Biochemistry, Biophysics, and Structural Biology Commons^™

Three-Dimensional Cell And Nuclear Geometries Inform Tissue Level Fluid Mechanics During Epithelial Remodeling, Liam Joseph Russell

Electronic Theses and Dissertations

During epithelial remodeling, mechanical and molecular programs must coordinate to drive the cell shape changes that enable new tissue topologies. Dynamic morphogenesis requires epithelia to preferentially exhibit solid- or fluidlike properties depending on developmental and biophysical constraints. Convergent extension in the Drosophila germband epithelium is one such remodeling event, during which the lateral ectoderm lengthens by two-fold along the primary body axis while concomitantly shortening orthogonally. This process is an incredibly dynamic and attractable system for studying tissue morphogenesis mechanics in vivo.

Germband extension is driven by oriented cell intercalation through T1 transitions, where cells directionally interdigitate with one another …

Synthesis, Utilization And Biological Evaluation Of Β-Hairpin Peptides As Inhibitors Of Immune Checkpoints, Sarah Naylon

Electronic Theses and Dissertations 2020 - Present

Peptide therapeutics have emerged as promising alternatives to monoclonal antibodies because of their smaller size, improved tissue penetration, and synthetic versatility. Yet their broader application is often limited by poor structural stability, rapid clearance, and reduced target residence times. This dissertation describes the design, synthesis, structural characterization, and biological evaluation of β-hairpin peptides as inhibitors of immune checkpoints and as peptide vaccine scaffolds while developing strategies to overcome these limitations. At first a series of antibody-derived β-hairpin peptides (mimics of complementary determining region heavy-chain 3: CDR-H3s) as covalent inhibitors of the PD-1/PD-L1 immune checkpoint were investigated. Electrophilic warheads were incorporated …

Instruction Guide, Mark C. Hall

Analytical Biochemistry: A Practical Handbook for Undergraduates

The instruction guide provides useful information for setting up and running the lab activities each week and assessing student preparation, performance, and comprehension.

The Defining Role Of Ago4 And Its Catalytic Activity During De Novo Rna-Directed Dna Methylation, Tianyi Li

Arts & Sciences Graduate Student Theses and Dissertations

Plant transposable elements and transgenes are continuously targeted for transcriptional repression via the pathway of RNA-directed DNA methylation (RdDM). Although perpetual RdDM of the endogenous genomic loci has been well studied in the field, much less is known about the de novo RdDM pathway, the pioneering round of DNA methylation responsible for triggering and initiating silencing of new transgenes. Despite being two distinct pathways, both perpetual and de novo mechanisms of RdDM require the production of small interfering RNAs (siRNAs) and the key proteins of the ARGONAUTE4 (AGO4) clade. However, the order and likely mechanism of recruitment of AGO4 to …

Enzymatic Synthesis Of Salicylate In Yersina Pestis Proceeds Via Intramolecular Hydroxyl Group Transfer., Clarke Miller

Georgia Journal of Science

The salicylate synthase (YbtS) of Yersinia pestis catalyzes the initial step in the biosynthesis of yersiniabactin, an iron-scavenging siderophore and critical virulence factor. While YbtS is proposed to share a  reaction mechanism with other anthranilate synthase homologs, the exact catalytic pathway has remained unresolved.  In this work, stable isotope (¹⁸O) labeling and mass spectrometry are utilized to clarify the catalytic mechanism of YbtS.  The results of the following set of experiments demonstrate that the salicylate hydroxyl group does not originate from solvent water, directly challenging previously proposed models. Instead, the lack of solvent-labeled oxygen incorporation and the absence …

Towards The Synthesis Of Dragonamide E And Analogs Thereof, Dante Glover

Chemistry Theses

Leishmaniasis is a disease caused by a parasite spread through the female sand fly. It is categorized as a Neglected Tropical Disease and can cause very severe symptoms, even death, if left untreated. Symptoms include skin lesions that can cause permanent scarring, and mucosal membrane infections that can cause facial deformities. More aggressive forms of leishmaniasis can lead to infections of internal organs like the liver and/or spleen and can lead to death. Drug resistance of these parasites has rendered treatment limited and the side effects of which can be harmful as well.

