Biochemistry, Biophysics, and Structural Biology Commons^™

The Role Of Small Extracellular Vesicles In Modulating Radiation Resistance In H3k27m-Pediatric Diffuse Midline Glioma, Viral Oza

Theses and Dissertations--Molecular and Cellular Biochemistry

Pediatric diffuse midline gliomas with H3K27M alteration (H3K27M-pDMG) are the leading cause of pediatric brain tumor-associated deaths. All H3K27M-pDMG are initially treated with fractionated radiotherapy, the standard of care, and most children succumb to their disease within two years of diagnosis. There are no universally effective chemotherapies and full resection is impossible due to the diffuse nature of the tumor and sensitive location. There has not been a significant clinical advancement in more than 40 years.

Tumors become completely resistant to radiation within the first six months of treatment. The mechanism of radiation resistance is unknown but is thought to …

A Major Update And Improved Validation Functionality In The Mwtab Python Library And The Metabolomics Workbench File Status Website, P. Travis Thompson, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background: The Metabolomics Workbench (MW) is a public scientific data repository consisting of experimental data and metadata from metabolomics studies collected with mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses. Although not as rapidly as in the past, MW has steadily evolved, updating its mwTab and JSON deposition text file formats and its web-based infrastructure. However, the growth of MW has been exponential since its inception in 2013 and continues to be exponential, with the number of datasets hosted on the repository increasing by 50% since April 2024. As part of regular maintenance to keep up with changes to …

Analysis Of Alternative Oxidase In Non-Angiosperm Plants, Anissa M. Francis

Theses and Dissertations (Comprehensive)

Alternative oxidase (AOX) is a mitochondrial terminal oxidase that provides an alternative pathway for electron transport, allowing plants to maintain respiratory flexibility under environmental stress conditions. While AOX has been extensively studied in angiosperms (flowering plants), little is known about its distribution and conservation in non-angiosperms. Based on gaps identified in the literature, this thesis investigated the distribution of AOX across non-angiosperm plant lineages. Although AOX is present in many green algae and is therefore considered to be an ancient protein that originated before the existence of non-angiosperm plants, it remains unclear whether the protein is uniformly distributed across these …

The Geminivirus Al2 Protein Interacts With Host Proteins Involved In The Plant Antiviral Response, Pheobean Atieno Odongo

Graduate Research Theses & Dissertations

Geminiviruses are economically important plant DNA viruses infecting a broad range of plant species and causing devastating crop diseases, resulting in up to 100% crop loss. As a result of these heavy losses on food and cash crops, these viruses represent a new threat to global food security and sustainability. In this research, I use Tomato golden mosaic virus (TGMV) to study host-virus relationships with an overall goal of developing sustainable and eco-friendly crop resistance. TGMV belongs to the Geminivirus subgroup, Begomovirus, that is characterized by a split genome consisting of two single-stranded circular DNAs. The TGMV genome encodes proteins …

Role Of The Osaa Transcription Factor Gene In Development, Secondary Metabolism And Virulence In The Mycotoxigenic Fungus Aspergillus Flavus, Farzana Ehetasum Hossain

Graduate Research Theses & Dissertations

Aspergillus flavus colonizes oil-seed crops, contaminating them with aflatoxins; highly carcinogenic mycotoxins that cause severe health and economic losses. Genetic studies may reveal new targets for effective control strategies. Here, we characterized a putative WOPR transcription factor gene, osaA, in A. flavus. Our results revealed that osaA regulates conidiation and sclerotial formation. Importantly, deletion of osaA reduces aflatoxin B1 production, while, unexpectedly, transcriptome analysis indicated upregulation of aflatoxin biosynthetic genes, suggesting post-transcriptional or cofactor-mediated regulation. Cyclopiazonic acid production also decreased in the absence of osaA. In addition, the osaA mutant exhibited upregulation of genes in the imizoquin and aspirochlorine clusters. …

Patterns Of Ovarian And Gonadotropin Hormones In Emerging Adult Oral Contraceptive Users, Summer Mcormond

UROP Posters

Oral contraceptives (OCs) are often initiated during adolescence and emerging adulthood, a period of continued maturation of the hypothalamic–pituitary–gonadal (HPG) axis. Because hormonal exposure during this window may shape emotional, biological, and reproductive outcomes, it is important to understand the specific formulations young women take and the hormonal profiles these formulations produce. This study characterizes OC formulation features and measured hormone levels in young adult OC users (n = 30).

