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The Roles Of Vasoactive Intestinal Polypeptide In Circadian Entrainment Of Suprachiasmatic Nucleus, Sungwon An
The Roles Of Vasoactive Intestinal Polypeptide In Circadian Entrainment Of Suprachiasmatic Nucleus, Sungwon An
All Theses and Dissertations (ETDs)
In mammalian hypothalamus, the suprachiasmatic nucleus: SCN) generates daily behavioral and physiological rhythms as a circadian pacemaker. The 20,000 SCN neurons synchronize to each other and to the ambient cues to generate coherent daily rhythms. Vasoactive intestinal polypeptide: VIP), a neuropeptide produced by SCN neurons, plays a major role in synchronizing SCN neurons to each other. Whether VIP mediates synchrony to environmental cues and how synchrony within the SCN is achieved has not been examined extensively. We recorded PERIOD::LUCIFERASE: PER2::LUC) expression from SCN explant cultures over multiple days following VIP application at different circadian time points to generate a phase …
Regulation Of Neutrophil Homeostasis By Chemokines Signaling Through The Cxcr2 And Cxcr4 Receptors, Kyle Eash
Regulation Of Neutrophil Homeostasis By Chemokines Signaling Through The Cxcr2 And Cxcr4 Receptors, Kyle Eash
All Theses and Dissertations (ETDs)
The number of neutrophils in the blood is tightly regulated to ensure adequate protection against microbial pathogens while minimizing damage to host tissue. Neutrophil homeostasis in the blood is achieved through a balance of neutrophil production, release from the bone marrow, and clearance from the circulation. Accumulating evidence suggests that chemokine signaling in the bone marrow may play a key role in maintaining neutrophil homeostasis. Based on this evidence, we developed a "tug-of-war" model in which opposing chemokine gradients, specifically release-inducing CXCR2 signals and retention-promoting CXCR4 signals, act antagonistically to regulate neutrophil release from the bone marrow. We generated mice …
The Manipulated Mechanism: Towards An Account Of The Experimental Discovery Of Mechanistic Explanations, Donald Goodman-Wilson
The Manipulated Mechanism: Towards An Account Of The Experimental Discovery Of Mechanistic Explanations, Donald Goodman-Wilson
All Theses and Dissertations (ETDs)
Recent work in the philosophy of biology has sought after an account of mechanistic explanation. Biologists frequently encounter causal relationships that beg for explanation. For example, genes appear to encode for particular phenotypes. How does gene expression work? Biologists posit mechanisms to explain the link between cause and effect. Thus, gene expression would be explained by an appeal to a complex mechanism linking the gene to the phenotype, as such an appeal will provide answers to broad ranges of "how" and "why" questions about the causal relationship, and predict novel effects. Here, I focus on a recent problem raised for …
Mhc Class I-Dependent Acquisition And Maintenance Of Natural Killer Cell Function, Julie Chase
Mhc Class I-Dependent Acquisition And Maintenance Of Natural Killer Cell Function, Julie Chase
All Theses and Dissertations (ETDs)
Natural killer: NK) cells are hematopoietically derived immune cells of the lymphoid lineage. Their effector functions, including cytokine secretion and cytotoxicity, are controlled by the integration of signals received from both activating and inhibitory receptors. In a phenomenon known as "missing-self" recognition, NK cells eliminate self-tissues with aberrantly low or absent MHC class I surface expression, as is common in settings of viral infection and transformation, when these cells fail to engage the critical NK cell inhibitory receptors. Interestingly, NK cells that develop in an MHC class I-deficient environment are defective in natural killing and hyporesponsive to stimulation through their …
The Evolution And Reproductive Ecology Of Oenothera (Onagraceae), Kyra Krakos
The Evolution And Reproductive Ecology Of Oenothera (Onagraceae), Kyra Krakos
All Theses and Dissertations (ETDs)
