552 research outputs found

    Regulation of splicing integrin É‘6 during development and differentiation

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    PhD ThesisAlternative splicing is an important mechanism for creating protein diversity. Integrins are significant in many aspects of cell biology, including cell signalling and interaction with the cell matrix. ITGA6 has two different cytoplasmic C-termini (a6A and a6B) that shift 100% between stem cells and fibroblasts. The primary aim in this thesis was to monitor splicing patterns during development and differentiation integrin subunit alpha 6 (ITGA6) to see which alternative splicing events are similarly regulated in fish and humans using early zebrafish development. The a6A and a6B integrins had been differentially implicated in the expression in the function of breast cancer and cancer stem cells. Therefore, the second aim was to monitor splicing patterns for ITGA6 in different cancer cell lines and to compare them with stem cell patterns, fibroblast, and zebrafish, determining which splicing regulator protein regulates the ITGA6 alternative exon. It was confirmed that the ITGA6 alternative exon 25 was activated by MBNL1, RBFOX2 and ESRP in cancer cell lines, and PTBP was discovered as a novel regulator for ITGA6 splicing that inhibited the exon of ITGA6 in cancer cell line. The third aim for this project was to identify the mechanism of splicing of this ITGA6 alternative exon, including identifying the PTB binding site that regulates ITGA6. A minigene system was established to study the regulation of the ITGA6 alternative exon. The ITGA6 1.3 minigene positively responded to siRNA mediated depletion of splicing factors in the same way as the endogenous gene, indicating this minigene was a good model. The alternative exon of ITGA6 was activated by MBNL1 and was inhibited by PTBP, leading to more production of ITGA6B. Using this minigene plasmid it was confirmed that PTBP inhibited alternative splicing of ITGA6. The last aim of this chapter was to discover the PTB binding sites. Through a series of in silico analyses, a binding site for PTB was identified downstream of the regulated exon. Surprisingly, loss of this PTB binding site actually repressed this splicing event. These data suggest that PTB both activates this alternative splicing event through direct RNA-protein interactions, but also more strongly represses this exon, possibly through protein interactions with other regulatory factors.Saudi Arabian culture bureau in London and the Najran Universit

    Plenum-to-plenum heat transfer characteristics under natural circulation in a scaled-down prismatic modular reactor

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    “Gas-cooled reactor (GCR) is being developed under the Next Generation Nuclear Plant Program (NGNP) in nuclear engineering studies. As the world searches for an energy source with high energy density, clean, abundant, and storable nature to avoid global warming issues, GCR seems to be a promising solution, particularly the possibility of producing hydrogen. Studying and developing the safety analysis and GCR technologies are required for the optimum design and safety of GCR system. Multiphase Reactors Engineering and Applications Laboratory (mReal) at Missouri University of Science and Technology (S&T) has developed a natural convection heat transfer test facility with one riser and one downcomer between two plena to investigate loss of flow accident scenario (LOFA) for a prismatic very high temperature reactor (VHTR). Using advanced heat transfer coefficient probe and T-thermocouples. The facility represents a scaled down prismatic modular reactor with a reference to High-Temperature Test Facility at Oregon State University (OSU-HTTF). The natural circulation heat transfer in terms of temperature fields and heat transfer coefficients across the core of current facility (i.e., channels) has been investigated at different conditions to understand the passive safety features of prismatic modular reactors (PMR). This dissertation advance knowledge and understanding of the intra core natural circulation phenomenon in the PMRs. Moreover, fill the gaps in the open literature and understanding of the natural circulation heat transfer and gaseous dynamics in the prismatic VHTR and provide experimental benchmark data, which is much needed and is missing in the literature for verification and validation”--Abstract, page iii

    Risk factors for deep vein thrombosis in a South African public hospital

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    Includes bibliographical referencesIncludes abstract.The evidence suggests an association between HIV, TB and DVT. There are no studies of this link in the Southern African setting, where the incidence of both of these conditions (HIV and TB) is high. We therefore undertook a study to define the incidence of HIV and TB in patients with confirmed DVT in this setting. The aim of this study is to describe the incidence of HIV, TB and the more commonly accepted risk factors in patients with confirmed DVT in a South African public hospital

    Anticancer activity of methanolic extarct of Momordica charantia against human colon, liver and breast cancer cell lines- In vitro

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    Natural products are the best source for various medicinal drugs. Regardless investigate the toxic effect of these plant extracts, the results will still unsafe and unacceptable. This study aimed to identify anti-cancer activity and cytotoxicity effect of Momordica charantia extract on different cancer cell line. Materials and Methods:to archive the aim of this study 3 different cancer cell lines (HCT116, MCF-7, and HepG2) were treated with different Momordicacharantiaextract doses (from 0-100µg) for each cell line. IC50, cell viability,apoptosis, were evaluated. Results:The effect of Momordicacharantiaextract was highly significant in HepG2 cells than HCT116 cell as well as MCF-7 which showing the IC50 of Momordicacharantia extract in HepG2 was 0.77 µg/ml while in HCT116 was 0.81µg/mland was 1.35µg/ml in MCF-7 cells respectively. Also, the effect of the Momordicacharantia extract was more potent in HCT116 compared to MCF-7 cells.Conclusions: in the light of these resultsMomordicacharantiaextract may use as anticancer pro-drugat a specific type of cancer (Liver HepG2 cell line) but still need further studies to explore the mechanism of action that led to observe different results from different cell lines despite the same extract. Keywords: Momordicacharantia, Apoptosis, MCF-7, HepG2, HCT116

    Regulation of splicing integrin É‘6 during development and differentiation

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    PhD ThesisAlternative splicing is an important mechanism for creating protein diversity. Integrins are significant in many aspects of cell biology, including cell signalling and interaction with the cell matrix. ITGA6 has two different cytoplasmic C-termini (a6A and a6B) that shift 100% between stem cells and fibroblasts. The primary aim in this thesis was to monitor splicing patterns during development and differentiation integrin subunit alpha 6 (ITGA6) to see which alternative splicing events are similarly regulated in fish and humans using early zebrafish development. The a6A and a6B integrins had been differentially implicated in the expression in the function of breast cancer and cancer stem cells. Therefore, the second aim was to monitor splicing patterns for ITGA6 in different cancer cell lines and to compare them with stem cell patterns, fibroblast, and zebrafish, determining which splicing regulator protein regulates the ITGA6 alternative exon. It was confirmed that the ITGA6 alternative exon 25 was activated by MBNL1, RBFOX2 and ESRP in cancer cell lines, and PTBP was discovered as a novel regulator for ITGA6 splicing that inhibited the exon of ITGA6 in cancer cell line. The third aim for this project was to identify the mechanism of splicing of this ITGA6 alternative exon, including identifying the PTB binding site that regulates ITGA6. A minigene system was established to study the regulation of the ITGA6 alternative exon. The ITGA6 1.3 minigene positively responded to siRNA mediated depletion of splicing factors in the same way as the endogenous gene, indicating this minigene was a good model. The alternative exon of ITGA6 was activated by MBNL1 and was inhibited by PTBP, leading to more production of ITGA6B. Using this minigene plasmid it was confirmed that PTBP inhibited alternative splicing of ITGA6. The last aim of this chapter was to discover the PTB binding sites. Through a series of in silico analyses, a binding site for PTB was identified downstream of the regulated exon. Surprisingly, loss of this PTB binding site actually repressed this splicing event. These data suggest that PTB both activates this alternative splicing event through direct RNA-protein interactions, but also more strongly represses this exon, possibly through protein interactions with other regulatory factors.Saudi Arabian culture bureau in London and the Najran Universit
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