Interactions Of The Sars-Cov-2 Viral Genome 3’-Untranslated Region With Viral And Host Rnas, Caleb Frye, Mihaela Rita Mihailescu

Electronic Theses and Dissertations

This dissertation focuses on the characterization of RNA-RNA interactions within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome and with host microRNAs. As the causative agent of coronavirus disease 2019 (COVID-19), SARS-CoV-2 has evolved rapidly since its appearance. This has warranted prompt characterization of the virus particularly of its single stranded RNA (ssRNA) genome. By using a combination of bioinformatics, biophysics, and/or biological assays, we analyzed the SARS-CoV-2 viral genomic RNA and uncovered interactions of genomic RNA with host RNAs, highlighting an underutilized method of targeting RNA viruses. We showed here that the conserved elements in the viral genomic …

Molten Flux Synthesis Of Plutonium (Iv) Silicates K2Pusi2O7 And Rb2Pusi6O15, Travis K. Deason, Gregory Morrison, Amir Mofrad, Jake Amoroso, David Diprete, Theodore M. Besmann, Shanna L. Estes, Hans Conrad Zur Loye

Faculty Publications

Few plutonium containing silicates have been reported in the literature and only one other tetravalent plutonium silicate structure has been reported using the flux growth method. With the goal of understanding actinide incorporation into silicates, we describe herein two new plutonium (IV) silicates, Rb2PuSi6O15 and K2PuSi2O7, synthesized using a mixed alkali chloride/alkali fluoride flux growth. Both structures crystallize in the C2/c space group with lattice parameters a=24.2980(10) Å, b=7.1466(3) Å, c=17.2025(8) Å and 96.6560(10)° for Rb2PuSi6O15, and a=9.9478(2) Å, b=5.59820 (10) Å, c=13.1848(2) Å, and 105.7400(10)° for K2PuSi2O7. Comparisons to the synthesis of other reported alkali actinide silicates (Ce, U, …

P85Α Degradation Mediated By Ubiquitin E3 Ligase Fbxo21 Offers Therapeutic Potential In Leukemia, Kasidy K. Weber

Theses & Dissertations

Acute myeloid leukemia (AML) is a complex and heterogeneous disease characterized by the clonal expansion of myeloid blasts in the bone marrow. Despite significant therapeutic advances over the years, the prognosis for AML patients remains dismal, with high relapse rates and poor overall survival. The ubiquitin-proteasome system (UPS) plays a critical role in maintaining cellular homeostasis by regulating the degradation of proteins involved in essential processes such as cell cycle control, DNA repair, apoptosis, and various signaling pathways. Given this vital function, targeting ubiquitin E3 ligases within the UPS presents a promising strategy for developing more effective and targeted therapies …

Chilling- And Dark-Regulated Photoprotection In Miscanthus, An Economically Important C4 Grass, Jared Haupt, Katarzyna Glowacka

Department of Biochemistry: Faculty Publications

Tolerance of chilling dictates the geographical distribution, establishment, and productivity of C4 crops. Chilling reduces enzyme rate, limiting the sink for the absorbed light energy leading to the need for quick energy dissipation via non-photochemical quenching (NPQ). Here, we characterize NPQ upon chilling in three Miscanthus accessions representing diverse chilling tolerance in C4 grasses. High chilling tolerant accessions accumulate substantial amounts of zeaxanthin during chilling nights in both field and growth chamber settings. Chilling-induced zeaxanthin accumulation in the dark enhances rate of NPQ induction by 66% in the following morning. Based on our data, the emerging ways for the unique …

Capacity-Weighted Figures-Of-Merit For Battery Transport Metrics, Cj Sturgill, Christopher Sutton, Julian Schwenzel, Morgan Stefik

Faculty Publications

New battery materials with improved transport are needed. Typical measurements yield widely varying voltage-dependent diffusivities and reporting practices are diverse. Some materials (e.g. first-order phase change) have most redox occur at a specific voltage and may be sufficiently represented by singular transport metrics. Many rapid intercalation materials, however, exhibit second-order phase transitions with redox over a broad voltage range. How should such cases be compared? The use of capacity-weighted average values is suggested where voltage-dependent metrics are consolidated into representative descriptors as figures-of-merit. Examples are elaborated where differential capacity (dQ/dV) is used to derive a …

