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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

Mutational studies of simian virus 40 large T antigen.
Tumor antigens. ; SV40 (Virus).
Dartmouth Dissertations

Post-translational modification in retinoid action: a role for UBEIL in cancer therapy and chemoprevention.
Retinoids -- Mechanism of action. ; Post-translational modification. ; Tretinoin -- Therapeutic use. ; Lungs -- Cancer -- Chemoprevention.
The retinoids--natural and synthetic derivatives of vitamin A--are active in cancer therapy and chemoprevention. The signals that underlie retinoid clinical activity are triggered by induction of retinoid target genes. Therefore, a greater...
Dartmouth Dissertations

MicroRNA-10b promotes pancreatic cancer cell invasion by suppressing TIP30 and enhancing EGF and TGF-[beta] actions / by Haoxu Ouyang
MicroRNA-10b (miR-10b) is considered a marker of disease aggressiveness in pancreatic ductal adenocarcinoma (PDAC), in view of the fact that lower levels of miR-10b are associated with better response to neoadjuvant therapy, likelihood of surgical...
Dartmouth Dissertations

Examining functional variation in oncogene biology : the role of somatic mutations and germline variation on c-Myc and c-Myb / by Scott Andrew Turner.
The identification and characterization of functional genetic variation is essential for future advances in molecular diagnostics, pharmacogenomics, and personalized medicine. Recent attempts at identifying nucleotide level variation (somatic...
Dartmouth Dissertations

Novel mechanisms of action of putative pro-apoptotic BH3 mimetics and their potential therapeutic use / by Ryan Scot Soderquist.
The BCL2 family of proteins control intrinsic apoptosis at the mitochondria through a delicate balance of pro and anti-apoptotic proteins. Anti-apoptotic proteins are frequently relied upon by cancer cells, making them ideal targets for...
Dartmouth Dissertations

Regulation of neuromuscular signalling: modulation of acetylcholine receptor function.
Neuromuscular transmission. Nicotinic receptors. Muscle contraction -- Regulation. Musculoskeletal system -- Differentiation -- Effect of androgens on.
Dartmouth Dissertations

Characterization of proteins that bind the conserved LVb and core sequences of mammalian type C retroviral enhancers.
Proteins. Protein binding. Mouse leukemia viruses. Retroviruses.
Dartmouth Dissertations

Mechanisms by which arsenite decreases CYP3A.
Cytochrome P-450 -- Pathophysiology. ; Cytochrome P-450 -- Genetics. ; Arsenic compounds -- Physiological effect. ; Liver cells.
Arsenic is implicated in numerous human pathologies, including cancer and several forms of liver disease. One contributing mechanism may involve alterations of CYP levels by arsenic. CYP3As are the most abundant CYP proteins in human liver and...
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

Mechanisms regulating interphase condensin II control of genome organization / by Huy Nguyen
How the genome is shaped directly influences how it is expressed. In fact, the genome is organized at many different levels, each imparting specific regulation over transcription. Fundamental principles regulating genome organization are poorly...
Dartmouth Dissertations

Plasmodium falciparum SERA protein transgenics used in the study of parasite immunobiology and drug resistance.
Plasmodium falciparum -- Immunological aspects. ; Plasmodium falciparum -- Genetics. ; Toxoplasma gondii -- Genetics. ; Serine proteinases. ; Transgenic organisms. ; Drug resistance in microorganisms -- Genetic aspects.
Genetic and immunological tools have been used to study two protozoan parasites, Plasmodium falciparum and Toxoplasma gondii. Toxoplasma gondii provides an excellent model for the study of protozoan parasite biology. Plasmodium falciparum causes...
Dartmouth Dissertations

Mechanisms for the regulation of fibrinolysis and cytokine expression by nickel.
Pulmonary fibrosis -- Pathophysiology. ; Fibrinolysis --Genetic aspects. ; Cytokines. ; Immune response -- Regulation. ; Nickel -- Toxicology. ; Lungs -- Dust diseases.
Human epidemiological and animal studies have associated inhalation of nickel dusts with increased incidence of pulmonary fibrosis. The current studies examined the hypothesis that nickel promotes pulmonary fibrosis by inhibiting fibrinolysis and...
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

Fibroblast gene expression in proliferative connective tissue disease.
Fibroblasts. ; Gene expression. ; Rheumatoid arthritis. ; Scleroderma (Disease).
Dartmouth Dissertations

