Morenokloster0391

Mechanistically, mNPC-exos were specifically internalized by retinal microglia and suppressed their activation in vitro and in vivo. RNA sequencing and miRNA profiling revealed a set of 17 miRNAs contained in mNPC-exos that markedly inhibited inflammatory signal pathways by targeting TNF-α, IL-1β, and COX-2 in activated microglia. The exosomes derived from hNPC (hNPC-exos) contained similar miRNAs to mNPC-exos that inhibited microglial activation. We demonstrated that NPC-exos markedly suppressed microglial activation to protect photoreceptors from apoptosis, suggesting that NPC-exos and their contents may be the mechanism of stem cell therapy for treating RD. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.K-Ras is the most frequently mutated protein in human cancers. However, until very recently, its oncogenic mutants were viewed as undruggable. To develop inhibitors that directly target oncogenic K-Ras mutants, we need to understand both their mutant-specific and pan-mutant dynamics and conformations. Recently, we have investigated how the most frequently observed K-Ras mutation in cancer patients, G12D, changes its local dynamics and conformations (Vatansever et al., 2019). Here, we extend our analysis to study and compare the local effects of other frequently observed oncogenic mutations, G12C, G12V, G13D and Q61H. For this purpose, we have performed Molecular Dynamics (MD) simulations of each mutant when active (GTP-bound) and inactive (GDP-bound), analyzed their trajectories, and compared how each mutant changes local residue conformations, inter-protein distance distributions, local flexibility and residue pair correlated motions. Our results reveal that in the four active oncogenic mutants we have studied, the α2 helix moves closer to the C-terminal of the α3 helix. However, P-loop mutations cause α3 helix to move away from Loop7, and only G12 mutations change the local conformational state populations of the protein. Furthermore, the motions of coupled residues are mutant-specific G12 mutations lead to new negative correlations between residue motions, while Q61H destroys them. Overall, our findings on the local conformational states and protein dynamics of oncogenic K-Ras mutants can provide insights for both mutant-selective and pan-mutant targeted inhibition efforts. © 2020 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.We present MaREA4Galaxy, a user-friendly tool that allows a user to characterize and to graphically compare groups of samples with different transcriptional regulation of metabolism, as estimated from cross-sectional RNA-seq data. The tool is available as plug-in for the widely-used Galaxy platform for comparative genomics and bioinformatics analyses. MaREA4Galaxy combines three modules. The Expression2RAS module, which, for each reaction of a specified set, computes a Reaction Activity Score (RAS) as a function of the expression level of genes encoding for the associated enzyme. The MaREA (Metabolic Reaction Enrichment Analysis) module that allows to highlight significant differences in reaction activities between specified groups of samples. The Clustering module which employs the RAS computed before as a metric for unsupervised clustering of samples into distinct metabolic subgroups; the Clustering tool provides different clustering techniques and implements standard methods to evaluate the goodness of the results. © 2020 The Authors.Few reports describe the clinical course and acute-care management of patients with recurrent multi-antibody paraneoplastic encephalitis. We describe a rare case of a patient having thymoma with multiple paraneoplastic syndromes who was found to have antibodies to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) followed by N-methyl-d-aspartate (NMDA) receptor in the setting of residual thymic tissue. He initially presented to the hospital with severe, rapidly progressive encephalitis with simultaneous antibodies to AMPA and voltage-gated potassium channel complex receptor. Brain magnetic resonance imaging revealed scattered white matter hyperintensities and an enhancing lesion adjacent to the left caudate. Computerized tomography showed an anterior mediastinal mass that was resected and revealed to be a thymoma. He was refractory to treatment with intravenous immunoglobulin, high-dose steroids, and plasmapheresis. He was then started on monthly cyclophosphamide. After 3 cyclophosphamide infusions, he began to show improvement in his alertness, ability to speak, and capacity to follow commands. One month later, he was readmitted to the hospital for new and unusual behavioral outbursts and agitation. He was found to have new anti-NMDA receptor antibodies in his cerebrospinal fluid in the setting of residual hyperplastic thymic tissue that required another resection. He was treated with rituximab and then cyclophosphamide (due to an infusion reaction with rituximab) with positive outcomes. The presence of multiple antibodies may be associated with poor prognosis, requiring prompt recognition and aggressive immunosuppressive treatment. New neurological symptoms should prompt a search for residual pathologic tissue or tumor recurrence causing new autoantibodies and additional paraneoplastic syndromes. © The Author(s) 2019.Herpes simplex virus encephalitis (HSVE) usually presents as a monophasic disease. Symptomatic HSVE relapsing with seizures, encephalopathy, or involuntary movements associated with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis have been recently reported. We report 2 cases of adult post-HSVE anti-NMDAR encephalitis from Portugal. Two female patients aged 50 years and 30 years were diagnosed with herpes simplex virus type 2 and type 1 encephalitis, respectively. RBPJ Inhibitor-1 mouse After the initial improvement with specific treatment and despite virologic negativization, both patients suffered clinical, electroencephalographic, and imaging deterioration. The autoimmune encephalitis hypothesis was confirmed with the demonstration of anti-NMDAR antibodies in both cerebrospinal fluid and serum. Both responded to human immunoglobulin and methylprednisolone, with progressive gain of autonomy along the follow-up period. Thymectomy for thymic hyperplasia diagnosed during follow-up was performed in 1 patient. Although being rare, post-HSVE anti-NMDAR encephalitis should be considered in all cases of symptomatic recrudescence after HSVE, since adequate immune-modulating treatment improves the outcome.