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Articles 301 - 330 of 1126
Full-Text Articles in Biology
The Effect Of Oxytocin Receptor Genetic Variants On Oxytocin Response, Manasi Malik
The Effect Of Oxytocin Receptor Genetic Variants On Oxytocin Response, Manasi Malik
Arts & Sciences Graduate Student Theses and Dissertations
Oxytocin is a nonapeptide hormone that modulates social behavior, mediates the lactation reflex, and induces and strengthens uterine contractions. Each year, oxytocin is administered to about half of laboring patients for induction and augmentation, and to almost all patients for prevention of post-partum hemorrhage – a total of four million patients per year in the United States alone. However, response to oxytocin varies widely between individuals, and complications including uterine hyperstimulation, uterine atony, required Cesarean section, and postpartum hemorrhage can arise from either excessive or inadequate oxytocin response. To avoid these adverse events, it is critically important to identify individuals …
The Role Of Mavs And Interferon-Lambda In Regulating Astrovirus And Norovirus Infections, Heyde Makimaa
The Role Of Mavs And Interferon-Lambda In Regulating Astrovirus And Norovirus Infections, Heyde Makimaa
Arts & Sciences Graduate Student Theses and Dissertations
Although they globally cause viral gastroenteritis in children, astroviruses are understudied due to the lack of well-defined animal models. While muAstVs chronically infect immunodeficient mice, a culture system and understanding of their pathogenesis is lacking. Here, we describe a platform to cultivate muAstV using air–liquid interface (ALI) cultures derived from mouse enteroids, which support apical infection and release. Chronic muAstV infection occurs in the small intestine and correlates with higher IFN-λ expression. MuAstV stimulates IFN-λ production in ALI, recapitulating our in vivo findings. We demonstrate that goblet cells and enterocytes are targets for chronic muAstV infection in vivo, and that …
Examining Therapeutic Targets For Central Nervous System Autoimmune Disease, Sindhu Manivasagam
Examining Therapeutic Targets For Central Nervous System Autoimmune Disease, Sindhu Manivasagam
Arts & Sciences Graduate Student Theses and Dissertations
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) that leads to demyelination, axonal damage, and neuronal loss. Patients are typically diagnosed early in adulthood and due to the chronic nature of the disease, will continue to develop symptoms over their lifetime. Currently available therapeutics for MS focus on symptomatic relief and reduce severity of relapses; however, they are unable to prevent disease progression or promote recovery. Therefore, there is a critical need to understand the biological mechanisms driving neuroinflammatory and neurodegenerative processes in MS and to translate these findings into novel therapeutic strategies.Here we …
Development Of Myelin In Wolfram Syndrome, Olga Reine Neyman
Development Of Myelin In Wolfram Syndrome, Olga Reine Neyman
Arts & Sciences Graduate Student Theses and Dissertations
Wolfram syndrome is a rare, autosomal recessive disease traditionally characterized by juvenile onset insulin dependent diabetes, optic atrophy, deafness, and neurodegeneration often beginning in childhood and adolescence. The disease is caused by mutations in WFS1, which encodes for the protein wolframin and is associated with endoplasmic (ER) stress-mediated apoptosis. ER stress-related dysfunction may inhibit production of myelin during neurodevelopment in Wolfram syndrome, as active and developing oligodendrocytes are more vulnerable to ER stress than mature ones. It is known that white matter tracts are compromised in the disease, but many questions related to the vulnerability of myelin and its impact …
Roles Of The Transcription Factors Bcl6, Irf2, And Notch2 In Myeloid Development, Kevin William O'Connor
Roles Of The Transcription Factors Bcl6, Irf2, And Notch2 In Myeloid Development, Kevin William O'Connor
Arts & Sciences Graduate Student Theses and Dissertations
Development of immune cells is orchestrated by expression of transcription factors which function to control differentiation of progenitor populations and survival of mature cells. Nonclassical monocytes are a population of myeloid cells which patrol the bloodstream and are thought to maintain vascular endothelium. Conventional dendritic cells (cDCs) are antigen-presenting myeloid cells which serve to activate naïve T cells during infections. cDCs are further differentiated into cDC1s capable of cross-presenting exogenous antigens to activate CD8 T cells and cDC2s which are thought to play essential roles in activating Th2 and Th17 responses. These disparate cells originate from a shared bone marrow …
