Special AT-rich sequence binding protein-1 (SATB1) is localized to the nucleus and remodels chromatin structure in T cells. SATB1-deficient CD4 T cells cannot respond to TCR stimulation; however, the cause of this unresponsiveness is to be clarified. Here, we demonstrate that SATB1 is indispensable to proper mitochondrial functioning and necessary for the activation of signal cascades via the TCR in CD4 T cells. Naïve SATB1-deficient CD4 T cells contain fewer mitochondria than WT T cells, as the former do not express mitochondrial transcription factor A (TFAM). Impaired mitochondrial function in SATB1-deficient T cells subverts mitochondrial ROS production and SHP-1 inactivation by constitutive oxidization. Ectopic TFAM expression increases mitochondrial mass and mitochondrial ROS production and rescues defects in the antigen-specific response in the SATB1-deficient T cells. Thus, SATB1 is vital for maintaining mitochondrial mass and function by regulating TFAM expression, which is necessary for TCR signaling.

This paper describes a simple determination method of the optimal operating threshold in step voltage regulators (SVRs) that allow us to avoid hunting operations even if multiple SVRs are installed in a distribution line, to which photovoltaic (PV) inverters are connected. The SVRs dealt with in this paper have either time integral action type or voltage integral action type. In the case of voltage integral action type, the response time varies according to the PV output fluctuation. In the proposed method, the average response time of voltage integral action type is first estimated with the facility information on the distribution line. Second, the operating threshold of multiple SVRs including voltage integral action type is decided based on the average response time of voltage integral action type. Simulation results showed the method can effectively reduce the number of hunting operations by 75% on average in an example distribution line with PVs.

The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4(+) T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions. If the inhibitory effects of T cells on these mechanisms are disrupted, T cells may incorrectly attack self-components, which can lead to autoimmune disease. The functions of T cells are supported by post-translational modifications, particularly phosphorylation, of signaling molecules, the proper regulation of which is controlled by endogenous mechanisms within the T cells themselves. In recent years, molecular targeted agents against kinases have been developed for treatment of autoimmune diseases. In this review, we discuss T-cell signal transduction in autoimmune disease and provide an overview of acetylation-mediated regulation of T-cell signaling pathways.

Interleukin-17 (IL-17) induces the production of granulocyte colony-stimulating factor (G-CSF) and chemokines such as CXCL1 and CXCL2 and is a cytokine that acts as an inflammation mediator. During infection, IL-17 is needed to eliminate extracellular bacteria and fungi, by inducing antimicrobial peptides such as defensin. This cytokine also plays an important role in chronic inflammation that occurs during the pathogenesis of autoimmune diseases and allergies such as human rheumatoid arthritis (RA) for which a mouse model of collagen-induced arthritis (CIA) is available. In autoimmune diseases such as RA and multiple sclerosis (MS), IL-17 is produced by helper T (Th) cells that are stimulated by IL-1β and IL-6 derived from phagocytes such as macrophages and from tissue cells. IL-17 contributes to various lesions that are produced by Th17 cells, one subset of helper T cells, and by γδ T cells and innate lymphoid cells. It strongly contributes to autoimmune diseases that are accompanied by chronic inflammation. Thus, a functional understanding of Th17 cells is extremely important. In this review, we highlight the roles of cytokines that promote the development and maintenance of pathogenic Th17 cells in autoimmune diseases.

We are developing a new eddy-current non-destructive evaluation (NDE) system using a high-temperature superconducting quantum interference device (HTS-SQUID) gradiometer with the aim of applying it to power plants. Electric power facilities such as ducts and vessels are generally untransportable because of their size, and thus it is difficult to apply a conventional SQUID NDE system. The new NDE system employs an external Cu pickup coil which is supposed to be driven flexibly by a robot arm at room temperature and an HTS-SQUID chip which is placed in a magnetically shielded vessel. In the present research, we investigated the performance of an HTS-SQUID sensor connected with external pickup coils before mounting them to a robot arm. By varying the Cu coil conditions such as their sizes, the number of turns, and the diameter of wire, we qualitatively evaluated the frequency dependence of the effective area and the cutoff frequency.