This dissertation describes the role of pollination in the floral diversification of Oenothera with an integration of both ecological and phylogenetic approaches. Oenothera: Onagraceae) is a model system for studying plant reproductive biology. It provides excellent examples of shifts in reproductive traits such as pollination and breeding system, features that have been important in angiosperm diversification. These systems are evolutionarily labile; they easily shift between different states. These different reproductive traits may shift in a concerted fashion; therefore, a more comprehensive approach to understanding the evolution of these plant systems simultaneously addresses shifts in pollination and breeding system. Using 54 …
Effects Of The Aquatic To Terrestrial Habitat Ratio On An Amphibian Predator And Its Prey, Amber Kramer
Effects Of The Aquatic To Terrestrial Habitat Ratio On An Amphibian Predator And Its Prey, Amber Kramer
All Theses and Dissertations (ETDs)
This dissertation explores the effects of varying the composition of aquatic and terrestrial habitats in a landscape: the aquatic to terrestrial ratio) on amphibians that use both the aquatic and terrestrial habitats during their lives. In Chapter 1, I first used meta-analysis and simulations to demonstrate that as the longevity of an amphibian increases, the elasticity of the population growth rate to perturbations in the aquatic: larval) habitat decreases. In Chapter 2, I examined the abundance of larvae of a long-lived amphibian, Ambystoma maculatum, across landscapes that varied in their aquatic to terrestrial ratios and found that larvae of this …
Interactions Between Bmp And Canonical Wnt Signaling Regulate Critical Stages Of The Osteoblast Lifecycle, Valerie Salazar
Interactions Between Bmp And Canonical Wnt Signaling Regulate Critical Stages Of The Osteoblast Lifecycle, Valerie Salazar
All Theses and Dissertations (ETDs)
Skeletal development and post-natal bone homeostasis are dependent on the coordinated activity of bone-forming cells called osteoblasts and bone-resorbing cells called osteoclasts. Over 10 million people in the US currently suffer from osteoporosis, which increases the risk of low-trauma fractures and accounts for health care expenditures exceeding $14 billion per year. Osteoporosis is often treated with anti-resorptive compounds, primarily bisphosphonates, which inhibit osteoclast-mediated bone destruction. However, these drugs do not restore bone mass, which can only be accomplished by activation new bone formation, as with intermittent parathyroid hormone therapy. The development of additional bone "anabolic" therapies will require genetic and …
The Role Of The Membrane Proximal Region Of The M2 Cytoplasmic Tail In Virus Replication, Shaun Stewart
The Role Of The Membrane Proximal Region Of The M2 Cytoplasmic Tail In Virus Replication, Shaun Stewart
All Theses and Dissertations (ETDs)
Influenza A virus encodes M2, a proton channel that has been shown to be important during virus entry and assembly. The primary aim of this thesis was to investigate the role of the membrane proximal region, residues 46-69, of the M2 cytoplasmic tail during virus replication. A cholesterol recognition/interaction amino consensus: CRAC) motif, previously identified in the membrane proximal region of M2 in some influenza A virus strains, was suggested to play a role in virus replication by mediating incorporation of M2 into budding virus particles. Alteration or completion of the M2 CRAC motif in two different recombinant virus strains …
Molecular Genetic Analysis Of Non-Catalytic Pol Iv And V Subunits, Ek Han Tan
Molecular Genetic Analysis Of Non-Catalytic Pol Iv And V Subunits, Ek Han Tan
All Theses and Dissertations (ETDs)
Among eukaryotes, plants have the distinction of encoding multisubunit RNA polymerases used exclusively for RNA directed DNA Methylation: RdDM) in addition to Pol I, II, and III. In Arabidopsis thaliana, Pol IV is required for the biogenesis of 24nt siRNAs whereas Pol V transcription is needed for cytosine methylation of the DNA sequences corresponding to these siRNAs. The ancestry of Pol IV and V can be traced back to Pol II, and Pol II, IV and V still utilize multiple non-catalytic subunits encoded by the same genes. Genetic analysis of non-catalytic subunits that are highly similar reveals that these subunits …
The Association Between Traumatic Brain Injury And Alzheimer's Disease: Mouse Models And Potential Mechanisms, Hien Tran
All Theses and Dissertations (ETDs)
