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Articles 1 - 19 of 19
Full-Text Articles in Life Sciences
Regulation Of Gene Expression By Rna Binding Proteins And Micrornas, Kyle Cottrell
Regulation Of Gene Expression By Rna Binding Proteins And Micrornas, Kyle Cottrell
Arts & Sciences Electronic Theses and Dissertations
Regulation of gene expression is essential to life. Post-transcriptional regulation of gene expression is a complex process with many inputs that lead to changes in localization, translation and stability of mRNAs. The translation and stability of many mRNAs is regulated by cis-elements, such as mRNA-structure or codon optimality; and by trans-acting factors such as RBPs and miRNAs. Here I report on the complex interactions between RBPs, miRNAs and characteristics of their target mRNAs in respect to effects on translation and RNA stability.
Using a reporter based approach we studied modulation of microRNA-mediated repression by various mRNA characteristics. We observed the …
Mechanics Of The Developing Brain: From Smooth-Walled Tube To The Folded Cortex, Kara Ellspermann Garcia
Mechanics Of The Developing Brain: From Smooth-Walled Tube To The Folded Cortex, Kara Ellspermann Garcia
McKelvey School of Engineering Theses & Dissertations
Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development.
First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for …
Binding Affinity And Specificity Of Sh2 Domain Interactions In Receptor Tyrosine Kinase Signaling Networks, Tom Ronan
McKelvey School of Engineering Theses & Dissertations
Receptor tyrosine kinase (RTK) signaling mechanisms play a central role in intracellular signaling and control development of multicellular organisms, cell growth, cell migration, and programmed cell death. Dysregulation of these signaling mechanisms results in defects of development and diseases such as cancer. Control of this network relies on the specificity and selectivity of Src Homology 2 (SH2) domain interactions with phosphorylated target peptides. In this work, we review and identify the limitations of current quantitative understanding of SH2 domain interactions, and identify severe limitations in accuracy and availability of SH2 domain interaction data. We propose a framework to address some …
Mechanism Of Gene Regulation By Coding Polya Tracks, Laura Lea Arthur
Mechanism Of Gene Regulation By Coding Polya Tracks, Laura Lea Arthur
Arts & Sciences Electronic Theses and Dissertations
Regulation of gene expression is essential for cellular development and survival. The great variety and complexity of regulatory mechanisms underscores this fact. Messenger RNA stability and translational efficiency are often key determinants of gene expression. mRNA surveillance pathways, discovered for their role in degradation of aberrant mRNA, are now known to be instrumental in the regulation of physiologically correct mRNA stability. Thus, the study of cis elements in a transcript that can induce mRNA surveillance pathways has become an area of particular interest.
Here I report on the mechanism of gene regulation by coding polyA tracks, defined as a sequence …
Regulation Of Early Zebrafish Embryogenesis By Calcium Signaling And Dachsous1b Cadherin, Jiakun Chen
Regulation Of Early Zebrafish Embryogenesis By Calcium Signaling And Dachsous1b Cadherin, Jiakun Chen
Arts & Sciences Electronic Theses and Dissertations
Early animal embryogenesis entails a dynamic combination of embryonic cleavages, axial patterning, and gastrulation movements to shape a basic body plan. The underlying molecular signaling responsible for regulating this process remains poorly understood. In this thesis work, I first review recent progress in understanding of gastrulation movements in various model organisms brought by advances in imaging techniques. The externally developing and optically translucent zebrafish embryo is an ideal model organism to study vertebrate embryonic development by in vivo imaging. The objective of my thesis research is to leverage experimental advantages in the zebrafish model to uncover novel regulators and elucidate …
Analysis Of Argonaute-Small Rna-Transcription Factor Circuits Controlling Leaf Development, John Steen Hoyer
Analysis Of Argonaute-Small Rna-Transcription Factor Circuits Controlling Leaf Development, John Steen Hoyer
Arts & Sciences Electronic Theses and Dissertations
Experimental studies of plant development have yielded many insights into gene regulation, revealing interactions between core transcriptional and post-transcriptional regulatory pathways present in all land plants. This work describes a direct connection between the three main small RNA-transcription factor circuits controlling leaf shape dynamics in the reference plant Arabidopsis thaliana. We used a high-throughput yeast 1-hybrid platform to identify factors directly binding the promoter of the highly specialized ARGONAUTE7 silencing factor. Two groups of developmentally significant microRNA-targeted transcription factors were the clearest hits from these screens, but transgenic complementation analysis indicated that their binding sites make only a small contribution …
The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger
The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger
Arts & Sciences Electronic Theses and Dissertations
