Monocytes and macrophages comprise a variety of subsets with diverse functions. It is thought that these cells play a crucial role in homeostasis of peripheral organs, key immunological processes and ...development of various diseases. Among these diseases, fibrosis is a life-threatening disease of unknown aetiology. Its pathogenesis is poorly understood, and there are few effective therapies. The development of fibrosis is associated with activation of monocytes and macrophages. However, the specific subtypes of monocytes and macrophages that are involved in fibrosis have not yet been identified. Here we show that Ceacam1
Msr1
Ly6C
F4/80
Mac1
monocytes, which we term segregated-nucleus-containing atypical monocytes (SatM), share granulocyte characteristics, are regulated by CCAAT/enhancer binding protein β (C/EBPβ), and are critical for fibrosis. Cebpb deficiency results in a complete lack of SatM. Furthermore, the development of bleomycin-induced fibrosis, but not inflammation, was prevented in chimaeric mice with Cebpb
haematopoietic cells. Adoptive transfer of SatM into Cebpb
mice resulted in fibrosis. Notably, SatM are derived from Ly6C
FcεRI
granulocyte/macrophage progenitors, and a newly identified SatM progenitor downstream of Ly6C
FcεRI
granulocyte/macrophage progenitors, but not from macrophage/dendritic-cell progenitors. Our results show that SatM are critical for fibrosis and that C/EBPβ licenses differentiation of SatM from their committed progenitor.
Endothelial-cell Schlafen 8 regulates EAE development
Abstract
Schlafen-8 (Slfn8) is a member of the Schlafen family of proteins, which harbor helicase domains and are induced by LPS and interferons. ...It has been reported that the Schlafen family are involved in various cellular functions, including proliferation, differentiation and regulation of virus replication. Slfn8 has been implicated in T-cell differentiation in the thymus. However, the roles of Slfn8 in the immune system remains unclear. In this study, we generated Slfn8 knockout mice (Slfn8−/−) and investigated the immunological role of Slfn8 using the T-cell-mediated autoimmune model experimental autoimmune encephalomyelitis (EAE). We found that the clinical score was reduced in Slfn8−/− mice. IL-6 and IL-17A cytokine production, which are associated with EAE onset and progression, were decreased in the lymph nodes of Slfn8−/− mice. Immune cell populations in Slfn8−/− mice, including macrophages, neutrophils, T cells and B cells, did not reveal significant differences compared with wild-type mice. In vitro activation of Slfn8−/− T cells in response to TCR stimulation also did not reveal significant differences. To confirm the involvement of non-hematopoietic cells, we isolated CD45− CD31+ endothelial cells and CD45−CD31− gp38+ fibroblastic reticular cells by FACS sorting. We showed that the levels of IL-6 and Slfn8 mRNA in CD45− CD31+ endothelial cells were increased after EAE induction. In contrast, the level of IL-6 mRNA after EAE induction was markedly decreased in CD31+ endothelial cells from Slfn8−/− mice. These results indicate that Slfn8 may play a role in EAE by regulating inflammation in endothelial cells.
The development of effective treatments against cancers is urgently needed, and the accumulation of CD8⁺ T cells within tumors is especially important for cancer prognosis. Although their mechanisms ...are still largely unknown, growing evidence has indicated that innate immune cells have important effects on cancer progression through the production of various cytokines. Here, we found that basic leucine zipper transcription factor ATF-like 2 (Batf2) has an antitumor effect. An s.c. inoculated tumor model produced fewer IL-12 p40⁺ macrophages and activated CD8⁺ T cells within the tumors of Batf2
−/− mice compared with WT mice. In vitro studies also revealed that the IL-12 p40 expression was significantly lower in Batf2
−/− macrophages following their stimulation by toll-like receptor ligands, such as R848. Additionally, we found that BATF2 interacts with p50/p65 and promotes IL-12 p40 expression. In conclusion, Batf2 has an antitumor effect through the up-regulation of IL-12 p40 in tumor-associated macrophages, which eventually induces CD8⁺ T-cell activation and accumulation within the tumor.
