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The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter Jan 2024

The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter

All ETDs from UAB

Chronic inflammation plays a role in the development and progression of airway diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). COPD is caused primarily by chronic cigarette smoke exposure. Conversely, CF is a single gene disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Although the causes of COPD and CF are different, there are common pathological features. Studies show that chronic inflammation plays a significant role in the pathogenesis of both COPD and CF. Moreover, chronic inflammation induces ageing-associated pathomechanisms like cellular senescence, which exacerbates chronic inflammation. Previous work demonstrates that …


Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman Jan 2024

Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman

All ETDs from UAB

As the largest and most dynamic family of GTPases within the mammalian cell, Rabs play an essential role as molecular switches in regulating intracellular vesicular trafficking and serve as significant signaling transducers. Over the last few decades, Rabs have been identified to regulate endocytic, transcytosis, and exocytotic pathways, and mutations in Rabs, or alterations in downstream effectors lead to embryonic lethality and diseases such as cancer and ciliopathies. Ciliopathies are a class of pathologies that result from defects in structure or function of the primary cilia. Primary cilia, found on virtually all mammalian cells, is a microtubule-derived appendage that relies …


Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker Jan 2024

Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker

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Chronic kidney disease (CKD) is characterized as irreversible progressive loss of renal function and affects over one tenth of the global population. Although CKD-associated comorbidities contribute significantly to its mortality, the lungs are often not considered. Lung diseases make up three of the top six leading causes of death worldwide and share many comorbidities with CKD. Clinical reports show that CKD patients are more likely to develop obstructive and restrictive lung diseases, but the mechanisms underlying this propensity for CKD-associated pulmonary complications are unknown. Hyperphosphatemia and associated elevations of fibroblast growth factor (FGF) 23, two of many consequences of reduced …


Associations Between Grit, Life Satisfaction, And Academic Outcomes In Elementary And Middle School Students, Charles Jaylon Williams Jan 2024

Associations Between Grit, Life Satisfaction, And Academic Outcomes In Elementary And Middle School Students, Charles Jaylon Williams

All ETDs from UAB

Grit is used to predict various positive benefits within students. Grit is trying to get back up to attempt another try at one’s goal after failure. Recently, grit has been seen as a potential candidate in improving the life satisfaction and academic performance of individuals. Grit is conceptualized as having two components, perseverance of effort and consistency of interest. Perseverance of effort is trying again until you finally accomplish your goal, while consistency of interest is a constant drive to complete one’s goals over a long-time span. This study measured the effects that grit has on elementary and middle school …


Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle Jan 2024

Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle

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This thesis focuses on two key questions: 1) how are bone development and regeneration regulated by the CREB3L1 transcription factor; and 2) what is the mechanism of action of the endoplasmic reticulum resident protein JAGN1, which when dysregulated, causes severe congenital neutropenia (SCN)? CREB3L1 regulates bone development and regeneration in mammalian models by facilitating the expression of COL1A1 and components of the secretory pathway required for collagen secretion. We generated two zebrafish models of Creb3l1 dysfunction (creb3l1ΔbZIP/ΔbZIP and creb3l1TA+/TA+). Both models showed that Creb3l1 functions in regulating col1a1a transcription and overall regenerate size are conserved in zebrafish. However, we also …


Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar Jan 2024

Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar

All ETDs from UAB

Around 39 million people globally are currently infected with Human immunodeficiency virus 1 (HIV-1), more than half of whom are women. HIV-1 is a retrovirus that infects and depletes an individual’s immune cells, culminating in the development of acquired immunodeficiency syndrome (AIDS) if not managed with anti-retroviral therapies (ART). Most women acquire HIV-1 through heterosexual intercourse. However, the early mechanisms and virologic determinants of HIV-1 transmission to women remain unclear. Herein, we demonstrate transmitted/founder (TF) HIV-1 representing two genetically and pathogenically distinct subtypes (A and D) in vivo have distinct replication phenotypes in an ex vivo cervical explant tissue (CET) …


Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans Jan 2024

Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans

All ETDs from UAB

The sympathetic nervous system is a key regulator of energy homeostasis, in part, through the control of white adipose tissue lipolysis. Sympathetic nerves modulate adipose tissue physiology through the release of catecholamines, particularly norepinephrine, onto alpha- and beta-adrenergic receptors (a-AR; B-AR). Lipolysis refers to the breakdown of triglycerides into glycerol and free fatty acids, often in response to activation of B2/3-AR. Beta adrenergic activation of lipolysis is widely known to be impaired in patients with metabolic syndrome and animal models thereof (catecholamine resistance). Recent studies have demonstrated that catecholamine regulation of adipokine release is also disrupted, suggesting that catecholamine resistance …


Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose Jan 2024

Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose

All ETDs from UAB

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a channel responsible for the transport of chloride and bicarbonate ions across the apical cell surface. In the respiratory tract, defective CFTR results in viscous and adherent mucus that becomes static within the airway, which leads to chronic infections, progressive lung damage, and early mortality. Historically, CF mucus stasis has been attributed to significant airway dehydration; however, growing evidence has demonstrated that aberrant electrostatic properties of mucins also contribute to mucus stasis in CF. Mucins are large, polymeric glycoproteins …


Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier Jan 2023

Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier

All ETDs from UAB

A broad spectrum of human birth defects arise from the disruption of morphogenesis, the critical process through which tissues and organs acquire their proper shape. Convergent extension (CE) is a universal morphogenetic engine that promotes polarized extension of diverse tissues and organs by regulating directional cell behavior, such as oriented cell intercalation. In vertebrates, CE is regulated by non-canonical Wnt/Planar Cell Polarity (PCP) pathway, an ancient signaling pathway that was originally discovered to coordinate the cellular polarity in the plane of the epithelium. Non-canonical Wnt/PCP signaling shares the Frizzled (Fz) receptor and cytoplasmic signal transducer Dishevelled (Dvl) with the canonical …


Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez Jan 2023

Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez

All ETDs from UAB

This dissertation covers data from published and pre-published studies exploring challenges and opportunities in the treatment of malignant glioma with emphasis in glioblastoma and oncolytic immunovirotherapy with an oncolytic herpes simplex virus type 1 (HSV-1) designed to induce expression of IL-12, M002 (murine IL-12) and M032 (human IL-12).It starts with the report of a study that uncovered important racial and socioeconomic disparities experienced by patients with glioblastoma treated in Alabama. Notable results also include the unexpected finding of increased survival in African American patients with glioblastoma even after controlling for factors associated with survival and socioeconomic disparities. The implications of …


The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith Jan 2023

The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith

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THE INFLUENCE OF PROXIMITY ON PATIENT OUTCOMES FOR DIFFERENTLY STRUCTURED AMBULATORY SURGERY CENTERSWENDY SMITH HEALTH SERVICES ADMINISTRATION ABSTRACT This study examines the complication rates and patient-reported outcome measures (PROMs) for total hip and knee replacement surgeries conducted in one of two differently structured ambulatory surgical centers (ASCs) with varying interprofessional surgical teams. There is an ongoing shift from in-hospital total joint replacement surgeries to ASCs. Additionally, there is specialization occurring within ASCs. In this study, we compare single specialty ASCs designed to perform solely TJR surgeries with one orthopedic group and interprofessional team, with multi-specialty ASCs that perform an array …


Neuropeptide Y Overexpression In The Presence Of P23h Rhodopsin Mutation, Jean Sun Jan 2023

Neuropeptide Y Overexpression In The Presence Of P23h Rhodopsin Mutation, Jean Sun

All ETDs from UAB

Neuropeptide Y (NPY), a 36-amino acid peptide, has been found to be the most abundant neuropeptide in the central nervous system, and it is widespread across mammalian species. NPY plays a dual role as a neurotransmitter and neuromodulator in the nervous system. NPY functions as a multifaceted neuromodulator through binding NPY receptors (NPYRs). NYP interacts with NPYRs and regulates various activities, such as cell growth, neurogenesis, neuroprotection, mitochondrial behaviors, food intake, anxiety, and addiction formation. In terms of NPY’s neuroprotective potential, NPY inhibits neuronal death signaling, thus preventing apoptosis, and displays anti-inflammatory and anti-oxidative effects. Additionally, it influences metabolism by …


Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White Jan 2023

Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White

All ETDs from UAB

We reported that Ca2+-independent phospholipase A2β (iPLA2) contributes to type 1 diabetes (T1D) development; however, the impact of lipid signaling from T-cells is unknown. To address this, we first administered splenocytes from NOD, NOD.iPLA2+/- (NOD.HET), or NOD.iPLA2-/- (NOD.KO) mice to 4-week-old NOD.scid recipients. As expected, T1D onset was rapid in NOD cell recipients and 100% by 12 weeks. However, onset was delayed by 1-3 weeks in NOD.HET or NOD.KO cell recipients and only 60% became diabetic, suggesting a role for T-cell iPLA2. Next, to establish importance of iPLA2 in CD4 or CD8 cells, purified cells were administered to NOD.scid mice. …


Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin Jan 2023

Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin

All ETDs from UAB

Circadian disruption is a disturbance in biological timing which can occur within or between different organizational levels, ranging from molecular rhythms within specific cells to misalignment of behavioral and environmental cycles. Previous work has shown that changing the timing of food availability is sufficient to lower blood pressure and improve insulin sensitivity in prediabetic males, demonstrating the importance of timing of food intake for cardiovascular health. Findings from our group demonstrated that less than one week of mistimed feeding is sufficient to invert diurnal blood pressure rhythms, although kidney excretory rhythms and kidney function remained aligned with the light-dark cycle. …


Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos Jan 2023

Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos

All ETDs from UAB

The overall risk of infection after total knee arthroplasty (TKA) has not improved over the past 20 years, remaining 10-40 times greater than the risk of infection of a native knee. Despite extensive research into periprosthetic joint infection (PJI), little is known about the synovial fluid immune homeostasis of the native knee joint and how TKA surgery itself impacts the local immune composition. While many postulate a role for cartilage in maintaining this immune homeostasis, the exact method in which it contributes remains elusive. Therefore, in this dissertation I have investigated the synovial fluid changes occurring in the knee joint …


Uncovering The Role Of Spt5 In Rna Polymerase I Transcription Through Targeted Protein Degradation Via The Auxin Inducible Degron System In Saccharomyces Cerevisiae, Nathan Bellis Jan 2023

Uncovering The Role Of Spt5 In Rna Polymerase I Transcription Through Targeted Protein Degradation Via The Auxin Inducible Degron System In Saccharomyces Cerevisiae, Nathan Bellis

All ETDs from UAB

RNA Polymerases are the molecular machines responsible for the synthesis of RNA from the DNA template. The presence of these machines is an absolute requirement for the function and replication of all cellular organisms. In eukaryotic organisms, there are a minimum of three RNA polymerases (Pols I, II, II). Despite shared subunits and homology, these three protein complexes are functionally distinct, with many unique sub-units and additional trans-acting factors. Pol I is responsible for the synthesis of three of the four ribosomal RNA species which is the first and rate limiting step of ribosome biogenesis. Pol I synthesizes the majority …


Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing Jan 2023

Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing

All ETDs from UAB

Oxidative phosphorylation is an oxygen-dependent metabolic process that provides the majority of ATP used to support essential cellular functions. However, in cancer, limitations in oxygen availability occur during the development and metastasis of tumors. To compensate for the demands of rapidly proliferating cells, many cancers exhibit an increased demand for glycolysis, the TCA cycle, and glutaminolysis. In this thesis, extracellular flux technology and metabolomics were applied in a hypoxia-reoxygenation model to investigate the metabolic adaptations that occur in dynamic changes in oxygen and nutrient availability in cancer cells. We show the significance of glutaminolysis and its substrates in regulating cancer …


Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang Jan 2023

Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang

All ETDs from UAB

Tumor suppressor gene TP53 is the most frequently mutated gene across human cancers (~50%). Patients with Li-Fraumeni syndrome (LFS) who carry germline p53 mutations exhibit a diverse spectrum of childhood- and adult-onset malignancies. Despite over 40 years of dedicated studies to understand the role of p53 in tumor prevention, there are still many unanswered questions regarding the underlying mechanisms of p53. Previous studies have supported the notion that p53 exerts its tumor-suppressive function through its transcriptional activities. Therefore, strategies to enhance p53’s functions in tumor suppression via manipulating of downstream target gene activities in cancers show promising. To better investigate …


Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde Jan 2023

Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde

All ETDs from UAB

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies with a five-year survival of ~10%. Recent studies in the US population suggest PDAC as the fourth leading cause of cancer-related deaths in 2022. ST6 β-galactoside α2,6-sialyltransferase (ST6GAL1) is a glycosyltransferase which is known to be upregulated in cancer. It acts as a master regulator of a cell by being the predominant sialyltransferase catalyzing the addition of a bulky negatively charged sialic acid to the galactose sugar in an α2,6-linkage. Due to this, the sialic acid changes the structure and function of cell surface receptor proteins and regulates signal …


Unveiling The Molecular Features Of Cancer Health Differences Through Multi-Omics Data Analysis, Fengyuan Huang Jan 2023

Unveiling The Molecular Features Of Cancer Health Differences Through Multi-Omics Data Analysis, Fengyuan Huang

All ETDs from UAB

Understanding the molecular features underlying cancer health differences is crucial for developing effective therapeutic strategies. Multi-omics data analysis, integrating various molecular layers such as genomics, transcriptomics, epigenomics, proteomics, and metabolomics, provides a comprehensive approach to characterize the molecular landscape of cancer differences. By integrating diverse omics data, researchers can identify genetic variations, gene expression patterns, epigenetic modifications, and protein alterations that contribute to differences in cancer progression, and treatment response. These molecular features can serve as potential biomarkers for predicting patient outcomes and guiding personalized treatment strategies. Furthermore, multi-omics data analysis enables the identification of molecular subtypes specific to different …


Modular Regulation And Function Of The Polypyrimidine Tract Binding Protein 1 (Ptbp1), Christine Carico Jan 2023

Modular Regulation And Function Of The Polypyrimidine Tract Binding Protein 1 (Ptbp1), Christine Carico

All ETDs from UAB

RNA binding proteins (RBPs) are critical regulators of gene expression as they are responsible for the chaperoning and processing of every nascent RNA transcript. Many studies have investigated mechanisms of specificity of RBP function and have identified factors such as cell-specific expression of RBPs and differential preferences for RNA secondary structure. However, RBPs are often multi-domain proteins that contain repeats of various RNA binding domains (e.g., RNA recognition motif) and little work in the genomic era of transcriptomic interrogation has been done to define the contribution of individual domains to the overall protein function. Polypyrimidine tract binding protein 1 (PTBP1) …


Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer Jan 2023

Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer

All ETDs from UAB

During the process of malignant transformation, cells have striking changes in their cell surface glycosylation. One of these changes is an enrichment for α2,6 sialic acid which is added by the sialyltransferase, ST6GAL1. ST6GAL1 is upregulated in numerous malignancies and acts by adding an α2,6 sialic acid onto receptors bound for the plasma membrane. This sialic acid, in turn, modulates the activity of the receptor by regulating conformation, clustering, and cell surface retention. The work presented in this dissertation focuses on how ST6GAL1-mediated sialylation of a specific cell surface receptor, epidermal growth factor receptor (EGFR), regulates many of its properties. …


Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty Jan 2023

Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty

All ETDs from UAB

Streptococcus parasanguinis is an oral commensal bacterium that produces hydrogen peroxide. Hydrogen peroxide can react with endogenous molecules such as nitrite to form reactive nitrogen intermediates (RNI). These S. parasanguinis-mediated RNI have been shown to inhibit oral pathogens such as Streptococcus mutans, Enterococcus faecalis, and Aggregatibacter actinomycetemcomitans. As such, S. parasanguinis plays a protective role in the oral microbial ecosystem by antagonizing and preventing colonization by oral pathogens. In addition to being an important organism for the health of the oral cavity, S. parasanguinis has also been associated with improved outcomes for people with cystic fibrosis. There are two explanations …


Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano Jan 2023

Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano

All ETDs from UAB

The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays a critical role in nervous system processes. This includes the maintenance of cellular homeostasis in neurons (1). It also includes synaptic efficacy and plasticity as well as protein turnover, presynaptic vesicle transport, and neuronal protesostasis. Proteasome function is impaired as a consequence of aging, which is aggravated by conditions like Alzheimer's Disease and Related-Dementias (AD, ADRD) (2). According to earlier work from our lab the proteasome is critical to how quickly AD progresses. In Drosophila, human cells, and …