Ethinyl estradiol (EE) doses ranged from 0.01–0.035 mg (mean = 0.022 mg), with 70% using ≤0.02 mg. Pill regimens included 21/7 packs (83%), 24/4 packs (10%), and 84/7 regimens (3%). …

Fluorescent Protein Imaging Approaches Uncover Dynamic Subcellular Distribution Of Core Clock Proteins In Neurospora Crassa, Ziyan Wang

Dartmouth College Ph.D Dissertations

Circadian clocks are endogenous self-sustained timekeeping systems that allow organisms to anticipate and adapt to daily environmental cycles. Found in diverse forms of life, these molecular clocks regulate the expression of ~ 40% of the genome in animals, fungi, and plants. In animals and fungi, circadian oscillators are built on transcription-translation feedback loops (TTFLs), in which positive regulators drive the expression of negative regulators which, once synthesized and imported into the nucleus, inhibit their own activators. This precisely regulated negative feedback incorporates multiple steps of delays that are essential for generating ~24-hour rhythms. Through these mechanisms, circadian clocks temporally coordinate …

From Theory To Ecosystems: Exploring Biodiversity And Ecosystem-Function In Pitcher Plant (Darlingtonia Californica) Microbial Communities, Gavin Sutter

Cal Poly Humboldt theses and projects

The relationship between biodiversity and ecosystem-function (BEF) has been a central focus of ecological research for the last three decades, yet the role of space in shaping BEF relationships remains relatively unknown. Research has shown that community diversity and composition can strongly influence productivity, nutrient cycling, and decomposition, but much of this work treats communities as spatially isolated, leaving open how dispersal and other spatial processes shape BEF at broader scales. To begin addressing this gap, I used microbial communities inhabiting Darlingtonia californica pitcher plant leaves to evaluate how spatial organization and successional change shape biodiversity and ecosystem-functioning. I quantified …

The Importance Of The Proline Residue In The Ldiapa Motif Of Cholera Toxin, Akash Bharathan

Honors Undergraduate Theses

Cholera is currently on its seventh global pandemic, disproportionately affecting developing countries. Vibrio cholerae, the bacterial etiologic agent, is able to cause infection by adhering to intestinal epithelial cells and secreting cholera toxin (CT), an AB-type exotoxin that dysregulates signaling pathways. Previous research by the Teter lab has shown that Hsp90, a host cytosolic chaperone, is required for CT to enter the cytosol where it produces toxic effects. Hsp90 binds to CT at two specific motifs, RPPDEI and LDIAPA. The prolines in the RPPDEI motif are essential for binding, but the proline in the LDIAPA has yet to be …

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk, Yasir A. Alshehry, Matthew S. Halquist Phd, Sandro R.P. Da Rocha Phd

Graduate Research Posters

Background

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance …

Shedding Light On Cellular Glycolysis Pathway Kinetics: Combining Kinetic, Mechanistic Modelling Approaches With Label Free Microspectroscopic Imaging. (Spectralomics), Nitin Patil

Doctoral

Cellular metabolism and its intricate biochemical mechanisms which allow the conversion of nutrients into energy to sustain life are well understood, leading to numerous breakthroughs in science and technology, human health and wellbeing. From an industrial perspective the pathway kinetics are significant for monitoring cellular bioprocesses, screening desired metabolite phenotypes in drug discovery processes, etc.

