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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
771

The role of N-terminal domain in regulation of mineralocorticoid receptor function

Swan, Katherine January 2003 (has links)
The N-terminal domain of the mineralocorticoid receptor (MR) exhibits no significant sequence homology to the highly related glucocorticoid receptor. I report here that amino acids 450--602 of the N-terminus play a role in three aspects of MR degradation: (1) degradation in the absence of aldosterone mediated by the 26S proteasome, (2) degradation in the presence of aldosterone mediated by the 26S proteasome, and (3) degradation in the presence of aldosterone not mediated by the 26S proteasome. Concurrently I determined that aldosterone treatment following transient expression of MR in Cos-7 cells induced the appearance of higher molecular weight forms of the receptor. I determined that two regions within the N-terminus of MR were required for the appearance of the aldosterone-stimulated shift in molecular weight. Furthermore, the type of agonist, nuclear occupancy and the cell type employed influenced the shift in molecular weight of MR.
772

Profiling apoptotic patterns during forelimb development and regeneration in the newt, Notophthalmus viridescens

Vlaskalin, Tatjana January 2003 (has links)
Recent studies have found that many of the genes involved in the initial development of the limb in higher vertebrates are also expressed during regeneration of the limb in urodeles. These similarities have lead researchers to conclude that the regeneration process is a recapitulation of development and that patterning of the regenerate mimics pattern formation in development. In this work, we address the issue of whether regeneration and development are similar by examining patterns of apoptosis during these processes. In contrast to higher vertebrates, forelimb development in the newt, Notophthalmus viridescens, does not follow conventional pattern formation utilizing interdigital apoptosis as the method of individualization of the digits. Similarly, forelimb regeneration does not undergo interdigital apoptosis during cartilage condensation and digit formation in the adult. Apoptosis seems to play an important role during the wound healing stage of regeneration and again during cartilage to bone turnover during digit and radius/ulna regeneration. We suggest that urodeles have adapted a mechanism of forelimb regeneration that may re-activate developmental pathways similar to higher vertebrates, yet without cell death between the digits, and furthermore, undergo a unique mechanism of limb development in which apoptosis plays a minor role.
773

Effects of a plant extract from Ruptiliocarpon caracolito on the growth and differentiation of P19 mouse embryonal carcinoma cells

Aghsani, Parisa January 2004 (has links)
Present data indicate that the Ruptiliocarpon caracolito extract exerted significant anti-proliferative activity against P19 EC cells, in the absence of toxicity and significant alterations in the differentiation status of the cells. The focus of this study was to determine whether the proliferation of P19 EC cells would decrease in response to Ruptiliocarpon caracolito extract and whether the anti-proliferative activity, if observed, would be accompanied by alterations in the cell differentiation status. According to the data obtained in the present study, the plant extract exerted a significant anti-proliferative activity against the P19 EC cell line. This activity was exhibited in a dose-related fashion. Amongst the doses tested (5--70mug/ml), concentrations ranging from 30--70mug/ml showed a significant anti-proliferative activity (P < 0.001). The highest growth reduction activity of the extract was noticed at a concentration of 50mug/ml of culture medium. Viability studies indicated that the decrease in cell proliferation was not secondary to the toxicity of the extract. (Abstract shortened by UMI.)
774

Insulin-like growth factor-II (IGF2) gene of zebrafish and its use as a biogenetic marker for the assay of epigenetic toxin exposure

Alazzabi, Mufida January 2004 (has links)
The purpose of this research was to determine whether expression analysis of the IGF2 gene in zebrafish, a gene whose transcription is known to be regulated by DNA methylation in mammals, can be used as a marker or indicator of DNA methylation due to toxin exposure in fish embryos. We examined the expression of IGF2, IGF1, and IGFBP-1 in zebrafish embryos treated with sodium arsenite (thought to inhibit DNA methylation), nickel chloride (thought to cause DNA hypermethylation), trichostatin A (a histone deacetylase inhibitor), 5-azaC (thought to cause methyltransferase inhibition), cadmium chloride (thought to cause DNA hypermethylation) and mercury chloride (unknown). (Abstract shortened by UMI.)
775

The role of Growth arrest-specific 6 in Notophthalmus viridescens forelimb regeneration

Beug, Shawn January 2004 (has links)
Red-spotted newts are capable of regenerating diverse structures and organs, including limb, tail and retina. The epimorphic regenerative response is a complex process that involves dedifferentiation, cellular proliferation and transdifferentiation. Although receptor tyrosine kinases (RTKs) and their ligands are important for normal cellular physiology, no studies have as of yet attempted to isolate and characterize any of these receptors and their ligands during newt forelimb regeneration. I isolated a newt homologue of growth arrest-specific 6 (NvGas6), a RTK ligand involved in multiple functions during ontogeny and normal physiological processes, and its expression was characterized in a polyclonal blastema cell line (B1H1) and during limb regeneration. NvGas6 encodes for a 671 amino acid polypeptide that shares 64% identity (78% similarity) with mammalian Gas6. In B1H1 cells, NvGas6 is upregulated during myogenesis and is downregulated during cell cycle reentry. Upon amputation, NvGas6 expression increases, peaking during maximal blastemal cell proliferation and declines during redifferentiation. NvGas6 transcripts were colocalized to distal mesenchymal cells during dedifferentiation and proliferation, and were found in areas of redifferentiation. Although the in vitro and in vivo results seem paradoxical, studies by others have shown that Gas6 can have diverse roles in cell survival, proliferation and differentiation, it is possible that NvGas6 is involved in cell survival in vitro and cellular proliferation in vivo. However, taken together, these results suggest that NvGas6 may be primarily involved in mediating cell survival and migration during regeneration.
776

