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Light and temperature entrainment of a circadian clock or two.
Circadian rhythms. ; Light -- Physiological effect. ; Temperature -- Physiological effect. ; Photoreceptors. ; Arabidopsis thaliana -- Effect of light on. ; Arabidopsis thaliana -- Effect of temperature on. ; Arabidopsis thaliana -- Genetics. ;...
The synchronization of a circadian clock to the outside environment is a crucial step in the daily life of most organisms. Light and temperature signals help an organism reset its circadian clock. In the model plant Arabidopsis thaliana, a number...
Dartmouth Dissertations

A novel role for visual arrestin in endocytosis-mediated retinal degeneration.
Phospholipase C -- Mechanism of action. Retinal degeneration -- Pathophysiology. Retinal degeneration -- Genetic aspects. Endocytosis. Rhodopsin. Cellular signal transduction. Light -- Physiological effect. Arrestin. Clathrin. Adaptor Proteins
Mutations in the Drosophila retinal-specific Phospholipase C (NORPA) cause massive retinal degeneration within five days of constant light exposure. We have previously shown that in norpA mutants persistent complexes between the light receptor...
Dartmouth Dissertations

Understanding PDZ affinity and selectivity: all residues considered / by Jeanine F. Amacher.
PDZ protein-protein interaction domains recognize short linear motif (SLiM) sequences typically at the extreme C-terminus of a target protein. These domains often act as scaffolds, connecting target proteins to additional interaction and catalytic...
Dartmouth Dissertations

Characterization and rescue of a Drosophila model of prion disease; and The role of carcinine in signaling at the Drosophila photoreceptor synapse.
Drosophila melanogaster -- Genetic aspects. Prion diseases. Neurotransmitters. Photoreceptors.
Drosophila melanogaster is a model organism often used when studying the complex processes of neuronal signaling and neurodegeneration. The short life cycle, malleable genetics, amenability to in vivo electrophysiological assays and sensitivity to...
Dartmouth Dissertations

UCN-01: a protein kinase antagonist abrogating cell cycle checkpoint control.
Protein kinase C -- Antagonists. Cells -- Growth -- Regulation. Antineoplastic agents -- Mechanism of action.
Dartmouth Dissertations

Characterization of two S. Cerevisiae genes implicated in mRNA export: RAT7, encoding a novel nuclear pore complex protein and NPL3, encoding a putative hnRNP protein.
Messenger RNA -- Genetic aspects. Proteins -- Synthesis -- Genetic aspects. Saccharomyces cerevisiae -- Genetics.
Dartmouth Dissertations

Single nucleotide polymorphisms in the human prostacyclin gene: implications for cardiovascular disease and genetic mutagenesis.
Prostacyclin -- Receptors. Chromosome polymorphism. Cardiovascular system -- Diseases -- Genetic aspects. Polymorphism.
Prostacyclin (PGI 2 ) is a major product of COX-2 catalyzed metabolism of arachidonic acid in the endothelium and has been shown to be atheroprotective. PGI 2 signals though its G-coupled protein receptor (GPCR) the human Prostacyclin receptor...
Dartmouth Dissertations

Wnt pathway activation by ADP-ribosylation / by Eungi Yang
Wnt/[beta]-catenin signaling directs metazoan development and is aberrantly activated in many cancers; however, effective inhibitors to treat Wnt-driven cancers have long been elusive. Following the recent discovery that the ADPribose polymerase...
Dartmouth Dissertations

The mechanism of action for angiotensin-1-7 in the rostral ventrolateral medulla in the modulation of cardiovascular sympathetic nerve activity / by Mark S. Bilodeau
Elevated sympathetic discharge from the CNS is an underlying pathogenic mechanism in neurogenic hypertension and an exacerbating factor in chronic heart failure (CHF). Current treatment of these diseases focuses on attenuation of the downstream...
Dartmouth Dissertations

