258 research outputs found

    Multiple Cancer Testis Antigens Function To Support Tumor Cell Mitotic Fidelity

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    While the expression of genes that are normally involved in spermatogenesis is frequently detected in tumors, the extent to which these gene products are required for neoplastic behaviors is unclear. To begin to address their functional relevance to tumorigenesis, we identified a cohort of proteins which display synthetic lethality with paclitaxel in non-small-cell lung cancer and whose expression is biased toward testes and tumors. Remarkably, these testis proteins, FMR1NB, NXF2, MAGEA5, FSIP1, and STARD6, are required for accurate chromosome segregation in tumor cells. Their individual depletion enhances the generation of multipolar spindles, increases mitotic transit time, and induces micronucleation in response to an otherwise innocuous dose of paclitaxel. The underlying basis for abnormal mitosis is an alteration in microtubule function, as their depletion increases microtubule cytaster formation and disrupts microtubule stability. Given these observations, we hypothesize that reactivated testis proteins may represent unique tumor cell vulnerabilities which, if targeted, could enhance responsiveness to antimitotic therapy. Indeed, we demonstrate that combining paclitaxel with a small-molecule inhibitor of the gametogenic and tumor cell mitotic protein TACC3 leads to enhanced centrosomal abnormalities, activation of death programs, and loss of anchorage-independent growth

    Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example

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    Childhood stressors including physical abuse predict adult cancer risk. Prior research portrays this finding as indirect through coping behaviors including adult smoking or through increased toxic exposures during childhood. Little is known about potential direct causal mechanisms between early-life stressors and adult cancer. Because prenatal conditions can affect gene expression by altering DNA methylation with implications for adult health, we hypothesize that maternal stress may program methylation of cancer-linked genes during gametogenesis

    Proposing a systems vision of knowledge management in emergency care

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    This paper makes a case for taking a systems view of knowledge management within health-care provision, concentrating on the emergency care process in the UK National Health Service. It draws upon research in two casestudy organizations (a hospital and an ambulance service). The case-study organizations appear to be approaching knowledge (and information) management in a somewhat fragmented way. They are trying to think more holistically, but (perhaps) because of the ways their organizations and their work are structured, they cannot ‘see’ the whole of the care process. The paper explores the complexity of knowledge management in emergency health care and draws the distinction for knowledge management between managing local and operational knowledge, and global and clinical knowledge

    Making a journey in knowledge management strategy

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    This paper reports results from an ongoing project examining what managers think about knowledge management in the context of their organisation. This was done in a facilitated computerassisted group workshop environment. Here we compare the outcomes of workshops held for two relatively large UK organisations, one public sector and the other private. Our conclusions are that there are relatively few differences between the perceptions of these two groups of managers, and that these differences stem more from the stage of the knowledge management life cycle that the two organisations have reached, rather than from the difference in context between public and private sector. © iKMS & World Scientific Publishing Co

    DNA methylation in insects

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    Cytosine DNA methylation has been demonstrated in numerous eukaryotic organisms and has been shown to play an important role in human disease. The function of DNA methylation has been studied extensively in vertebrates, but establishing its primary role has proved difficult and controversial. Analysing methylation in insects has indicated an apparent functional diversity that seems to argue against a strict functional conservation. To investigate this hypothesis, we here assess the data reported in four different insect species in which DNA methylation has been analysed more thoroughly: the fruit fly Drosophila melanogaster, the cabbage moth Mamestra brassicae, the peach-potato aphid Myzus persicae and the mealybug Planococcus citri

    Managing software engineers and their knowledge

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    This chapter begins by reviewing the history of software engineering as a profession, especially the so-called software crisis and responses to it, to help focus on what it is that software engineers do. This leads into a discussion of the areas in software engineering that are problematic as a basis for considering knowledge management issues. Some of the previous work on knowledge management in software engineering is then examined, much of it not actually going under a knowledge management title, but rather “learning” or “expertise”. The chapter goes on to consider the potential for knowledge management in software engineering and the different types of knowledge management solutions and strategies that might be adopted, and it touches on the crucial importance of cultural issues. It concludes with a list of challenges that knowledge management in software engineering needs to address
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