4,957 research outputs found

    Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways

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    Rab family guanosine triphosphatases (GTPases) together with their regulators define specific pathways of membrane traffic within eukaryotic cells. In this study, we have investigated which Rab GTPase-activating proteins (GAPs) can interfere with the trafficking of Shiga toxin from the cell surface to the Golgi apparatus and studied transport of the epidermal growth factor (EGF) from the cell surface to endosomes. This screen identifies 6 (EVI5, RN-tre/USP6NL, TBC1D10A–C, and TBC1D17) of 39 predicted human Rab GAPs as specific regulators of Shiga toxin but not EGF uptake. We show that Rab43 is the target of RN-tre and is required for Shiga toxin uptake. In contrast, RabGAP-5, a Rab5 GAP, was unique among the GAPs tested and reduced the uptake of EGF but not Shiga toxin. These results suggest that Shiga toxin trafficking to the Golgi is a multistep process controlled by several Rab GAPs and their target Rabs and that this process is discrete from ligand-induced EGF receptor trafficking

    Large-Scale Magnetic-Field Generation by Randomly Forced Shearing Waves

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    A rigorous theory for the generation of a large-scale magnetic field by random non-helically forced motions of a conducting fluid combined with a linear shear is presented in the analytically tractable limit of low Rm and weak shear. The dynamo is kinematic and due to fluctuations in the net (volume-averaged) electromotive force. This is a minimal proof-of-concept quasilinear calculation aiming to put the shear dynamo, a new effect recently found in numerical experiments, on a firm theoretical footing. Numerically observed scalings of the wavenumber and growth rate of the fastest growing mode, previously not understood, are derived analytically. The simplicity of the model suggests that shear dynamo action may be a generic property of sheared magnetohydrodynamic turbulence.Comment: Paper substantially rewritten, results changed (relative to v1). Revised versio

    The History of Farm Foxes Undermines the Animal Domestication Syndrome

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    The Russian Farm-Fox Experiment is the best known experimental study in animal domestication. By subjecting a population of foxes to selection for tameness alone, Dimitry Belyaev generated foxes that possessed a suite of characteristics that mimicked those found across domesticated species. This \u27domestication syndrome\u27 has been a central focus of research into the biological pathways modified during domestication. Here, we chart the origins of Belyaev\u27s foxes in eastern Canada and critically assess the appearance of domestication syndrome traits across animal domesticates. Our results suggest that both the conclusions of the Farm-Fox Experiment and the ubiquity of domestication syndrome have been overstated. To understand the process of domestication requires a more comprehensive approach focused on essential adaptations to human-modified environments

    International Labor Standards, Soft Regulation, and National Government Roles

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    [Excerpt] In this article, we briefly describe the different approaches to the regulation of international labor standards, and then argue for a new role for national governments based on soft rather than hard regulation approaches. We argue that this new role shows potential for significantly enhancing progress in international labor standards, since it enables governments to articulate a position without having to deal with the enforcement issues that hard regulation mandates. We justify this new role for governments based on the increasing use of soft regulation in the international arena. Of course, this approach is not without its own problems, but given that existing approaches have all provided imperfect solutions to the problem of improving labor standards globally, re-visiting the role of national governments is in our view, highly important

    Mechanical Instabilities of Biological Tubes

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    We study theoretically the shapes of biological tubes affected by various pathologies. When epithelial cells grow at an uncontrolled rate, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated : varicose, enlarged, sinusoidal or sausage-like, all of which are found in pathologies of tracheal, renal tubes or arteries. The final shape depends crucially on the mechanical parameters of the tissues : Young modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation