5 research outputs found

    The ubiquitin-conjugating enzyme CDC34 is essential for cytokinesis in contrast to putative subunits of a SCF complex in Trypanosoma brucei

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    The ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes, including cell cycle progression. Target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade composed of E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, and E3 ubiquitin ligases. One of the E3 ligases known to be responsible for the ubiquitination of cell cycle regulators in eukaryotes is the SKP1-CUL1-F-box complex (SCFC). In this work, we identified and studied the function of homologue proteins of the SCFC in the life cycle of Trypanosoma brucei, the causal agent of the African sleeping sickness. Depletion of trypanosomal SCFC components TbRBX1, TbSKP1, and TbCDC34 by RNAi resulted in decreased growth rate and contrasting cell cycle abnormalities for both procyclic (PCF) and bloodstream (BSF) forms. Depletion of TbRBX1 in PCF cells interfered with kinetoplast replication, whilst depletion of TbSKP1 arrested PCF and BSF cells in the G1/S transition. Silencing of TbCDC34 in BSF cells resulted in a block in cytokinesis and caused rapid clearance of parasites from infected mice. We also show that TbCDC34 is able to conjugate ubiquitin in vitro and in vivo, and that its activity is necessary for T. brucei infection progression in mice. This study reveals that different components of a putative SCFC have contrasting phenotypes once depleted from the cells, and that TbCDC34 is essential for trypanosome replication, making it a potential target for therapeutic intervention

    Grid Portal Application

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    This project concerns EMMIL (E-Marketplace Model Integrated with Logistics) and its viability as a grid application. The model was evaluated on a single processor and on the SEEGRID network using MTA-SZTAKI's P-GRADE Portal. A granularity heuristic was developed to guide the mapping of EMMIL datasets to processes. A portlet for P-GRADE Portal was also created to aid in data entry. Finally, pre-processing filters were added. These were designed to discard useless combinations and reduce overall computing time

    Mapping Building Characteristics In Mitcham

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    The London Borough of Merton has begun the development of a district heat and power system. In order to financially model the feasibility of this scheme, energy consumption data for borough buildings must be known. The objective of this project was to investigate and apply methods for mapping the energy use of buildings within the borough of Merton. Difficulties encountered in data collection led to a revision of our project to include the drafting of sustainable information gathering mechanisms. With these in place the Merton Council will be able to base future plans on an accurate and thorough knowledge base

    The Miami-Dade Juvenile Assessment Center National Demonstration Project: An Overview

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    Demonstration Project (NDP) is serving as a national model for the transformation of front end services in the juvenile justice system in a unique sociocultural setting. We discuss the background and vision of the NDP, its implementation and accomplishments in sixmajor programareas: (1) screening and assessment, (2) post-arrest diversion, (3) gender specific services, (4) a new service for the younger siblings of serious habitual offenders, (5) Haitian juvenile arrestee services, and (6) an information resource center. We end our discussion by presenting current and future plans for the NDP. We hope the experiences of, and procedures, protocols and program designs developed by, the NDP will be helpful to other jurisdictions with centralized intake facilities in improving their screening, assessment and intervention services
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