A proteomics approach to NIMA-related kinase signaling in mitosis / by Sierra N. Cullati
NIMA-related kinases (Neks) control several aspects of cell division downstream of master mitotic regulators such as Cdk1 and Plk1. Though depletion of Nek6, Nek7, or Nek9 results in cytokinesis failure, to date no molecular mechanism has been...
Dartmouth Dissertations

Serotonin signaling in the nucleus tractus solitarius modulates the larybgeal chemoreflex : implications for sudden infant death syndrome / by William T. Donnelly
Sudden infant death syndrome (SIDS) occurs when a sleeping infant experiences a challenge to cardiorespiratory homeostasis which it fails to overcome. Analyses of brain tissue from SIDS cases from around the world consistently show abnormalities in...
Dartmouth Dissertations

Rhodopsin-arrestin complex formation as a novel mechanism for light-dependent retinal degeneration.
Visual pigments. ; Cellular signal transduction. ; Rhodopsin. ; G proteins. ; Phosphorylation. ; Photoreceptors. ; Retinal degeneration.
Arrestins are regulatory proteins that participate in the termination of G protein-mediated signal transduction. The major arrestin in the Drosophila visual system, Arrestin 2 (Arr2), has been demonstrated to be essential for the termination of the...
Dartmouth Dissertations

Identification and characterization of two mutants that affect Drosophila phototransduction.
Drosophila. Photoreceptors. TRP channels. Cellular signal transduction.
The phototransduction cascade in Drosophila is a prototypical G-protein signaling pathway and many of its components have been well-studied. Early genetic screens identified many of the major proteins involved in this pathway and study over the...
Dartmouth Dissertations

Control of developmental timing in Caenorhabditis elegans by lin-14.
Caenorhabditis elegans -- Genetics. ; Caenorhabditis elegans -- Growth. ; Cellular control mechanisms. ; Heterochrony (Biology). ; Developmental genetics.
The heterochronic gene lin-14 affects certain somatic cell-fate choices during post-embryonic development in C. elegans. In lin-14 mutants, cells express stage-specific developmental programs, such as cell divisions or dauer entry, at inappropriate...
Dartmouth Dissertations

Novel levels of Ras1 regulation in the human fungal pathogen, Candida albicans / by Amy Elizabeth Piispanen.
Neurotrophic functions.;""Growth factors."";""Exercise -- Physiological aspects."";""Cognition -- Effect of exercise on."";""Cognition -- physiology.""
Dartmouth Dissertations

Engineering new tools for targeted drug discovery : design and development of soluble, screenable mimics for challenging proteins / by Chirstopher O. Audu.
The design and synthesis of biomimetic receptor systems capable of binding a target molecule with similar affinities and specificities to their natural counterparts, which are often difficult to obtain in large quantities, has long been a goal of...
Dartmouth Dissertations

Evaluation and engineering of Saccharomyces cerevisiae for cellulase expression and growth on insoluble cellulose.
Saccharomyces cerevisiae -- Genetics. Cellulase -- Biotechnology. Cellulose -- Biotechnology. Biomass conversion -- Technological innovations.
Dartmouth Dissertations

Dissecting the heterogeneity of breast tumor subtypes / by Nima Pouladi.
Breast cancer is the most common cancer in women. The discovery of breast tumor subtypes and the subsequent development of treatments aimed at them has allowed a reduction in the mortality of breast cancer. However, tumors with similar...
Dartmouth Dissertations

The role of DEG/ENaC ion channel subunits in pheromone detection and mating behaviors in Drosophila melanogaster / by Vinoy Vijayan.
Gustatory pheromones regulate mating behaviors in Drosophila melanogaster and represent an important model for understanding how sensory stimuli can drive behavior. However, the genes and cells involved in pheromone detection have remained poorly...
Dartmouth Dissertations

