39 research outputs found

    PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice.

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    B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes, such as Rfx7, a transcription factor, and Phip, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology

    Aportaciones a la flora vascular del norte de la Península Ibérica

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    Se citan varios taxones nuevos o interesantes de la flora vascular del norte de la Península Ibérica, concretamente de las provincias vascas de Álava, Vizcaya y Guipúzcoa y de las comunidades de Cantabria, Asturias, Castilla-León y Navarra

    Aportaciones a la flora vascular de Álava, Burgos, Navarra y Soria

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    Se citan varios taxones nuevos o interesantes de la flora vascular de las provincias y territorios de Álava, Burgos, Navarra, Sori

    Aportaciones a la flora vascular de Vizcaya, Guipúzcoa y Cantabria (III)

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    Se citan varios taxones nuevos o interesantes para la flora vascular de las provincias vascas de Vizcaya y Guipúzcoa y la comunidad de Cantabri

    Fluorescent protein vectors for promoter analysis in lactic acid bacteria and Escherichia coli

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    Fluorescent reporter genes are valuable tools for real-time monitoring of gene expression in living cells. In this study we describe the construction of novel promoter-probe vectors containing a synthetic mCherry fluorescent protein gene, codon-optimized for lactic acid bacteria, divergently linked, or not, to a gene encoding the S65T and F64L variant of the green fluorescent protein. The utility of the transcriptional fusion vectors was demonstrated by the cloning of a single or two divergent promoter regions and by the quantitative evaluation of fluorescence during growth of Lactococcus lactis, Enterococcus faecalis, and Escherichia coli

    Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice

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    The mouse ortholog of human FACE-1, Zmpste24, is a multi-spanning membrane protein widely distributed in mammalian tissues and structurally related to Afc1p/ste24p, a yeast metalloproteinase involved in the maturation of fungal pheromones. Disruption of the gene Zmpste24 caused severe growth retardation and premature death in homozygous-null mice. Histopathological analysis of the mutant mice revealed several abnormalities, including dilated cardiomyopathy, muscular dystrophy and lipodystrophy. These alterations are similar to those developed by mice deficient in A-type lamin, a major component of the nuclear lamina, and phenocopy most defects observed in humans with diverse congenital laminopathies. In agreement with this finding, Zmpste24-null mice are defective in the proteolytic processing of prelamin A. This deficiency in prelamin A maturation leads to the generation of abnormalities in nuclear architecture that probably underlie the many phenotypes observed in both mice and humans with mutations in the lamin A gene. These results indicate that prelamin A is a specific substrate for Zmpste24 and demonstrate the usefulness of genetic approaches for identifying the in vivo substrates of proteolytic enzymes.link_to_subscribed_fulltex

    Fluorescent protein vectors for promoter analysis in lactic acid bacteria and Escherichia coli

    No full text
    Fluorescent reporter genes are valuable tools for real-time monitoring of gene expression in living cells. In this study we describe the construction of novel promoter-probe vectors containing a synthetic mCherry fluorescent protein gene, codon-optimized for lactic acid bacteria, divergently linked, or not, to a gene encoding the S65T and F64L variant of the green fluorescent protein. The utility of the transcriptional fusion vectors was demonstrated by the cloning of a single or two divergent promoter regions and by the quantitative evaluation of fluorescence during growth of Lactococcus lactis, Enterococcus faecalis, and Escherichia coli

    Towards a participatory integrated assessment approach for planning and managing Natura 2000 network sites

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    Managing protected areas implies dealing with complex social-ecological systems where multiple dimensions (social, institutional, economic and ecological) interact over time for the delivery of ecosystem services. Uni-dimensional and top-down management approaches have been unable to capture this complexity. Instead, new integrated approaches that acknowledge the diversity of social actors in the decision making process are required. In this paper we put forward a novel participatory assessment approach which integrates multiple methodologies to reflect different value articulating institutions in the case of a Natura 2000 network site in the Basque Country. It integrates within a social multi-criteria evaluation framework, both the economic values of ecosystem services through a choice experiment model and ecological values by means of a spatial bio-geographic assessment. By capturing confronting social and institutional conflicts in protected areas the participatory integrated assessment approach presented here can help decision makers for better planning and managing Natura 2000 sites.Funding provided by IHOBE (Basque Environmental Agency) through the research project coded as OTRI 2008.0101 (UPV/EHU)
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