Digital Commons Network^™

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 …

Economic Impacts Of Establishing A Neutron Source Facility In Windsor, Abdur Rahman

Major Papers

Cancer poses a significant health challenge in Canada, with two in five individuals likely to develop the disease. This paper explores the economic impacts of establishing a prototype compact accelerator-based neutron source (PC-CANS) facility in Windsor that will produce medical isotopes locally in Windsor, Ontario, rather than relying on centralized production and transportation from London, Ontario. Fluorine-18 medical isotopes, crucial for positron emission tomography (PET) scans, experience significant decay losses during transportation due to their short half-life of 109.8 minutes, increasing costs and restricting availability. Using a differential analysis approach, the study quantifies economic benefits, focusing on three main impacts: …

Exploring Biosignatures And Biogeochemical Processes In Lanzarote Lava Tubes: Implications For Martian Analog Research, Vera Palma, Ana Z. Miller, Francesco Sauro, Bogdan P. Onac, José M. De La Rosa, Sara Gutiérrez-Patricio, Beatriz Cubero, José A. Gonzalez-Perez, Jesus Martínez-Frías, A Teresa Caldeira

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.

Exploring Pristine Microbial Ecosystems From The Uninhabited Volcanic Selvagens Islands, Pedro N. Jiménez-Morillo, Sara Gutiérrez-Patricio, Vera Palma, Ana Teresa Caldeira, Nicasio Tomás Jiménez-Morillo, Ana Z. Miller

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.

Investigating Therapeutic Activity Of Br-Ormeloxifene (Br-Orm) Against Cervical Cancer, Mohammed Sikander, Shabnam Malik, John Apraku, Sonam Kumari, Parvez Khan, Daniel Zubieta, Hassan Mandil, Aditya Ganju, Bhavin Chauhan, Maria C. Bell, Man Mohan Singh, Sheema Khan, Murali Yallapu, Fathi T. Halaweish, Meena Jaggi, Subhash Chauhan

Research Colloquium

Aberrant activation of β-catenin signaling is strongly associated with cancer proliferation, invasion, migration, and metastasis, thus small molecules that can inhibit this pathway might have great clinical significance. Our molecular modeling studies suggest that Ormeloxifene (ORM), a triphenylethylene molecule docks with β-catenin, and its brominated analogue (Br-ORM) bind more effectively with relatively less energy (-7.6 kcal/mol) to the active site of β-catenin as compared to parent ORM. Herein, we report the synthesis and characterization of a Br-ORM by NMR and FTIR, as well as its anti-cancer potential in cervical cancer models in vitro and in vivo. Br-ORM treatment effectively …

Dissecting The Interplay Of Protein Synthesis And Degradation Pathways In Cellular Adaptation To Stress, Brittany Friedson

Theses and Dissertations

Adaptation to stress requires cells to reprogram transcription, translation, and proteolytic pathways. Although much is known about the response of each program, it remains unclear how they coordinate following stress. My studies in S. cerevisiae identified the Cdk8 kinase module (CKM) of the Mediator complex as a new player in coordinating these processes. It is well established that the CKM consists of four highly conserved proteins (cyclin C, its cognate kinase Cdk8, and two structural proteins Med12 and Med13) and predominantly represses a subset of stress responsive genes in yeast. We demonstrated for the first time that the CKM also …

Engineered Nls-Chimera Downregulates Expression Of Aggregation-Prone Endogenous Fus, Miyuki Hayashi, Amandeep Girdhar, Ying-Hui Ko, Kevin Kim, Jacquelyn Depierro, Joseph R. Buchler, Nikhita Arunprakash, Aditya Bajaj, Gino Cingolani, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Importin β-superfamily nuclear import receptors (NIRs) mitigate mislocalization and aggregation of RNA-binding proteins (RBPs), like FUS and TDP-43, which are implicated in neurodegenerative diseases. NIRs potently disaggregate RBPs by recognizing their nuclear localization signal (NLS). However, disease-causing mutations in NLS compromise NIR binding and activity. Here, we define features that characterize the anti-aggregation activity of NIR and NLS. We find that high binding affinity between NIR and NLS, and optimal NLS location relative to the aggregating domain plays a role in determining NIR disaggregation activity. A designed FUS chimera (FUS_IBB), carrying the importin β binding (IBB) domain, is …

Serum Proteomic Profile Of Subclinical Babesia Bovis Infection In Pcr-Positive Eld's Deer Using Serum Protein Electrophoresis Coupled With Lc-Ms/Ms, Vichayanee Pumpitakkul, Sittiruk Roytrakul, Narumon Phaonakrop, Gunnaporn Suriyaphol Assoc. Prof.