The causes and consequences of regulation of [Delta]NP63[alpha] in mammary and breast cancer stem cells / by Andrew Joseph DeCastro.
Despite the array of targeted therapeutics that currently exist to combat breast cancer, disease progression leading to metastasis, and tumor recurrence still remains a significant clinical challenge. Efforts to identify novel pathways and...
Dartmouth Dissertations

Fusion proteins and select lipids cooperate as membrane receptors for the soluble snare Vam7p / by Vidya Karunakaran.
Yeast vacuole fusion involves three transmembrane SNAREs and a unique soluble SNARE, Vam7p. This SNARE cycles between vacuolar membrane-bound and cytosolic state. In its membrane-bound state, it is able to participate in vacuolar fusion by...
Dartmouth Dissertations

The role of cell stress signalling in the induction of [gamma]-globin gene expression / by Emily K. Schaeffer.
Increased fetal hemoglobin (HbF) expression is beneficial for [beta]-hemoglobinopathy patients; however, most inducing agents do not possess the ideal combination of efficacy, safety and availability. Better understanding the mechanisms involved in...
Dartmouth Dissertations

Novel techniques for the investigation of GPCR structure and function / by Joshua A. Weiner.
G protein coupled receptors (GPCRs) make up somewhere between 30-50% of all current drug targets, yet the structural characterization of these receptors has been moderate at best. Until recently, structural data were almost nonexistent and...
Dartmouth Dissertations

Molecular mechanisms underlying the induction of neuronal Na channel expression by growth factors.
Neurons -- Growth -- Effect of growth factors on. Cell differentiation -- Molecular aspects. Developmental neurobiology.
Dartmouth Dissertations

Effects of chronic anabolic androgenic steroid exposure on GABAergic neurotransmission and neuronal activity in the mamalian forebrain.
GABA -- Receptors. Anabolic steroids -- Physiological effect. Androgens -- Physiological effect. Prosencephalon. Neurotransmitters -- Effect of drugs on. Psychoneuroendocrinology.
Anabolic androgenic steroids (AAS) are derivatives of testosterone originally designed for therapeutic applications to enhance anabolic potency (protein synthesis and muscle growth) while exerting low androgenic (masculinizing) effects. The...
Dartmouth Dissertations

From target discovery to high-throughput screens--selective CAL PDZ inhibitors as candidate CF therapeutics
Peptides -- Therapeutic use. ; Chloride channels -- Pathophysiology. ; Ligands (Biochemistry) ; Protein-protein interactions. ; Cystic fibrosis -- Molecular aspects. ; High throughput screening (Drug development) ; PDZ Domains. ; Cystic Fibrosis...
PDZ domains are protein:protein interaction domains that serve as molecular scaffolds, especially in the case of specialized cellular environments like polarized airway epithelial cells of the human lung. Historically the domains have been thought...
Dartmouth Dissertations

The effects of endocrine disruptors on the development of Xenopus embryos.
Xenopus laevis -- Embryology. Xenopus laevis -- Endocrinology. ; Estrogen -- Physiological effect. ; Estrogen -- Toxicology. ; Nonylphenol -- Physiological effect. Endocrine toxicology.
Many environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes. Xenopus embryos were exposed to commonly encountered endocrine...
Dartmouth Dissertations

Allosteric modulation of GABAa receptors by anabolic-androgenic steroids.
GABA -- Receptors. Allosteric regulation. ; Anabolic steroids -- Physiological effect. ; Androgens -- Physiological effect. ; Receptors
Anabolic-androgenic steroids (AAS) are synthetic derivatives of the gonadal hormone, testosterone. Despite their many untoward side effects, AAS are wildly abused for their ergogenic properties. AAS have numerous effects on many organ systems,...
Dartmouth Dissertations

The novel p53 target gene STK17A : implications for cancer therapy / by Pingping Mao
Testicular germ cell tumors (TGCTs) are highly curable with cisplatin-based therapy. The p53 tumor suppressor is induced in response to a variety of cellular stresses. Our previous work has implicated an important role for p53 in TGCT...
Dartmouth Dissertations