Scientists looking towards new treatments for tropical …

Crystal Structure Of New Polar Rare Earth Borates Na2.62Ln2.12(Bo3)3 (Ln = Pr, Nd, Sm) Containing Isolated Bo3 Groups, Alevtina A. Maksimova, Mark D. Smith, Hans Conrad Zur Loye

Faculty Publications

Three new rare earth borates, Na2.62Ln2.12(BO3)3 (Ln = Pr, Nd, Sm), were synthesized via a high-temperature solution reaction using a BaCO3–H3BO3–NaF flux and structurally characterized by single-crystal X-ray diffraction analysis. The compounds crystallize in the orthorhombic space group Amm2 with lattice parameters a = 5.0985(10) Å, b = 11.180(2) Å, c = 7.1483(14) Å, and a unit cell volume of 407.48(14) ų (Z = 2) for Na2.62Pr2.12(BO3)3, a = 5.0983(10) Å, b = 11.181(2) Å, c = 7.1491(14) Å, and a unit cell volume of 407.51(14) ų (Z = 2) for Na2.62Nd2.12(BO3)3, and a = 5.08630(10) Å, b …

Single Crystal Growth Of The Orthoborate Nabalu(Bo3)2 And Optical Investigation Of Eu3+ And Tb3+ Doped Nabalu(Bo3)2, Alevtina A. Maksimova, Mark D. Smith, Lakshani W. Masachchi, Hans Conrad Zur Loye

Faculty Publications

Sodium barium lutetium borate NaBaLu(BO₃)₂ crystals were synthesized using a high-temperature solution method. The crystal structure of this layered orthoborate is described and corresponds to that of an extensive orthoborates family, NaBaR(BO₃)₂ (R = Sc, Y, Yb, Tb – Lu). NaBaLu(BO₃)₂ was doped by Eu³⁺ and Tb³⁺ to explore its performance as a host material and to investigate the luminescent properties of the Eu³⁺ and Tb³⁺ doped materials. The emission spectra of the NaBaLu(BO₃)₂:Ln (Ln = Eu, Tb) crystals are presented. The most …

A Genetic Analysis Of The Rare Endemic Astragalus Ripleyi Barneby, Juan Antonio Jaramillo-Chico

Master's Theses

Astragalus ripleyi Barneby is a rare endemic species found in the San Luis Valley of the southern portions of the Rocky Mountains in Colorado and New Mexico. Though not federally listed as endangered, the species is on the Bureau of Land Management’s Sensitive Species List, warranting protection and continued management. This study aims to provide information about the genetic health of the species to inform conservation efforts and provide updated management recommendations. A genetic health analysis was conducted investigating the levels of diversity present in the species, how genetic diversity is structured across the known range of the species and …

Expression Levels Of Heat Shock Protein 72 And Their Correlation With Biomarkers Of Renal Function Among Hispanic Construction Workers Exposed To Ambient Heat In El Paso, Texas, Maria Fuentes

Open Access Theses & Dissertations

Heat shock proteins (HSP) are intracellular molecular proteins that are upregulated in response to cellular stress, including heat exposure. Through their protective functions, HSP help maintain protein structure, prevent protein denaturation, and preserve cellular homeostasis during states of physiological stress. Because of their cytoprotective properties, HSP have emerged as potential biomarkers for detecting early signs of tissue injury and predicting clinical outcomes associated with heat related illnesses (HRI), including acute kidney injuries (AKI). AKI is a leading cause of hospitalizations due to heat stress exposure and heat stroke. In the absence of early detection and effective therapeutic interventions, AKI may …

Polyphenol Diet And Exercise As Neuroprotection From Effects Of Alzheimer's Disease, Michelle Morgan

Loma Linda University Electronic Theses, Dissertations & Projects

Healthy non-pharmacological lifestyle factors, such as regular physical exercise and a dietary supplementation, have been shown to significantly improve cognitive outcomes over time compared to a more sedentary lifestyle and poor diet. Furthermore, exercise may serve as a potential protective factor in attenuating the effects associated with cognitive decline that are characteristic of neurodegenerative disorders, such as Alzheimer's disease (AD). Further, evidence indicates that certain diet interventions can also attenuate the effects of neurodegeneration and positively impact longevity. Supplementation of polyphenols, such as ellagic acid (EA), which are abundant in pomegranate juice, may help provide neuroprotective benefits and elicit a …

Prenatal Acoustic Programming Of The Developing Hypothalamus: A Multi-Omic Analysis Of Heat Call Exposure In Zebra Finch Embryos, Prakrit Subba

All Dissertations

Climate change is intensifying thermal stress on wildlife globally, yet the developmental mechanisms by which embryos use prenatal cues to adjust to predicted environments remain unclear. In Australian zebra finches (Taeniopygia guttata), incubating parents produce distinctive heat call vocalizations at high ambient temperatures, and embryos exposed to these calls during late incubation develop altered growth trajectories, thermoregulatory capacity, and reproductive outcomes, suggesting a form of anticipatory developmental programming triggered by sound alone. To investigate the molecular basis of this response, I initially hypothesized that prenatal heat call exposure would act primarily through hypothalamic neuroendocrine reprogramming, given the central …

The Rpm-1/Phr Signaling Hub Modulates Tau-Induced Neurodegeneration Through Regulation Of Microtubule Stability And Mapk Pathways In C. Elegans, Xinxing Ding

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, are characterized by the accumulation of pathological tau proteins and progressive neuronal loss. Although research regarding tau-mediated toxicity is extensive, the specific pathology that determine whether neurons maintain homeostasis or succumb to collapse under tau-induced stress remain incompletely elucidated. A central, yet still insufficiently understood, feature of these diseases is the disruption of the microtubule (MT) cytoskeleton . The PHR protein family is evolutionarily highly conserved; within this family, RPM-1 in C. elegans functions as an intracellular signaling hub that regulates axon development, synapse formation, axon termination, and various microtubule-associated processes. This …

From Geometry To Recognition: A Quantitative Framework For Tcr-Pmhc Structural Analysis In The Age Of Predicted Structures, Kun Hee Kim

Dissertations and Theses (Open Access)

Recognition of antigen by a T cell begins with a single physical event, the engagement of the T cell receptor (TCR) with a peptide-major histocompatibility complex (pMHC), and this interaction is encoded in the geometry with which the receptor docks onto the composite pMHC surface. Whether that docking geometry is biologically organized, and whether the structures now produced at scale by prediction preserve recognition or only reproduce that organization, are the two questions this thesis addresses. Two gaps stand in the way. The first is a gap of measurement, because docking geometry has never been made quantitatively comparable across many …

Machine Learning Integrated Designing And Screening Of 8-Hydroxyquinoline Based Metallo-Beta-Lactamase Inhibitors, Anthony M. Baudino, Kari Stone

Chemistry Department Faculty Articles

The rapid emergence of metallo-b-lactamase-mediated antibiotic resistance has created an urgent need for new inhibitor discovery strategies. In this work, a machine-learning-guided workflow was developed to generate and prioritize potential inhibitors targeting NDM-1. A SMILES-based variational autoencoder was first pretrained on a broad molecular dataset to learn general chemical syntax and latent molecular representations. The model was then fine-tuned on an 8-hydroxyquinoline-enriched dataset to bias molecular generation toward zinc-binding chemical space relevant to metallo-β-lactamase inhibition. Generated compounds were processed through structural filtering and docking-based evaluation to create training data for downstream predictive modeling. Molecular fingerprints and physicochemical descriptors were then …