An initial review of glycolysis pathway kinetics highlighted the lack of sophisticated approaches to monitor the metabolic pathway kinetics as a function of time in a non-destructive, non-invasive, label-free manner. Fluxomics, a metabolomics based approach providing high-throughput insights, can be considered a gold standard approach, …

Preliminary Analysis Of Soil Volatile Organic Compounds As Soil Health Indicators, Thorne Taul

Graduate Theses, Dissertations, and Problem Reports (ETD)

Over the past decade, soil health (SH) has gained popularity due to the novelty of sustainable soil use related to human wellbeing. Soil health describes the overall quality of soil and its capacity to function over time. As interest in SH grows, researchers continue to explore new soil health indicators that can improve knowledge on how soil health is assessed and managed. Some indicators directly reflect soil health status, and some indirectly relate to processes and functions occurring within the soil. Volatile organic compounds (VOCs) are naturally occurring compounds that play a role in multiple soil processes. They are associated …

Ornithine Metabolism In Retinal Pigment Epithelium And Retina And Implications In Gyrate Atrophy, Artjola Puja

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ornithine aminotransferase (OAT) is a mitochondrial enzyme that regulates ornithine metabolism by converting ornithine to pyrroline-5-carboxylate, a precursor for proline and glutamate synthesis. Deficiency of OAT causes systemic ornithine accumulation and leads to gyrate atrophy (GA) of the choroid and retina, a hereditary disorder characterized by progressive chorioretinal degeneration and irreversible vision loss. Chorioretinal atrophy typically starts at the mid-peripheral retina and progresses toward the macula. Although elevated ornithine is considered toxic to the eye, how ornithine is metabolized in ocular tissues and why OAT deficiency causes selective, region-specific vulnerability remain unclear. We combined ex vivo and in vivo stable …

Antiestrogens As Bone Protective Therapeutics For Estrogen Receptor-Positive Breast Cancer In The Presence Of Osteoporosis, Faith E. Parker, Emily K. Zboril, David C. Boyd, Rachel Myrick, J. Chuck Harrell

UROP Posters

Breast cancer (BC) is one of the most significant causes of mortality among women and the second leading cause of cancer death in women. The estrogen receptor (ER) is a key oncogenic driver in the majority of breast cancer. ER+ BC is the most common molecular subtype of BC. Management of ER+ breast cancer varies depending on menopausal status. For premenopausal women, the goal is to suppress estradiol production from the ovaries with surgical oophorectomy and/or aromatase inhibitors. In postmenopausal women, endocrine therapy (ET) serves to suppress estradiol production from sources other than the ovaries. During the menopausal transition, estradiol …

Investigating The Effects Of Nucleopore Defects On The Cellular Response To Stress In Als/Ftd Ipsc-Derived Neurons, Alicia Christine Collins

Open Access Dissertations

Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a progressive neurodegenerative disease spectrum characterized by motor dysfunction, cognitive decline, and death within a few years of clinical onset. Hallmark features of ALS/FTD include defects in nucleocytoplasmic transport (NCT) and abnormal cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43, both of which have been shown to be exasperated by oxidative stress (OS). It remains unclear how these processes are connected and how they collectively contribute to neurodegeneration. To fill this gap of knowledge, we used human embryonic kidney cells, neuroblastoma cells, and induced pluripotent stem cell-derived cortical neurons harboring the ALS/FTD C9ORF72 …

Mechanisms Of Glyphosate Toxicity: Uptake, Mitochondrial Function, And Metabolism, Dionysios Patriarcheas

Graduate Theses, Dissertations, and Problem Reports (ETD)

Glyphosate, the most widely used herbicide in the world, is an inhibitor of chorismate biosynthesis, the precursor of aromatic amino acids. The target of glyphosate is absent in animals, but findings reporting toxicity in model organisms without a known mechanism or target are increasing. Saccharomyces cerevisiae is a useful and versatile model for understanding molecular mechanisms of toxicity. In yeast, previous work has shown that the aspartate/glutamate permease Dip5 is the proposed transporter for glyphosate and that mitochondrial metabolism has been implicated in response to glyphosate toxicity. This dissertation aimed to identify the effects of glyphosate on mitochondrial function through …

