Ouabain-sensitive fatty acid release from isolated fat cells

Résumé La mobilisation des acides gras libres (FFA) induite par les hormones lipolytiques dans les cellules adipeuses isolées est inhibée par l'adjonction d'ouabaÏne. Le transport des FFA hors de la cellule semble lié en partie à la pompe Na⁺-K⁺. Une hypothèse sur le mode d'action de l'ouabaÏne est discutée.

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This work has been supported by the Fonds National Suisse de la Recherche Scientifique, Grant No. 3244, Bern (Switzerland) and by a grant-in-aid from the Fondation Emil Barell pour le Développement des Recherches Médico-Scientifiques, Basel (Switzerland).     

Colorectal carcinomas in mice lacking the catalytic subunit of PI(3)Kgamma

Phosphoinositide-3-OH kinases (PI(3)Ks) constitute a family of evolutionarily conserved lipid kinases that regulate a vast array of fundamental cellular responses, including proliferation, transformation, differentiation and protection from apoptosis. PI(3)K-mediated activation of the cell survival kinase PKB/Akt, and negative regulation of PI(3)K signalling by the tumour suppressor PTEN (refs 3, 4) are key regulatory events in tumorigenesis. Thus, a model has arisen that PI(3)Ks promote development of cancers. Here we report that genetic inactivation of the p110gamma catalytic subunit of PI(3)Kgamma (ref. 8) leads to development of invasive colorectal adenocarcinomas in mice. In humans, p110gamma protein expression is lost in primary colorectal adenocarcinomas from patients and in colon cancer cell lines. Overexpression of wild-type or kinase-dead p110gamma in human colon cancer cells with mutations of the tumour suppressors APC and p53, or the oncogenes beta-catenin and Ki-ras, suppressed tumorigenesis. Thus, loss of p110gamma in mice leads to spontaneous, malignant epithelial tumours in the colorectum and p110gamma can block the growth of human colon cancer cells.     

Bv8 regulates myeloid-cell-dependent tumour angiogenesis

Bone-marrow-derived cells facilitate tumour angiogenesis, but the molecular mechanisms of this facilitation are incompletely understood. We have previously shown that the related EG-VEGF and Bv8 proteins, also known as prokineticin 1 (Prok1) and prokineticin 2 (Prok2), promote both tissue-specific angiogenesis and haematopoietic cell mobilization. Unlike EG-VEGF, Bv8 is expressed in the bone marrow. Here we show that implantation of tumour cells in mice resulted in upregulation of Bv8 in CD11b+Gr1+ myeloid cells. We identified granulocyte colony-stimulating factor as a major positive regulator of Bv8 expression. Anti-Bv8 antibodies reduced CD11b+Gr1+ cell mobilization elicited by granulocyte colony-stimulating factor. Adenoviral delivery of Bv8 into tumours was shown to promote angiogenesis. Anti-Bv8 antibodies inhibited growth of several tumours in mice and suppressed angiogenesis. Anti-Bv8 treatment also reduced CD11b+Gr1+ cells, both in peripheral blood and in tumours. The effects of anti-Bv8 antibodies were additive to those of anti-Vegf antibodies or cytotoxic chemotherapy. Thus, Bv8 modulates mobilization of CD11b+Gr1+ cells from the bone marrow during tumour development and also promotes angiogenesis locally.     

Iron meteorite evidence for early formation and catastrophic disruption of protoplanets

In our Solar System, the planets formed by collisional growth from smaller bodies. Planetesimals collided to form Moon-to-Mars-sized protoplanets in the inner Solar System in 0.1-1 Myr, and these collided more energetically to form planets. Insights into the timing and nature of collisions during planetary accretion can be gained from meteorite studies. In particular, iron meteorites offer the best constraints on early stages of planetary accretion because most are remnants of the oldest bodies, which accreted and melted in <1.5 Myr, forming silicate mantles and iron-nickel metallic cores. Cooling rates for various groups of iron meteorites suggest that if the irons cooled isothermally in the cores of differentiated bodies, as conventionally assumed, these bodies were 5-200 km in diameter. This picture is incompatible, however, with the diverse cooling rates observed within certain groups, most notably the IVA group, but the large uncertainties associated with the measurements do not preclude it. Here we report cooling rates for group IVA iron meteorites that range from 100 to 6,000 K Myr(-1), increasing with decreasing bulk Ni. Improvements in the cooling rate model, smaller error bars, and new data from an independent cooling rate indicator show that the conventional interpretation is no longer viable. Our results require that the IVA meteorites cooled in a 300-km-diameter metallic body that lacked an insulating mantle. This body probably formed approximately 4,500 Myr ago in a 'hit-and-run' collision between Moon-to-Mars-sized protoplanets. This demonstrates that protoplanets of approximately 10(3) km size accreted within the first 1.5 Myr, as proposed by theory, and that fragments of these bodies survived as asteroids.