Alzheimer's disease: AD) is a neurodegenerative disorder characterized pathologically by progressive neuronal loss, extracellular plaques containing the amyloid-β: Aβ) peptides, and neurofibrillary tangles: NFTs) composed of hyperphosphorylated tau proteins. Aβ is thought to act upstream of tau, affecting its phosphorylation and therefore aggregation state. One of the major risk factors for AD is traumatic brain injury: TBI). Acute intra-axonal Aβ and diffuse extracellular plaques occur in approximately 30% of human subjects following severe TBI. Intra-axonal accumulations of total and phospho-tau and less frequently NFTs have also been found in these patients. Due to the lack of an appropriate small animal …
The Gut Microbiome In Healthy And Severely Malnourished Humans, Tanya Yatsunenko
The Gut Microbiome In Healthy And Severely Malnourished Humans, Tanya Yatsunenko
All Theses and Dissertations (ETDs)
Human large intestine is home to tens of trillions of microbes belonging to all three do- mains of life. The functions encoded by the genes in this community: microbiome) include processing and production of macro- and micronutrients. Much remains unknown about the factors that determine the assembly of the gut microbial community starting at birth, and if disruptions in the assembly of this `microbial metabolic organ' early in life result in physiologic and metabolic deficits later in life. The central goal of my thesis was to char- acterize development of the gut microbiome early in life, with a focus on …
Discovering Conserved Cis-Regulatory Elements That Regulate Expression In Caenorhabditis Elegans, Nnamdi Ihuegbu
Discovering Conserved Cis-Regulatory Elements That Regulate Expression In Caenorhabditis Elegans, Nnamdi Ihuegbu
All Theses and Dissertations (ETDs)
The aim of this dissertation is two-fold:: 1) To catalog all cis-regulatory elements within the intergenic and intronic regions surrounding every gene in C.elegans: i.e. the regulome) and: 2) to determine which cis-regulatory elements are associated with expression under specific conditions. We initially use PhyloNet to predict conserved motifs with instances in about half of the protein-coding genes. This initial first step was valuable as it recovered some known elements and cis-regulatory modules. Yet the results had a lot of redundant motifs and sites, and the approach was not efficiently scalable to the entire regulome of C. elegans or other …
The Functions Of Human Dna2 In Mitochondrial And Nuclear Dna Maintenance, Julien Duxin
The Functions Of Human Dna2 In Mitochondrial And Nuclear Dna Maintenance, Julien Duxin
All Theses and Dissertations (ETDs)
Coordination between DNA replication, DNA repair and cell-cycle progression ensures high fidelity DNA replication thus preventing mutations and DNA rearrangements. Interestingly, in addition to nuclear DNA stability, mitochondrial DNA: mtDNA) integrity is also essential for normal development. The current challenge resides in unraveling the different mechanisms that govern nuclear and mtDNA stability and to understand how these two separated genomes have evolved. This work focuses on delineating the biological functions of human Dna2: hDna2). Dna2 is a highly conserved helicase/nuclease that in yeast participates in DNA replication and Okazaki fragment maturation, DNA repair, and telomere maintenance. Immunofluorescence and biochemical fractionation …
Protein-Dna Recognition Models For The Homeodomain And C2h2 Zinc Finger Transcription Factor Families, Ryan Christensen
Protein-Dna Recognition Models For The Homeodomain And C2h2 Zinc Finger Transcription Factor Families, Ryan Christensen
All Theses and Dissertations (ETDs)
Transcription factors: TFs) play a central role in the gene regulatory network of each cell. They can stimulate or inhibit transcription of their target genes by binding to short, degenerate DNA sequence motifs. The goal of this research is to build improved models of TF binding site recognition. This can facilitate the determination of regulatory networks and also allow for the prediction of binding site motifs based only on the TF protein sequence. Recent technological advances have rapidly expanded the amount of quantitative TF binding data available. PBMs: Protein Binding Microarrays) have recently been implemented in a format that allows …