Biochemistry, Biophysics, and Structural Biology Commons^™

Endogenous Light In The Brain: Investigating Sources, Propagation, And State-Dependent Emission, Emre Cicek

Theses and Dissertations (Comprehensive)

Ultraweak photon emission (UPE), and by extension light, has long been thought to be a modality of communication in nature. Prior studies have already identified that UPE can depend on cell type and can be used to discern between malignant and benign cells. However, besides theoretical models, not much effort has been made to identify possible biological structures that would allow for light to be used as a method of communication in the human body. According to the framework set by Shannon’s Information Theory, for communication to be possible at minimum a transmitter, a transmission channel, and a receiver are …

Sediment Redox-Driven Iron Flux And Phytoplankton Community Responses: Implications For Cyanobacterial Suppression And Functional Stability Across Boreal Lakes, Julia K. Kozak

Theses and Dissertations (Comprehensive)

Freshwater eutrophication contributes towards the development of cyanobacterial harmful algal blooms (cHABs), but nutrient availability alone does not fully explain variation in phytoplankton community composition or physiological performance. While phosphorus (P) availability has been known to regulate phytoplanktonic biomass, iron (Fe) is an important micronutrient supporting Fe-heavy processes within cyanobacteria (i.e., nitrogen fixation and photosynthetic electron transport). Sediment Fe availability in freshwater ecosystems is regulated by reduction oxidation (redox) conditions at the sediment-water interface (SWI), where nitrate (NO₃^-) has been found to maintain oxidizing conditions and prevent the reduction of Fe(III) to more readily bioavailable soluble Fe(II), …

Investigating The Ability Of Presequences To Influence Mitochondrial Protein Import, Youmian Yan

WUSM Theses and Dissertations – All Programs

Mitochondria are essential organelles housing over 1000 proteins, 99% of which are nuclear-encoded and synthesized in the cytosol. Most mitochondrial proteins are targeted by a positively charged sequence called the presequence, which lacks a common sequence motif and is poorly conserved across evolution. Accumulating evidence suggests that presequences encode meaningful information that influences mitochondrial protein uptake. For instance, multiple stress response models propose that stress sensing proteins contain “weak” presequences which allows them to monitor mitochondrial health. However, there is a lack of systematic examination about how presequences influence import kinetics and what constitutes presequence strength. These gaps in knowledge …

Sec-Saxs And Sans Analyses Of The Talin•Vinculin Complex, Gilbert Reyes

Dissertations, Theses, and Capstone Projects

Focal adhesions (FA) are integrin-based cell-matrix adhesion sites composed of adaptor proteins that facilitate the generation of traction forces important for biological functions such as cell migration, embryo development, wound healing, tissue organization and stability, and immune responses. Mature FA are observed when both autoinhibited multi-domain scaffolding protein talin and membrane-cytoskeletal protein vinculin are activated and interact thus promoting the assembly and function of FA. While research has resolved truncated sections of autoinhibited talin and recruitment of vinculin due to mechanotransduction that exposes cryptic vinculin binding sites (VBS), little is known about the global modifications of full length talin in …

The Role Of External Factors In Shaping Carbohydrate Conformational Landscapes, Murat Yaman

Dissertations, Theses, and Capstone Projects

Carbohydrates (glycans) are among the most structurally diverse biomolecules and participate in a wide range of biological processes, including molecular recognition, cell adhesion, immune response, host-pathogen interactions, and cellular signaling. Their biological functions are governed by a complex interplay between sequence, stereochemistry, conformational flexibility, and environmental factors. However, the structural heterogeneity and dynamic nature of glycans present significant challenges for both experimental characterization and theoretical modeling. In particular, the relationships between glycan structure, conformational dynamics, and the resulting potential energy surfaces remain incomplete.

