leads to ISGylation of BECN1 at Lys117, as well as Lys263, Lys265, and Lys266 which competes with Lys63 ubiquitination of BECN1. We demonstrate that ISGylation of BECN1 at Lys117, as well as Lys263, Lys265, and Lys266 serve an important role in negative regulation of intracellular processes including autophagy and EGFR degradation that are critically dependent upon the activity of class III PtdIns 3-kinase. Our studies provide fundamental new mechanistic insights into the innate immunity response implemented by type I IFNs.1f:T421,Spinal cord injury (SCI) is a traumatic lesion that can result in the loss of motor or sensory neurons. Stem cell (SC)-based therapies have been demonstrated to promote neuronal regeneration following SCI, by releasing a range of trophic factors that support endogenous repair or by differentiating into neurons, or glial cells in order to replace the damaged cells. However, numerous limitations remain for therapies based on SC transplantion alone, including a low rate of survival/engraftment. Nevertheless, scaffolds are 3-dimentional substrates that have revealed to support cell survival, proliferation and differentiation in vivo, by mimicking a more favorable endogenous microenvironment. A multidisciplinary approach, which combines engineered scaffolds with SCs has been proposed as a promising strategy for encouraging spinal cord regeneration. The present review has focused on the regenerative potential of mesenchymal SCs isolated from different sources and combined with various scaffold types, in preclinical and clinical SCI studies.20:T4e6,Type I interferon (IFN-I) signaling paradoxically impairs host immune responses during many primary and secondary bacterial infections. Lack of IFN-I receptor reduces bacterial replication and/or bacterial persistence during infection with several bacteria. However, the mechanisms that mediate the adverse IFN-I effect are incompletely understood. Here, we show that Usp18, an interferon-stimulated gene that negatively regulates IFN-I signaling, is primarily responsible for the deleterious effect of IFN-I signaling during infection of mice with Listeria monocytogenes or Staphylococcus aureus Mechanistically, USP18 promoted bacterial replication by inhibiting antibacterial tumor necrosis factor-α (TNF-α) signaling. Deleting IFNAR1 or USP18 in CD11c-Cre⁺ cells similarly reduced bacterial titers in multiple organs and enhanced survival. Our results demonstrate that inhibiting USP18 function can promote control of primary and secondary bacterial infection by enhancing the antibacterial effect of TNF-α, which correlates with induction of reactive oxygen species (ROS). These findings suggest that USP18 could be targeted therapeutically in patients to ameliorate disease caused by serious bacterial infections.

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