Liver Immune Cells Release Type 1 Interferon Due to DNA Sensing and Amplify Liver Injury from Acetaminophen Overdose.

Hepatocytes may rupture after a drug overdose, and their intracellular contents act as damage-associated molecular patterns (DAMPs) that lead to additional leukocyte infiltration, amplifying the original injury. Necrosis-derived DNA can be recognized as a DAMP, activating liver non-parenchymal cells (NPCs). We hypothesized that NPCs react to DNA by releasing interferon (IFN)-1, which amplifies acetaminophen (APAP)-triggered liver necrosis. We orally overdosed different knockout mouse strains to investigate the pathways involved in DNA-mediated amplification of APAP-induced necrosis. Mice were imaged under intravital confocal microscopy to estimate injury progression, and hepatocytes and liver NPCs were differentially isolated for gene expression assays. Flow cytometry (FACS) using a fluorescent reporter mouse estimated the interferon-beta production by liver leukocytes under different injury conditions. We also treated mice with DNase to investigate the role of necrosis DNA signaling in IFN-1 production. Hepatocytes released a large amount of DNA after APAP overdose, which was not primarily sensed by these cells. However, liver NPCs promptly sensed such environmental disturbances and activated several DNA sensing pathways. Liver NPCs synthesized and released IFN-1, which was associated with concomitant hepatocyte necrosis. Ablation of IFN-1 recognition in interferon α/ß receptor (IFNAR-/-) mice delayed APAP-mediated liver necrosis and dampened IFN-1 sensing pathways. We demonstrated a novel loop involving DNA recognition by hepatic NPCs and additional IFN-1 mediated hepatocyte death.

DIY: "Do Imaging Yourself" - Conventional microscopes as powerful tools for in vivo investigation.

Intravital imaging has been increasingly employed in cell biology studies and it is becoming one of the most powerful tools for in vivo investigation. Although some protocols can be extremely complex, most intravital imaging procedures can be performed using basic surgery and animal maintenance techniques. More importantly, regular confocal microscopes - the same that are used for imaging immunofluorescence slides - can also acquire high quality intravital images and movies after minor adaptations. Here we propose minimal adaptations in stock microscopes that allow major improvements in different fields of scientific investigation.

Habilidades de consciência fonológica e letramento em crianças de Ensino Fundamental / Phonological awareness abilities and literacy en elementary school children

Objetivo: analisar o perfil de crianças do ensino fundamental em relação às habilidades de consciência fonológica e de letramento antes e após um Programa Fonoaudiológico em Leitura e Escrita. Métodos: fizeram parte do estudo 34 (1º semestre) e 31 crianças (2º semestre), com média de idade de 7,2 anos. Todos os participantes cursavam a 1ª série do Ensino Fundamental de uma escola estadual. O programa fonoaudiológico foi elaborado juntamente com a professora da classe, e teve as duração de sete semenas. As crianças foram avaliadas indivudualmente no início do ano escolar e após a conclusão do programa. Resultados: o perfil de letramento e consciência fonológica dos escolares de primeira série demonstrou, em geral, mudanças significativas, principalmente em relação às provas de letramento que envolvem um conhecimento maior de habilidades escritas, bem como de habilidades de segmentação fonológica orais e escritas. Conclusão: as mudanças no perfil de letramento e consciência fonológica dos escolares de primeira série, observadas nestes estudo, sugerem que estas habilidades podem ser incentivadas por meio de práticas de promoção de leitura e escrita no âmbito escolar.