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The formation of immunological synapse (IS) is essential for natural killer (NK) cells to eliminate target cells. Although elucidation of the overall characteristics and formation processes of IS is ongoing, the mechanisms for regulating the stability of IS by cytoskeleton remain to be understood. The current study reports that Nogo receptor 1 (NgR1) plays a key role in modulating NK cell-mediated killing by destabilization of IS formation. NgR1 deficiency or blockade results in improved tumor control of NK cells by enhancing NK-to-target cell contact stability and regulating F-actin dynamics during IS formation. Clinically, patients with a tumor expressing abundant NgR1 ligand showed poor prognosis despite high levels of NK cell infiltration. Thus, our study identifies NgR1 as an immune checkpoint involved in IS formation and reveals a potential approach to improve the killing effect of NK cells in cancer immunotherapy.

MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8(+) T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8(+) T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8(+) T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8(+) T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8(+) T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics.

Tryptophanyl-tRNA synthetase (WRS) is an essential enzyme that catalyzes the ligation of tryptophan (Trp) to its cognate tRNAtrp during translation via aminoacylation. Interestingly, WRS also plays physiopathological roles in diseases including sepsis, cancer, and autoimmune and brain diseases and has potential as a pharmacological target and therapeutic. However, WRS is still generally regarded simply as an enzyme that produces Trp in polypeptides; therefore, studies of the pharmacological effects, therapeutic targets, and mechanisms of action of WRS are still at an emerging stage. This review summarizes the involvement of WRS in human diseases. We hope that this will encourage further investigation into WRS as a potential target for drug development in various pathological states including infection, tumorigenesis, and autoimmune and brain diseases.

Regulation of intracellular Ca2+ signaling is a major determinant of CD8+ T cell responsiveness, but the mechanisms underlying this regulation of Ca2+ levels, especially in naïve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ levels in naïve CD8+ T cells required for activation by suppressing TMEM20, a negative regulator of Ca2+ extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca2+ levels in naïve CD8+ T cells. The subsequent increase in Ca2+ levels induced expression of anergy-inducing genes, such as Cbl-b, Egr2, and p27, through activation of NFAT1, as well as reduced cell proliferation, cytokine production, and the antitumor activity of CD8+ T cells upon antigenic stimulation. The anergy-promoting molecular milieu and function induced by miR-150 deficiency were rescued by reinstatement of miR-150. Additionally, knockdown of TMEM20 in miR-150-deficient naïve CD8+ T cells reduced intracellular Ca2+ levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca2+ level and activation in naïve CD8+ T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca2+ levels.

Regulation of intracellular Ca2+ signaling is a major determinant of CD8+ T cell responsiveness, but the mechanisms underlying this regulation of Ca2+ levels, especially in naïve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ levels in naïve CD8+ T cells required for activation by suppressing TMEM20, a negative regulator of Ca2+ extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca2+ levels in naïve CD8+ T cells. The subsequent increase in Ca2+ levels induced expression of anergy-inducing genes, such as Cbl-b, Egr2, and p27, through activation of NFAT1, as well as reduced cell proliferation, cytokine production, and the antitumor activity of CD8+ T cells upon antigenic stimulation. The anergy-promoting molecular milieu and function induced by miR-150 deficiency were rescued by reinstatement of miR-150. Additionally, knockdown of TMEM20 in miR-150-deficient naïve CD8+ T cells reduced intracellular Ca2+ levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca2+ level and activation in naïve CD8+ T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca2+ levels.

