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Cardiac-Derived Fibroblast Growth Factor 23 Contributes To Physiologic And Pathologic Cardiac Remodeling, Isaac Daniel Campos Jun 2025

Cardiac-Derived Fibroblast Growth Factor 23 Contributes To Physiologic And Pathologic Cardiac Remodeling, Isaac Daniel Campos

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Chronic Kidney Disease (CKD) is a global health risk that increases patients’ risk for premature mortality and is accompanied by pathologic cardiac hypertrophy and fibrosis. Declining kidney function results in elevations of serum phosphate and Fibroblast Growth Factor (FGF) 23, a bone-derived phosphaturic hormone. Hyperphosphatemia and elevated FGF23 are associated with cardiovascular mortality in CKD. FGF23 can directly target cardiac myocytes via FGF Receptor (FGFR) 4 and induce cardiac hypertrophy and blocking FGFR4 signaling in CKD models reduces cardiac hypertrophy, but not fibrosis. FGF23 elevations are also observed following exercise and during pregnancy, two scenarios of physiologic hypertrophy not associated …

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Exploring The Role Of Brain Angiogenesis Inhibitor 3 (Bai3) In Regulating Body Weight, Haifa Alsahrif Jan 2025

Exploring The Role Of Brain Angiogenesis Inhibitor 3 (Bai3) In Regulating Body Weight, Haifa Alsahrif

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Obesity is a significant public health issue, strongly associated with various metabolic disorders, including type 2 diabetes and cardiovascular disease. Understanding the mechanisms that contribute to obesity is essential for developing effective interventions. One critical area of interest involves G-protein-coupled receptors (GPCRs), which are important in regulating metabolic health. These receptors are known to be involved in critical metabolic functions such as insulin secretion, lipid metabolism, and glucose uptake. The role of the GPCR, brain angiogenesis inhibitor-3 (BAI3), in metabolic regulation has not been fully explored. This dissertation focuses on the known functions of the BAI isoforms (BAI1-3) and presents …

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Impacts Of Climate Change On Members Of Shallow Water Antarctic Communities, Hannah Elise Oswalt Jan 2025

Impacts Of Climate Change On Members Of Shallow Water Antarctic Communities, Hannah Elise Oswalt

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Human-derived CO2 emissions have lowered the ocean’s pH and increased global temperatures. Low seawater pH can decrease the calcification, growth, and survival of calcifying invertebrates. Furthermore, low pH changes macroalgal growth and stress, possibly altering palatability to consumers. Global warming has decreased sea ice coverage, profoundly influencing photosynthetic organisms by altering subsurface irradiance. Shallow, hard-bottom communities along the Western Antarctic Peninsula are characterized by large macroalgal forests that shelter large numbers of mesograzers. Amphipods and macroalgae have a community-wide mutualistic relationship where macroalgae provide refuge from predatory fish while amphipods remove competing epiphytes. To understand how climate change could impact …

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Sialylation Of Tnfr1 By St6gal1 Modulates Receptor Dynamics And Determines Cell Fate, Jihye Hwang Jan 2025

Sialylation Of Tnfr1 By St6gal1 Modulates Receptor Dynamics And Determines Cell Fate, Jihye Hwang

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Abnormal glycosylation has long been identified as a key feature of cancer. Aberrant glycan structures on tumor cells arise from the dysregulation of select glycosyltransferases. For example, sialyltransferase ST6GAL1 is notable for its high expression in various cancers, including breast, colon, ovarian, and pancreatic. ST6GAL1 introduces α2-6-linkage sialylation to N-glycans on proteins, endowing cancer cells with stem cell-like properties. This modification contributes to resistance to apoptosis mediated by death receptors like TNFR1. Despite its significance in cancer, the regulatory mechanisms controlling ST6GAL1 expression remain largely unexplored. Additionally, it is unclear whether the apoptosis-resistant effect of sialylation is caused by an …

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Development Of Momordica Saponin-Based Vaccine Adjuvants, Hyunjung Kim Jan 2025

Development Of Momordica Saponin-Based Vaccine Adjuvants, Hyunjung Kim

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Vaccine adjuvants are indispensable substances that help induce a fast, potent, and durable immune response when administered with vaccine antigens. Among the FDA-approved vaccine adjuvants for human use, three of the most recently approved ones contain saponin adjuvant QS-21. To address QS-21’s inherent drawbacks, we investigated the adjuvant activity of a series of saponin-based semisynthetic vaccine adjuvants, including VSA-1 and VSA-2, prepared from natural Momordica saponins I and II in one-step. The natural saponins precursors are isolated from the widely available and inexpensive seeds of Momordica cochinchinensis SPRENG. In general, VSA adjuvants can enhance both humoral and cellular immune responses …