Brain extracellular concentration of the peptide amyloid-β (Aβ) is a major contributor to Alzheimer’s disease (AD) pathogenesis. High Aβ levels in the extracellular space precipitate aggregation of the peptide into soluble and insoluble toxic species. This process begins decades before cognitive impairment and triggers the cascade of pathology that eventually leads to AD. Synaptic activity is key to the regulation of extracellular Aβ levels. Presynaptic activity drives the production of Aβ, while postsynaptic receptor activation exhibits more nuanced regulation. For example, high levels of NMDA receptor (NMDA-R) activation have been shown to decrease Aβ production through the extracellular signal-regulated kinase …
Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy
Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy
Arts & Sciences Electronic Theses and Dissertations
The seemingly limitless capacities of mammals to sense, respond, and manipulate their environments stems from their structurally and functionally diverse nervous systems. Establishing these complex behaviors requires the integration of many biological phenomena including, morphogenetic gradients, cell-cell signaling, transcriptional networks, cell migration and epigenetic gene regulation. As mammalian development progresses, these pathways coordinate the production of highly specialized neuronal and glial cells, that connect and communicate with another in an even more complex manner. While evolution has shaped a multitude of pathways to produce numerous favorable traits, it has also created an intricate system vulnerable to disease. The loss of …
The Solid & The Shifting: Darwinian Time, Evolutionary Form And The Greek Ideal In The Early Works Of Virginia Woolf, Joseph Monroe Kreutziger
The Solid & The Shifting: Darwinian Time, Evolutionary Form And The Greek Ideal In The Early Works Of Virginia Woolf, Joseph Monroe Kreutziger
Arts & Sciences Electronic Theses and Dissertations
ABSTRACT OF THE DISSERTATION
“The Solid & the Shifting”: Evolutionary Form, Darwinian Time, and the Greek Ideal in the Early Works of Virginia Woolf
By
Joseph Kreutziger
Doctor of Philosophy in English and American Literature
Washington University in St. Louis, 2017
Professors Melanie Micir, Robert Milder, Steven Meyer, Vincent Sherry, Zoe Stamatopoulou
_____________________________________________________________________
“Now is life very solid or very shifting?” Virginia Woolf asks in her diary of 1931, a question she claims haunts her in its contradictions. This dynamism between the solid and the shifting aspects of life and temporality is fundamental to an analysis of Woolf’s writing process. …
Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris
Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris
Arts & Sciences Electronic Theses and Dissertations
Here we characterized the initial antigen presenting cells (APCs) within the islet of Langerhans to ascertain their identity and functional role as it pertains to autoimmune diabetes. The activation of the adaptive immune system is induced by the innate immune system, and more specifically APCs. Therefore, it is crucial to identify the APCs that are initiating T1D in order to elucidate the break in tolerance and intervene in order to inhibit progression. We have found that there is a resident macrophage that is present in all strains of mice. This islet macrophage has a distinct transcriptional profile that is unique …
Nuclear Export Factor 3 Regulates The Localization Of Small Nucleolar Rnas, Melissa Wanling Li
Nuclear Export Factor 3 Regulates The Localization Of Small Nucleolar Rnas, Melissa Wanling Li
Arts & Sciences Electronic Theses and Dissertations
Metabolic diseases, such as obesity and diabetes, are associated with excess levels of lipids, which can lead to organelle dysfunction, cell death and eventually organ dysfunction. This process, termed lipotoxicity, is still not completely understood. In a genetic screen used to identify genes critical for lipotoxicity, the Schaffer lab has identified small nucleolar RNAs (snoRNAs) within the ribosomal protein L13a (Rpl13a) locus that mediate the cellular response to lipotoxic and general metabolic stress. These snoRNAs are non-canonical in that they accumulate in the cytosol after metabolic stresses like lipotoxicity and oxidative stress, suggesting that cells have specific mechanisms for regulating …
Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures
Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures
Arts & Sciences Electronic Theses and Dissertations
The developmental origins of health and disease (DoHAD) hypothesis suggests that negative maternal lifestyle choices, such as obesity, affect the health of her offspring. Clinical and laboratory studies support this hypothesis – offspring born to obese mothers are at increased risk for health conditions including cardiometabolic syndrome and congenital abnormalities. Maternal obesity damages the oocytes, contributing to the increased disease risk by transmitting damaged organelles and epigenetic modifications to the offspring. Mitochondria, the most abundant organelle in the oocyte, are damaged in oocytes from obese females. However, we do not understand if mitochondrial damage in oocytes is reversible nor why …
Regulation Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Kevin Flanagan
Regulation Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Kevin Flanagan
Arts & Sciences Electronic Theses and Dissertations