Novel inhibitors of MMP-1 and MMP-13 gene expression as potential therapies for arthritis.
Collagenases -- Genetic aspects. Collagenases -- Pathophysiology. Metalloproteinases -- Genetic aspects. Metalloproteinases -- Pathophysiology. Transcription factors. Extracellular matrix proteins. Cartilage -- Diseases. Arthritis -- Genetic...
Matrix metalloproteinases (MMPs) are a family of endopeptidases that collectively degrade all components of the extracellular matrix (ECM) at neutral pH. During the progression of arthritis, MMPs mediate the degradation of cartilage, which consists...
Dartmouth Dissertations

Muscle-specific and activity-dependent transcriptional regulation of nicotinic acetylcholine receptor subunit gene.
Acetylcholine -- Receptors -- Genetic aspects. ; Muscles -- Innervation. ; Neuroplasticity.
Dartmouth Dissertations

The regulation of AMP-activated protein kinase (AMPK) in an insulinoma cell line, adipocytes and muscle.
Protein kinases. ; Adenylic acid. ; Islands of Langerhans -- Tumors. ; Fat cells. ; Muscle cells. ; Adenoviruses.
Dartmouth Dissertations

FGF signaling and collagenase-1 expression in invasive melanoma cells.
Melanoma -- Genetic aspects. Fibroblast growth factors. Metalloproteinases -- Genetic aspects. Metalloproteinases -- Pathophysiology. Collagenases -- Genetic aspects. Collagenases -- Pathophysiology.
Melanoma progresses as a multi-step process, where the thickness of the lesion and depth of tumor invasion are the best prognostic indicators of clinical outcome. Degradation of the interstitial collagens in the extracellular matrix is an integral...
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

Biophysical and ligand-binding characterization of the interleukin-2 receptor ß-subunit ectodomain.
Interleukin-2. ; T cells -- Receptors. ; Ligand binding (Biochemistry).
Dartmouth Dissertations

Differentiating and anti-inflammatory activities of the triterpenoid, CDDO: interactions with transcription factors PPARγ and NF-κ B.
Triterpenoid saponins -- Physiology. ; Cell receptors. ; Receptor-ligand complexes. ; NF-kappa B (DNA-binding protein). ; Peroxisomes. ; Nucleophilic reactions. ; Dithiole.
Dartmouth Dissertations

Functional analysis of the Runx1 C-terminal sequences.
Transcription factors. ; Hematopoiesis -- Regulation. ; Genetic transcription -- Regulation. ; DNA-binding proteins.
RUNX1 is a transcription factor regulating hematopoietic development. Study of the RUNX1 structure revealed two functional domains. The runt domain binds DNA and mediates interaction with CBFß. Sequences C terminal to the runt domain form the...
Dartmouth Dissertations

Characterizing the heterodimerization interface of core-binding factors (CBFs).
Transcription factors. DNA-protein interactions. Genetic transcription -- Regulation.
Core-binding factors (CBFs) are a small family of transcription factors that play important roles in several developmental processes and in human disease. CBFs consist of CBFα (Runx1, Runx2, or Runx3) and CBFβ. The CBFα subunit binds DNA in a...
Dartmouth Dissertations

Isolation and characterization of two distinct mutations affecting cholesteryl ester synthesis in mammalian cells.
Cholesterol. ; Esters. ; Mammals -- Cytology. ; Cell metabolism.
Dartmouth Dissertations

The role of p38 MAP kinase in the regulation of mRNA stability.
Messenger RNA -- Metabolism. ; Mitogens. ; Thalidomide. ; Glucose -- Physiological transport. ; Mitogen-Activated Protein Kinases. ; MAP Kinase Signaling System. ; Protein processings Post-transcriptional. ; Hippel-Lindau Disease.
We have investigated the role of the p38 MAP kinase pathway in regulating gene expression at the level of mRNA stability. The inhibitory effect of thalidomide on Tumor Necrosis Factor (TNF)α production was characterized. Activation of the MAPK...
Dartmouth Dissertations

The role of p53 in retinoic acid-induced differentiation of human germ cell tumors.
p53 antioncogene -- Regulation. ; Retinoids -- Physiological effect. ; Retinoids -- Receptors. ; Cell differentiation -- Molecular aspects. ; Genetic transcription -- Regulation. ; Germ cells -- Tumors. ; Receptors.
The retinoids exert potent growth and differentiation effects on normal, embryonic and neoplastic cells. Although retinoids are known to regulate gene transcription through activation of retinoid receptors, the direct target genes of retinoid...
Dartmouth Dissertations

