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University of Macau / Institute of Chinese Medical Sciences

University of Macau / Institute of Chinese Medical Sciences

Growing tissues are communities of cells that cooperate to form a robust, functional organ. Cooperative behavior is enforced by cell competition, wherein comparisons of fitness lead to selective elimination of cells sensed as relatively less healthy. Elimination of these ‘loser’ cells from Drosophila wing imaginal discs results in cell death induced by deployment of a genetic module consisting of the secreted Toll ligand Spätzle (Spz), several Toll related receptors, and NFkB factors. How signaling by this module is activated and restricted only to competing cells is unknown. Here, we investigate the signaling role of Spz in Myc-induced cell competition. We demonstrate that elimination of wild-type loser cells requires local synthesis and activation of Spz in the wing disc. We identify Spätzle Processing Enzyme (SPE) and Modular Serine Protease (modSP) as upstream mediators of Spz-mediated loser cell elimination, and show that an increase in SPE in ‘winner’ cells is required for Spz to kill loser cells. Finally, we show that Spz requires both Toll and Toll-8 to induce apoptosis of wing disc cells. Our results indicate that during cell competition, Spz-mediated signaling is strictly confined to the imaginal disc, allowing errors in tissue fitness to be corrected without compromising organismal physiology.

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Progress in understanding cancer progression has been hampered over the years by the different types of mutations present and irregular changes of gene regulation associated with any given cancer. In this work, molecular interactions between TALI, LMO1, and decorin were investigated. Numerous studies have shown that ectopic expression of decorin protein induced growth suppression in neoplastic cells of various histogenic origins. Furthermore, ectopic expression of TAL1 and LMOI oncoproteins has been shown to occur in approximately 50% of the cases of T-cell acute lymphoblastic leukemia (T-ALL). It was of interest then to determine the preventive or interactive role decorin played with the oncogenic activity of TAL I and LMO1. In this investigation, decorin was introduced into a murine T-cell line (AKR-DP-603) through the use of the mammalian expression vector pcDNA3.1 (-). This particular cell line was previously engineered to express TALI and LMO1. Protein expression patterns in all cell populations were analyzed using the Western blot technique and a proteoglycan with a molecular weight of 100 kDa before chondroitinase ABC treatment and a core protein of55 kDa after treatment with chondroitinase ABC was seen. This finding is significant since it implies that the pcDNA3. 1(-) vector containing decorin cDNA was present, and the corresponding decorin peptides were expressed in both cytoplasmic and nuclear extracts. Furthermore, Northern blot analysis was performed on total RNA extracts to determine the transcriptional state of endogenous decorin rRNA, as well as exogenously introduced decorin. Northern blot analysis revealed no decorin-specific mRNA transcripts from the various cell populations. This result did not imply a lack of possible regulatory effect on protein and mRNA levels of TALL and LMOI by decorin. Finally, cell growth assays were performed on all cell populations and cell counts were used to assess the growth pattern of each population after serum withdrawal. The results show possible growth suppressive effects of decorin on TAL1 and LMOI expressing cells. Results obtained from this study shed further light on the molecular interactions influencing T-ALL and may also help in the design of potentially beneficial cancer treatments using decorin. / Department of Biology

The aim of this study was to examine the claim that a single, mutant oncogene can transform NIH 3T3 mouse fibroblasts into transformed, tumorigenic cells, acting in a genetically dominant fashion. A c.Ha-ras 1 oncogene, cloned from the EJ human bladder carcinoma cell line, was inserted into a shuttle vector carrying the selectable marker gene gpt, which encodes the enzyme XPRT (xanthine-guanine phosphoribosyl transferase). This construct, pSV2gptEJ, was transfected into NIH 3T3 cells by the calcium phosphate precipitation method and cells which had incorporated the plasmid were selected by growth in mycophenolic acidcontaining medium, to which gpt confers resistance. A number of clonal lines were established and their tumorigenicity tested. Tumour cell lines derived from these transfectants were back-selected using 2-thioxanthine, a cytotoxic analogue of the xanthine-guanine phosphoribosyl transferase substrate, to isolate clones which no longer contained functional pSV2gptEJ sequences. Six sub-clones which did not express detectable levels of the ras oncogene product, p21^H.ras , were obtained. All were judged to be less transformed than the transfected parent cells: they appeared morphologically normal, were more serum-sensitive, showed clear saturation densities and were more anchorage-dependent. Three of these sub-clones were found to be tumorigenic at all sites tested. Cytological examination of the NIH 3T3 transfectants revealed that significant perturbation of their chromosome complement accompanied transfection. The transfection process, in the absence of DNA or with pSV2gpt alone, was found to be capable of transforming NIH 3T3 cells. Finally, a brief investigation of the effect of a "functional EJ-ras gene upon the differentiated phenotypes of these cell lines was attempted by comparing their ability to produce an extracellular matrix.

Much effort has been spent over the last decade in producing so called "Machine Vision" systems for use in robotics, automated inspection, assembly and numerous other fields. Because of the large amount of data involved in an image (typically ¼ MByte) and the complexity of many algorithms used, the processing times required have been far in excess of real time on a VAX-class serial processor. We review a number of image understanding algorithms that compute a globally defined "state", and show that they may be computed using simple local operations that are suited to parallel implementation. In recent years, many massively parallel machines have been designed to apply local operations rapidly across an image. We review several vision machines. We develop an algebraic analysis of the performance of a vision machine and show that, contrary to the commonly-held belief, the time taken to relay images between serial streams can exceed by far the time spent processing. We proceed to investigate the roles that a variety of pipelining techniques might play. We then present three pipelined designs for vision, one of which has been built. This is a parallel pipelined bit slice convolution processor, capable of operating at video rates. This design is examined in detail, and its performance analysed in relation to the theoretical framework of the preceeding chapters. The construction and debugging of the device, which is now operational in its hardware is detailed.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2005. / Härtill 4 uppsatser.