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The tuberous sclerosis-2 (Tsc-2) gene product, tuberin, functions as a renal tumor suppressor. Treatment of Eker (Tsc-2 EK/+) rats and primary renal epithelial cells derived from Tsc-2 EK/+ rats (QTRRE cells) with 2,3,5-tris-(glutathion-S-yl) hydroquinone (TGHQ) results in loss of heterozygosity at the Tsc-2 locus in kidney tumors and QTRRE cells. QTRRE cells are carcinogenic in athymic nude mice. Analysis of kidney tumors formed in Tsc-2 EK/+ + rats following 8-months of TGHQ treatment reveals increases in B-Raf, Raf-1, pERK, cyclin D1, p27Kip1, 4EBP1, p-4EBP1(Thr70), p-4EBP1(Ser65), and p-4EBP1(Thr37/46) protein expression. These data establish the involvement of mTOR and MAPK signaling cascades in tuberin null tumors. Similar increases in 4EBP1 and p4EBP1 are observed in renal tumor QTRRE-xenografts in nude mice. Concomitant with increases in expression of these proteins in TGHQ-induced renal tumors, similar changes are observed in QTRRE cells, which also exhibit high ERK, B-Raf and Raf-1 kinase activity; and increased expression of cyclin D1, p27, p-4EBP1 (Thr70), p-4EBP1 (Ser65), and p-4EBP1 (Thr37/46). Manipulation of the Raf/MEK/ERK kinase cascade in QTRRE cells, with kinase inhibitors and siRNA, indicates that Raf-1/MEK/ERK participates in crosstalk with 4EBP1 to regulate translation of cyclin D1.Cyclin D1 and p27 protein levels are increased in the cytoplasm in our RCC models. In normal HK-2 cells, p27 and cyclin D1 are localized to the nucleus. Due to the instability of the cyclin D1-CDK4 complex, p27 interaction is necessary for cyclin D1-CDK4 complex assembly and stabilization in the nucleus. Manipulation of p27 protein levels in QTRRE cells with phosphodiesterase inhibitors, dibutyryl cAMP, and the proteosome inhibitor MG132, all result in a parallel increase in p27 and cyclin D1. Furthermore, p27 siRNA and sorafenib treatment both cause a decrease in p27 and cyclin D1. Further manipulation of cAMP, Rap1B, and B-Raf proteins, revealed that cAMP/PKA/Rap1B/B-Raf activation and B-Raf//ERK MAPK inhibition both modulate p27 expression and compartmental localization in tuberous sclerosis renal cancer. Phosphodiesterase inhibitors play a role in regulating the expression, degradation, and cytoplasmic localization of p27. Therefore, cytoplasmic p27-cyclin D1 mislocalization and stabilization may have an oncogenic role in the cytosol and play a crucial role in tumor formation.

The study was undertaken to discover if the summer camp experience enhanced personality traits of participants in the camp program. The study was implemented at Greene Family Camp in Bruceville, Texas, during the summer of 1985. Utilized were analyses of variance and two types of factor analyses: principal-components analysis with varimax rotation and principal axis factoring with oblique rotation of factor matrices elicited. Five personality areas were analyzed--sociability, independence, achievement, environmental awareness, and spirituality. Spirituality emerged so strongly that it was removed from further analyses. Remaining personality areas emerged, but groupings of variables, especially those relating to achievement and independence, suggest an inherent commonality among the complex facets of personality. Based on these findings, the researcher recommends further investigation and careful replication.

Adenylate cyclase toxin (CyaA) is a key virulence factor of Bordetella pertussis, the causative agent of whooping cough. The toxin targets primarily myeloid phagocytes expressing CD11b/CD18 (αMβ2, CR3, Mac-1) and by elevation of cytosolic cAMP levels it paralyses their macropinocytic and opsono-phagocytic functions. Here, we dissected the cAMP-regulated pathway responsible for the block of macrophage macropinocytosis and characterized the capacity of CyaA-treated macrophages to shut- down Akt (protein kinase B, PKB) signaling; that controls nitric oxide (NO) production by macrophages. By using specific activators of protein kinase A (PKA) and for the exchange protein activated by cAMP (Epac), we show that activation of the cAMP effector Epac inhibits macropinocytosis in macrophages. Moreover, upon transfection of macrophages by the constitutively active and dominant negative variants of a downstream effector of Epac, the small GTPase Rap1, inhibition or upregulation of macrophage macropinocytosis was observed, respectively. It was reported previously that the Epac/Rap1 pathway regulates activity of tyrosin phosphatase SHP-1 as well as of protein phosphatase 2 A (PP2A). We show that inhibition of both tyrosin phosphatases and PP2A interferes with CyaA-mediated block of macropinocytosis. These...

