31 research outputs found

    mTOR: from growth signal integration to cancer, diabetes and ageing

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    In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France

    Of yeast, mice and men: MAMs come in two flavors

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    An assessment of geologic sequestration potential in the panhandle of Florida USA

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    One alternative to reduce global greenhouse gas emissions is to store the emissions in underground geologic sequestration repositories. The efficacy of this approach has been favorably evaluated by numerous authors over the last 15 years. This paper discusses an assessment of the overall feasibility of storing emissions in three different repositories in the Florida panhandle located in the Southeastern United States. The feasibility assessment evaluates both saline aquifers and oil reservoirs located in the panhandle region. The overall feasibility is driven by the available geologic sequestration capacity, the transportation cost to deliver emissions to a respective repository, and other engineering and regulatory issues. The geologic sequestration capacity is generally controlled by the so-called storage efficiency, a variable dependent on the site-specific geology, reservoir conditions, and the injected fluid characteristics. For this paper, storage efficiency for saline repositories was assessed in more detail using numerical modeling. Based on the work completed, the 3 repositories studied have at least 4.55 gigatonnes of capacity to sequester CO2

    A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1

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    Erv1 is a flavin-dependent sulfhydryl oxidase in the mitochondrial intermembrane space (IMS) that functions in the import of cysteine-rich proteins. Redox titrations of recombinant Erv1 showed that it contains three distinct couples with midpoint potentials of −320, −215, and −150 mV. Like all redox-active enzymes, Erv1 requires one or more electron acceptors. We have generated strains with erv1 conditional alleles and employed biochemical and genetic strategies to facilitate identifying redox pathways involving Erv1. Here, we report that Erv1 forms a 1:1 complex with cytochrome c and a reduced Erv1 can transfer electrons directly to the ferric form of the cytochrome. Erv1 also utilized molecular oxygen as an electron acceptor to generate hydrogen peroxide, which is subsequently reduced to water by cytochrome c peroxidase (Ccp1). Oxidized Ccp1 was in turn reduced by the Erv1-reduced cytochrome c. By coupling these pathways, cytochrome c and Ccp1 function efficiently as Erv1-dependent electron acceptors. Thus, we propose that Erv1 utilizes diverse pathways for electron shuttling in the IMS
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