each year. Small shifts in the balance of soil carbon storage and soil carbon emissions could make climate change less severe, by acting as a sink for the carbon plants pull from the atmosphere, or make climate change worse, by releasing even more planet-warming greenhouse gases. The processes governing whether soils store or release carbon depend on tiny soil microorganisms which convert plant carbon to soil organic matter, releasing CO₂ in the process. In …

Integrated Transcriptomics And Proteomics Study Of Starvation Selected Drosophila Melanogaster, Aavash Adhikari

UNLV Theses, Dissertations, Professional Papers, and Capstones

Drosophila melanogaster, selected for starvation resistance exhibits phenotypic traits such as increased body size, slower development, reduced fecundity and obesity like characteristics including higher lipid reserves and cardiac dysfunction. While prior studies have explored the metabolic and biochemical changes in these flies, the underlying genetic and molecular mechanisms remain unclear. This study aims to investigate the gene expression and protein abundance in starvation-selected Drosophila through RNAseq, proteomics, and integrating both datasets using the MixOmics package in R. I found differential gene expression in the fat body at the third instar larval stage, particularly in pathways related to lipid metabolism, calcium …

Investigation Of Reproductive Inhibition During Chronic Heat Stress In C. Elegans, Macy Makenna Nielander

Theses and Dissertations

Nearly all organisms experience heterogeneity in environmental conditions that can negatively impact fitness. A common adaptive strategy to reduce the impact of this stress is called facultative diapause, where development and reproduction are temporarily arrested to promote survival. Facultative diapause is characterized by three major criteria, the arrest must be (i) induced by an unfavorable environmental condition, (ii) reversible, and (iii) driven by genetically regulated mechanisms. The aim of this thesis was to determine whether chronic heat-induced inhibition of egg laying in Caenorhabditis elegans represents a novel form of facultative diapause. It was found that the inhibition of egg-laying is …

Characterization Of An Acetogenin-Carrying Nanosuspension And Its Effect On Bacteria Of Interest In The Poultry Industry, Brandon A. Lopez-Romero, Gabriela Aguilar-Hernandez, Billy M. Hargis, Maria De Lourdes Garcia-Magana, Ulises M. Lopez-Garcia, Rosa I. Ortiz-Basurto, Adalberto Zamudio-Ojeda, Juan D. Latorre, Efigenia Montalvo-Gonzalez

Poultry Science Faculty Publications and Presentations

This work aimed to develop a nanosuspension (NSps) as an acetogenin (ACGs) carrier, using soy lecithin (SL) and hydroxypropyl-β-cyclodextrin (βCD) named NSps-βCDSL-ACGs. It was characterized by various spectroscopic techniques (DLS, FTIR, UV-vis diffuse reflectance). Moreover, the NSps morphology was observed by transmission electron microscopy (TEM). Also, the antibacterial activity of NSps-βCDSL-ACGs was evaluated against strains of interest in the poultry sector. NSps-βCDSL-ACGs presented nanometric size (207–239 nm), acceptable polydispersity index (PDI) values (0.13–0.17) and a high Z potential value (−47.17–50.36 mV), demonstrating high stability. The presence of ACGs in NSps-βCDSL-ACGs was confirmed by FTIR analysis. The nanoparticles had a spherical …

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 …

Evaluating Human Plasma Biomakers For Alzheimer's Disease; Phosphorylated-Tau 217, Phosphorylated-Tau 181, And Glial Fibrillary Acidic Protein, Mason Jonah, Mayarae N. Mugosa, Bella Hou, Emma-Nikole Krilchev, Zhengshi Yang, Dietmar Cordes, Aaron Ritter, Jefferson W. Kinney

Undergraduate Research Symposium Posters

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease that is primarily identifiable by amyloid-beta (Aβ) neuronal plaques, neurofibrillary tangles (NFT) that form as aggregates of hyperphosphorylated tau (ptau) proteins clump together, and the presence of neuroinflammation; all of which are otherwise known as the hallmarks of AD pathology. Recent emerging research has discovered striking similarities between AD and diabetes mellitus pathology, illustrating how insulin deficiency and insulin resistance–both of which result in the chronic hyperglycemic state seen in the diabetic–are involved in an increase in the phosphorylation of tau. This leads to and intensifies the formation of intracellular NFTs serving …

Effects Of Low Dose Exposure To Radiation And Sleep Fragmentation On Discrimination In String-Pulling Behavior With Female Rats, Jonathan F. Cortez, Diana Lloyd, T. L. Garcia, A. Adhikari, N. M. Attallah, N. Moges, D. H. Rodgers, K. S. Dhede, K. D. Omengan, A. A. Blackwell

Undergraduate Research Symposium Posters

Astronauts will face harmful stressors, such as galactic cosmic radiation (GCR) and sleep fragmentation (SF), on a three-year space flight mission to Mars and back. Astronauts perform skilled reach-to-grasp behaviors on these missions, including interacting with controls to navigate the spacecraft. Recent work has shown that GCR and SF disrupt skilled reach-to-grasp behavior in rodent models; however, the underlying nature of these deficits is unknown. To determine if tactile sensation and proprioceptive feedback contribute to these impairments, this study evaluated the effects of radiation and SF exposure on memory and sensorimotor discrimination in a rodent model. Twenty-one outbred Wistar, retired …