A Kinetic Model For Compound Heterozygous Pathogenic Variants In Tyrosyl-Trna Synthetase Gene Yars2-Associated Neonatal Phenotype, Thomas W Christian, Sunita Maharjan, Sitao Yin, Yuka Yamaki, Isao Masuda, Fenglin Li, Colleen Muraresku, Sheila Clever, Rebecca Ganetzky, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Human genetic disorders are often caused by mutations of compound heterozygosity, where each allele of the mutant gene harbors a different genetic lesion. However, studies of such mutations are hampered due to the lack of an appropriate model. Here we describe a kinetic model of compound heterozygous variants in an obligate enzyme dimer that contains one mutation in one monomer and the other mutation in the second monomer. This enzyme is encoded by human YARS2 for mitochondrial tyrosyl-tRNA synthetase (mt-TyrRS), which aminoacylates tyrosine to mt-tRNA^Tyr. YARS2 is a member of the genes for mt-aminoacyl-tRNA synthetases, where pathogenic mutations …

Hypoxia-Inducible Factor 3Α1'S Role In Promoting Iron Loading, Tumorigenesis, And Metastasis In Colorectal Cancer, Luke B. Villareal

Biomedical Sciences ETDs

The interplay between hypoxia and iron metabolism drives colorectal cancer (CRC) progression. This dissertation investigates hypoxia-inducible factor 3α1 (HIF-3α1), a protein linked to poor CRC outcomes, focusing on its roles in metastasis, epithelial-to-mesenchymal transition (EMT), and iron loading via transferrin receptor (TFRC). HIF-3α1 promotes CRC cell migration by upregulating zinc finger E-box binding homeobox 2 (ZEB2) and suppressing N-myc downstream-regulated gene 1 (NDRG1), while TFRC-mediated iron accumulation supports tumor growth and survival. Iron chelation reduced EMT markers, migration, and tumor growth, highlighting iron's critical role. Additionally, HIF-3α1-induced TFRC expression altered nucleotide synthesis enzymes carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase (CAD) and phosphoribosyl pyrophosphate …

Analysis Of Natural Structures And Chemical Mapping Data Reveals Local Stability Compensation In Rna, Robert L. Cornwell-Arquitt, Riley Nigh, Michael T. Hathaway, Joseph D. Yesselman, David A. Hendrix

Department of Biochemistry: Faculty Publications

RNA molecules adopt complex structures that perform essential biological functions across all forms of life, making them promising candidates for therapeutic applications. However, our ability to design new RNA structures remains limited by an incomplete understanding of their folding principles. While global metrics such as the minimum free energy are widely used, they are at odds with naturally occurring structures and incompatible with established design rules. Here, we introduce local stability compensation (LSC), a principle that RNA folding is governed by the local balance between destabilizing loops and their stabilizing adjacent stems, challenging the focus on global energetic optimization. Analysis …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Directed Evolution Of Hedgehog Protein Autoprocessing Activity: Combined Experimental & Computational Approach, Ted Kuke

Undergraduate Honors Theses

Sonic hedgehog protein is vital for embryonic development while also being linked to multiple cancers and holoprosencephaly. The native reaction of hedgehog is a sterolysis reaction whereby cholesterol binds to the HhC catalytic domain and attacks the HhN signaling domain, resulting in a covalent HhN-cholesterol signaling product. The structure of the sterol recognition region (SRR) of Sonic Hedgehog, where cholesterol binds, is currently unknown. In this thesis, I used directed evolution to select a triple mutant of Hedgehog’s catalytic HhC domain, (D46H, Q150H, A196T), which is over 5000 times more catalytically efficient at reacting with epicoprostanol (ECP), a non-native substrate …

Angiogenin-Catalyzed Cleavage Within Trna Anticodon-Loops Identified By Cp-Rna-Seq, Megumi Shigematsu, Ryuma Matsubara, Justin Gumas, Takuya Kawamura, Yohei Kirino

Computational Medicine Center Faculty Papers

Angiogenin (Ang), an endoribonuclease belonging to the RNase A superfamily, cleaves the anticodon-loops of tRNAs to produce tRNA-half molecules. Although previous studies have demonstrated the involvement of Ang in the pathobiology of neurodegenerative disorders, the characterization of Ang-generated tRNA halves in neuronal cells remains limited. This is partly due to the technical limitations of standard RNA-seq methods, which cannot capture Ang-generated RNAs containing a 2',3'-cyclic phosphate (cP). In this report, we established an Ang-treatment model using SH-SY5Y, a human neuroblastoma cell line, and demonstrated Ang-dependent accumulation of tRNA halves. By performing cP-RNA-seq, which selectively captures cP-containing RNAs, we identified Ang-generated …

Na2B12Si6Se18: A Novel B12-Cluster-Containing Quaternary Selenoborate Framework Material, Gopabandhu Panigrahi, Hunter B. Tisdale, Gregory Morrison, Hans Conrad Zur Loye