If mass renewable energy sources are introduced into the electric power system, frequency control for the power system will be difficult by a rapid output change of the sources. In the case that a change of renewable energy output exceeds the ability of frequency control by power plants, it is considered that to control customer's loads is useful. We considered a method to control mass customer's loads using a multi-agent system. A prototype program, in which the every load turns ON/OFF autonomously when the renewable energy output changes, was developed. About 500 agents could work autonomously to control demand and supply balance. Power system simulations were conducted with the 500 agents working. By the agent's working, frequency fluctuations could be suppressed.

PKA phosphorylates multiple molecules involved in calcium (Ca2+) handling in cardiac myocytes and is considered to be the predominant regulator of β-adrenergic receptor-mediated enhancement of cardiac contractility; however, recent identification of exchange protein activated by cAMP (EPAC), which is independently activated by cAMP, has challenged this paradigm. Mice lacking Epac1 (Epac1 KO) exhibited decreased cardiac contractility with reduced phospholamban (PLN) phosphorylation at serine-16, the major PKA-mediated phosphorylation site. In Epac1 KO mice, intracellular Ca2+ storage and the magnitude of Ca2+ movement were decreased; however, PKA expression remained unchanged, and activation of PKA with isoproterenol improved cardiac contractility. In contrast, direct activation of EPAC in cardiomyocytes led to increased PLN phosphorylation at serine-16, which was dependent on PLC and PKCε. Importantly, Epac1 deletion protected the heart from various stresses, while Epac2 deletion was not protective. Compared with WT mice, aortic banding induced a similar degree of cardiac hypertrophy in Epac1 KO; however, lack of Epac1 prevented subsequent cardiac dysfunction as a result of decreased cardiac myocyte apoptosis and fibrosis. Similarly, Epac1 KO animals showed resistance to isoproterenol- and aging-induced cardiomyopathy and attenuation of arrhythmogenic activity. These data support Epac1 as an important regulator of PKA-independent PLN phosphorylation and indicate that Epac1 regulates cardiac responsiveness to various stresses.

We investigated the role of macrophage colony-stimulating factor (M-CSF) in the pituitary gland to understand the effect of M-CSF on pituitary hormones and the relationship between the endocrine and immune systems. When we attempted to establish pituitary cell lines from a thyrotropic pituitary tumor (TtT), a macrophage cell line, TtT/M-87, was established. We evaluated M-CSF-like activity in conditioned media (CM) from seven pituitary cell lines using TtT/M-87 cells. TtT/M-87 proliferation significantly increased in the presence of CM from TtT/GF cells, a pituitary folliculostellate (FS) cell line. M-CSF mRNA was detected in TtT/GF and MtT/E cells by reverse transcriptase-polymerase chain reaction (RT-PCR), and its expression in TtT/GF cells was increased in a lipopolysaccharide (LPS) dose-dependent manner. M-CSF mRNA expression was also increased in rat anterior pituitary glands by LPS. M-CSF receptor (M-CSFR) mRNA was only detected in TtT/ M-87 cells and increased in the LPS-stimulated rat pituitary glands. In rat pituitary glands, M-CSF and M-CSFR were found to be localized in FS cells and prolactin (PRL)-secreting cells, respectively, by immunohistochemistry. The PRL concentration in rat sera was significantly increased at 24 h after M-CSF administration, and mRNA levels significantly increased in primary culture cells of rat anterior pituitary glands. In addition, TNF-α mRNA was increased in the primary culture cells by M-CSF. These results revealed that M-CSF was secreted from FS cells and M-CSF regulated PRL expression in rat pituitary glands.