Bridging The Gap In Science Research: Preparing Students For College- Level Research In The Sciences, Victoria Helwig, Yaoguang Li

UConn Library Presentations

Many first-year students enter college unprepared to fully engage with scientific literature and academic library resources. Drawing on experiences from academic librarians working with STEM students, this session explores common gaps in science research skills, including navigating databases, identifying scholarly sources, and understanding the structure of scientific literature. Participants will be introduced to practical strategies and classroom-ready activities to better prepare students for college-level research. Discussion questions: What science research skills do students struggle with most when entering college? How can high school instruction better support these skills? Where can librarians and educators collaborate to support student success?

Analysis Of The Atypical Temperature Dependence And Conformational Changes During Turnover Of A Lactobacillus Chlorogenic Acid Esterase, Nathaniel Carl, Yianni Tsigaris, Dan Ji, Nora K. Anpree, Kellie K. Omori, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Many bacterial chlorogenic acid esterases (ChlEs) exhibit atypical temperature behavior, featuring activities that barely change with temperature and activity maxima that fall below the thermal denaturation point. This work focuses on a ChlE from Lactobacillus helveticus (Lh–ChlE), which has a flat temperature dependence. First, it was determined that conformational changes during Lh–ChlE turnover are not rate-limiting and that the overall rate depends on the chemical step at all temperatures. Next, Lh–ChlE’s temperature dependence was investigated using a conformational equilibrium model that assumes the existence of a temperature-dependent equilibrium between an active and an inactive conformation and an activation heat capacity …

Uv Damage Mapping Reveals Different Impacts Of Xpd Mutations On Global Genomic And Transcription-Coupled Dna Repair, Allyson Hoag

Biomedical Sciences ETDs

Nucleotide Excision Repair (NER) is a fundamental cellular process that removes bulky and helical distorting lesions from the genome through the separate responses of its two subpathways – global genomic (GG-NER) and transcription coupled (TC-NER) DNA repair. The pathways converge with the recruitment of the TFIIH complex, a key step that is mediated by the translocase and helicase activities of  its XPD subunit. Germline mutations in XPD result in the clinical disorders, Xeroderma Pigmentosum (XP) and XP combined with Cockayne Syndrome (XP/CS). The goal of this thesis was to understand if XPD XP and XP/CS mutations differentially impact GG-NER and …

Ionophore-Based Plga Nanosensor For Selective Ion Detection And Imaging, Zhiyu Tang

Electronic Theses and Dissertations 2020 - Present

Accurate detection of electrolyte ions is essential for biological research, disease diagnosis, and the investigation of cellular function. In this study, we developed ionophore-based PLGA nanosensors for the optical detection of biologically important ions. The nanosensors were prepared by encapsulating ionophores, chromoionophore III, and ion exchangers within PLGA nanoparticles. The resulting nanosensors showed uniform morphology, good colloidal stability, and concentration-dependent optical responses toward Na⁺, K⁺, and Ca²⁺ over the range of 10⁻⁶ to 10⁻¹ M. Reversible fluorescence responses under repeated ion concentration changes confirmed the stability and robustness of the sensors. The nanosensors also demonstrated reliable analytical performance for K⁺ …

Effects Of Variable Light On Sexual Competition In Kelp Species, Jaycee Lanza

Master's Theses

As foundation species, kelps significantly influence the structure and composition of their surrounding habitat by modifying environmental conditions, including light levels, currents, nutrient availability, sedimentation, and seawater chemistry. Light, in particular, is a critical resource that varies greatly within kelp forests, affecting kelp reproductive processes such as gametogenesis, fertilization, and recruitment, which are vital to population persistence. Biological factors, such as density-dependent competition for resources and sexual competition with other kelps, can also affect such processes. To understand how environmental variables influence kelp populations, it is crucial to recognize their combined effects. This study investigated the impacts of light levels …