This dissertation investigates how external factors modulate the potential energy surfaces of carbohydrates through a combination of …

Riluzole As A Dual-Targeted Radiosensitizer For Osteosarcoma: Targeting Tumor Cells And Angiogenic Vasculature To Enhance Single High-Dose Radiotherapy Efficacy, Pooja P. Rao

Dissertations, Theses, and Capstone Projects

Osteosarcoma (OS), the most common primary bone malignancy of children and young adults, is intrinsically radioresistant, and outcomes for patients with unresectable or metastatic disease have not improved in over four decades. Single-dose radiation therapy (SDRT) is a potent modality against radioresistant, highly vascularized sarcomas, but its application in OS is constrained by dose-dependent normal tissue toxicity. Radiosensitizers achieving tumor control at lower doses therefore offer a direct route to widening the therapeutic window. Critically, OS radioresistance is not tumor-cell-autonomous. It emerges from two coordinated compartments: aberrant DNA repair and antioxidant capacity intrinsic to the tumor cell, and a radioprotective, …

Analysis Of Diterpenoid Alkaloids From American Aconitum Using Lc-Ms Metabolomic Methods, Yi Zhao

Dissertations, Theses, and Capstone Projects

Analysis of Diterpenoid Alkaloids from American Aconitum Using LC-MS Metabolomic Methods

by

Yi Zhao

Advisor: Edward J. Kennelly

Aconitum plants have been used as a traditional medicine in Asian countries for millennia to treat pain, rheumatism, syncope, fever, and other conditions. These therapeutic effects are mainly due to the bioactive diterpenoid alkaloids accumulated in the roots. Comparing with the large records and studies of Asian Aconitum and their medicinal use and the broad bioactive compounds, American Aconitum has been rarely investigated, not to mention how American Aconitum has been used medicinally. Based on previous phylogenetic and chemotaxonomic studies of Aconitum …

Development Of Ultrafast Protein Digestion And Standards Free Quantitation Methods For Mass Spectrometric Analysis, Praneeth Ivan Joel Fnu

Dissertations

A wide variety of biologically important molecules, such as enzymes, antibodies, hormones, transporters and receptors are proteins by composition and they play key roles in biological functions such as cellular regulation, communication, metabolism and physiological function. Protein dysfunctions and abnormalities are associated with numerous diseases, making proteins critical targets for understanding disease mechanisms and developing therapeutic interventions. Protein-based therapeutics such as monoclonal antibodies, hormones and vaccines gained popularity due to their high specificity, efficacy, and ability to treat complex diseases that are often difficult to address with small-molecule drugs.

Given the important role of proteins in a variety of biological …

Modeling Kinetics Of 5-Aminolevulinic Acid-Induced Protoporphyrin Ix Accumulation For Optimal Photodynamic Therapy, Priscilla Melebor

Graduate Masters Theses

Photodynamic therapy (PDT) is a minimally invasive treatment that uses light-activated photosensitizers to selectively destroy diseased tissue through the generation of reactive oxygen species. However, conventional in vitro models often fail to accurately reproduce the pharmacokinetics of photosensitizer accumulation and clearance observed in vivo. This study investigated protoporphyrin IX (PpIX) accumulation following 5-aminolevulinic acid (ALA) exposure under physiologically relevant conditions using two-dimensional (2D) monolayers and three-dimensional (3D) spheroids. By comparing continuous ALA exposure with transient exposure followed by ALA washout, this work provides a more biologically relevant framework for studying PpIX kinetics and optimizing photodynamic therapy.

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Modulation Of Electrophysiology And Plaque Aggregation In Huntington’S Disease Patient-Derived Cells By Picosecond Pulsed Electric Fields, Mackenzie A. Tardif-Kunk

Biomedical Sciences Theses & Dissertations

Huntington’s Disease (HD) is a fatal, autosomal dominant neurodegenerative disorder characterized by progressive motor and cognitive decline. Unstable expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin gene, often exceeding 35–40 repeats, results in an extended polyglutamine (PolyQ) tract in the translated protein. Abnormal folding of the mutant huntingtin (mHTT) protein leads to accumulation and aggregation within the cell, dysregulating various cellular processes through molecular sequestration. While several therapeutic strategies have been proposed, this disease remains incurable with treatments limited to symptom management.

Pulsed electric fields (PEF), primarily in the microsecond and nanosecond ranges, have been studied extensively for the …

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 …

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 …

Nanoscale Morphological Perturbations Of Lipid Membranes Induced By Membrane Active Peptides, Yasith Sandeepa Indigahawela Gamage

USF Tampa Graduate Theses and Dissertations

Membrane-active peptides (MAPs) are a diverse group of biologically relevant molecules that induce nanoscale modulations during their interactions with cell membranes. Understanding the precise mechanism by which these MAPs perturb or modulate the cell membranes is a cornerstone of membrane biophysics, as it facilitates rational design of useful therapeutics. That is, if we have the knowledge to determine what the peptide can do, how selective it is, or how toxic it might be, we can optimize them and design new peptide therapeutics such as for antimicrobial, anticancer, or drug-delivery applications. In general, MAPs can be categorized into two classes based …

