223 research outputs found

    A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation

    Get PDF
    The chronic induction of inflammation underlies multiple pathological conditions, including metabolic, autoimmune disorders and cancer. The mitochondrial citrate carrier (CIC), encoded by the SLC25A1 gene, promotes the export of citrate from the mitochondria to the cytoplasm, a process that profoundly influences energy balance in the cells. We have previously shown that SLC25A1 is a target gene for lipopolysaccharide signaling and promotes the production of inflammatory mediators. We now demonstrate that SLC25A1 is induced at the transcriptional level by two key pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ), and such induction involves the activity of the nuclear factor kappa B and STAT1 transcription factors. By studying the down-stream events following SLC25A1 activation during signals that mimic inflammation, we demonstrate that CIC is required for regulating the levels of nitric oxide and of prostaglandins by TNFα or IFNγ. Importantly, we show that the citrate exported from mitochondria via CIC and its downstream metabolic intermediate, acetyl-coenzyme A, are necessary for TNFα or IFNγ to induce nitric oxide and prostaglandin production. These findings provide the first line of evidence that the citrate export pathway, via CIC, is central for cytokine-induced inflammatory signals and shed new light on the relationship between energy metabolism and inflammation

    The indentation rolling resistance in belt conveyors: A model for the viscoelastic friction

    Get PDF
    In this paper, we study the steady-state rolling contact of a linear viscoelastic layer of finite thickness and a rigid indenter made of a periodic array of equally spaced rigid cylinders. The viscoelastic contact model is derived by means of Green’s function approach, which allows solving the contact problem with the sliding velocity as a control parameter. The contact problem is solved by means of an accurate numerical procedure developed for general two-dimensional contact geometries. The effect of geometrical quantities (layer thickness, cylinders radii, and cylinders spacing), material properties (viscoelastic moduli, relaxation time) and operative conditions (load, velocity) are all investigated. Physical quantities typical of contact problems (contact areas, deformed profiles, etc.) are calculated and discussed. Special emphasis is dedicated to the viscoelastic friction force coefficient and to the energy dissipated per unit time. The discussion is focused on the role played by the deformation localized at the contact spots and the one in the bulk of the thin layer, due to layer bending. The model is proposed as an accurate solution for engineering applications such as belt conveyors, in which the energy dissipated on the rolling contact of idle rollers can, in some cases, be by far the most important contribution to their energy consumption

    Dynamically induced friction reduction in micro-structured interfaces

    Get PDF
    We investigate the dynamic behavior of a regular array of in-plane elastic supports interposed between a sliding rigid body and a rigid substrate. Each support is modelled as a mass connected to a fixed pivot by means of radial and tangential elastic elements. Frictional interactions are considered at the interface between the supports and the sliding body. Depending on the specific elastic properties of the supports, different dynamic regimes can be achieved, which, in turn, affect the system frictional behavior. Specifically, due to transverse microscopic vibration of the supports, a lower friction force opposing the macroscopic motion of the rigid body can be achieved compared to the case where no supports are present and rubbing occurs with the substrate. Furthermore, we found that the supports static orientation plays a key role in determining the frictional interactions, thus offering the chance to specifically design the array aiming at controlling the resulting interfacial friction force

    Dynamic political contexts and power asymmetries: the cases of the Blue Nile and the Yarmouk Rivers

    Get PDF
    This paper explores the evolving patterns of hydropolitical relations in the dynamic contexts of Yarmouk and Blue Nile Rivers in comparison. The analysis aims at shedding light over the complex implications that recent political and social changes have aroused for the water disputes between Jordan and Syria on the one hand, and Ethiopia and Egypt on the other. In both basins, cooperative efforts toward the integrated management of transboundary waters have been only partially effective and largely undermined by the perpetuation of unilateral actions by riparian states. In the case studies, the lack of a basin-wide vision over the control and use of shared waters has resulted in disputes among the basin states and ultimately in an unsustainable, unfair, and unwise utilization of the resources. This paper argues that a substantive and effective integration of national water policies is unlikely to occur, unless power asymmetries are properly addressed in order to overcome the likelihood of hegemonic regimes
    • …
    corecore