The Thai Journal of Veterinary Medicine

Subclinical babesiosis observed in captive Eld’s deer, which act as reservoirs for ticks, poses a risk to healthy herds. However, the knowledge of biomarkers for subclinically infected Eld’s deer and host-parasite interactions is limited. This study aimed to investigate the serum proteomic profiles and protein interactions of Babesia bovis and subclinically infected Eld’s deer, PCR-positive for B. bovis, using automated serum protein electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The findings revealed albumin and four globulin fractions: alpha-1, alpha-2, beta, and gamma globulin. Albumin protein (ALB) was consistently detected across all fractions, highlighting its role in maintaining osmotic balance …

Methane Fluxes In Tidal Marshes Of The Conterminous United States, Ariane Arias-Ortiz, Jaxine Wolfe, Scott D. Bridgham, Sara Knox, Gavin Mcnicol, Brian A. Needelman, Julie Shahan, Ellen J. Stuart-Haëntjens, Lisamarie Windham-Myers, Patty Y. Oikawa, Dennis D. Baldocchi, Joshua S. Caplan, Margaret Capooci, Kenneth M. Czapla, R. Kyle Derby, Heida L. Diefenderfer, Inke Forbrich, Gina Groseclose, Jason K. Keller, Cheryl Kelley, Amir E. Keshta, Helena S. Kleiner, Ken W. Krauss, Robert R. Lane, Sarah Mack, Serena Moseman-Valtierra, Thomas J. Mozdzer, Peter Mueller, Scott C. Neubauer, Genevieve Noyce, Katrina V. R. Schäfer, Rebecca Sanders-Demott, Charles A. Schutte, Rodrigo Vargas, Nathaniel B. Weston, Benjamin Wilson, J. Patrick Megonigal, James R. Homquist

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Methane (CH4) is a potent greenhouse gas (GHG) with atmospheric concentrations that have nearly tripled since pre-industrial times. Wetlands account for a large share of global CH4 emissions, yet the magnitude and factors controlling CH4 fluxes in tidal wetlands remain uncertain. We synthesized CH4 flux data from 100 chamber and 9 eddy covariance (EC) sites across tidal marshes in the conterminous United States to assess controlling factors and improve predictions of CH4 emissions. This effort included creating an open-source database of chamber-based GHG fluxes (https://doi.org/10.25573/serc.14227085). Annual fluxes across chamber and EC sites averaged 26 ± 53 g CH4 …

Incorporating Solvation Thermodynamic Mapping In Computer-Aided Drug Design, Yeonji Ji

Dissertations, Theses, and Capstone Projects

Advancements in computational techniques have revolutionized structure-based drug design, substantially improving the efficiency and effectiveness of the drug discovery process by reducing time, costs, and labor requirements. These advancements include various methods, such as investigating small molecule ligands binding to proteins, exploring alternative protein conformations, and solvation mapping on the protein surfaces. Among these methods, understanding the correlation between protein-ligand binding and the role of solvation is important.

A fundamental concept in protein-ligand binding is shape and electrostatic complementarity, which is complicated by the inherent flexibility of proteins. In the absence of small molecule ligands, proteins are complementary to surface …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Prostate Tissue Motion Tracking And Ultrasound Elastography Using Tissue Mechanics Derived Constraints, Tristan S. Curry

Electronic Thesis and Dissertation Repository

Current prostate cancer detection methods can be costly to obtain, such as magnetic resonance imaging, or lack specificity, such as a digital rectal exam. Ultrasound elastography, a method that can be used to develop and test algorithms that output stiffness, strain, and displacement data captured by ultrasound radio frequency readings, offers a potential solution to these challenges. An initial algorithm utilizing dynamic programming and analytic minimization estimates the radial and angular displacements from a pre- and post-compression data set to determine the required material properties. This estimate of displacements is then refined through an algorithm where incompressibility, Laplacian smoothing, and …

