44 research outputs found

    Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states.

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    Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recent cryo-EM analyses have produced near-complete models of all 45 subunits in the bovine, ovine and porcine complexes and have identified two states relevant to complex I in ischemia-reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically relevant model system, in the 'active' state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside kinase homolog, and define mechanistically critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the 'deactive' state and with known bacterial structures, we identify differences in helical geometry in the membrane domain that occur upon activation or that alter the positions of catalytically important charged residues. Our results demonstrate the capability of cryo-EM analyses to challenge and develop mechanistic models for mammalian complex I

    Pediatric T- and NK-cell lymphomas: new biologic insights and treatment strategies

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    T- and natural killer (NK)-cell lymphomas are challenging childhood neoplasms. These cancers have varying presentations, vast molecular heterogeneity, and several are quite unusual in the West, creating diagnostic challenges. Over 20 distinct T- and NK-cell neoplasms are recognized by the 2008 World Health Organization classification, demonstrating the diversity and potential complexity of these cases. In pediatric populations, selection of optimal therapy poses an additional quandary, as most of these malignancies have not been studied in large randomized clinical trials. Despite their rarity, exciting molecular discoveries are yielding insights into these clinicopathologic entities, improving the accuracy of our diagnoses of these cancers, and expanding our ability to effectively treat them, including the use of new targeted therapies. Here, we summarize this fascinating group of lymphomas, with particular attention to the three most common subtypes: T-lymphoblastic lymphoma, anaplastic large cell lymphoma, and peripheral T-cell lymphoma-not otherwise specified. We highlight recent findings regarding their molecular etiologies, new biologic markers, and cutting-edge therapeutic strategies applied to this intriguing class of neoplasms

    Dependencies Of Reservoir Oil Properties On Surface Oil

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    Knowledge of the properties of reservoir oil is necessary when calculating reserves, creating projects development, creating hydrodynamic models of development objects. Reservoir oil properties are determined by downhole samples taken, as usual, from exploration and production wells. In some cases, it is impossible to create conditions for the selection of high-quality downhole samples at exploration and production wells. In such cases, we must use samples of surface oil to obtain information about the reservoir properties of this oil. In this work and as a result of the analysis of the accumulated data, dependencies with a high degree of correlation were obtained, which make it possible to quickly assess the expected parameters of reservoir oil, having only the density of surface oil.</p

    Prospects of High Viscosity Oil Flow Rate in Horizontal Wells

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    The non-Newtonian nature of fluid flow represents one of the most important features of the development of high-viscosity oil (HVO) deposits .The deviation from the linear law of the fluid flow is associated, first of all, with the formation of a strong spatial structure due to the presence of high-molecular components and dissolved gases in the composition. The stress required to destroy the formed structure is called the shear stress of the ultimate destruction of the structure. In this regard, in order to ensure the flow of HVO through the pore space, it is necessary to create certain values of pressure gradients above the dynamic shear pressure gradient (DSPG). With increasing pressure gradients above the DSPG, the oil structure begins to collapse, and after overcoming the critical value of the pressure gradient of the ultimate destruction of the structure (PGUDS), flow begins to be described by the Newtonianlaw. The article considers the influence of various factors on the oil flow rate of a horizontal well (HW) that exploits the HVO Deposit. At the same time, numerical experiments were carried out on a hydrodynamic model for the non-Newtonian oil flow regime (in the presence of DSPG) and the results obtained were compared with calculations of the oil flow rate using an analytical formula.</p
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