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Full-Text Articles in Medicine and Health Sciences

The Regulation Of Nnos During Neuronal Differentiation And The Effect Of Nitric Oxide On Hdm2-P53 Binding: A Dissertation, Christopher M. Schonhoff Dec 2000

The Regulation Of Nnos During Neuronal Differentiation And The Effect Of Nitric Oxide On Hdm2-P53 Binding: A Dissertation, Christopher M. Schonhoff

GSBS Dissertations and Theses

Nitric oxide is a ubiquitous signaling molecule with both physiological and pathological functions in biological systems. Formed by the enzymatic conversion of arginine to citrulline, NO, has known roles in circulatory, immune and nervous tissues. In the nervous system nitric oxide has been implicated in long-term potentiation, neurotransmitter release, channel function, neuronal protection and neuronal degeneration. Much of our work has focused on yet another role for nitric oxide in cells, namely, neuronal differentiation.

During development, neuronal differentiation is closely coupled with cessation of proliferation. We use nerve growth factor (NGF)-induced differentiation of PC12 pheochromocytoma cells as a model ...


A Study On The Cellular Localization Of Factors Involved In Yeast Nonsense-Mediated Mrna Decay And Their Mechanisms Of Control On Nonsense Mrna Translation: A Dissertation, Alan Baer Maderazo Dec 2000

A Study On The Cellular Localization Of Factors Involved In Yeast Nonsense-Mediated Mrna Decay And Their Mechanisms Of Control On Nonsense Mrna Translation: A Dissertation, Alan Baer Maderazo

GSBS Dissertations and Theses

Nonsense-mediated mRNA decay (NMD) is an important mRNA surveillance mechanism conserved in eukaryotes. This thesis explores several interesting aspects of the NMD pathway. One important aspect of NMD which is presently the subject of intense controversy is the subcellular localization of NMD. In one set of experiments, the decay kinetics of the ade2-1 and pgk1 nonsense mRNAs (substrates for NMD) were investigated in response to activating the NMD pathway to determine if cytoplasmic nonsense mRNAs are immune to NMD in the yeast system. The results of these studies demonstrated that activation of NMD caused rapid and immediate degradation of both ...


The Role Of Mkk3 In Mediating Signals To The P38 Map Kinase Pathway: A Dissertation, Mark Allen Wysk Nov 2000

The Role Of Mkk3 In Mediating Signals To The P38 Map Kinase Pathway: A Dissertation, Mark Allen Wysk

GSBS Dissertations and Theses

p38 mitogen-activated protein (MAP) kinases represent a subgroup of MAP kinases that respond to environmental stress and inflammatory cytokines. p38 MAPK is activated by two upstream kinases, MKK3 and MKK6, by dual phosphorylation on threonine and tyrosine in conserved kinase subdomain VII. Until recently the relative roles of MKK3 and MKK6 have remained unclear. I have undertaken two strategies in an effort to understand the importance of MKK3 as a p38 MAPK activator. First, I cloned and characterized the murine mkk3 gene and determined the structure of the 5'-terminus. Comparison of the murine and human mkk3 genes revealed that ...


Differential Mechanisms Of Nuclear Receptor Regulation By The Coactivator Rac3: A Dissertation, Christopher Leo Oct 2000

Differential Mechanisms Of Nuclear Receptor Regulation By The Coactivator Rac3: A Dissertation, Christopher Leo

GSBS Dissertations and Theses

The steroid/thyroid hormone receptor superfamily is a large class of ligand-dependent transcription factors that plays a critical role in regulating the expression of genes involved in a broad range of physiological functions, including development, homeostasis, and reproduction. In the absence of cognate hormone, several receptors are able to repress transcription below the basal level via the recruitment of the nuclear receptor corepressors SMRT and NCoR. Upon hormone binding by the receptor, the corepressor complex is dissociated and a coactivator complex is subsequently recruited. This thesis details the mechanisms by which receptor-associated coactivator 3 (RAC3) interacts with nuclear receptors, particularly ...


Cis/Socs Proteins In Growth Hormone Action: A Dissertation, Ling Du Oct 2000

Cis/Socs Proteins In Growth Hormone Action: A Dissertation, Ling Du

GSBS Dissertations and Theses

CIS/SOCS (cytokine-inducible SH2 protein/suppressor of cytokine signaling) are a family of proteins that are thought to act as negative regulators of signaling by erythropoetin, interleukin-6 and other cytokines whose receptors are related to the growth hormone receptor (GHR), and like growth hormone (GH), signal through the JAK/STAT pathway. We examined the possibility that CIS/SOCS proteins may also be involved in GH signaling, in particular, in termination of the transient insulin-like effects of GH. mRNAs for CIS, SOCS3, and to a lesser extent SOCS1 were detectable by Northern blot analysis of rat adipocyte total RNA, and the ...


Mutational Analysis Of The Muth From Escherichia Coli: A Dissertation, Tamalette Loh Sep 2000

Mutational Analysis Of The Muth From Escherichia Coli: A Dissertation, Tamalette Loh

GSBS Dissertations and Theses

DNA mismatch repair is one process in the preservation of genomic integrity. It has been found in Archeae, bacteria, plants, yeast and mammals. The mismatch repair system is highly conserved among species and allows the strand-specific elimination of base-base mispairs, chemical base modifications, as well as short insertion/deletion loops following DNA replication. The repair system also has important effects on homeologous recombination, contributing to the frequency of reciprocal exchanges. In humans, defects in the repair system have been found to be associated with tumorigenesis.