Faculty Publications

We report the successful synthesis of the new quaternary, three-dimensional Na₂B₁₂Si₆Se₁₈ material using a solid-state synthesis route. This compound is characterized by a unique framework structure that features the rare icosahedral [B₁₂]¹⁰⁺ cation which is connected via Si2Se6 polyhedral units into a 3D framework structure with Na+ ions located inside the channels. The Na₂B₁₂Si₆Se₁₈ compound crystallizes in the cubic crystal system in the space group Im, with lattice parameter a = 11.91110(10) Å and unit cell volume of 1689.88(4) ų. …

Targeting The Cholesterol Storage Enzyme Acat1/Soat1 In Brain Cells And Mouse Model: A Novel Approach To Address Aging And Apoe4-Related Neuroinflammation, Thao Nguyen Phuong Huynh Krumeich

Dartmouth College Ph.D Dissertations

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease that significantly impacts nearly 7 million people in the United States. AD is characterized by the deposition of amyloid beta (Ab) plaque, tau neurofibrillary tangles (NFTs), lipids granules, and neuroinflammation. Age and apolipoprotein E4 (APOE4) are the two biggest risk factors for AD. Recent AD therapeutic development has mostly benefited the patient population with milder symptoms while causing serious side effects in APOE4 carriers, leaving the most impacted patients’ group - aged APOE4 carriers with no treatment option. With the increasing aging population, there is an urgent need for a …

D101n: A Unique And Ill-Understood Familial Als-Related Sod1 Mutant, Analisa Lott

Honors Program Theses and Research Projects

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, with 90% of documented cases considered sporadic and about 10% showing a hereditary link; such cases are deemed as familial ALS (fALS). Superoxide dismutase (SOD), a copper-zinc binding enzyme that protects cells from damaging free radicals, has been linked to fALS with certain toxic gain of function mutations, such as the D101N mutant. The human SOD1 D101N mutant has been shown to be associated with rapidly progressing neurodegeneration yet is less prone to aggregation than similar mutants, but its deviation from wild-type (WT) SOD1 remains misunderstood.

Objective: Although the D101N …

Synthesis Of Novel Chromenone Esters For Biochemical Assays, Andrew Dean Helmerich

Undergraduate Honors Thesis Collection

This project details the synthesis of a variety of novel chromenone esters to be used as enzymatic probes. A robust, initial library of 22 chromenone esters was successfully synthesized with differences in chain length, branching, and the incorporation of cyclic and heteroatomic moieties. These new chromenones were fully characterized by 1HNMR, 13CNMR, DEPT HRMS, 19FNMR, and HSQC. The utility of these compounds comes from the fact that they will fluoresce upon cleavage of the ester; thus, this property makes them ideal candidates to be used in the monitoring of enzymatic activity of esterases. Elucidating the enzyme-substrate structure activity relationship (SAR) …

Polymeric Sumo-2/3 Chain Signals Are Antagonistically Regulated By The Sumo-Targeted Ubiquitin E3 Ligase Rnf4 And The Sumo-Specific Isopeptidase Senp6, Shaniah A. Irving M.A., Xiang-Dong Zhang Ph.D.

Biology Theses

Polymeric SUMO-2/3 chain modification is critical for chromosome segregation, DNA damage repair, genome stability, stress responses, and protein degradation. However, how these signals are regulated remains poorly understood. Both the SUMO-targeted ubiquitin E3 ligase (STUbL) RNF4 and the SUMO-specific isopeptidase SENP6 recognize poly-SUMO-2/3 chains through multiple SUMO-interacting motifs (SIMs). RNF4 contains four tandem SIMs within a short (~80 amino acids) region, whereas SENP6 possesses eight SIMs spanning a much larger (~500 amino acids) domain.

Our preliminary results show that overexpressing an RNF4 N-terminal fragment containing four tandem SIMs (wild type, WT), but not an inactive SIMs mutant (Mut), increases levels …

Decoding Fgf/Fgfr Signaling: Insights Into Biological Functions And Disease Relevance, Oshadi Edirisinghe, Gaetane Ternier, Zeina Alraawi, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast Growth Factors (FGFs) and their cognate receptors, FGFRs, play pivotal roles in a plethora of biological processes, including cell proliferation, differentiation, tissue repair, and metabolic homeostasis. This review provides a comprehensive overview of FGF-FGFR signaling pathways while highlighting their complex regulatory mechanisms and interconnections with other signaling networks. Further, we briefly discuss the FGFs involvement in developmental, metabolic, and housekeeping functions. By complementing current knowledge and emerging research, this review aims to enhance the understanding of FGF-FGFR-mediated signaling and its implications for health and disease, which will be crucial for therapeutic development against FGF-related pathological conditions.