CXCR3 and its cognate-chemokine expression : implications for cancer immunotherapy / by Eleanor Clancy-Thompson
Despite immunogenicity, melanoma-specific vaccines have demonstrated minimal clinical efficacy in patients with established disease, but enhance survival when administered in the adjuvant setting. It has been shown that T cell infiltration of...
Dartmouth Dissertations

Relating behavioral control and brain development : insights from adolescence / by Heidi Catherine Meyer
Across mammalian species, adolescence is characterized by a unique combination of cognitive, behavioral and neurobiological changes. Behavioral tendencies observed during this period promote a variety of flexible interactions with the surrounding...
Dartmouth Dissertations

Discovering MII1 regulated pathways in hematopoietic stem cells.
Hematopoietic stem cells. ; Hematopoietic stem cell disorders -- Genetic aspects. ; Genetic transcription -- Regulation. ; Leukemia -- Genetic aspects. ; Cell proliferation. ; Myeloid-Lymphoid Leukemia Protein -- genetics.
Hematopoietic stem cells (HSCs) balance self-renewal with the continuous production of the suitable numbers of lineage-restricted progenitor cells. In this work we demonstrate that the Mixed lineage leukemia 1 (Mll1) gene is essential for this...
Dartmouth Dissertations

Methods for prevention of oral Toxoplasma gondii infection-induced hyperimmune response in mice.
Toxoplasma gondii. ; Biological response modifiers. ; Immune response -- Regulation. ; Toxoplasmosis -- Immunotherapy. ; Interleukin-10 -- therapeutic use. ; Cholera Toxin -- therapeutic use. ; Anti-Inflammatory Agents -- therapeutic use.
Dartmouth Dissertations

Characterization of the molecular mechanism by which arsenic and chromium alter inducible gene expression.
Arsenic -- Mechanism of action. ; Arsenic -- Toxicology. ; Chromium -- Mechanism of action. ; Chromium -- Toxicology. ; Gene expression.
Metals are ubiquitous in our environment. Through evolution, many biological processes have taken advantage of and have become dependent on specific metals for various biochemical functions. Metals can also be toxic to biological systems at...
Dartmouth Dissertations

Identification of crucial residues involved in the catalysis of acyl-coenzyme A:cholesterol acyltransferase.
Acyltransferases. ; Cholesterol -- Metabolism. ; Catalysis. ; Acyl Coenzyme A. ; Cholesterol Acyltransferase.
Acyl-coenzyme A: cholesterol acyltransferase (ACAT) plays important roles in cellular cholesterol homeostasis and in early stages of atherogenesis. ACAT has been investigated as a pharmaceutical target, yet its active site(s) remain largely...
Dartmouth Dissertations

Effects of anabolic androgenic steroids on GABAA receptor function and expression.
Anabolic steroids -- Physiological effect. ; Androgens -- Physiological effect. ; GABA -- Receptors. ; GABA -- Physiological effect. ; Neurotransmitter receptors. ; Brain -- Physiology. ; Receptors GABA-A -- drug effects.
Dartmouth Dissertations

The regulation of apoptosis by protein phosphatases: impact on intracellular acidification and processing of the retinoblastoma protein.
Apoptosis. ; Phosphoprotein phosphatases. ; Retinoblastoma. ; Immunosuppression.
Dartmouth Dissertations

Molecular mechanisms of vacuole membrane fusion.
Membrane fusion. ; Tonoplasts. ; Plant vacuoles. ; Saccharomyces cerevisiae -- Molecular aspects.
The docking and fusion of cellular membranes plays an essential role in the secretory and endocytic pathways and in organelle inheritance. The homotypic fusion of vacuoles from the yeast Saccharomyces cerevisiae has been used as a model system to...
Dartmouth Dissertations