Diploma thesis was divided into three main parts: the historical part, true stories of survivors and psychological part. The order of these three parts is not accidental. One follows the other, and each of the following, you might say, is clear. The second part contains the real stories of survivors and two stories of survivors of the Auschwitz concentration camp, and two stories from the Theresienstadt ghetto.On the stories of former prisoners trying to illustrate what life was like lágrového prisoner what they had to endure what he had to give up what had become accustomed to, and what a great inner strength had to use that he managed to survive. In every story outlines the change that is in man during detention takes place. The main task of the second part is to offer readers a chance to try to put yourself in the characters and try to bring your inner feelings at least a partial understanding of the urgency of the topic. The third and last part, the part psychological. Its mission is to gather, grab and name phenomena that occur freely in the stories of survivors. Another aim is to highlight the consequences of the concentration camp experience entails. Liberation of prisoners in concentration camps do not stop there. On the other hand, surviving thanks to her horror experiences we take away...

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My work uses hair as both a subject depicted in drawings, paintings, and prints; as well as a medium for sculpture, installation, and video created with synthetic hair pieces and wigs. I am interested in deconstructing gendered codes of appearance, and visions of the ideal woman and man as objects. I remove all identifiable traits from my characters, apart from their hair which appears to be consuming or erasing them. In doing so, I force the people viewing my work to rely on cultural stereotypes associated with hair to identify my characters. My work is heavily influenced by Drag culture and Camp, for their ability to mock identity, gender, and cultural stereotypes and portray them as something fluid that can be constructed and changed on a daily basis, instead of a biological trait forced upon them at birth. I view my artwork as my own form of Drag.

Thesis advisor: Charles S. Hoffman / Transcription of the Schizosaccharomyces pombe fbp1 gene is subject to repression by environmental glucose that is detected through a cAMP signaling pathway. Previous research has identified several glucose insensitive transcription (git) genes that are required for glucose repression. One of these genes, git7, is required for cAMP signaling, but its exact function in the process is unknown. Analysis of this gene is complicated because it carries out additional essential functions that are unrelated to cAMP signaling. The git7-93 allele encodes a protein that possesses an18 amino acid duplication in the carboxy-terminus and only displays a defect in cAMP signaling, while two other mutant alleles that affect all Git7-dependent processes alter residues in the amino-terminus. My thesis work was composed of two projects designed to investigate the role of the Git7 carboxy-terminus in cAMP signaling and to identify more precisely the carboxy-terminal domain that is required for cAMP signaling. The first part of my study involved a genetic screen to isolate and characterize mutations that suppress the git7-93 allele, but fail to suppress a git7 mutant allele in which the amino-terminus of the protein is altered. Such allele-specific suppression may identify the direct target of Git7 function in the cAMP pathway. I have isolated a collection of 55 suppressor strains. Molecular and genetic analyses of these strains have reduced this number to nine candidates, which could have represented allele specific suppressors. However, the final genetic screen determined that all the candidates were extragenic suppressors. The second part of my study involved a screen for new mutant alleles of git7 that resemble git7-93 in that they confer a cAMP signaling defect, but do not confer cell wall or septation defects caused by the git7-27 or git7-235 alleles. This was carried out by performing a random mutagenesis on a cloned wild type git7 gene and then screening for plasmids that could suppress the cell wall or septation defects, but not the cAMP signaling defect, in a git7-235 host strain. Taken together, these two studies should help to identify the role that git7 plays in the cAMP signaling pathway Schizosaccharomyces pombe. / Thesis (BS) — Boston College, 2004. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Biology. / Discipline: College Honors Program.

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Thesis (M.S.)--Boston University