Investigation Of Magnesium-Potassium Phosphates As Potential Nuclear Waste Form For The Immobilization Of Minor Actinides, Hans Conrad Zur Loye, Petr Vecernik, Monika Kiselova, Vlastislav Kašpar, Hana Korenkova, Vlastimil Miller, Petr Bezdicka, Jan Šubrt, Natalija Murafa, Volodymyr Shkuropatenko, Sergey Sayenko

Faculty Publications

Several recent studies have evaluated technologies of spent nuclear fuel processing specifically for solidifying transuranic (TRU) waste as a by-product of fission. Of the TRU group, plutonium and the minor actinides will be responsible for the bulk of the radiotoxicity and heat generation of spent nuclear fuel in the long term (300 to 20,000 years). In this study, we investigated magnesium potassium phosphate (MKP)-based compounds as host waste forms for the encapsulation of inactive trivalent Nd and Sm as analogues of the minor trivalent actinides, Am and Cm. Waste forms were fabricated under ambient atmospheric conditions by adding 5 wt.% …

Anti-Inflammatory Potential Of Black Cumin Seed Oil And Its Nanoemulsion Formulation Against Lipopolysaccharide-Induced Liver Injury In Mice, Shady Swidan, Hesham Hafez, Rehab Hosni, Hatem Amin

Pharmacy

Original Article

Anti-inflammatory potential of black cumin seed oil and its nanoemulsion formulation against lipopolysaccharide-induced liver injury in mice

Haffez, Hesham^1,2,✉; Hosni, Rehab³; Swidan, Shady A.⁴; Amin, Hatem K.^1,5

Author Information

¹Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, 11795, Cairo, Egypt

²Center of Scientific Excellence “Helwan Structural Biology Research”, Helwan University, Helwan, 11795, Cairo, Egypt

³El Sisi Comprehensive Clinic, General Authority for Health Insurance-Giza, Haram, 12556, Giza, Egypt

⁴Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk, 11837, Cairo, …

Traittrainr: Accelerating Large-Scale Simulation Under Models Of Continuous Trait Evolution, Jenniffer Roa Lozano, Mataya Duncan, Duane D. Mckenna, Todd A. Castoe, Michael Degiorgio, Richard Adams

Entomology and Plant Pathology Faculty Publications and Presentations

Abstract

The scale and scope of comparative trait data are expanding at unprecedented rates, and recent advances in evolutionary modeling and simulation sometimes struggle to match this pace. Well-organized and flexible applications for conducting large-scale simulations of evolution hold promise in this context for understanding models and more so our ability to confidently estimate them with real trait data sampled from nature. Results

We introduce TraitTrainR, an R package designed to facilitate efficient, large-scale simulations under complex models of continuous trait evolution. TraitTrainR employs several output formats, supports popular trait data transformations, accommodates multi-trait evolution, and exhibits flexibility …

Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior

Saha Cardiovascular Research Center Faculty Publications

Abstract The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity. APOA2 likewise increased the cholesterol efflux capacity of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up …

Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler

Saha Cardiovascular Research Center Faculty Publications

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Lam-Ha T. Dang, Alice Lee, Sharon Krinsky-Mchale, Deborah Pang, Lisa Melilli, Sid E. O’Bryant, Rachel L. Henson, Charles Laymon, Florence Lai, H. Diana Rosas, Beau Ances, Ira Lott, Christy Hom, Bradley Christian, Sigan Hartley, Shahid Zaman, Elizabeth Head, Mark Mapstone, Zhezhen Jin, Wayne Silverman, Nicole Schupf, Benjamin Handen, Joseph H. Lee, Alzheimer’S Biomarker Consortium – Down Syndrome (Abc-Ds)

Neurology Faculty Publications

Background Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer’s disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

Methods We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium–Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Characterization Of The Final Enzyme In The Coenzyme M Biosynthesis Pathway In Methanosarcina, Connor John Hines

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Methanogenesis is known to be one of the oldest forms of energy generation on our planet. Methanogens rely on this method of energy conservation and have evolved to metabolize a variety of substrates, including the waste products of other organisms. This feature has made methanogens beneficial to both wastewater treatment and landfill-to-energy projects. Methane itself is a greenhouse gas twenty times more potent than carbon dioxide, viewed as a particularly influential contributor to global greenhouse emissions. Climate change was known to be on the horizon throughout the 20^th century but has made itself known vocally during this 21^{st …}

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 …

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 …

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 …

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 …