The chemotropic guidance cue netrin-1 promotes neurite outgrowth through its receptor Deleted in Colorectal Cancer (DCC) via activation of Rac1. The guanine nucleotide exchange factor (GEF) linking netrin-1/ DCC to Rac1 activation has not yet been identified. Here, we show that the RhoGEF Trio mediates Rac1 activation in netrin-1 signaling. We found that Trio interacts with the netrin-1 receptor DCC in mouse embryonic brains and that netrin-1-induced Rac1 activation in brain is impaired in the absence of Trio. Trio ؊/؊ cortical neurons fail to extend neurites in response to netrin-1, while they are able to respond to glutamate. Accordingly, netrin-1-induced commissural axon outgrowth is reduced in Trio ؊/؊ spinal cord explants, and the guidance of commissural axons toward the floor plate is affected by the absence of Trio. The anterior commissure is absent in Trio-null embryos, and netrin-1/DCC-dependent axonal projections that form the internal capsule and the corpus callosum are defective in the mutants. Taken together, these findings establish Trio as a GEF that mediates netrin-1 signaling in axon outgrowth and guidance through its ability to activate Rac1.During the development of the central nervous system, axons are guided to their targets in response to molecular cues that can be either membrane-bound factors or secreted molecules, acting over short or long distances. The neuronal growth cone is a specialized structure found at the tip of the axon that integrates attractive and repulsive signals elicited by these extracellular cues and responds to them by triggering signaling pathways that regulate growth cone motility (16,18). Netrins are a family of secreted proteins that control axon outgrowth and guidance in multiple vertebrate and invertebrate species (3). Netrin-1 is a bifunctional molecule that attracts and repels different classes of axons. In vertebrates, netrin-1 was first shown to attract commissural axons of the developing spinal cord toward the ventral midline (21, 44). Since then, netrin-1 has been shown to promote outgrowth of a wide variety of axons, including growing cortical axons (30, 41). Two families of netrin-1 receptors in mammals have been identified: the Deleted in Colorectal Cancer (DCC) family, comprising DCC and neogenin, and the UNC-5 family of proteins (1,20,25). DCC mediates growth cone attraction induced by netrin-1 (1, 20, 25, 43) whereas the repulsive effect of netrin-1 is mediated by the UNC-5 family of netrin receptors, alone or in combination with DCC (17,22,35).DCC is a transmembrane protein without any obvious catalytic activity in its intracellular domain, and for this reason, it was unclear until recently how the intracellular signaling machinery leading to axon outgrowth was initiated. This process has begun to be elucidated with the identification in cortical and commissural neurons of different DCC-binding proteins, including the protein tyrosine kinases focal adhesion kinase, Src, and Fyn; the Nck adaptor protein; and phosphatidylinositol transfer protein ␣ (26...

Liver autoimmune response can be initiated using molecular mimicry over a long period of time, validating the hit-and-run hypothesis. Initial liver inflammatory injury is neither necessary, nor detrimental to the development of AIH. These results highlight the significance of initial events on the pathogenesis of autoimmune liver injury.

Background: Endoscopic percutaneous tracheostomy (PT) is a safe technique that is performed frequently by otolaryngologists and intensivists. New challenges have been identified in order to maintain the safety of this procedure during the COVID-19 pandemic. A novel approach, using a modified demistifier canopy, was developed during the first wave of the pandemic and implemented for 17 consecutive percutaneous tracheostomies in order to enhance procedural safety. Methods: A protocol was developed after performing a literature review of tracheostomy in COVID-19 patients. A multidisciplinary tracheostomy team was established, including the departments of otolaryngology, critical care, and respiratory therapy. Simulation was performed prior to each PT, and postoperative debriefings were done. Results: A protocol and technical description of PT using a modified demistifier canopy covering was written and video documented. Data were collected on 17 patients who underwent this procedure safely in our tertiary care hospital. There were no procedure-related complications, and no evidence of COVID-19 transmission to any member of the health care team during the study period. Conclusion: As patients continue to recover from COVID-19, their need for tracheostomy will increase. The technique described provides a safe, multidisciplinary method of performing PT in COVID-19 patients.

Des symptômes de mosaïque virale ont été observés dans des champs expérimentaux de lupin (Lupinus albus) dans Test du Canada. Les plants affectés montraient des symptômes de mosaïque, de réduction et de déformation des feuilles, et de nanisme du plant. Les symptômes ont pu être reproduits en serre par inoculation mécanique sur le cultivar de lupin Ultra. Les symptômes observés sur des espèces diagnostiques, l'observation par microscopie électronique, la détection sérologique ELISA et l'analyse immunologique Western ont été utilisés pour identifier le virus présent. Un potyvirus, identifié comme le virus de la mosaïque jaune du haricot (BYMV), a été détecté dans les plants affectés. Ces résultats sont les premiers à caractériser une maladie virale du lupin au Canada. Puisque le virus est transmis par les pucerons et par la graine, la présence du virus peut devenir une limitation à la production du lupin.Virus-like symptoms were observed in fields of white lupine (Lupinus albus) in Eastern Canada. Affected plants displayed mosaic, leaf stunting and deformation, and bunchy growth habit. The disease was successfully reproduced in greenhouse by mechanical inoculation of white lupine cv. Ultra. The causal virus was identified as bean yellow mosaic virus (BYMV) by symptomatology on diagnostic species, electron microscopy, enzyme linked immunosorbent assay (ELISA) and immunodetection after Western blotting. This is the first report of a viral disease of lupine in Canada. BYMV may represent a significant limitation to lupine culture since it is transmitted by aphids and through infected seed