Characterization of pathways and intermediates involved in CD40 signal transduction.
CD antigens. ; Cellular signal transduction. ; Immune response -- Regulation. ; Antigens CD40.
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

Structural and functional characterization of Runx1 point mutations identified in leukemia and cleidocranial dysplasia patients.
Transcription factors -- Pathophysiology. Hematopoiesis -- Genetic aspects. Genetic transcription -- Regulation. DNA-binding proteins. Leukemia -- Genetic aspects. Core Binding Factor Alpha 2 Subunit. Core Binding Factor beta Subunit. Cleidocranial...
Core binding factors are heterodimeric transcription factors involved in diverse developmental processes. They consist of a DNA binding Runx subunit and a non-DNA binding CBFβ sub-unit. Runx proteins are encoded by three genes: Runx1, Runx2 , and...
Dartmouth Dissertations

Biophysical analysis of the role of γc in the assembly of the interleukin-2 receptor.
Interleukin-2. ; T cells -- Receptors. ; Structure-activity relationships (Biochemistry). ; Biophysics.
Dartmouth Dissertations

Molecular cloning and functional characterization of BRCA1 splice variants in human mammary cells.
Antioncogenes. ; Breast -- Cancer -- Genetic aspects.
BRCA1 has been identified as a tumor suppressor gene that is mutated in many cases of inherited breast and ovarian cancer. Recent data suggest that multiple splice forms of BRCA1 exist, but the structure and function of these alternative...
Dartmouth Dissertations

IL-1 regulation of collagenase-3 (MMP-13) gene expression in chondrocytic cells.
Interleukin-1. ; Extracellular matrix proteins -- Metabolism. ; Cartilage cells -- Metabolism. ; Metalloproteinases -- Genetic aspects. ; Collagenases -- Genetic aspects. ; Genetic transcription -- Regulation. ; Chondrocytes
The matrix metalloproteinases (MMPs) are family of enzymes with a common domain structure that degrade extracellular matrix proteins; these enzymes are overexpressed in numerous diseases including cancer and arthritis. Collagenase-1, 2, 3 (MMP-1,...
Dartmouth Dissertations

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

Regulation of constitutive MMP-1 expression by the ERK signaling cascade in tumor cells.
Metalloproteinases -- Genetic aspects. ; Metalloproteinases -- Pathophysiology. ; Cellular signal transduction. ; Breast -- Cancer -- Genetic aspects. ; Protein kinases -- Genetic aspects. ; Extracellular matrix proteins. ; Extracellular...
Matrix metalloproteinase-1 (MMP-1) expression is controlled by the mitogen activated protein kinase (MAPK) pathway(s) via the activity of activator protein-1 (AP-1) and polyoma enhancing activity-3/E26 virus (PEA3/ETS) transcription factors through...
Dartmouth Dissertations

The interplay between GATA4-FOG2 transcriptional regulation and the canonical WNT signaling pathway in mouse organogenesis.
Mice -- Morphogenesis. ; Mice -- Genetics. ; Transcription factors. ; Cellular signal transduction. ; Genetic regulation. ; GATA4 Transcription Factor -- genetics. ; Wnt Proteins -- physiology.
Dartmouth Dissertations

Analysis of intracellular ion homeostasis during apoptotic cell death.
Apoptosis. ; Endonucleases. ; Calcium ions. ; Magnesium ions. ; Hydrogen-ion concentration.
A hallmark of apoptosis is internucleosomal DNA fragmentation catalyzed by an endogenous endonuclease. Many laboratories have implicated the activation of Ca2+/Mg2+-dependent endonucleases or the acid-dependent deoxyribonucleases, (DNase II),...
Dartmouth Dissertations

Regulation of ENaC expression by corticosteroids and SGK1 in cortical collection duct cells and mammary epithelial cells.
Sodium channels. Adrenocortical hormones. Protein kinases. Epithelial cells. Mammary glands. Sgk protein.
Regulation of transepithelial sodium transport by corticosteroids occurs in two phases: early and delayed. The early phase involves the activation and translocation of pre-existing epithelial sodium channels (ENaC); whereas, the delayed phase...
Dartmouth Dissertations

