63 research outputs found

    A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect

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    Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.Seventh Framework Programme (European Commission) (Grant HEALTH-F5-2010-258236-SYSCOL)Seventh Framework Programme (European Commission) (Grant HEALTH-F2-2011-259015-COLTHERES)Cellex FoundationOlga Torres FoundationEuropean Research Council (EPINORC Project Grant Agreement 268626)Spain. Ministerio de Economia y Competividad (MINECO Project SAF2011-22803)Institute of Health Carlos III (RTICC Grant RD12/0036/0039

    Branch xylem density variations across Amazonia

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    International audienceMeasurements of branch xylem density, Dx, were made for 1466 trees representing 503 species, sampled from 80 sites across the Amazon basin. Measured values ranged from 240 kg m?3 for a Brosimum parinarioides from Tapajos in West ParĂĄ, Brazil to 1130 kg m?3 for an Aiouea sp. from Caxiuana, Central ParĂĄ, Brazil. Analysis of variance showed significant differences in average Dx across the sample plots as well as significant differences between families, genera and species. A partitioning of the total variance in the dataset showed that geographic location and plot accounted for 33% of the variation with species identity accounting for an additional 27%; the remaining "residual" 40% of the variance accounted for by tree to tree (within species) variation. Variations in plot means, were, however, hardly accountable at all by differences in species composition. Rather, it would seem that variations of xylem density at plot level must be explained by the effects of soils and/or climate. This conclusion is supported by the observation that the xylem density of the more widely distributed species varied systematically from plot to plot. Thus, as well as having a genetic component branch xylem density is a plastic trait that, for any given species, varies according to where the tree is growing and in a predictable manner. Exceptions to this general rule may be some pioneers belonging to Pourouma and Miconia and some species within the genera Brosimum, Rinorea and Trichillia which seem to be more constrained in terms of this plasticity than most species sampled as part of this study

    The genetic structure and adaptation of Andean highlanders and Amazonian dwellers is influenced by the interplay between geography and culture

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    Western South America was one of the worldwide cradles of civilization. The well known Inca Empire was the tip of the iceberg of a cultural and biological evolutionary process that started 14-11 thousand years ago. Genetic data from 18 Peruvian populations reveal that: (1) The between-population homogenization of the central-southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes and Amazonia accompanied cultural and socioeconomic interactions revealed by archeological studies. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower; and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia (2). The genetic homogenization between the populations of the arid Andes is not only due to migration during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the pre-Inca Wari Empire (600-1000 YBP) (3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, HAND2-AS1 (heart and neural crest derivatives expressed 2 antisense RNA1, related with cardiovascular function) and DUOX2 (dual oxidase 2, related to thyroid function and innate immunity) genes; in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T/B lymphocytes in viral-host interaction, consistent with the host-virus arms race hypothesis

    Refining tools for studying cuttlefish ( Sepia officinalis ) reproduction in captivity: in vivo sexual determination, tagging and DNA collection

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    To overcome the bottleneck of reproduction in cuttlefish, Sepia officinalis, aquaculture development, there is need for new tools or refinement of methods. While attaining low welfare impact on individuals, procedures to allow for in vivo individual sexual and maturity determination, tagging and collection of samples for high quality DNA are needed. The present study evaluated the use of an endoscope, visual implant elastomer and swabbing for each, respectively, in a set of 3 experiments that registered its effects on growth, mortality and reproduction. Results showed that all the methodologies tested herein were of easy application, did not promote injuries nor poor growth, abnormal reproduction or increased mortality. This indicates that cuttlefish would not be experiencing pain, suffering, distress and lasting harm (PSDLH), resulting from the application of these procedures and that these are therefore recommended as new standards for reproduction studies in the species.info:eu-repo/semantics/publishedVersio
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