A novel insertion pathway of mitochondrial outer membrane proteins with multiple transmembrane segments

The central channel Tom40 of the preprotein translocase of outer membrane (TOM) complex is thought to be responsible for the import of virtually all preproteins synthesized outside the mitochondria. In this study, we analyze the topogenesis of the peripheral benzodiazepine receptor (PBR), which integrates into the mitochondrial outer membrane (MOM) through five hydrophobic transmembrane segments (TMSs) and functions in cholesterol import into the inner membrane. Analyses of in vitro and in vivo import into TOM component–depleted mitochondria reveal that PBR import (1) depends on the import receptor Tom70 but requires neither the Tom20 and Tom22 import receptors nor the import channel Tom40, (2) shares the post-Tom70 pathway with the C-tail–anchored proteins, and (3) requires factors of the mitochondrial intermembrane space. Furthermore, membrane integration of mitofusins and mitochondrial ubiquitin ligase, the MOM proteins with two and four TMSs, respectively, proceeds through the same initial pathway. These findings reveal a previously unidentified pathway of the membrane integration of MOM proteins with multiple TMSs

microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity

褐色脂肪細胞の燃焼を促す新たなメカニズムを解明 --体の熱産生にマイクロRNA-33が関与--. 京都大学プレスリリース. 2021-02-17.Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress

Late Proterozoic juvenile arc metatonalite and adakitic granitoids in the Sør Rondane Mountains, East Antarctica

第3回極域科学シンポジウム/第32回極域地学シンポジウム 11月30日（金） 国立極地研究所 ３階ラウン

Emplois et valeurs de la forme (R)ARE en japonais

The goal of this study is to explore the usages and the variety of meanings of the form (r)are in Japanese through the notions of « event » and « property ». (R)are expresses at the same time (i) the passive, forming a pair with the active, (ii) an event with adversative effect on someone, (iii) the predication of a property for the subject and (iv) a potential meaning. This study will begin by revisiting adversative passive constructions to illustrate that they are eventive and associated to the speaker’s subjectivity and that some syntactic patterns can be generalized (relation of possession, nature of the subject [±animate], relation of empathy between the subject [+animate] and the speaker). A detailed analysis of the aspectual verbal suffixes in the passive utterances leads to a definition of the eventive and of the generic meanings. To justify the distinction between eventive passive and property passive, the interaction with the specific character of the agent is analyzed. Then, we distinguish between two types of passives containing a locative, using the distinction between a temporary and a permanent property. This accounts for the fact that the passives containing a locative are part of attributive sentences. Finally, we show how some attributive passives lead to a generic interpretation.Cette étude porte sur les emplois de la forme (r)are et ses différentes valeurs en japonais à travers les notions d’« événement » et de « propriété ». (R)are exprime à la fois, (i) le passif formant une paire avec l’actif, (ii) un événement au détriment de quelqu'un, (iii) une prédication de propriété sur le sujet et (iv) une valeur potentielle. Les constructions passives détrimentales sont revisitées et on montre qu'elles sont événementielles et associées à la subjectivité de l’énonciateur et que certains patrons syntaxiques peuvent être généralisés (relation de possession, nature du sujet [±animé], relation d'empathie entre le sujet [+animé] et l’énonciateur). Une analyse détaillée des suffixes verbaux aspectuels dans les énoncés passifs permet ensuite de caractériser les significations événementielle et générique. Afin de justifier l’opposition entre passifs événementiel et passifs de propriété, on met en évidence le caractère spécifique de l’agent. Puis, en distinguant deux sortes de localisations, momentanée et permanente, nous justifions le fait que les passifs locatifs font partie des phrases attributives. Enfin, nous montrons comment certains passifs attributifs relèvent de la généricité

Emplois et valeurs de la forme (r)are en japonais

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Introduction of direct-acting antiviral agents alters frequencies of anti-GPIIb/IIIa antibody-producing B cells in chronic hepatitis C patients with thrombocytopenia

The pathogenesis of thrombocytopenia in chronic hepatitis C (CHC) conceivably involves autoimmunity; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear. In this study, we examined the changes in the frequency of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells and the levels of plasma B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and interleukin (IL)-21 following treatment of CHC with direct-acting antiviral agents (DAA). We recruited 28 patients with CHC who underwent treatment with DAA for 8–12 weeks and subsequently tested negative for serum hepatitis C virus RNA. Thirty healthy controls were recruited for comparison. Platelet counts increased significantly (p = .016), and the frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly (p = .002) in CHC patients with thrombocytopenia at the end of treatment (EOT) than before DAA treatment (baseline). However, these changes were not observed in CHC patients without thrombocytopenia. Plasma BAFF levels in CHC patients with thrombocytopenia significantly decreased from baseline to EOT (p = .002). Anti-GPIIb/IIIa antibody-producing B cells were positively correlated with plasma BAFF levels in these patients (r = 0.669, p = .039). These results suggest that DAA treatment suppresses the autoimmune response against platelets and improves thrombocytopenia