The Matrix Metalloproteinase-1/protease activated receptor-1 signaling axis in melanoma progression.
Collagenases -- Pathophysiology. Metalloproteinases -- Pathophysiology. Melanoma -- Molecular aspects. Matrix Metalloproteinase 1.
The inappropriate expression of Matrix Metalloproteinases (MMPs) contributes to the pathology of many cancers. Among these, melanoma is a particularly insidious disease in that it is almost completely resistant to every known the therapy, and the...
Dartmouth Dissertations

Characterization of novel cofactors for oncogenic transcription factors Myc and FoxM1 and cytotoxic peptides derived from an essential Myc domain.
Transcription factors -- Genetics. Carcinogenesis. Peptides. Cell cycle -- Regulation. Genetic regulation. Medical Terms: Genes, myc -- genetics; Forkhead Transcription Factors -- genetics; Neoplasm Proteins -- genetics; Trans-Activators --...
Human cancer is developed as the consequence of the activation of oncogenes and inactivation of tumor suppression genes. Modern sciences has identified and characterized the functions of such genes to understand the mechanism of cancer development...
Dartmouth Dissertations

Myc post-transcriptionally iduces HIF1 protein and target gene expression in normal and cancer cells
Myc oncogenes.;""Transcription factors."";""Genetic regulation."";""Genesmyc."";""Hypoxia-Inducible Factor 1 alpha Subunit.""
Dartmouth Dissertations

Causes and consequences of DeltaNp63 expression in mammary epithelial progenitors.
Epithelium -- Tumors -- Genetic aspects. p53 antioncogene -- Regulation. Stem cells. Breast -- Cancer -- Genetic aspects. Breast -- Cancer -- Etiology. Medical Terms: TP63 protein, human; Tumor Suppressor Proteins -- genetics; Breast Neoplasms --...
Efforts to elucidate the events that account for breast cancer initiation have focused sharply on a small subset of mammary epithelial cells, referred to in this document at mammary stem cells, whose features may enable them to accumulate and...
Dartmouth Dissertations

Molecular mechanisms of estrogen receptor regulation and signaling in human monocytes and macrophages.
Estradiol -- Physiological effect. Estrogen -- Receptors -- Regulation. Macrophages. Monocytes. Cellular signal transduction. Tumor necrosis factor. NF-kappa B (DNA-binding protein) Endometrium -- Immunology. Endometrium -- Physiology.
Sexual dimorphism in immune responses suggests that sex steroid hormones are involved in modulating immune mechanisms in vivo . Sepsis-related mortality rates increase after menopause, implicating 17ß-estradiol (estradiol) as an important factor...
Dartmouth Dissertations

Helix aspersa NHE1: cDNA cloning and characterization.
Sodium cotransport systems. Chemoreceptors. Respiration -- Regulation -- Genetic aspects. Brown garden snail -- Respiration. Carbon dioxide in the body. Arginine. Antisense DNA -- Genetics.
Studies of central CO 2 chemosensors are hampered by the complexity of mammalian central nervous systems. Our laboratory developed the pulmonate snail, Helix aspersa , as a relatively simple alternative to mammalian models. A question concerning...
Dartmouth Dissertations

Pharmacological targeting of Wnt and Hedgehog pathways in lung cancer / by Alexander M. Busch
The Hedgehog (Hh) and Wnt pathways are key biological signaling pathways responsible for embryonic development, cellular proliferation, stem cell maintenance and self-renewal, and adult somatic tissue homeostasis. Because these pathways serve as...
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

Investigation of the ISG15 deisgylase UBP43 in carcinogenesis : tumor suppressor or oncogene? / by Fadzai Chinyengetere.
ISGylation is a type 1 interferon-regulated process that involves conjugation of ISG15, an ubiquitin-like protein, to target proteins. This posttranslational modification is reversed by a deubiquitinase known as UBP43 or USP18. UBP43 is deregulated...
Dartmouth Dissertations

Investigations of a novel retinoid target gene : G0S2 / by Tian Ma.
In a search for target genes for all-trans retinoic acid (RA) treatment of acute promyelocytic leukemia (APL), G0/G1 switch gene 2 (G0S2) was found to be one of the most prominently and rapidly induced species. G0S2 is a small, basic protein with...
Dartmouth Dissertations

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