The growth-arrest-specific protein gas7 potentiates neuronal differentiation

Lortie, Karine January 2004 (has links)
The growth-arrest-specific gas7 protein is involved in neuronal development. Its role in neuronal differentiation and its potential neuroprotective activity were investigated in PC 12 and NT2 cells. gas7 overexpression in PC12 cells promoted neurite outgrowth and potentiated nerve growth factor-induced expression of the neuronal markers betaIII-tubulin, synaptotagmin, alpha7 subunit of the acethylcholine receptor, and dihydropyrimidinase related protein-3. This effect was exerted independently of cellular proliferation, as gas7 did not affect cell cycle progression. Endogenous gas7 expression was induced during neuronal differentiation of NT2 cells with retinoic acid, suggesting a role for gas7 in neuronal development. Finally, gas7 overexpression in PC 12 cells did not protect against toxicity triggered by oxygen-glucose deprivation, the calcium ionophore A23187 or sodium nitroprusside. The ability of gas7 to potentiate neuritogenesis and neuronal differentiation makes it a potential therapeutic target to promote re-establishment of neuronal connections in the injured or diseased brain, such as following stroke.
777

The role of prostaglandin EP receptors in a model of glomerulonephritis

Rahal, Sherine S January 2004 (has links)
Prostaglandin E2 (PGE2) interacts with four E-Prostanoid (EP) receptor subtypes---designated EP1--4 . In glomerulonephritis (GN), a renal inflammatory disease, inhibition of enhanced renal PGE2 synthesis by nonsteroidal-anti-inflammatory drugs (NSAIDs), results in both beneficial anti-proteinuric effects and deleterious side effects on renal blood flow (RBF) and Na+ homeostasis, implying that one or more EP subtypes may mediate these actions. We set out to investigate the role of the EP1 receptor in GN since it localizes to the collecting duct, where it may regulate Na+ homeostasis, in podocytes and mesangial cells, where it could alter the permeability of the glomerulus, and in arterioles, where EP, receptors may induce vasoconstriction thereby reducing RBF. A mouse model of GN was induced in wildtype (wt) and EP1-/- mice using an anti-rat-glomerular basement membrane (anti-GBM) antibody. Proteinuria was similar in GN wt and GN EP1-/- groups thereby negating a role for this subtype in modulating filtration barrier permeability. (Abstract shortened by UMI.)
778

Gene reprogramming by K48R mutant ubiquitin in a mouse model of SCA1

Tang, Matthew Y January 2005 (has links)
Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease resulting from the loss of Purkinje neurons within the cerebellum. The causative agent of the disease is the expansion of a trinucleotide repeat in its gene product ataxin-1. The ubiquitin proteasome pathway (UPP) has been implicated in SCA1 but the role of proteolysis in the disease is still poorly understood. To further investigate this issue in vivo , genetic crosses were performed between a well established mouse model of SCA1 and novel strains expressing elevated levels of wild type or mutant isoforms of ubiquitin. The K48R mutant isoform of ubiquitin (a dominant negative inhibitor of proteolysis) was found to significantly delay the deterioration of Purkinje neurons as evidenced by behavioral, morphological, and molecular indicators. This delay was accompanied by the restoration of genes involved in calcium and glutamate signalling and by the stabilization of postsynaptic density proteins whose abundance/activity would otherwise decline in the course of the SCA1 disease. These results are consistent with transcriptional dysregulation as a key mechanism in neurodegeneration and suggest that the UPP is a useful target for the development of novel therapies.
779

Evaluation of mammalian cell-free systems of nuclear assembly and disassembly

Vaillant, Dominique January 2005 (has links)
Mammalian cell-free systems are very useful for the biochemical and structural study of nuclear disassembly and assembly. Through manipulation, the role of specific proteins in these processes can be investigated. I first intended to examine the involvement of integral and peripheral inner nuclear membrane proteins in nuclear disassembly and assembly. However, I was unable to achieve disassembly when isolated interphase HeLa nuclei were exposed to mitotic soluble extracts containing cyclin B1. Homogenates of synchronized mitotic HeLa cells left to reassemble nuclei resulted in incomplete nuclear envelope assembly on chromatin masses. Digitonin permeabilized mitotic cells also assembled incomplete nuclei, generating a lot of cytoplasmic inclusions of inner nuclear membrane proteins as an intermediate. These results were therefore used as a basis for the experimental evaluation of mammalian cell-free systems. Synchronization itself induced incomplete nuclear assembly. This may be caused by the prior aberrant nuclear disassembly, or by the abnormal number of mitotic spindles.
780

Molecular mechanisms underlying the valproic acid-induced degradation of transcriptional coactivators p300 and CBP

St-Germain, Jonathan R January 2006 (has links)
p300 and CBP are closely related transcriptional coactivators involved in a wide range of cellular processes. They interact with a large array of transcription factors and possess intrinsic acetyltransferase activity which allows them to acetylate many nuclear proteins including nucleosomal histones. Although much is known about the functions of p300 and CBP, what in turn regulates these coactivators is less understood. The present study reveals that the stability of both proteins is affected by the histone deacetylase inhibitor valproic acid and elucidates the molecular mechanisms involved in this pathway. These results show that valproic acid induces degradation of p300 and CBP through the 26S proteasome, and suggest that this occurs in an ubiquitin-dependent manner and that this effect is mediated by the B56gamma3 regulatory subunit of protein phosphatase 2A. Considering the involvement of valproic acid, p300 and CBP in such processes as embryonic development and tumorigenicity, these findings potentially entail important biological significance.

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