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Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham Jan 2025

Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham

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Immunoglobulin A1 (IgA1) is the second most abundantly produced immunoglobulin in circulation per day and plays a key role in human immunity. Two molecular complexities of IgA1 make accurately studying the protein challenging. The first is that IgA1 exists in three main molecular forms in the serum of humans: monomeric (mIgA1, 80-90% of serum IgA1), polymeric (pIgA1, 10-20% of serum IgA1), and IgA1-containing immune complexes (IgA1-IC, <0.5% of serum IgA1). The second complexity is that the hinge-region of IgA1 is extensively O-glycosylated and exhibits a high level of variation in its O-glycans, particularly in the degree of sialylation. In context of the autoimmune disease IgA nephropathy (IgAN), patients have elevated levels of IgA1 that has reduced levels of galactose (Gal) in the IgA1 hinge-region (Gal-deficient IgA1). This Gal-deficient IgA1 forms immune complexes with IgG autoantibodies (IgA1-IC), deposits in the glomeruli, and induces kidney injury. While it is established that these large IgA1-IC (>700 kDa) formed in the circulation are pathogenic, there remains a gap in knowledge about other blood proteins that may be associating with IgA1 in complexes. It is also necessary to understand the native …

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A Mixed Methods Approach To Understanding What Knowledge Alabama K-12 In-Service Educators Hold In Regard To School-Based Trauma-Informed Practices, Katherine Busch Jan 2025

A Mixed Methods Approach To Understanding What Knowledge Alabama K-12 In-Service Educators Hold In Regard To School-Based Trauma-Informed Practices, Katherine Busch

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Childhood trauma is prevalent in epidemic proportions, with data showing 40%-90% of individuals experiencing one or more childhood traumatic events that permanently changes neurobiology and stress response. These stress responses can manifest in behaviors that lead to problems in schools, including behavior issues, special education referrals, suspensions or expulsions, and decreased academic achievement. In adulthood, these traumatic stressors increase the odds of engaging in risky behaviors and developing chronic health conditions. Schools can be places of healing, promoting resilience and utilizing trauma-informed practices to help children and educators. Emerging studies show promise in the benefits of school-based trauma-informed practices, but …

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Where The Black Women At? Exploring The Narratives & Experiences Of Black Women In Higher Education Leadership, Jasmine P. Jean Jan 2025

Where The Black Women At? Exploring The Narratives & Experiences Of Black Women In Higher Education Leadership, Jasmine P. Jean

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WHERE THE BLACK WOMEN AT? EXPLORING THE NARRATIVES & EXPERIENCES OF BLACK WOMEN IN HIGHER EDUCATION LEADERSHIP JASMINE P. PARKER JEAN HIGHER EDUCATION ADMINISTRATION ABSTRACT This thesis explores the experiences of Black Women in mid- and senior-level leadership roles in higher education, with a focus on the unique challenges they face due to the intersection of race and gender. Black Women remain significantly underrepresented in leadership positions across the academic landscape, despite earning higher education degrees at high rates. The study seeks to amplify the voices of Black Women leaders, providing insight into the barriers they encounter, the strategies they …

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Transcriptomic Transformations And Epigenetic Elements: The Heart Of The Matter Across Diverse Cardiac Pathophysiologies, Sayan Bakshi Jan 2025

Transcriptomic Transformations And Epigenetic Elements: The Heart Of The Matter Across Diverse Cardiac Pathophysiologies, Sayan Bakshi

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Cardiovascular disease (CVD) comprises a complex array of disorders affecting the heart and blood vessels, representing the leading cause of mortality worldwide. This multifaceted nature of CVD has prompted extensive research into its molecular underpinnings and etiological diversity. Despite significant advances, the majority of CVD management strategies are guideline-based symptomatic treatment. This necessitates extensive research studies on therapeutic interventions aimed at disease prevention or cure. In this dissertation, we have employed next-generation sequencing (NGS) techniques to elucidate the cardiac transcriptional and epigenetic landscape across various conditions, including ischemic heart failure (IHF), Cardiogenic shock (CS), and diabetic heart failure (DHF). Our …

