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Conflitos Armados , Neurociências , Editoração , Pesquisadores , Conflitos Armados/psicologia , Pesquisadores/psicologia , Federação Russa , Ucrânia , Laboratórios , Humanos , MasculinoRESUMO
We must start publishing ethnicity data for covid-19 vaccinations to make sure no group is treated unfairly, says Layal Liverpool.
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Inequalities mean a disproportionate number of covid-19 patients are from minority ethnic backgrounds, reports Layal Liverpool.
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The UK government ignored scientific advice and is bringing in three levels of restrictions for England, reports Layal Liverpool.
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Nucleic acids derived from microorganisms are powerful triggers for innate immune responses. Proteins called RNA and DNA sensors detect foreign nucleic acids and, in mammalian cells, include RIG-I, cGAS, and AIM2. On binding to nucleic acids, these proteins initiate signaling cascades that activate host defense responses. An important aspect of this defense program is the production of cytokines such as type I interferons and IL-1ß. Studies conducted over recent years have revealed that nucleic acid sensors also activate programmed cell death pathways as an innate immune response to infection. Indeed, RNA and DNA sensors induce apoptosis, pyroptosis, and necroptosis. Cell death via these pathways prevents replication of pathogens by eliminating the infected cell and additionally contributes to the release of cytokines and inflammatory mediators. Interestingly, recent evidence suggests that programmed cell death triggered by nucleic acid sensors plays an important role in a number of noninfectious pathologies. In addition to nonself DNA and RNA from microorganisms, nucleic acid sensors also recognize endogenous nucleic acids, for example when cells are damaged by genotoxic agents and in certain autoinflammatory diseases. This review article summarizes current knowledge on the links between nucleic acid sensing and cell death and explores important open questions for future studies in this area.
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Morte Celular/genética , Imunidade Inata/genética , Ácidos Nucleicos/genética , Proteína DEAD-box 58/química , Proteína DEAD-box 58/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Humanos , Interferon Tipo I/genética , Interleucina-1beta/genética , Ácidos Nucleicos/química , Nucleotidiltransferases/química , Nucleotidiltransferases/genética , Proteínas de Ligação a RNA/genética , Receptores ImunológicosRESUMO
Nucleic acids are potent triggers for innate immunity. Double-stranded DNA and RNA adopt different helical conformations, including the unusual Z-conformation. Z-DNA/RNA is recognised by Z-binding domains (ZBDs), which are present in proteins implicated in antiviral immunity. These include ZBP1 (also known as DAI or DLM-1), which induces necroptosis, an inflammatory form of cell death. Using reconstitution and knock-in models, we report that mutation of key amino acids involved in Z-DNA/RNA binding in ZBP1's ZBDs prevented necroptosis upon infection with mouse cytomegalovirus. Induction of cell death was cell autonomous and required RNA synthesis but not viral DNA replication. Accordingly, ZBP1 directly bound to RNA via its ZBDs. Intact ZBP1-ZBDs were also required for necroptosis triggered by ectopic expression of ZBP1 and caspase blockade, and ZBP1 cross-linked to endogenous RNA These observations show that Z-RNA may constitute a molecular pattern that induces inflammatory cell death upon sensing by ZBP1.