Molecular Docking, Pharmacological Profiling, And Molecular Dynamics Simulation Of Potential Antihyperuricemic Agent From Secondary Metabolites Of Dillenia Philippinensis Rolfe (Dilleniaceae), Louie Rince C. Suyo, John P. Paulin, Nicole Clarence Louise L. Gapaz, Markus Brent S. Arevalo, Vince Tyrell P. Yongco, Librado A. Santiago

Karbala International Journal of Modern Science

Crystal accumulation in the joints due to increased serum uric acid (sUA) may lead to an inflammatory condition called gout. Increased sUA is caused by the excessive reabsorption of the urate anion transporter-1 (URAT-1). Therefore, URAT-1 inhibition will promote uric acid excretion and reduce the risk of having gout. Dillenia philippinensis Rolfe, often known as katmon, is an endemic plant in the Philippines with bioactive compounds associated with several therapeutic benefits. The present study represents the first scientific inquiry into the antihyperuricemic potential of compounds isolated from D. philippinensis. This study aimed to assess the interaction of URAT-1 with …

Informatics-Based Discovery Of New Natural Products, Their Biosynthesis, And Their Biological Roles, Ethan Older

Theses and Dissertations

In this work, genome mining and biosynthetic knowledge are applied for the discovery of new natural products, their biosynthetic pathways, and their promising biological activities and roles through the development of two unique new informatics-based approaches.

In chapter one, an overview of microbial natural product biological functions and biosynthesis is provided. The use of bioinformatics leveraging microbial natural product biosynthetic knowledge is also introduced. This chapter highlights the importance and need for developing innovative approaches to accessing microbial natural products, a vastly untapped source of new molecules with promising biological activities.

In chapter two, a correlational network linking the gene-encoded …

Structural Basis For Substrate Binding And Selection By Human Mitochondrial Rna Polymerase, Karl Herbine, Ashok Nayak, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

The mechanism by which RNAP selects cognate substrates and discriminates between deoxy and ribonucleotides is of fundamental importance to the fidelity of transcription. Here, we present cryo-EM structures of human mitochondrial transcription elongation complexes that reveal substrate ATP bound in Entry and Insertion Sites. In the Entry Site, the substrate binds along the O helix of the fingers domain of mtRNAP but does not interact with the templating DNA base. Interactions between RNAP and the triphosphate moiety of the NTP in the Entry Site ensure discrimination against nucleosides and their diphosphate and monophosphate derivatives but not against non-cognate rNTPs and …

Investigation Of P27 Tumor Suppressor Gene (Cdkn1b) Polymorphisms In Dogs With Malignant Mammary Tumors, Gizem Kırmızıoğlu, Iraz Akış

The Thai Journal of Veterinary Medicine

Mammary tumors are the most common neoplasm in dogs, with a high mortality rate. The development of canine mammary tumors (CMT) is multifactorial, but different incidence rates between breeds suggest the effects of genetic risk factors. Many CMT-associated candidate genes were reported, mainly involved in cell cycle control. This study aims to investigate p27 tumor suppressor gene polymorphisms in dogs with mammary tumors and analyze the association between variations and CMTs. For this purpose, case and control groups were formed from 22 dogs diagnosed with malignant mammary tumors and 10 dogs with healthy mammary glands. The whole canine p27 gene …

Assimilating Satellite-Derived Snow Cover And Albedo Data To Improve 3-D Weather And Photochemical Models, Colleen Jones, Huy Tran, Trang Tran, Seth Lyman

Chemistry and Biochemistry Faculty Publications

During wintertime temperature inversion episodes, ozone in the Uinta Basin sometimes exceeds the standard of 70 ppb set by the US Environmental Protection Agency. Since ozone formation depends on sunlight, and less sunlight is available during winter, wintertime ozone can only form if snow cover and albedo are high. Researchers have encountered difficulties replicating high albedo values in 3-D weather and photochemical transport model simulations for winter episodes. In this study, a process to assimilate MODIS satellite data into WRF and CAMx models was developed, streamlined, and tested to demonstrate the impacts of data assimilation on the models’ performance. Improvements …

Determining If Cx45 Acts As An Arrythmogenic Substrate In The Diseased Myocardium, Stephen R. Sobota