Dynamics Of Epithelial Differentiation Following Intestinal Villus Injury, Takahiro Erick Ohara
Dynamics Of Epithelial Differentiation Following Intestinal Villus Injury, Takahiro Erick Ohara
Arts & Sciences Graduate Student Theses and Dissertations
Millions of finger-like structures called villi line the small intestine, providing an enormous surface area for rapid and efficient nutrient absorption. Collapse of the villus architecture, known as villus atrophy, is often observed in response to pathogen invasion, inflammation, medications, and ischemia due to loss of intestinal epithelial cells, resulting in symptoms of diarrhea and malabsorption. Though removal of the inciting agent generally allows for near complete tissue recovery, some individuals take longer to restore their villi, a condition known as persistent villus atrophy, for reasons that are unknown. How intestinal villi cope with tissue damage and re-establish their structure …
An Investigation Of Second-Site Non-Complementation Among Motile Cilia Genes In Chlamydomonas Reinhardtii, Gervette M. Penny
An Investigation Of Second-Site Non-Complementation Among Motile Cilia Genes In Chlamydomonas Reinhardtii, Gervette M. Penny
Arts & Sciences Graduate Student Theses and Dissertations
ABSTRACT OF THE DISSERTATIONAn Investigation of Second-Site Non-Complementation among Motile Cilia Genes in Chlamydomonas reinhardtii by Gervette M. Penny Doctor of Philosophy in Biology and Biomedical Sciences Molecular Genetics and Genomics Washington University in St. Louis, 2023 Professor Susan K. Dutcher, ChairMotile cilia are complex microtubule-based organelles used by eukaryotic cells for locomotion or directing fluid flow. In humans, motile cilia defects cause primary ciliary dyskinesia (PCD), characterized by neonatal respiratory distress, recurrent lung infections, bronchiectasis, and low nitric oxide. Situs inversus and/or male infertility are present in about 50% of cases. PCD inheritance is recessive; both copies (alleles) of …
Characterizing The Significance Of Polya Tracks In Gene Regulation And Disease, Geralle Norlene Powell-Rodgers
Characterizing The Significance Of Polya Tracks In Gene Regulation And Disease, Geralle Norlene Powell-Rodgers
Arts & Sciences Graduate Student Theses and Dissertations
The regulation of gene expression is essential for all domains of life. Control of gene expression occurs during each of the three steps of mRNA translation into protein. The fidelity and rate of the third step of translation, elongation, has been established as a key regulator of gene expression through its effects on mRNA stability and, thus, protein abundance. Consequently, studies focusing on factors that affect mRNA stability, including mRNA sequence composition and structure, have become integral to understanding the role of translational control in gene regulation. In Chapter 1, I discuss mechanisms of translational control, focusing on the gene …
Identifying Molecular Targets Of Adar1 Dependency In Breast Cancer, Sua Ryu
Identifying Molecular Targets Of Adar1 Dependency In Breast Cancer, Sua Ryu
Arts & Sciences Graduate Student Theses and Dissertations
Innate immunity is a fundamental defense mechanism against non-self. Similar to its role in pathogenic infections, innate immunity is capable of eliminating cancerous cells by activating cytotoxic inflammatory signaling. Adenosine deaminase acting on RNA 1 (ADAR1) is a key regulator of cell-intrinsic innate immunity. ADAR1 converts adenosines to inosines on double-stranded RNAs (dsRNAs), altering dsRNA structure and its interactive properties. This suppresses cytoplasmic sensing of immunogenic dsRNA and activation of the type I interferon (IFN) signaling pathway. Frequently, suppressing endogenous dsRNA from triggering cytotoxic inflammatory signaling is essential for cancer cell survival. This is known as ADAR1 dependency, which has …
Mapping Brain Development And Decoding Brain Activity With Diffuse Optical Tomography, Kalyan Tripathy
Mapping Brain Development And Decoding Brain Activity With Diffuse Optical Tomography, Kalyan Tripathy
Arts & Sciences Graduate Student Theses and Dissertations
Functional neuroimaging has been used to map brain function as well as decode information from brain activity. However, applications like studying early brain development or enabling augmentative communication in patients with severe motor disabilities have been constrained by extant imaging modalities, which can be challenging to use in young children and entail major tradeoffs between logistics and image quality. Diffuse optical tomography (DOT) is an emerging method combining logistical advantages of optical imaging with enhanced image quality. Here, we developed one of the world’s largest DOT systems for high-performance optical brain imaging in children. From visual cortex activity in adults, …