We have investigated the performance of an eddy-current non-destructive evaluation (NDE) system using an HTS Superconducting quantum interference device (SQUID) gradiometer with the aim of applying it to the equipment in power plants. Use of the SQUID-NDE technique has an advantage, because SQUID has a high sensitivity or low noise characteristics at low frequencies for detecting magnetic signals. In the present research, we have tried to detect flaws in test samples simulating a multilayer duct in a plant, which consists of multilayer aluminum and resin plates. In the test samples, resin plates were sandwiched by aluminum plates. The top aluminum plate and the bottom multilayer aluminum plates were assumed as outer and inner duct layers, and the resin plates were assumed as an insulation layer in a multilayer duct of the plant. A slit-shaped through hole was opened in the bottom layer, and was assumed as a flaw in the duct layer. By using a SQUID-ECT system, we could detect signals from flaws located at more than 10mm deep positions in the test samples.

ABSTRACT Uterine natural killer (uNK) cells remarkably increase in number after implantation. NK cells or their precursors migrate from the blood stream and contribute to the increase. However, the contribution of uNK cells present in the virgin uterus has been unclear. To elucidate this issue, we examined uterine leukocyte subsets during pregnancy in BALB/c mice. The most dramatic change was the massive decrease in CD11b− or Gr-1− cells at Gestation Day (gd) 6. Uterine NK cells at gd 0 were CD11b−, and severely decreased at gd 6. The decrease was selective, and the proportion of other cells examined did not decrease. Uterine NK cells almost recovered at gd 12. These cells at gd 12 were more mature and/or activated in terms of expression of CD11b, CD27, CD127, or B220 than at gd 0. CXCL12 expression was observed on uterine cells at gd 0 or 6, but not at gd 12, whereas CXCR4 was detected on uNK cells at gds 0 and 12. A much higher expression of IL-15 in uterine cells or interferon-gamma expression in uNK cells was observed at gd 12 than at gd 0. IL-15 receptor alpha chain was detected on uNK cells at gd 12, but not at gd 0. Taken together, these findings were consistent with our interpretation that uNK cells present at gd 0 do not contribute to the increase of uNK cell number after implantation, and NK cells or their precursors migrate into the uterus, mature, and produce interferon-gamma to support pregnancy.

In Poland, the expansion of the introduction of wind power generation has been recently accelerating as a global warming countermeasure mainly in the area of northern Poland along the Baltic Sea. The transmission company (PSE-Operator, “PSE”) and the distribution company in the northern area (ENERGA-Operator, “ENERGA”) have faced an urgent issue of reinforcement in transmission lines to tackle with such expansion. Moreover, concerns have been increasing about negative impacts on the supply-demand balance and the power quality due to fluctuations in wind power generation output.We have analyzed and examined power system stabilization measures such as special protection scheme (SPS) with a minimum cost for expanding the introduction volume of wind power generation in order to address such concerns. In addition, we have examined measures for stable operation of the power system through the application of smart grid technologies such as storage batteries for the power system, and studied the possible commercialization of such measures.Through the analysis we confirmed the effect of introduction of SPS or decision support system for operators which conduct a control of the power system such as generation shedding against overload which could be caused in the event of N-1 fault when the introduction volume of wind power generation is expanded. And we also confirmed the effect of introduction of storage batteries that suppress extra area flow fluctuations of wind power generation and shave a peak of demand.

Multiple sclerosis is a chronic, inflammatory, and demyelinating disease of the central nervous system characterized by the pathological infiltration of autoreactive leukocytes. Experimental autoimmune encephalomyelitis serves as a disease model for human multiple sclerosis in mouse and rat (Conlon et al., 1999). Experimental autoimmune encephalomyelitis is induced through sensitization with neuroantigens such as myelin oligodendrocyte glycoprotein that activates neuroantigen-reactive T cells in the peripheral lymphoid organs. These T cells subsequently migrate into the central nervous system and encounter endogenous neuroantigens, which reactivates them and leads to nerve demyelination. Thus, induction of encephalitogenic T cells and their migration into the central nervous system are critical for development of experimental autoimmune encephalomyelitis.