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Keep Your Head Up King, Your Crown Is Slippin': An Anti-Deficit Critical Phenomenological Analysis Of Black Male Stem Educators' Experiences, Desmond R. Parker Jan 2025

Keep Your Head Up King, Your Crown Is Slippin': An Anti-Deficit Critical Phenomenological Analysis Of Black Male Stem Educators' Experiences, Desmond R. Parker

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Black males comprise approximately 3% to 5% of the overall K-12 teaching workforce. The science, technology, engineering, and mathematics (STEM) fields are overrepresented in this shortage. This research project aimed to shed light on the experiences of Black male STEM educators to better understand what garnered their interests in STEM, and what ultimately led them to step into the STEM classroom. This study used a critical anti-deficit framework and hermeneutic phenomenological philosophy to understand the experiences of 10 Black male STEM educators in Alabama ranging from three to 30 years of teaching experience. Research data were collected through two semi-structured …

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Targeting Streptococcus Mutans Diadenylate Cyclase For The Prevention Of Dental Caries, Edwin Miguel Rojas Jan 2025

Targeting Streptococcus Mutans Diadenylate Cyclase For The Prevention Of Dental Caries, Edwin Miguel Rojas

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Streptococcus mutans (S. mutans) is the primary etiological agent involved in the initiation and progression of dental caries. S. mutans forms robust biofilms on the tooth surface, and current preventative treatments, such as oral rinses, eliminate both pathogenic and commensal oral species. Therefore, there is an urgent need for therapeutics which selectively inhibit S. mutans biofilms while keeping the oral microbiome intact. The diadenylate cyclase (DAC) enzyme in S. mutans plays a key role in biofilm formation. DAC converts adenosine triphosphate (ATP) into cyclic di-AMP (c-di-AMP), a secondary messenger involved in several cellular pathways. Increased levels of c-di-AMP have shown …

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Characterization Of Dhdds Rp59 Knock-In Mouse Models Of Retinitis Pigmentosa, Mai Ngoc Nguyen Jan 2025

Characterization Of Dhdds Rp59 Knock-In Mouse Models Of Retinitis Pigmentosa, Mai Ngoc Nguyen

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Cis-prenyltransferase (CPT), a prenyl chain elongation enzyme made up of two copies of dehydrodolichyl diphosphate synthase (DHDDS) and two copies of Nogo-B Receptor (NgBR), condenses metabolites from the mevalonate pathway to create dolichol, a sugar carrier required for glycosylation in all cells of the body. However, certain missense mutations in DHDDS cause non-syndromic retinitis pigmentosa (RP59). Three missense mutations, K42E, T206A, and R98W have been found in RP59 patients that present the cardinal phenotypes of RP – diminished ERG responses, attenuated retinal vessels, bone spicule-like pigmentation, and retinal thinning due to photoreceptor loss. However, no global changes in glycosylation are …

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Evaluations Of Hand-Arm Vibration (Hav) Exposure And Related Vascular And Musculoskeletal Heath Effects Among Groundskeeping Workers In Southeastern U.S., Nathan Chen Jan 2025

Evaluations Of Hand-Arm Vibration (Hav) Exposure And Related Vascular And Musculoskeletal Heath Effects Among Groundskeeping Workers In Southeastern U.S., Nathan Chen

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Long-term, excessive exposure to hand-arm vibration (HAV) may induce vascular, neurological, and musculoskeletal disorders, collectively known as hand-arm vibration syndrome (HAVS). However, concerns arise when adopting the currently available guidelines and standards to protect workers who regularly use vibrating tools due to the lack of standardized exposure assessment methods for HAV and reliable health indicators for HAVS. The existing exposure-response relationship addressed in ISO 5349-1 was developed based on epidemiological studies predominantly performed in temperate zones. Thus, this dissertation aimed to evaluate the HAV exposure levels and vascular and muscular health effects from vibration exposure among groundskeepers in the southeastern …

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The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop Jan 2025

The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop

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Circadian rhythms are crucial endogenous cycles with period of ~24 hours that evolved to adapt to light – dark driven changes in environmental conditions. At a molecular level, circadian rhythms are generated by the actions of clock genes that form a transcriptional- translational feedback loop and regulate the rhythmic expression of downstream clock-controlled genes. Cumulatively, the actions of these molecular clocks regulate rhythmicity of physiological and behavioral processes and are extensively characterized within the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Like SCN neurons, dopaminergic neurons of the SN are intrinsically pacemaking, though it is unknown if this intrinsic firing …