Recirculated Submarine Groundwater Discharge Dominates Nutrient Inputs And Enhances Eutrophication Risk In A Coastal Lagoon, Júlia Rodriguez-Puig, Clara Ruiz-González, Marc Diego-Feliu, Irene Alorda-Montiel, Aaron Alorda-Kleinglass, Daniel Romano-Gude, Andrea G. Bravo, Júlia Dordal-Soriano, Javier Gilabert, Sophia Bergeler, Celine Lavergne, Gemma Casas, Marisol Manzano, Jordi Garcia-Orellana, Valentí Rodellas

OES Faculty Publications

Submarine groundwater discharge (SGD) is a widely recognized pathway for nutrient transport to coastal systems. Prior studies overlook the unique biogeochemical signatures of different SGD pathways, neglecting their differences in biogeochemical transformations and spatiotemporal factors. Here, we present an integrated assessment of nutrient delivery through three SGD pathways (fresh SGD, long‐scale recirculated SGD, and short‐scale porewater exchange), alongside surface water inputs, to evaluate their seasonality and impact on nutrient dynamics in a coastal lagoon. We conducted five field surveys in March, July, and November 2021, July 2024, and March 2025 in the Mar Menor lagoon, an ecosystem facing severe ecological …

Methylseleninic Acid Transformations In Nutrient Rich Water Containing Algae Exposed To Simulated Sunlight, Mikayla Cormier

Theses and Dissertations (Comprehensive)

Methylseleninic acid (MSA(IV)) is an organic form of selenium that has been suggested to be one of the most bioaccumulative forms of selenium in aquatic ecosystems. However, there have been no lab studies that confirm this, which is the reason this study was conducted. Once MSA(IV) and other bioavailable forms of selenium enter aquatic ecosystems, organisms such as algae take up these compounds which then bioaccumulate through the food chain. S. obliquus was exposed to 10 ppb MSA(IV) in 10% Bold’s basal medium (BBM) in a growth chamber to mimic environmental conditions over a 7-day period. Carbon traps and filters …

Evaluating Novel Targeted Combination Therapies For Gastrointestinal Cancers, Joseph A. Goode

Graduate Studies Theses and Dissertations 2026

Gastrointestinal (GI) cancers remain among the leading causes of cancer-related mortality worldwide, with therapeutic resistance continuing to limit the effectiveness of current treatments. Three complementary studies were conducted to identify therapeutic vulnerabilities and evaluate novel combination strategies in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC).  First, dual inhibition of fibroblast growth factor receptor 4 (FGFR4) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling was investigated in PDAC models. A combination of targeted drug treatments reduced viability, clonogenic survival, migration, and suppressed signaling pathways involved in translational control. This supported a functional interaction between FGFR4 and PI3K-mTOR co-activation in …

The Biosynthesis Of The Natural Product N-Nitroglycine, Gabriel Padilla

Graduate Studies Theses and Dissertations 2026

N-Nitroglycine (NNG) is a nitramine [R(R′)N–NO2; R′=H or alkyl] natural product (NP) produced by certain actinomycetes, such as Streptomyces noursei. At the beginning of this project, the biosynthesis of this NP was unknown. The goal was to determine how NNG and its nitramine moiety are enzymatically formed. This could lead to the discovery of novel nitramine NPs with diverse applications as well as alternative/green synthesis of nitramine explosives. This work begins by examining diverse biochemical N–N bond formation strategies. Nitrogen cycle enzymes, nitration of NPs, kutzneride biosynthesis, the aspartate/nitrosuccinate superfamily, hydrazinoacetic acid (HAA) biosynthesis, and streptozocin biosynthesis are among the …