Theses & Dissertations

Proper contraction of the heart relies on gap junction channels (GJCs) composed of Cx40 and Cx43 in the atrial and ventricular tissues which mediate electrical conductance in the working myocardium. Also expressed is Cx45, which is limited to the pacemaker system. Studies in diseased human hypertrophic cardiac tissue have shown expression of Cx45 and decrease of Cx43 in the myocardium. Cx43 and Cx45 in vitro form heterometric GJCs, where the channel characteristics (metabolite transfer, electrical conductance, etc.) resemble those of Cx45. There is little-to-no data showing whether GJCs composed of Cx43 and Cx45 in cardiac hypertrophy result in altered conductance. …

Enpp1 Enzyme Replacement Therapy Improves Ectopic Calcification But Does Not Rescue Skeletal Phenotype In A Mouse Model For Craniometaphyseal Dysplasia, Ernst Reichenberger, Kevin O'Brien, Ayano Hatori, Thomas Carpenter, Koen Van De Wetering, Lisa Flaman, Jennifer Howe, Daniel Ortiz, Yves Sabbagh, I-Ping Chen

Jefferson Institute of Molecular Medicine Papers and Presentations

Craniometaphyseal dysplasia (CMD) is a rare genetic bone disorder, characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. Craniofacial hyperostosis leads to the obstruction of neural foramina and neurological symptoms such as facial palsy, blindness, deafness, or severe headache. Mutations in ANKH (mouse ortholog ANK), a transporter of small molecules such as citrate and ATP, are responsible for autosomal dominant CMD. Knock-in (KI) mice carrying an ANK_F377del mutation (Ank^KI/KI) replicate many features of human CMD. Pyrophosphate (PPi) levels in plasma are significantly reduced in Ank^KI/KI mice. PPi is a potent inhibitor of …

Stem-Loop And Circle-Loop Tads Generated By Directional Pairing Of Boundary Elements Have Distinct Physical And Regulatory Properties, Wenfan Ke, Miki Fujioka, Paul Schedl, James Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs are formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing interactions between boundaries are typically orientation-dependent. Pairing can be head-to-tail or head-to-head. The former generates a stem-loop TAD, while the latter gives a circle-loop TAD. The TAD that encompasses the Drosophila even skipped (eve) gene is formed by the head-to-tail pairing of the nhomie and homie boundaries. To explore the relationship between loop topology and the physical and regulatory landscape, we flanked the nhomie boundary …

Investigating The Stability Of Different Sizes Of Gold Nanoparticles In Physiological Environments And Different Gold Nanoclusters In Water., Narges Hajighasemi

Electronic Thesis and Dissertation Repository

Gold nanoparticles (AuNPs) have become promising candidates for various biomedical applications due to their unique physicochemical properties and biocompatibility. Nevertheless, the efficacy of AuNPs in these applications highly relies on their stability and ability to maintain their desired properties within the complex environment of the human body. This thesis investigates the stability and aggregation behavior of citrate-coated AuNPs in in-vitro physiological environments and nitrogen heterocyclic carbene (NHC)-coated gold nanoclusters (AuNCs) in water over time. Analytical techniques such as electrophoretic mobility, dynamic light scattering, and inductively coupled plasma mass spectrometry were employed. It was shown that cell media (in contrast to …

G12/13 Signaling In Asthma, Elizabeth L. Mcduffie, Reynold A Panettieri, Charles P. Scott

Department of Biochemistry and Molecular Biology Faculty Papers

Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood. Our review of the literature suggests that pro-contractile G protein coupled receptors likely signal through G12/13 to activate RhoA and mediate calcium sensitization. This hypothesis is consistent with the effects of pro-contractile agonists on RhoA and Rho kinase activation, actin polymerization and myosin light chain phosphorylation. Recognizing the likely role of G12/13 signaling in the pathophysiology …

How Local Interactions Give Rise To Large-Scale Conformational Changes In Proteins: A Molecular Dynamics Study, Shadi A. Badiee

Graduate Theses and Dissertations

Proteins are dynamic entities that undergo conformational changes essential for their biological functions. These structural changes often correspond with chemical events such as lipid interactions or environmental changes like protonation or acidification. Understanding the complex relationship between these chemical perturbations and the resultant mechanical responses is crucial for elucidating protein mechanisms. This dissertation investigates the chemo-mechanical coupling in the conformational dynamics of the bacterial ABC transporter Sav1866 and the impact of protonation on the Influenza virus hemagglutinin HA0. Using molecular dynamics simulations, we explore the conformational landscapes of Sav1866 and HA0. Our study examines how varying lipid compositions affect the …