The Role Of Ns1 In Flavivirus Immunity And Pathogenesis, Alex W. Wessel
The Role Of Ns1 In Flavivirus Immunity And Pathogenesis, Alex W. Wessel
Arts & Sciences Graduate Student Theses and Dissertations
ABSTRACT OF THE DISSERTATIONThe Role of NS1 in Flavivirus Immunity and Pathogenesis by Alex W. Wessel Doctor of Philosophy in Biology and Biomedical Sciences Immunology Washington University in St. Louis, 2023 Professor Michael Diamond, Chair Flaviviruses are a genus of enveloped, arthropod-transmitted RNA viruses that include clinically relevant pathogens such as yellow fever, dengue, Zika, and West Nile viruses. These viruses cause a spectrum of potentially life-threatening diseases including hepatitis, vascular shock, congenital abnormalities, and encephalitis. Dengue virus, alone, infects up to 390 million individuals in any given year, and its endemic regions continue to expand along with the geographical …
Trpm5'S Role In Vascular Development, Megan Goeckel
Trpm5'S Role In Vascular Development, Megan Goeckel
Arts & Sciences Graduate Student Theses and Dissertations
Blood vessels are composed of two main cell types, endothelial cells (ECs) and mural cells (MCs). Endothelial cells comprise of the inner-most layer of the vessel and sense changes in blood flow to recruit mural cells. The mechanism for how endothelial cells sense these hemodynamic changes is not well understood and deciphering this mechanism is the focus of this thesis. We hypothesize that transient receptor potential melastatin 5 (TRPM5), a transmembrane channel protein, is involved in this process. Here, using cultured human endothelial cells and the zebrafish model, we show that inhibition of TRPM5 decreases vessel formation and increases EC-MC …
Cancer Immunogenomics Approaches To Characterizing And Treating Malignant Brain Tumors, Maximilian Oswald Schaettler
Cancer Immunogenomics Approaches To Characterizing And Treating Malignant Brain Tumors, Maximilian Oswald Schaettler
Arts & Sciences Graduate Student Theses and Dissertations
Fueled by a deeper understanding of the fundamental mechanisms of anti-tumor immune responses, cancer immunotherapy has experienced a resurgence over the last decade with remarkable success in the treatment of certain malignancies. However, despite a multitude of treatment approaches ranging from immune checkpoint blockade to adoptive cellular therapy to neoantigen vaccines, certain cancer types have shown limited response to immunotherapy. Glioblastoma multiforme (GBM), the most common primary malignancy of the central nervous system, represents a particularly challenging tumor where new treatment approaches are desperately needed. Despite multimodality treatment consisting of surgical resection, chemotherapy, and radiation therapy, patients with GBM face …
Immunity To Emerging Rna Viruses, Emma Winkler
Immunity To Emerging Rna Viruses, Emma Winkler
Arts & Sciences Graduate Student Theses and Dissertations
In the past decade, newly emerged and re-emerged pathogenic RNA viruses such as Ebola, H1N1, and Zika virus have become substantial threats to global health. Two notable examples include the explosive re-appearance of chikungunya virus in the 2000s in Asia and the Western Hemisphere and, more recently, the global COVID-19 pandemic. Therefore, an improved understanding of immunity to emerging RNA viruses is critical for defining host susceptibility and restriction factors to viral infection as well as appropriate vaccine and antiviral therapeutic design. Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that is maintained in an urban epidemic transmission cycle. While most …
Evaluating The Function Of Dnmt3a Mutations Associated With Acute Myeloid Leukemia And Dnmt3a Overgrowth Syndrome, Yang Li
Arts & Sciences Graduate Student Theses and Dissertations
Heterozygous loss-of-function mutations in the DNMT3A gene are the most common cause of clonal hematopoiesis, and among the most common initiating events for Acute Myeloid Leukemia (AML). Meanwhile, mutant DNMT3A cause an overgrowth syndrome, DNMT3A Overgrowth Syndrome (DOS, also known as Tatten-Brown-Rahmen syndrome, TBRS). Amino acid R882H mutation is the most frequent variance of DNMT3A, while the rest of the mutations spread out on the entire gene of DNMT3A. Over 70% of DNMT3A mutants cause loss of function change. A reduction of DNMT3A activity causes a canonical, focal hypomethylation phenotype in hematopoietic cells, which is associated with immortalization of hematopoietic …
Influence Of Environmental Gradients On Genomic Variation In Pediatric Commensals And Pathogens, Sanjam Sawhney
