Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

BACKGROUND: Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia) and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL), considers the spatial proximity of loci in interphase nuclei (static "contact first" model). The second model is based on the dynamics of double strand break ends during repair processes (dynamic "breakage first" model). Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4) and a less frequent partner gene (ENL), should elucidate the MLL translocation mechanism. METHODS: Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. RESULTS: In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value < 0.0001). According to the static "contact first" model of the translocation mechanism, a minimal distance between loci would indicate a greater probability of the occurrence of t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in contradiction to the epidemiology of 11q23 translocation. CONCLUSION: The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static "contact first" model of translocation. The recently proposed dynamic "breakage first" model offers an attractive alternative explanation

DeadEasy Mito-Glia: Automatic Counting of Mitotic Cells and Glial Cells in Drosophila

Cell number changes during normal development, and in disease (e.g., neurodegeneration, cancer). Many genes affect cell number, thus functional genetic analysis frequently requires analysis of cell number alterations upon loss of function mutations or in gain of function experiments. Drosophila is a most powerful model organism to investigate the function of genes involved in development or disease in vivo. Image processing and pattern recognition techniques can be used to extract information from microscopy images to quantify automatically distinct cellular features, but these methods are still not very extended in this model organism. Thus cellular quantification is often carried out manually, which is laborious, tedious, error prone or humanly unfeasible. Here, we present DeadEasy Mito-Glia, an image processing method to count automatically the number of mitotic cells labelled with anti-phospho-histone H3 and of glial cells labelled with anti-Repo in Drosophila embryos. This programme belongs to the DeadEasy suite of which we have previously developed versions to count apoptotic cells and neuronal nuclei. Having separate programmes is paramount for accuracy. DeadEasy Mito-Glia is very easy to use, fast, objective and very accurate when counting dividing cells and glial cells labelled with a nuclear marker. Although this method has been validated for Drosophila embryos, we provide an interactive window for biologists to easily extend its application to other nuclear markers and other sample types. DeadEasy MitoGlia is freely available as an ImageJ plug-in, it increases the repertoire of tools for in vivo genetic analysis, and it will be of interest to a broad community of developmental, cancer and neuro-biologists

Understanding innovation platform effectiveness through experiences from west and central Africa

Innovation platforms (IPs) are a way of organizing multistakeholder interactions, marshalling ideas, people and resources to address challenges and opportunities embedded in complex settings. The approach has its roots in theories of complexity, the concept of innovation systems and practices of participatory action research. IPs have been widely adopted across Africa and beyond in recent years as a “must have” tool in a range of “for development” modes of agricultural research. Our experiences with establishing and facilitating nine IPs in local settings in west and central Africa contribute to understanding factors that impact on their effectiveness. The nine IPs were variously focused on developing dairy, crop and/or meat value chains by strengthening mixed crop-livestock production systems or seed systems. Using case study methods, we identified variables that contribute to explaining the performance of these IPs in relation to six domains of change in the agricultural system and the sustainability of changes. Thematic analysis was guided by a conceptual framework which grouped variables into four categories (context, structure, conduct, and process) that interact to influence IP performance. Stronger market connections and value chains were generated through some of these IPs but the most prevalent changes overall were in farm productivity and technical knowledge of producers. The structures evolved in some IPs, akin to those of producer collectives, suggested they were filling an institutional gap locally. The effect of the IPs on deeper level institutions that influence agricultural systems and food security was modest, constraining prospects for the IPs to generate impact at scale. Impacts from the IPs on research and development organisations were uncommon but had transformative significance. Our conceptual framework did not offer optimal guidance to understanding how the many variables that contributed to performance of these IPs combined and sequenced, but the pattern of interactions was consistent with increased social capital being the prime mediator for change. Achieving greater prospects for transformational change and impact at scale warrants at least equal attention to three other interconnected change pathways: through markets, institutions and innovation capacity. Important factors for increased impact are individuals and organisations with capacity to purposefully build and manage inter-organisational and cross-scale networks, early diagnostic studies of the institutional landscape, and adaptive processes of critical reflection and learning that continue beyond the short term

Educomunicação e suas áreas de intervenção: Novos paradigmas para o diálogo intercultural

oai:omp.abpeducom.org.br:publicationFormat/1O material aqui divulgado representa, em essência, a contribuição do VII Encontro Brasileiro de Educomunicação ao V Global MIL Week, da UNESCO, ocorrido na ECA/USP, entre 3&nbsp;e 5 de novembro de 2016. Estamos diante de um conjunto de 104 papers executivos, com uma média de entre 7 e 10 páginas, cada um. Com este rico e abundante material, chegamos ao sétimo e-book publicado pela ABPEducom, em seus seis primeiros anos de existência. A especificidade desta obra é a de trazer as “Áreas de Intervenção” do campo da Educomunicação, colocando-as a serviço de uma meta essencial ao agir educomunicativo: o diálogo intercultural, trabalhado na linha do tema geral do evento internacional: Media and Information Literacy: New Paradigms for Intercultural Dialogue

The kappa agonist fedotozine modulates colonic distention-induced inhibition of gastric motility and emptying in dogs

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Influence of stress on gastric emptying depends on the nature of meals, stressors, and animal species

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Action locale des kappas agonistes sur la vidange gastrique des phases solide et liquide d'un repas conventionnel chez le chien

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