Background Intraepithelial lymphocytes (IELs) in the intestines play pivotal roles in maintaining the integrity of the mucosa, regulating immune cells, and protecting against pathogenic invasion. Although several extrinsic factors, such as TGF-β, have been identified to contribute to IEL generation, intrinsic regulatory factors have not been determined fully. Objective Here we investigated the regulation of IEL differentiation and the underlying mechanisms in mice. Methods We analyzed IELs and the expression of molecules associated with IEL differentiation in wild-type control and microRNA (miRNA)-150 knockout mice. Methotrexate was administered to mice lacking miR-150 and control mice. Results miR-150 deficiency reduced the IEL population in the small intestine and increased susceptibility to methotrexate-induced mucositis. Evaluation of expression of IEL differentiation–associated molecules showed that miR-150–deficient IELs exhibited decreased expression of TGF-β receptor (TGF-βR) II, CD103, CD8αα, and Runt-related transcription factor 3 in all the IEL subpopulations. The reduced expression of TGF-βRII in miR-150–deficient IELs was caused by increased expression of c-Myb/miR-20a. Restoration of miR-150 or inhibition of miR-20a recovered the TGF-βRII expression. Conclusion miR-150 is an intrinsic regulator of IEL differentiation through TGF-βRII regulation. miR-150–mediated IEL generation is crucial for maintaining intestinal integrity against anticancer drug–induced mucositis.

Bioassay of mosquito, Culex pipiens molestus, larva was investigated by several environment-friendly insecticides. These insecticides were Novaluron as chitin synthesis inhibitor, Metho-xyfenozide as ecdysone agonist, Pyriproxyfen as juvenile hormone mimic, and Spiromesifen as lipid biosynthesis inhibitor. The 50% lethal concentration of these insecticides were 0.00039, 0.07193, 0.65006 and 0.04839 ppm, respectively. Novaluron has lower concentration than any other insecticide. To determine the treatment time against larval stages, insecticides were applied to different larval stages of C. pipiens molestus. Mortality ratios of mosquito larva treated with Novaluron were 100.0, 84.5, 71.0 and 48.5% on 2, 4, 7 and 10 days after hatching from eggs, respectively. Otherwise, with the other insecticides, mortality ratios were under 80% with 2 days old larva. When exposure periods were tested to 3 or 4 days old larva against 4 insecticides, at least 3 hours were needed to 100% control effect against Novaluron, and over 12 hours with other insecticides.

The efficient system for plant regeneration from cotyledon and primary feat explants of lettuce was established. Plant regeneration efficiency was shown 91.3% from cotyledon and 85.9% from primary leaf explants of variety `Jungtongpogi` in KN medium. Plant regeneration efficiency was also estimated with various plant regeneration media in variety` Chungchima`, which was lowest plant regeneration efficient showing 35.4% from cotyledon and 30.3% from prima leaf explants in KN medium. Kl medium increased 77.9% and 80.7% of plant regeneration efficiencies from cotyledon and primary leaf explants of variety `Jungtongpogi` were cultured on KN medium. In case of varie쇼 ‘Chungchima`, efficient plant regeneration was shown when primary leaf explants were cultured on SH and KI media.

It is the stage of development or testing the train control system for the signal system of branch interval of low density such as ERTMS Regional, FFB, COMBAT. Similar to the signal system used by the mainline and branch sections of low density domestic portions not suitable in terms of maintenance operational efficiency in accordance with the installation and operation in many cases. Therefore these low-density branch railway lines required that oriented train control system of wireless communication to improve the operation efficiency and line side equipment controlled on board the train. In this paper, We was published a route on setting is the operation of the new on-board oriented train control system for controlling a line converter of the train so that it is possible to improve the operational efficiency of the branch of the low density.

The main part of the system is operated by the software. Besides the safety critical system such as railways, airplanes, and nuclear power plants is applied by the software. The software can perform more varying and highly complex functions efficiently because software can be flexibly designed and implemented. But the flexible design makes it difficult to predict the software failures. We need to show that the safety critical railway software is developed to ensure the safety. This paper is suggested safety criteria and software development methodology to enhance safety for the safety critical railway system.

Ariane 5 rocket which is a test flight of European Space Agency was exploded 37 seconds after launch due to a malfunction in the control software. The amount of this loss is more than US$370 million. The accident has initiated the criticality of the software safety. Nowadays software is widely used in the safety critical system because of the merit of the flexibility. But the flexibility makes it difficult to predict the software failures. This paper suggests software safety criteria for the safety critical railway system and describes the quality management procedure of the railway software.