Tumorigenesis results from the convergence of cell autonomous mutations and corresponding stromal changes that promote tumor cell growth. Mutations and stromal changes both accumulate with age and together account for the dramatic increase in cancer incidence with age. One change that occurs with age is the accumulation of stromal senescent cells. Senescent stromal cells secrete pro-tumorigenic factors collectively termed the senescence-associated secretory phenotype (SASP). The SASP impacts every stage of tumorigenesis and is a promising therapeutic target. As such, it is important to understand how the SASP is regulated. Many but not all SASP factors are regulated transcriptionally by NF-kB …
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Arts & Sciences Electronic Theses and Dissertations
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …
Genetic And Genomic Dissections Of Myelinating Glial Cell Development, Breanne Leigh Harty
Genetic And Genomic Dissections Of Myelinating Glial Cell Development, Breanne Leigh Harty
Arts & Sciences Electronic Theses and Dissertations
Myelin is a multilamellar sheath made by specialized glial cells that iteratively spiral and compact their plasma membranes around axon segments. In vertebrate nervous systems, myelination facilitates rapid action propagation and provides trophic support critical for neuronal survival. In the central nervous system (CNS), oligodendrocytes (OLs) extend many processes to simultaneously ensheath multiple axons, while in the peripheral nervous system (PNS), myelinating Schwann cells (SCs) pair 1:1 with a single axon segment. Elaboration of the myelin sheath is one of the most exquisite and complex examples of massive coordinated cellular shape changes in the vertebrate nervous system. Furthermore, the importance …
Mechanisms Of G Protein Regulation By Rgs Proteins And Small Molecule Inhibitors, Stanley Michinobu Kanai
Mechanisms Of G Protein Regulation By Rgs Proteins And Small Molecule Inhibitors, Stanley Michinobu Kanai
Arts & Sciences Electronic Theses and Dissertations
G protein coupled receptors transduce diverse extracellular signals like hormones, neurotransmitters, and photons to specific cellular responses through heterotrimeric G proteins. G proteins activate numerous effectors and signal transduction pathways, and therefore the regulation of G proteins is crucial for faithful propagation of specific cellular and physiological responses. A better understanding of the mechanisms that regulate G proteins should provide new insight into signaling pathways that govern healthy and disease states, and also provide opportunities for discovery of novel therapeutic targets.Regulator of G protein signaling (RGS) proteins are crucial regulators of G proteins, for they control amplitude and duration of …
Factors That Contribute To De Novo Protein Misfolding And Prion Formation In Saccharomyces Cerevisiae, Kathryn Morgan Keefer
Factors That Contribute To De Novo Protein Misfolding And Prion Formation In Saccharomyces Cerevisiae, Kathryn Morgan Keefer
Arts & Sciences Electronic Theses and Dissertations
Protein misfolding is a common phenomenon that can have severe consequences on cellular and organismal health. Despite this, the causes of protein misfolding remain poorly understood. Prions are a class of proteins that, when misfolded, can convert other molecules into a heritable, non-native conformation. The yeast Saccharomyces cerevisiae naturally harbors several diverse prion-forming proteins; thus, it is an ideal model with which to investigate the factors that influence misfolding and aggregation.This thesis utilizes the yeast prions [PSI+] and [RNQ+] to investigate two distinct steps of the protein misfolding pathway: interactions with chaperones and their cofactors, and heterologous templating by other …
Investigating Localization And Activity-Dependent Translation Of Astrocyte Mrna, Rohan Khazanchi
Investigating Localization And Activity-Dependent Translation Of Astrocyte Mrna, Rohan Khazanchi
Senior Honors Papers / Undergraduate Theses
Over the past two and a half years, I have studied fundamental aspects of astrocyte biology by investigating the existence and mechanism of astrocyte local translation peripherally around tripartite synapses consisting of pre- and post-synaptic neuron terminals and an associated astrocyte. Astrocytes are critical components of central nervous system synapses (which are predominately tripartite in nature); thus, it is important to consider how astrocyte dysregulation and dysfunction could contribute to the pathogenesis of diseases of synaptic connectivity such as autism spectrum disorders, Alzheimer’s disease, seizure disorders, and more. Overall, my projects involved the development of novel methods to identify astrocyte-specific …
The Localization And Function Of Novel Tetrahymena Thermophila Cytoskeletal Genes Bbc29 And Bbc39, Emily K. Moore, Nicole C. Zanolli
The Localization And Function Of Novel Tetrahymena Thermophila Cytoskeletal Genes Bbc29 And Bbc39, Emily K. Moore, Nicole C. Zanolli
Undergraduate Research Symposium Posters
Ciliary function is known to play an important role in many human conditions, including chronic sinus and pulmonary diseases and problems with infertility. Cilia are cytoskeletal structures that protrude from the cell body to facilitate movement. Ciliary structure is conserved throughout eukaryotes, from unicellular to multicellular organisms, including humans. A clear understanding the proteins that compose cilia and how they interact with one another will increase our knowledge about important cytoskeletal elements. Because cilia are difficult to study in multicellular organisms, the unicellular eukaryote Tetrahymena thermophila serves as a useful model for the study of cytoskeletal genes, due to their …