We summarize the lightning data for 17 years from 1992 to 2008 obtained with lightning location systems of nine electric power utilities in Japan and analyze them. The observed annual number of lightning flashes of which the current is more than 10 kA is 400 000–800 000 and the 50% value of the cumulative distribution of lightning peak currents is about 23 kA in recent times. The variation of lightning occurrence characteristics by areas, seasons, and so on, is clarified. Comparison of the obtained data with those obtained by another lightning location system is also made. The relationship between lightning occurrence and climate is discussed. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

We reported previously that the production of IL-23 is impaired in DCs from mice that lack expression of the chemokines CCL19 and CCL21, which share the receptor CCR7, suggesting that these chemokines are required for IL-23 expression. However, the molecular mechanism of CCR7-mediated IL-23 production in DCs is unknown. We found that CCL19 and CCL21 stimulated DCs through CCR7 and induced transcription of IL-23p19 mRNA and IL-23 production in splenic and BMDC. Stimulation of DCs with CCR7 ligands induced phosphorylation of MAPK family members and of Akt, but only a specific PI3K inhibitor, LY294002, not inhibitors of ERK, JNK, or p38, decreased IL-23p19 transcription and IL-23 production. In DCs stimulated with CCL19 or CCL21, I κ B α was degraded, and NF-κ B was translocated into the nucleus. Prevention of NF-κ B activation blocked chemokine-mediated IL-23p19 transcription. A PI3K inhibitor abolished NF-κ B activation and IL-23 production. Based on these findings, we concluded that PI3K and NF-κ B signaling pathways play a critical role in CCR7-mediated IL-23 production in murine DCs. As IL-23 contributes to Th17 cell generation, and Th17 cells are pathogenic in autoimmune diseases, precise elucidation of these mechanisms would contribute to the development of strategies to control autoimmune diseases.

Alcohol consumption impairs Th1-mediated cellular immune responses and enhances serum IgE levels. It has been reported that the elevated IgE levels are associated with a Th2 polarization response, but the mechanisms for enhancing Th2 polarization by the ethanol treatment remain to be elucidated. The aim of this review is to present and discuss the mechanism of Th2 polarization response by alcohol. IL-12 production by APCs such as monocytes, macrophages, and dendritic cells (DCs) preferentially leads to Th1 polarization. Acute ethanol consumption results in a significant decrease in IL-12 production in LPS-stimulated DCs and a CD40/CD40L interaction between CD40 on the DCs and CD40 ligand expressed on activated T cells. This suggests that Th2 polarization by ethanol is caused by impaired IL-12 production from APCs. In contrast, the induction of IL-10 by LPS is enhanced by ethanol treatment, suggesting that elevated IL-10 may play a role in ethanol-induced suppression of IL-12. However, ethanol inhibited IL-12 production in LPS-stimulated DCs devoid of IL-10 (IL-10/DC), suggesting that down-regulation of IL-12 by ethanol is independent of the IL-10 levels. Furthermore, several studies report that PGE2, cAMP and linolic acid, and endogenous lipid mediators released in inflammatory conditions, also inhibit IL-12 production. These inhibitory effects are similar to the IL-12 inhibition by ethanol. In addition, increase in the levels of these lipid mediators is induced by ethanol treatment. Alternatively, cytokine signaling studies indicate that IL-12 production by DCs is negatively regulated by PI3K and GSK-3, but positively regulated by p38 MAPK, mTOR, and NF-kappa B. Thus, it seems possible that ethanol may interact on the upstream of IL-12 producing a signal pathway. In fact, ethanol alters the stability of cell membrane, and suppresses clustering of TLR4 and recruitment of signaling molecules into lipid rafts, where it associates with the Ser/Thr kinase and the adaptor proteins, and forms a signaling complex. Down-regulation of lipid raft signaling is results in the impaired IL-12 production leading to the Th1 polarization, and causes CD4+ T cells to differentiation toward the Th2 lineage.

17 years of lightning data from 1992 to 2008 obtained with lightning location system of 9 electric power companies in Japan have been summarized and analyzed. The recent annual number of lightning flashes of which current is more than 10 kA in Japan is around one million and the 50% value of cumulative distribution of lightning peak currents is about 20kA. The variation of lightning occurrence characteristics by areas, seasons and so on are clarified. The relationship between lightning occurrence and climate, detection efficiency and the version of lightning detection systems are discussed.