L-Arabinose Induced Overexpression For Crystallographic Analysis Of The Spoiie Protein From Clostridioides Difficile, Danielle M. Maynard

Graduate Theses and Dissertations

The SpoIIE protein plays a crucial role in the sporulation process of Clostridioides difficile, a pathogen responsible for severe gastrointestinal diseases. Understanding the structural and functional aspects of SpoIIE is pivotal for deciphering its role in sporulation and exploring its potential as a therapeutic target. This study investigates the impact of varying concentrations of L-arabinose on the overexpression of SpoIIE in C. difficile, aiming to optimize protein yield and purity for subsequent crystallization and structural determination via X-ray crystallography. Using a recombinant expression system in Escherichia coli, different concentrations of L-arabinose were employed to induce SpoIIE overexpression. Protein purification was …

Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes, Heather Sonnemann

Dissertations & Theses (Open Access)

Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists. The aim of this study was to evaluate …

Metal Assisted O2-Dependent Carbon-Carbon Bond Cleavage Of Β-Diketones And Flavonols, Stephen N. Anderson

All Graduate Theses and Dissertations, Fall 2023 to Present

Almost everything we interact with on a daily basis has been synthesized by chemists ranging from plastics, food preservatives, and medications. The diversity of synthetic molecules are achieved by the formation of new bonds between existing molecules and/or through the cleaving of bonds found in a molecule. There are uncountable amount of conditions reported to facilitate chemical reactions which all depend on the nature of molecules being used and the environment it is used in.

In recent years, more attention has been paid to identify chemical reactions that can use more environmentally favorable conditions and reduce the use of limited …

Candida Albicans Farnesol Synthesis And Secretion, Daniel J. Gutzmann

School of Biological Sciences: Dissertations, Theses, and Student Research

Candida albicans is a polymorphic fungus and opportunistic commensal found primarily in the gastrointestinal and skin of healthy individuals. Several barriers prevent C. albicans from causing disease including a healthy immune system and microbiome. When these barriers become comprised, C. albicans can transition to a pathogen and disseminate through the intestinal mucosa leading to life-threatening bloodstream and invasive infections with mortality rates of up to 64%. Morphogenic plasticity is key to this transition and impacts virulence, adaptation to different host environments, and evasion of host immune responses. One regulator of morphogenesis is farnesol. Farnesol is a secondary metabolite …

Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera

All Dissertations

Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …

Exploring Acetate Metabolism: Genetically Characterizing Acetate Production And Acetate Utilization In The Fungal Pathogen Cryptococcus Neoformans, Rodrigo Catalan-Hurtado

All Dissertations

The basidiomycete Cryptococcus neoformans is an invasive opportunistic fungal pathogen and the most frequent cause of fungal meningitis resulting in approximately 112,000 deaths per year worldwide. Recently, the World Health Organization systematically prioritized fungal pathogens in which C. neoformans was among four fungal pathogens deemed critically important. Current methods of treatment are inadequate for most of the infected population; therefore, it is imperative to find novel therapeutic targets. Previous studies have shown that acetate is a major metabolite found in biopsies of C. neoformans infected mouse brain and lung tissues. Two potential pathways for acetate production have been identified. …

Assessment Of Tce And Chiral Pcb Dechlorination Rate, Congener Diversity, And Enantioselectivity In Town Creek, Sc, Usa Sediment Microcosms, Catherine P. Sumner

All Dissertations

Polychlorinated biphenyls (PCBs) and trichloroethene (TCE) are ubiquitous contaminants and are recognized as persistent organic pollutants due to their extreme chemical stability. PCBs were manufactured by chlorinating biphenyls that created 209 congeners with various structures, of which 19 are chiral and can exist as a pair of stable atropisomers. PCBs have been known to cause developmental and neurological toxicity in humans and wildlife; they can act as endocrine disrupters, carcinogens, and teratogens. Sangamo Weston Inc. was an industrial plant located near Town Creek in Pickens Country, South Carolina, that manufactured capacitors and used Aroclors 1016 and 1254 as dialectic fluids …