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Understanding The Insecticidal Toxin Xpta2: A Shift In Toxin Complex Biology, Cole Lorenza Martin Jan 2025

Understanding The Insecticidal Toxin Xpta2: A Shift In Toxin Complex Biology, Cole Lorenza Martin

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Pore forming toxins (PFTs) belonging to the ABC toxin complex (Tc) family are responsible for targeting and translocating toxins into target cells. ABC toxins consist of three separate subunits, each subunit providing a vital role in the cytotoxic mechanism of the Tc. The A subunit or TcA is the largest subunit of the complex and contains the binding domains and the translocation channel that perforates the membrane. The B subunit or TcB functions as a gated linker that forms a cocoon with the TcC which houses the toxic peptide and subsequently gets translocated through the TcB and TcA into the …

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Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar Jan 2025

Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar

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The bone matrix synthesis by osteoblast during skeletogenesis is regulated by several transcription factors and signaling pathways. Runx2 and Sp7 are master regulators of osteoblast differentiation and bone formation. Deletion of both genes in mice results in the complete failure of ossification. In humans, Sp7 and Runx2 genes mutations cause osteogenesis imperfecta and cleidocranial dysplasia, respectively. The progression of osteoblast differentiation requires a coordinated and temporal expression of Runx2 and Sp7 genes. Posttranslational modifications regulate the cellular levels and function of Runx2 and Sp7 proteins. Ubiquitination controls protein turnover through targeted degradation. The multi-subunit SCF-complex is the largest class of …

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Gendered Sexual Behaviors: Unintended Pregnancies, And Sexually-Transmitted Infections, Deirdre Ferguson Jan 2025

Gendered Sexual Behaviors: Unintended Pregnancies, And Sexually-Transmitted Infections, Deirdre Ferguson

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Education is the most effective way to address unintended pregnancies and sexually-transmitted infections (STIs). Education through preventative counseling has been negatively correlated with unintended pregnancies. Although research has shed light on the risks posing challenges to the prevention of unintended pregnancies, the consequential costs of these pregnancies continue to mount, both individually and societally. Birth control counseling corresponds with reducing the behavior of nonuse of contraceptives significantly. Education is thus associated with combatting inaccurate information passed along via primary social groups. To gain insight into the prevention of unintended pregnancies and STIs, data was gathered using a mixed-method approach incorporating …

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St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva Jan 2025

St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva

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The sialyltransferase ST6GAL1 is overexpressed in several cancers, including pancreatic ductal adenocarcinoma (PDAC). ST6GAL1 adds an α2-6-linked sialic acid to N-glycosylated membrane proteins, modifying their structure and function. Despite extensive research on how ST6GAL1 affects cell phenotype, the mechanisms regulating its expression remain largely unexplored. In this study, we investigated how two pro-inflammatory cytokines, IL-1β and IL-6, prevalent in the PDAC tumor microenvironment, regulate ST6GAL1 expression. We used the Suit-2 PDAC cell line and its metastatic subclones, S2-013 and S2-LM7AA, to monitor cytokine activity. Treatment with IL-1β or IL-6 increased ST6GAL1 protein and mRNA expression across all cell models. Specifically, …

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Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher Jan 2025

Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher

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A nonsense mutation is a point mutation in DNA that gives rise to a premature termination codon (PTC) in the open reading frame of the transcribed mRNA. Translation of this PTC-containing transcript terminates prematurely, leading to the creation of truncated non-functional protein. Translational readthrough is one therapeutic option being explored to suppress nonsense mutations that cause disease. Here, we further elucidate amino acid incorporation and the functional consequences of readthrough of nonsense mutations that cause cystic fibrosis. Additionally, we reveal the molecular mechanisms activated by a recently described small molecule readthrough agent, SRI- 41315. Finally, we discuss the various therapeutic …

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Production And Radiochemistry Of Theranostic Radioscandium Nuclides, Shelbie Jaylene Cingoranelli Jan 2025

Production And Radiochemistry Of Theranostic Radioscandium Nuclides, Shelbie Jaylene Cingoranelli

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In nuclear medicine, theranostics utilizes radionuclide pairs for diagnosis and therapy. Radioscandium isotopes (43Sc, 44Sc, and 47Sc) offer a promising alternative to the 68Ga/177Lu theranostic pair due to their identical radiolabeling conditions, complexes and in vivo pharmacokinetics. 43Sc (t1/2=3.89h, β+=88%) and 44Sc (t1/2 =3.97h. β+=94.3%) are suitable for Positron Emission Tomography (PET) imaging whereas 47Sc (t1/2=3.3d. Eβ-ave=162keV) is suitable for targeted radiotherapy and Single Photon Emission Computed Tomography (SPECT). These isotopes require production routes that lead to high radionuclidic purity and radiochemistry development for incorporation into radiopharmaceuticals. This study explores the production, purification, and application of these isotopes. The proton …