Von Hippel Lindau (VHL) tumor suppressor regulation of MT1-MMP in renal cell carcinoma.
Antioncogenes. Metalloproteinases. Genetic regulation. Kidneys -- Cancer.
Dartmouth Dissertations

Regulation of epithelial chloride channels: implications for cell volume regulation and cystic fibrosis.
Chloride channels. ; Epithelial cells. ; Cellular control mechanisms. ; Cystic fibrosis.
Dartmouth Dissertations

Structure and function of misfolded rhodopsin protein in Retinitis pigmentosa.
Retinitis pigmentosa -- Pathogenesis. Retinitis pigmentosa -- Genetic aspects. Rhodopsin. G proteins -- Receptors. Prostacyclin -- Receptors.
Retinitis Pigmentosa is an inherited retinal degenerative disorder, initiated by point mutations on the rhodopsin gene. This thesis set forth to understand the mechanism of this pathogenesis, as well as to further improve our understanding of...
Dartmouth Dissertations

Tumor necrosis factor contributes to early diabetic nephropathy.
Tumor necrosis factor. ; Diabetic nephropathies -- Pathogenesis. ; Renal tubular transport Disorders of.
Early renal changes during diabetes include sodium (Na) retention and renal hypertrophy. Tumor Necrosis Factor (TNF) is elevated during diabetes and is implicated in the pathogenesis of diabetic nephropathy. We tested the hypothesis that TNF...
Dartmouth Dissertations

Hedgehog signaling is a critical mediator for urinary bladder cancer.
Bladder -- Cancer -- Molecular aspects. ; Cellular signal transduction. ; Transcription factors -- Pathophysiology. ; Arsenic -- Carcinogenicity. ; Urinary Bladder Neoplasms -- genetics. ; Hedgehog Proteins.
The role of Hedgehog (HH) signaling in bladder cancer is controversial. The HH receptor and negative regulator Patched1 (PTCH1) resides on a region of chromosome 9q, one copy of which is frequently lost in bladder cancer. Inconsistent with PTCH1...
Dartmouth Dissertations

SGK1 is an important determinant of sodium channel activity in the mammalian collecting duct.
Aldosterone -- Mechanism of action. ; Aldosterone -- Physiological effect. ; Adrenocortical hormones -- Genetic aspects. ; Sodium channels -- Genetic aspects. ; Genetic regulation.
Hypertensive disorders, as well as congestive heart disease. Despite extensive research on the regulatory events that occur between aldosterone induced transcription and the early activation of epithelial sodium channels (ENaC ) in cortical...
Dartmouth Dissertations

Enolase in vacuole fusion and enolase and Bor1p in trafficking of proteins to the vacuole in Saccharomyces cerevisiae.
Membrane proteins -- Physiological transport. Membrane fusion. Plant vacuoles. Biological transport -- Regulation. Saccharomyces cerevisiae -- Cytology.
Dartmouth Dissertations

Biochemical analysis of stimulus-secretion coupling in permeabilized mast cells.
Cellular signal transduction. ; Secretion. ; Mast cells.
Dartmouth Dissertations

The effects of Niemann-Pick type C disease on the development of Purkinje cell form and function.
Purkinje cells. Neurons -- Physiology. Neurons -- Growth. Developmental neurobiology. Nerve growth factor. Niemann-Pick Diseases. Central Nervous System -- growth & development.
Dartmouth Dissertations

Studies on the role of the SH2 domain-containing phosphotyrosine phosphatase, PTP2C, in insulin signaling.
Insulin -- Receptors. ; Phosphatases. ; Phosphorylation. ; Cellular control mechanisms.
Dartmouth Dissertations

TGF-beta1 regulation of Th1 development and autoimmunity.
Transforming growth factors-beta. ; Th1 cells. ; Transcription factors. ; Autoimmunity. ; Cytokines. ; Immune response -- Regulation. ; T cells. ; CD4-Positive T-Lymphocytes -- immunology.
Dartmouth Dissertations

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