Influence Of Environmental Gradients On Genomic Variation In Pediatric Commensals And Pathogens, Sanjam Sawhney
Arts & Sciences Graduate Student Theses and Dissertations
Microbes interact with humans in a myriad of ways. They come together in the human gut to form complex communities that collectively transform and individually evolve in response to changing environmental conditions. Individual microbes can also cause human infection and escape antibiotic clearance through acquisition and development of novel resistance mechanisms. In this thesis, I chronicle the relationships between microbes and humans across two axes: from complex communities to single isolates, and from targeted studies of pediatric populations vulnerable to microbiome perturbations and pathogen challenge, to broader human and animal cohorts spanning colonizing and diagnostic environments.In Chapter 2, I extensively …
Function And Regulation Of Virulence-Associated Siderophores In Uropathogenic Enterobacterales, James Robert Heffernan
Function And Regulation Of Virulence-Associated Siderophores In Uropathogenic Enterobacterales, James Robert Heffernan
Arts & Sciences Graduate Student Theses and Dissertations
Siderophores are small molecules created by fungi and bacterial cells to help obtain iron. This may extend to cells in iron-limiting environments within host organisms. Certain siderophores are associated with increased virulence in urinary tract infections (UTIs). Siderophore system activity is typically regulated by feedback inhibition via ferric uptake regulator (Fur) which, in the presence of cytosolic iron, binds to a ~19 base pair inverted DNA repeat (9-1-9) called a Fur box. Once bound to this motif, the iron-Fur complex suppresses siderophore expression when adequate bacterial iron status is achieved. Many organisms produce more than one siderophore, and in the …
An Investigation Of Second-Site Non-Complementation Among Motile Cilia Genes In Chlamydomonas Reinhardtii, Gervette M. Penny
An Investigation Of Second-Site Non-Complementation Among Motile Cilia Genes In Chlamydomonas Reinhardtii, Gervette M. Penny
Arts & Sciences Graduate Student Theses and Dissertations
ABSTRACT OF THE DISSERTATION An Investigation of Second-Site Non-Complementation among Motile Cilia Genes in Chlamydomonas reinhardtii by Gervette M. Penny Doctor of Philosophy in Biology and Biomedical Sciences Molecular Genetics and Genomics Washington University in St. Louis, 2023 Professor Susan K. Dutcher, Chair Motile cilia are complex microtubule-based organelles used by eukaryotic cells for locomotion or directing fluid flow. In humans, motile cilia defects cause primary ciliary dyskinesia (PCD), characterized by neonatal respiratory distress, recurrent lung infections, bronchiectasis, and low nitric oxide. Situs inversus and/or male infertility are present in about 50% of cases. PCD inheritance is recessive; both copies …
The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen
The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen
Arts & Sciences Graduate Student Theses and Dissertations
Recent human genetic studies have associated mutations in a gene called Myelin Transcription Factor 1 Like (MYT1L) with neurodevelopmental disorders (NDDs). Patients with MYT1L loss of function (LoF) mutations (MYT1L Syndrome patients) demonstrate shared symptoms such as microcephaly, attention deficit and hyperactivity disorder (ADHD), and obesity. Despite prior studies showing MYT1L overexpression facilitates neuronal differentiation in vitro, its functions in vivo, especially in the mammalian brain, and how its mutation leads to human disease pathology remains poorly understood. Here, I established the first mouse model of MYT1L Syndrome mimicking a patient specific LoF mutation. I found mice with Myt1l heterozygous …
Analysis Of Regulatory Element Variation In Autism Spectrum Disorder, Evin Mitchel Padhi
Analysis Of Regulatory Element Variation In Autism Spectrum Disorder, Evin Mitchel Padhi
Arts & Sciences Graduate Student Theses and Dissertations
Autism Spectrum Disorder (ASD) is a highly prevalent neurodevelopmental disorder that affects over 2% of the population. Studies of this disorder have demonstrated that genetics plays a strong role in the underlying etiology and over the past decade, substantial progress has been made in elucidating the genetic architecture. Large-scale studies have now been conducted to identify the genes involved in the genetic architecture by analyzing data from over 40,000 probands. However, the identification and characterization of regulatory elements involved have remained non-trivial for many reasons. Generally, studies that have analyzed whole genome sequencing (WGS) have demonstrated enrichment of de novo …
Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy
Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy
Arts & Sciences Graduate Student Theses and Dissertations
Worldwide incidence rates of cutaneous melanoma are increasing, and while survival rates for early stages of melanoma are high, rates drop precipitously for metastatic melanomas or those that are unable to be targeted by currently available treatments. As melanomas have a propensity to quickly metastasize, understanding the contributions of melanoma initiation remains critical for early intervention. Onset of melanoma is characterized most by mutations that stimulate mitogen-activated protein kinase (MAPK) signaling, disrupt DNA damage checkpoints, and trigger mechanisms to bypass senescence through elongation of telomeres. Additionally, in zebrafish melanoma models, the earliest cluster of melanoma-initiating cells activate expression of a …
The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan
The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan
Arts & Sciences Graduate Student Theses and Dissertations
The circadian clock and inflammation have a well-described bidirectional relationship in the peripheral immune system: the circadian clock regulates inflammatory responses, but inflammation also impacts oscillatory gene transcription controlled by the clock. The purpose of this thesis work is to understand if manipulation of the circadian clock can impact Alzheimer’s disease pathology, and if pathology itself can alter the circadian clock and its outputs. Here, I show that astrocyte-specific disruption of the circadian clock via deletion of the clock gene Bmal1 surprisingly decreased intra-neuronal protein pathologies. Further investigation found that deletion of the circadian clock resulted in a transcriptomic profile …
Using Proteomics To Discover New Connections In The Arabidopsis Circadian Clock, Maria Lynn Sorkin
Using Proteomics To Discover New Connections In The Arabidopsis Circadian Clock, Maria Lynn Sorkin
Arts & Sciences Graduate Student Theses and Dissertations
The plant circadian clock is an endogenous timekeeping mechanism that uses daylength and temperature cycles to synchronize internal physiology with the external environment. Much of our understanding of the clock in the model plant Arabidopsis thaliana comes from genetic approaches. In this thesis, I use affinity purification coupled with mass spectrometry (APMS) to identify protein-protein interactions for core clock components on a proteomic scale. I developed and optimized a protocol to perform APMS on a core set of circadian clock proteins: CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), LATE ELONGATED HYPOCOTYL (LHY), PSEUDORESPONSE REGULATOR 5 (PRR5), PRR7, PRR9, TIMING OF CAB 1 …
Bioinformatics And Cancer Genomics Approaches To Advance Precision Medicine And Elucidate Tumor Mutational Landscapes, Kelsy Cotto
Bioinformatics And Cancer Genomics Approaches To Advance Precision Medicine And Elucidate Tumor Mutational Landscapes, Kelsy Cotto
Arts & Sciences Graduate Student Theses and Dissertations
Next-generation sequencing of DNA and RNA continues to be integrated into pre-clinical and clinical research. However, challenges still remain that impede the translation of findings into an improved understanding of human diseases or clinically actionable alterations. The projects described in this dissertation start with compiling efforts from experts who have identified druggable genes within the human genome, followed by in-depth analyses which characterize the pan-cancer landscape of splice-associated mutations and noncoding, regulatory mutations across multiple subtypes of breast cancer. In Chapters 2 and 3, substantial efforts were made to update the content and the user experience for the drug-gene interaction …
Characterizing Complex Affective Processing Across Age And In Relation To Social Anxiety Symptoms, M. Catalina Camacho
Characterizing Complex Affective Processing Across Age And In Relation To Social Anxiety Symptoms, M. Catalina Camacho
Arts & Sciences Graduate Student Theses and Dissertations
Humans require a shared understanding of others’ emotions for adaptive social functioning. For instance, if someone tells a joke and another person laughs, we assume the laughing person was happy because we have a shared concept for such positive interactions. Children develop and refine these concepts as they grow up, but the underlying neural processing that supports this development is unknown. Identifying the neurodevelopment underlying emotion processing could provide important insight to emotional disorders. For example, social anxiety is associated differences in the detection and interpretation of negative or neutral emotional cues, but the underlying neurodevelopment of this behavior is …