Upstream open reading frames (uORFs) are often found in the 5'-leader regions of eukaryotic mRNAs and can negatively modulate the translational efficiency of the downstream main ORF. Although the ...effects of most uORFs are thought to be independent of their encoded peptide sequences, certain uORFs control translation of the main ORF in a peptide sequence-dependent manner. For genome-wide identification of such peptide sequence-dependent regulatory uORFs, exhaustive searches for uORFs with conserved amino acid sequences have been conducted using bioinformatic analyses. However, whether the conserved uORFs identified by these bioinformatic approaches encode regulatory peptides has not been experimentally determined. Here we analyzed 16 recently identified Arabidopsis thaliana conserved uORFs for the effects of their amino acid sequences on the expression of the main ORF using a transient expression assay. We identified five novel uORFs that repress main ORF expression in a peptide sequence-dependent manner. Mutational analysis revealed that, in four of them, the C-terminal region of the uORF-encoded peptide is critical for the repression of main ORF expression. Intriguingly, we also identified one exceptional sequence-dependent regulatory uORF, in which the stop codon position is not conserved and the C-terminal region is not important for the repression of main ORF expression.
An experimental study to generate T-S (Tollmien-Schlichting) waves and oblique waves in a flat plate boundary layer is carried out. This is considered to be the first step towards controlling ...boundary-layer transition. In order to generate T-S waves and oblique waves, an array of piezoelectrically driven actuator pieces attached to a flat plate surface was used. The actuator pieces were sufficiently thin to keep the boundary layer in the laminar state. In order to generate various oblique waves, ten actuator pieces were aligned in the spanwise direction, each of which could be controlled separately. It is shown that both two-dimensional T-S wave and oblique waves of various angles could be generated using this device. It is also shown that when a flow pattern similar to the Craik-type three-dimensionalization mode was excited, the onset of turbulence took place early and locally at a certain spanwise location.
Experimental study to generate T-S waves and oblique waves in a flat plate boundary layer is carried out. It is regarded as the first step towards controlling the boundary-layer transition. In order ...to generate T-S waves and oblique waves, an array of piezoelectrically driven actuator pieces attached to the flat plate surface is used. The actuator is thin enough to keep the boundary layer in the laminar-state. In order to generate various oblique waves, the actuator consists of an array of 10 small pieces aligned in the spanwise direction. Each piece can be controlled separately. It is shown that various oblique waves can be successfully generated using this actuator. It is also shown that when the three-dimensionalization mode is induced, the onset of turbulence takes place locally at a certain spanwise location.
An experimental study to generate T-S (Tollmien-Schlichting) waves and oblique waves in a flat plate boundary layer is carried out. This is considered to be the first step towards controlling ...boundary-layer transition. In order to generate T-S waves and oblique waves, an array of piezoelectrically driven actuator pieces attached to a flat plate surface was used. The actuator pieces were sufficiently thin to keep the boundary layer in the laminar state. In order to generate various oblique waves, ten actuator pieces were aligned in the spanwise direction, each of which could be controlled separately. It is shown that both two-dimensional T-S wave and oblique waves of various angles could be generated using this device. It is also shown that when a flow pattern similar to the Craik-type three-dimensionalization mode was excited, the onset of turbulence took place early and locally at a certain spanwise location.
The Geospatial Information Authority of Japan (GSI) has been conducting geomagnetic surveys in Japan since 1949 to clarify the geographical distribution of direction, intensity of the geomagnetic ...field, and their secular variations. Recently, we have carried out continuous observations at geodetic observatories and continuous geomagnetic stations and repetitive observations at several first-order geomagnetic stations. The results of the surveys, “geomagnetic charts”, have been published every 10 years. In 2011, GSI released the newest geomagnetic charts for the epoch 2010.0 created by adopting a new spatial-temporal model. This model needs continuous data of good quality. In addition to the GSI geodetic observatories, the Kakioka Magnetic Observatory, which has been conducting high-quality and stable observations for 100 years, makes a large contribution.
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