The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock Jan 2023

The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock

All ETDs from UAB

SET binding protein 1 (SETBP1) encodes a transcription factor (TF) participating in diverse cellular processes. SETBP1 is an epigenetic hub associated with variants linked to three distinct diseases. Germline variants cause rare pediatric Schinzel Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disorder (SETBP1-HD), featuring multisystemic abnormalities and neurodegeneration or milder brain issues with hypotonia, respectively. On the other hand, somatic variants contribute to hematological malignancies and adult cancer. To understand tissue-specific SETBP1 mechanisms, public RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project were analyzed. SETBP1 and targets were broadly expressed across 31 adult human tissues, revealing three distinct expression patterns: transcription …


Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter Jan 2023

Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter

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Gout is a common inflammatory arthritis that is increasing in prevalence globally. It has clear sex differences, being more common among men, though comorbidities appear to be more common among women. It also varies in prevalence between populations, driven by a combination of genetic and socioeconomic factors. Genetic studies have identified gout-associated genetic variants, several of which are shared between different populations. Here, I combined gout-associated genetic variants into a gout polygenic risk score. This score was then used to elucidate the genetic underpinning of gout severity and presence of comorbidities, comparing its effects in different sexes and populations. I …


Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz Jan 2023

Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz

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T follicular helper (Tfh) cells constitute a distinct subset of CD4 T cells that reside within B cell follicles, playing an indispensable role in orchestrating the Germinal Center (GC) response. In response to polarizing environments, such as Influenza A virus infection (IAV), Tfh cells secrete effector cytokines, including IFN-γ and IL-4. Nevertheless, the specific functions of cytokine-producing Tfh cell subsets, beyond their involvement in driving class switch recombination (CSR), remain largely unexplored. Here, we demonstrate that, following IAV infection, Tfh cell cytokine production undergoes a dynamic shift, transitioning from early IFN-γ dominance to later predominance of IL-4. The initial IFN-γ …


Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin Jan 2023

Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin

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Polyphosphate (polyP) is an ancient, conserved, inorganic biomolecule. Biological systems have adapted many functions for this high-energy molecule, ranging from immune regulation in mammals to gene regulation in prokaryotes. Of particular interest is its use in bacterial stress responses. Bacteria use polyP to resist hazardous environmental elements like toxic molecules or nutrient starvation. In many bacterial species, polyP is synthesized by polyphosphate kinases (PPKs). PPK – discovered in Escherica coli (E. coli) – hydrolyzes adenosine-5’-triphosphate (ATP) to synthesize polyP. Species that use PPK develop multiple pathogenic defects when PPK activity is impaired, including, among others, antibiotic susceptibility. There is no …


Molecular Imaging To Evaluate Tumor Heterogeneity And Guide Treatment Of Breast Cancer, Yun Lu Jan 2023

Molecular Imaging To Evaluate Tumor Heterogeneity And Guide Treatment Of Breast Cancer, Yun Lu

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Molecular imaging plays an important role in predicting and evaluating treatment response and revealing the underlying biological mechanisms in the cancer field. Especially, PET imaging serves as a valuable tool for comprehending the tumor microenvironment (TME), allowing us to track tumor metabolism, proliferation, receptor expression, and immune infiltration. In this comprehensive study, three distinct aspects of cancer research were explored using molecular imaging techniques.The first study aimed to evaluate the accuracy of the fluorescence ubiquitination cell cycle indicator (FUCCI) system with fluorescence in vivo imaging compared to 3'-Deoxy-3'-[18F]fluorothymidine ([18F]-FLT) positron emission tomography (PET)/computed tomography (CT) in assessing cancer cell proliferation. …


Exercise-Driven Epigenetic And Transcriptomic Changes In An Experimental Model Of Temporal Lobe Epilepsy, Silvienne C. Sint Jago Jan 2023

Exercise-Driven Epigenetic And Transcriptomic Changes In An Experimental Model Of Temporal Lobe Epilepsy, Silvienne C. Sint Jago

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Temporal lobe epilepsy (TLE) is a neurological disease marked by recurring unprovoked seizures originating from temporal lobe structures and is frequently associated with cognitive deficits. Exercise holds promise as a therapeutic approach to alleviate seizures and cognitive impairments in TLE. However, the exact cellular and molecular mechanisms by which exercise influences pathways related to seizure activity and cognition in the context of TLE still need to be understood. Neuronal network formation relies on the regulation of gene expression, which can lead to either an increase or a decrease in the production of essential proteins involved in neuronal signaling. Genes are …