E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis

Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis.The expression and localization of synoviolin in the liver were analyzed in CCl(4)-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno(+/-) mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno(+/-) mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno(-/-) mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno(-/-) MEF cells.In the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno(+/-) mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno(+/-) mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno(-/-) MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum.Our findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis

A recepção natural e proveitosa da literatura no processo de ensino e aquisição de japonês como língua estrangeira

This work presents thoughts on the approach of literary texts inside the teaching and learning context of the japanese language as a foreign language, focusing on the view of the apprentice and professor towards the nuances of the target language that are present and visible in authentic texts such as literature. Our deliberation starts on studying the implementation of literary texts on the untermediary course of japanese language classes at the CLDP (Center for the Development of Language and Professors).Este trabalho apresenta algumas reflexões sobre a abordagem  de textos literários no contexto de ensino e aquisição de japonês como língua estrangeira, tendo como prioridade o direcionamento do olhar do aprendiz e do professor para as nuanças da língua-alvo, presentes e perceptíveis em textos autênticos como a literatura. Nossas considerações se originam na observação do trabalho realizadocom textos literários nas aulas de um curso de japonês – nível intermediário, ministrado no Centro de Línguas e Desenvolvimento de Perofessores (CLDP)

α1,6-Fucosyltransferase-deficient Mice Exhibit Multiple Behavioral Abnormalities Associated with a Schizophrenia-like Phenotype: IMPORTANCE OF THE BALANCE BETWEEN THE DOPAMINE AND SEROTONIN SYSTEMS*

Previously, we reported that α1,6-fucosyltransferase (Fut8)-deficient (Fut8−/−) mice exhibit emphysema-like changes in the lung and severe growth retardation due to dysregulation of TGF-β1 and EGF receptors and to abnormal integrin activation, respectively. To study the role of α1,6-fucosylation in brain tissue where Fut8 is highly expressed, we examined Fut8−/− mice using a combination of neurological and behavioral tests. Fut8−/− mice exhibited multiple behavioral abnormalities consistent with a schizophrenia-like phenotype. Fut8−/− mice displayed increased locomotion compared with wild-type (Fut8+/+) and heterozygous (Fut8+/−) mice. In particular, Fut8−/− mice showed strenuous hopping behavior in a novel environment. Working memory performance was impaired in Fut8−/− mice as evidenced by the Y-maze tests. Furthermore, Fut8−/− mice showed prepulse inhibition (PPI) deficiency. Intriguingly, although there was no significant difference between Fut8+/+ and Fut8+/− mice in the PPI test under normal conditions, Fut8+/− mice showed impaired PPI after exposure to a restraint stress. This result suggests that reduced expression of Fut8 is a plausible cause of schizophrenia and related disorders. The levels of serotonin metabolites were significantly decreased in both the striatum and nucleus accumbens of the Fut8−/− mice. Likewise, treatment with haloperidol, which is an antipsychotic drug that antagonizes dopaminergic and serotonergic receptors, significantly reduced hopping behaviors. The present study is the first to clearly demonstrate that α1,6-fucosylation plays an important role in the brain, and that it might be related to schizophrenia-like behaviors. Thus, the results of the present study provide new insights into the underlying mechanisms responsible for schizophrenia and related disorders