1,324 research outputs found

    Interferon-lambda: A potent regulator of intestinal viral infections

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    Interferon-lambda (IFN-位) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-位 has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-位 has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-位-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-位 interactions with other cytokines important in the intestine, and how IFN-位 may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-位 control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule

    Regulation of Smad anchor necessary for receptor activation (SARA) protein levels by the E3 ubiquitin-protein ligase Smurf2 and Smad7

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    The TGF尾 pathway, which regulates cell proliferation and differentiation, has also been shown to induce non-small cell lung cancer cell (NSCLC) migration and invasion. The TGF尾 pathway is initiated through the binding of TGF尾 to cell surface Ser/Thr kinase receptors. Activated receptors then phosphorylate intracellular signaling proteins, termed Smads, which translocate into the nucleus to regulate transcriptional responses. The protein Smad anchor for receptor activation (SARA) facilitates the phosphorylation of Smads and allows for efficient signal transduction. On the other hand, the inhibitory Smad, Smad7, recruits the E3 ubiquitin ligase, Smurf2, to catalyze the degradation of TGF尾 receptors. Since the signaling and degradation pathways target active receptor complexes, SARA and Smurf2-Smad7 may interact with common TGF尾 receptors. Therefore, the Smurf2-Smad7 complex may affect SARA steady state levels and influence TGF尾 signaling. I hypothesized that Smurf2-Smad7 induces SARA degradation through an ubiquitin-dependent pathway. I observed that SARA steady state levels decrease in the presence of Smurf2 and Smad7, and this is dependent on the HECT E3 ubiquitin ligase activity of Smurf2. In addition, I observed that SARA interacts with ubiquitinated proteins and is protected from degradation by the pharmacological inhibition of the proteasome. Finally, I assessed the functional outcome of reducing endogenous SARA levels. I observed that siRNA directed at SARA decreased both TGF尾-dependent Smad2 phosphorylation as well as EMT. These data suggest that the interplay between SARA and Smurf2-Smad7 complexes can influence TGF尾 receptor signaling and may provide for a novel approach in targeting this pathway in NSCLC

    Numerical Simulations of Bouncing Jets

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    Bouncing jets are fascinating phenomenons occurring under certain conditions when a jet impinges on a free surface. This effect is observed when the fluid is Newtonian and the jet falls in a bath undergoing a solid motion. It occurs also for non-Newtonian fluids when the jets falls in a vessel at rest containing the same fluid. We investigate numerically the impact of the experimental setting and the rheological properties of the fluid on the onset of the bouncing phenomenon. Our investigations show that the occurrence of a thin lubricating layer of air separating the jet and the rest of the liquid is a key factor for the bouncing of the jet to happen. The numerical technique that is used consists of a projection method for the Navier-Stokes system coupled with a level set formulation for the representation of the interface. The space approximation is done with adaptive finite elements. Adaptive refinement is shown to be very important to capture the thin layer of air that is responsible for the bouncing
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