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Chronic Inflammation Compromises Natural Killer Cell Phenotype And Function In Myeloid Leukemia, Valeriya Kuznetsova Jan 2025

Chronic Inflammation Compromises Natural Killer Cell Phenotype And Function In Myeloid Leukemia, Valeriya Kuznetsova

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Chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) are blood malignancies characterized by clonal expansion and a compromised immune system. Tyrosine kinase inhibitors (TKI) revolutionized CML treatment; however, TKI discontinuation leads to relapses in half of the cases. Further, up to 10% of patients are TKI-resistant and develop a blast crisis resembling AML. Natural killer (NK) cells can clear malignant cells, representing a promising immunotherapy. However, NK cell activity is suppressed in leukemia, and the microenvironmental drivers of this impairment remain understudied. Despite this, the existing mouse models have not been tested to assess the effect of CML on …

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Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones Jan 2025

Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones

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Molecular phenotype heterogeneity is prevalent across multiple contexts and is mediated by mRNA expression differences and the gene and isoform level. Isoform-level mRNA complexity in the brain is essential for healthy neurodevelopment, and perturbations in AS are associated with many neurological and psychiatric disorders. While previous research has examined how AS changes in the brain, there is still a gap in using newer techniques to study these changes with greater specificity. Therefore, we address this gap by using long-read and scRNA-seq technologies to study isoform-level diversity in AS across four contexts (i.e., disease, sex, region, and cell type) in the …

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Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul Jan 2025

Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul

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RNA-binding proteins (RBPs) play critical roles in RNA processing and regulation. Among these RBPs, U1-70K is a key protein involved in RNA processing, nuclear speckle formation, and has implications in neurodegenerative diseases such as Alzheimer's. Despite its significance in transcription, RNA processing, nuclear speckle formation, and nonsense-mediated decay, studies on U1-70K have been limited primarily to its well-structured N-terminal domain due to challenges in solubilizing and expressing the full-length protein. In this dissertation, we address these challenges by optimizing cell strain and co expressing DnaK and DnaJ, enabling the successful expression, solubilization, and purification of full-length U1-70K. Using fluorescence polarization …

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Perceptions And Preferences Of Virtual Health To Promote Exercise Among People With Physical Disabilities: An Exploratory Mixed Methods Study, Madison Mintz Jan 2025

Perceptions And Preferences Of Virtual Health To Promote Exercise Among People With Physical Disabilities: An Exploratory Mixed Methods Study, Madison Mintz

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People with physical disabilities and mobility limitations can greatly benefit from participating in a physically active lifestyle and adopting health-promoting strategies and behaviors. Benefits of physical activity include better sleep quality and quantity; decreased anxiety; weight loss or healthy weight maintenance; and maintained or increased balance, coordination, strength, and endurance, to name a few. However, rates of physical activity and exercise participation are disproportionate among people with disabilities (PWD). Current literature suggests a myriad of barriers and environmental inaccessibility as a leading cause of PWD not engaging or meeting physical activity guidelines. However, community-based, virtually-delivered programs have become dramatically available …

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Cytotoxic, Genotoxic, And Metabolic Effects Of Dihydroxyacetone In Heart, Liver And Lung Models, Arlet Hernandez Jan 2025

Cytotoxic, Genotoxic, And Metabolic Effects Of Dihydroxyacetone In Heart, Liver And Lung Models, Arlet Hernandez

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Dihydroxyacetone (DHA) is a triose sugar found as an active ingredient in sunless tanning products (STPs) and by-product in electronic cigarettes (e-cigarettes). DHA can rapidly be absorbed into cells and tissues and incorporated into several metabolic pathways through its conversion into dihydroxyacetone phosphate (DHAP). Previous studies have shown that DHA promotes cytotoxicity and genotoxicity primarily characterized in skin models. The extent of these effects in systemic models is highly cell-type specific. Here we investigate the cytotoxic, genotoxic, and metabolic effects of DHA across several cell models. First, we investigated the effects of DHA in a metabolically active cell line, hepatocellular …

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Vitamin D Receptor Signaling Antagonizes RorT Signaling To Reprogram Th17 Cells, Blake Frey Jan 2025

Vitamin D Receptor Signaling Antagonizes RorT Signaling To Reprogram Th17 Cells, Blake Frey

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Vitamin D3 has long been associated with protection against a myriad of autoimmune diseases commonly linked to dysregulation of the T helper 17 (Th17) program. Th17 cells rely on the nuclear receptor (NR) RORγt as the master transcription factor for differentiation and function, establishing a metastate that can drive pro-inflammatory or alternative pathways depending on external cues. Vitamin D3 signals through another NR, the vitamin D receptor (VDR), to inhibit IL-17A in favor of the immunosuppressive cytokine IL-10; however, the precise mechanisms remain unclear. We developed a novel dual Vdr reporter and conditional knockout mouse model, and for the first …

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The Evolutionary Ecology Of Reproductive System Variation In Haploid-Diploid Freshwater Red Macroalgae, Sarah Connelly Jan 2025

The Evolutionary Ecology Of Reproductive System Variation In Haploid-Diploid Freshwater Red Macroalgae, Sarah Connelly

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Reproductive systems describe the relative rates of sexual versus asexual reproduction and selfing versus outcrossing, governing the transmission of genetic diversity between generations and shaping evolutionary responses to environmental change. Though sex has inherent costs, it contributes to the reproductive system for most eukaryotes, generating incredible life cycle diversity. Life cycles are expected to be correlated with different reproductive systems. Diploid life cycles should be associated with outcrossing, whereas life cycles with a long-lived haploid phase are hypothesized to be associated with selfing and asexual reproduction. To test this hypothesis, we used ten polymorphic microsatellite loci to genotype 311 gametophytes …

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Targeted Exon Skipping Of Nf1 Exon 52 As A Mutation Specific Therapeutic For Neurofibromatosis Type 1, Cameron Lee Church Jan 2025

Targeted Exon Skipping Of Nf1 Exon 52 As A Mutation Specific Therapeutic For Neurofibromatosis Type 1, Cameron Lee Church

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Modification of pre-mRNA splicing using antisense oligonucleotides (ASOs) can be used to skip one or more exons carrying pathogenic DNA sequence variants. Our previ-ously published data indicates NF1 exon 52 is a good target for exon skipping as a cDNA screen indicates an NF1 isoform lacking exon 52 maintains both high neurofi-bromin expression and the ability to suppress Ras activity. To develop an exon skipping approach, we designed antisense phosphorodiamidate morpholino oligomers (PMOs) to skip exon 52. Our lead PMO has a low IC50 of 45nM and is able to restore NF1 expres-sion and Ras-suppression in a cell line with …

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Single Nucleus Multiomics Reveals The Drought-Driven Gene Regulatory Atlas In Arabidopsis, Jinbao Liu Jan 2025

Single Nucleus Multiomics Reveals The Drought-Driven Gene Regulatory Atlas In Arabidopsis, Jinbao Liu

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The regulation of gene expression in plant responses to drought has been thoroughly in-vestigated in previous studies. Despite this, a detailed understanding of the cell type-specific regulatory mechanisms, encompassing multi-layered biological processes, is lack-ing. In this study, we report the use of single nucleus multiomic analysis in Arabidopsis seedlings in response to drought stress. Our single-nuclei RNA (snRNA) analysis deline-ated 14 distinct clusters representing major root and shoot cell types and discovered new cell type-specific drought markers. Integration of snRNA with single-nuclei ATAC (snATAC) data in leaf epidermis, root endodermis, and guard cells revealed accessible chromatin regions (ACRs)-linked genes predominantly …

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Scalable Resonance-Based Multi-Coil Inductive Links For Wireless Power Transmission And Passive Sensing In Biomedical Applications, Reepa Saha Jan 2025

Scalable Resonance-Based Multi-Coil Inductive Links For Wireless Power Transmission And Passive Sensing In Biomedical Applications, Reepa Saha

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Type 2 Diabetes (T2D) has become a major health crisis, affecting up to 95% of the 38.4 million diabetes cases in the United States and costing approximately $327 billion annually. Current treatments mainly focus on symptom management rather than reversing the disease. However, clinical observations suggest a promising link between certain stomach surgeries, such as the removal of the upper stomach, and diabetes reversal within a year. This raises the possibility of anatomical changes influencing diabetes outcomes, though the underlying neural mechanisms remain unclear. This dissertation is organized into three interconnected research segments, each contributing to a platform that deepens …

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