Histone Deacetylases In Kidney Injury: Distribution, Injury-Specific Regulation, And Fibroblast Hdac1 Function, Huy Nguyen

ETDs from 2020-2029

Acute kidney injury (AKI) is increasingly recognized as a major contributor to the development of chronic kidney disease (CKD) through maladaptive repair and interstitial fibrosis. Epigenetic regulation has emerged as a critical factor of kidney injury responses, however the injury-specific and cell-type specific roles of histone deacetylases (HDACs) remain poorly defined. This dissertation investigates the regulation and functional significance of HDACs in kidney injury, with a particular focus on fibroblast HDAC1 as a mediator of interstitial fibrosis development following AKI. In my cisplatin-induced AKI model, a single dose of cisplatin caused a significant decline in kidney function in both male …

Elucidating The Mechanisms Of Complex Flavoprotein Dehydrogenases, Tyler Alt

Dissertations

Flavins are ubiquitous redox active cofactors that can catalyze electron transfer between substrates. They offer the advantage of being able to stabilize a range of oxidation and protonation states, as well being amenable to covalent modification, which can further alter their activity. As such, the scope of reactions catalyzed by flavoproteins is broad and flavin has implications in a range of biological processes. The two predominant forms of flavin that serve as redox active cofactors are flavin adenine mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are functionally homologous. A major complication of studying flavoprotein dehydrogenases, and one that has …

A Rho5-Cnc1-Dnm1 Signalling Module Coordinates Multi-Organelle Execution Of Regulated Cell Death In Yeast, Justin Bauer

Theses and Dissertations

Regulated cell death is a conserved process with major implications for health and disease, yet how yeast cells integrate stress signals to determine survival versus death remains unclear. This thesis investigates Cyclin C (Cnc1), a conserved Mediator kinase module component with both transcriptional and mitochondrial roles. Together with Cdk8 Cnc1 primarily represses stress response genes, while upon stress it translocates to the mitochondria to induce mitochondrial fragmentation with the dynamin-related GTPase Dnm1. Using structure-guided separation-of-function mutants, I demonstrate that Cnc1-dependent death requires its mitochondrial function rather than its transcriptional role, and that its effector Dnm1 acts as a signaling node …

Elucidating The Function Of Yedk In Response To Dna Damage, Hank Munro

University Honors Theses

Apurinic/Apyrimidinic (AP) sites are one of the most prevalent forms of DNA damage. These lesions arise spontaneously or during base excision repair of modified DNA bases and are potentially mutagenic in both mammalian and bacterial cells. 5-hydroxymethylcytosine binding, ES cell specific (HMCES), a protein found in eukaryotic cells, has been shown to form a stable DNA-protein crosslink with AP sites in single stranded DNA and to reduce the number of AP sites occurring either spontaneously or after alkylative DNA damage, resulting in increased genome stability. YedK, the Escherichia coli ortholog of HMCES exhibits some of the same biochemical properties as …

The Neuroprotective Effect Of Cdc42 Inhibition In The G93a Mutant Hsod1 Mouse Model Of Als, Andrea Koly

Undergraduate Theses, Capstones, and Recitals

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, leading to muscle weakness, neuromuscular junction (NMJ) degeneration, paralysis, and eventual death due to respiratory failure. Despite extensive research, effective disease-modifying therapies remain limited, underscoring the need to identify novel molecular targets involved in ALS pathogenesis. Dysregulation of Rho family GTPases has been implicated in neurodegeneration, with Rac and Rho exerting opposing effects on neuronal survival; however, the role of the closely related GTPase Cdc42 remains poorly understood in ALS. In this study, the therapeutic potential of inhibiting …

A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin

Electronic Theses and Dissertations

Caveolae are specialized, flask-shaped membrane invaginations highly expressed in endothelium and dysregulated in atherosclerosis. Caveolae play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. Thus, we sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. However, cell culturing, the backbone of human-focused biological research, does not standardly do well to model physiologically relevant cell behaviors such as migration or polarity-based tissue formation, particularly for punctate proteins and structures like caveolae. Micropatterns are cell-adhesive shapes that biophysically confine cell(s) to a user defined geometry which stereotype organelle …