Host Development And Microbiota Influences On Norovirus Infection, Elizabeth Alexandra Kennedy
Host Development And Microbiota Influences On Norovirus Infection, Elizabeth Alexandra Kennedy
Arts & Sciences Graduate Student Theses and Dissertations
The mammalian gut is a complex organ which changes over the course of development and is influenced by the presence of a dense community of gut-resident microbes. Enteric viruses infect the gastrointestinal tract in the context of the commensal microbiota and host immunity. Here, we dissect the influence of host developmental stage and the gut microbiota in norovirus infection. From this work, we determine that murine norovirus (MNoV) infection in early life is restricted by an absence of the target MNoV cell tuft cells and intact interferon (IFN) signaling. However, viral inoculum taken up by non-specific endocytosis in the neonatal …
Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard
Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard
Arts & Sciences Graduate Student Theses and Dissertations
The Williams Syndrome Critical Region (WSCR) at chromosome 7q11.23 provides a unique opportunity to untangle the relationship between genotype and phenotype in complex behaviors, from fear and anxiety to sociability and sensorimotor processing. Copy number variations (CNVs) in this region result in two syndromes, Williams Syndrome (WS) and Duplication 7q11.23 Syndrome (Dup7), which display phenotypes that may align, indicating a common disruption of a system, or diverge, reflecting an underlying gene dosage-dependent effect. While case studies of atypical deletions resulting in WS have implicated telomeric genes Gtf2ird1 and Gtf2i in the cognitive and behavioral profiles of WS, proving causation requires …
Circadian Circuitry And Glioblastoma: Interactions With Behavior, Carcinogenesis, And Clinical Practice., Anna R. Damato
Circadian Circuitry And Glioblastoma: Interactions With Behavior, Carcinogenesis, And Clinical Practice., Anna R. Damato
Arts & Sciences Graduate Student Theses and Dissertations
Glioblastoma (GBM) is the most common primary adult brain tumor diagnosed, with a 15-month prognosis using current standard of care treatment which includes chemotherapy with temozolomide (Temodar, TMZ). Chronotherapy, the practice of considering time of day in treating a disease, has been shown to improve outcome in several cancers, but had not been applied to GBM. Previous work in the lab on a cultured murine mesenchymal GBM cell line showed a time-of-day dependent maximum in sensitivity to TMZ corresponding with the daily peak of Bmal1 and trough of Per2 expression, two core clock genes. Based on this finding, we sought …
Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones
Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones
Arts & Sciences Graduate Student Theses and Dissertations
K+ homeostasis is important for maintaining healthy, physiological levels of neuronal activity. Glial cells play a central role in maintaining homeostatic ion gradients. In previous work from our lab, we unravel a glial K+ buffering program that is centered on a key kinase, salt-inducible kinase 3 (SIK3). SIK3-HDAC4 signaling in glial regulates the transcription of channels and transporters involved in water and ion transport. Defects in this pathway lead to peripheral nerve edema, neuronal hyperactivity, and seizure sensitivity. In an hyperexcitability mutant, eag Shaker, we show this pathway is downregulated and genetic activation suppresses seizure behavior. In this thesis, I …
Emerging Insights Into A Role For Topoisomerase Iib And Methyl-Cpg Binding Protein 2 In Regulating Neuronal Transcription, Sabin Nettles
Emerging Insights Into A Role For Topoisomerase Iib And Methyl-Cpg Binding Protein 2 In Regulating Neuronal Transcription, Sabin Nettles
Arts & Sciences Graduate Student Theses and Dissertations
The mammalian brain has unparalleled diversity of cell types with distinct molecular, morphological, connectional and functional properties. The specialization of these cells occurs during development through a series of spatially and temporally controlled changes in gene expression that are critical for proper assembly and function. Neurons in particular have complex and elaborate gene regulatory systems which allow specific combinations of genes to be expressed at distinct levels and at discrete developmental stages, giving rise to heterogenous neuronal subtypes. Identifying unique neuronal gene regulatory factors that contribute to the dynamic changes in gene expression are critical to understanding the molecular mechanism …