In Escherichia coli, this pathway was originally called long patch repair before being renamed the ...


In Vitro And In Vivo Studies Of Murine Polytropic Retrovirus Infections: A Dissertation, Scott A. Loiler Sep 2000

In Vitro And In Vivo Studies Of Murine Polytropic Retrovirus Infections: A Dissertation, Scott A. Loiler

GSBS Dissertations and Theses

Murine leukemia viruses (MuLV) are retroviruses that play important roles in the study of oncogenes, integration, transcriptional regulation and gene therapy. Mink cell focus-inducing (MCF) viruses are polytropic MuLVs that by definition infect cells from a wide variety of species. Their ability to infect human cells and their utility as gene therapy vectors were not well characterized. To address this issue, primary and immortalized human cells were tested for their ability to be infected by MCF packaged defective vectors as well as replication competent MCF virus. A new packaging cell line, called MPAC, was created to package defective retroviral vectors ...


Conserved Features Of Chromatin Remodeling Enzymes: A Dissertation, Laurie A. Boyer Aug 2000

Conserved Features Of Chromatin Remodeling Enzymes: A Dissertation, Laurie A. Boyer

GSBS Dissertations and Theses

Chromatin structure plays an essential role in the regulation of many nuclear processes such as transcription, replication, recombination, and repair. It is generally accepted that chromatin remodeling is a prerequisite step in gene activation. Over recent years, large multisubunit enzymes that regulate the accessibility of nucleosomal DNA have emerged as key regulators of eukaryotic transcription. It seems likely that similar enzymes contribute to the efficiency of DNA replication, recombination, and repair. These chromatin remodeling complexes can be classified into two broad groups: (1) the ATP-dependent enzymes, which utilize the energy of ATP hydrolysis to increase the accessibility of nucleosomal DNA ...


Allosteric Regulation Of Recombination Enzymes E. Coli Reca And Human Rad51: A Dissertation, Julie Kelley De Zutter Aug 2000

Allosteric Regulation Of Recombination Enzymes E. Coli Reca And Human Rad51: A Dissertation, Julie Kelley De Zutter

GSBS Dissertations and Theses

ATP plays a critical role in the regulation of many enzyme processes. In this work, I have focused on the ATP mediated regulation of the recombination processes catalyzed by the E. coliRecA and the human Rad51 proteins. The RecA protein is a multifunctional enzyme, which plays a central role in the processes of recombinational DNA repair, homologous genetic recombination and in the activation of the cellular SOS response to DNA damage. Each of these functions requires a common activating step, which is the formation of a RecA-ATP-ssDNA nucleoprotein filament. The binding of ATP results in the induction of a ...


Characterization Of Immune Responses Following Neonatal Dna Immunization: A Dissertation, Tamera Marie Pertmer Apr 2000

Characterization Of Immune Responses Following Neonatal Dna Immunization: A Dissertation, Tamera Marie Pertmer

GSBS Dissertations and Theses

Neonatal mice have immature immune systems with defects in several components of inflammatory, innate, and specific immune responses and develop a preferential T helper type 2 (Th2) response following immunization with many vaccine antigens. Although maternal antibody is the major form of protection from disease in early life when the neonatal immune system is still immature, the presence of maternal antibody also interferes with active immunization, placing infants at risk for severe bacterial and viral infection. Recent studies have suggested that immunizing with DNA plasmids encoding the vaccine antigen of interest is highly efficacious in a variety of adult animal ...


The Role Of The Light Intermediate Chains In Cytoplasmic Dynein Function: A Dissertation, Sharon H. Tynan Mar 2000

The Role Of The Light Intermediate Chains In Cytoplasmic Dynein Function: A Dissertation, Sharon H. Tynan

GSBS Dissertations and Theses

Cytoplasmic dynein is a multisubunit complex involved in retrograde transport of cellular components along microtubules. The heavy chains (HC) are very large catalytic subunits which possess microtubule binding ability. The intermediate chains (IC) are responsible for targeting dynein to its appropriate cargo by interacting with the dynactin complex. The light intermediate chains (LIC) are previously unexplored subunits that have been proposed to modulate dynein activity by regulating the motor or the IC-dynactin interaction. The light chains (LC) are a newly identified class of subunit which are also thought to have regulatory functions.

In the first part of this work, I ...


Sequences Required For Neurotensin Receptor-1 Gene Expression In N1e-115 Neurosblastoma Cells: Critical Importance Of A Caccc Element For Activation During Dmso-Induced Neuronal Differentiation: A Dissertation, Daniel Jorge Tavares Feb 2000

Sequences Required For Neurotensin Receptor-1 Gene Expression In N1e-115 Neurosblastoma Cells: Critical Importance Of A Caccc Element For Activation During Dmso-Induced Neuronal Differentiation: A Dissertation, Daniel Jorge Tavares

GSBS Dissertations and Theses

The promoter sequence of the mouse high affinity neurotensin receptor, Ntr-1, gene was cloned and characterized, sequences required for positive regulation in N1E-115 cells were localized, and at least two different peptides from these cells were shown to make specific contacts within the most potent positive regulatory element. A mouse neuroblastoma cell line, N1E-115, treated with 1.5% DMSO for 72 hours induces gene expression of both endogenous Ntr-l, and reporter constructs driven by the NTR-1 promoter, by 3 - 4 fold. The sequence ofthe NTR-1 promoter has no canonical TATA box, but is GC rich and contains consensus SP1, CACCC ...