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Fibroblast growth factor 21 (FGF21), a member of the FGF subfamily that acts through the FGF receptor 1 with the co-receptor β-Klotho, functions as an important metabolic regulator of peripheral glucose tolerance and lipid homeostasis in an endocrine or autocrine and/or paracrine manner. Previous studies showed that FGF21 ameliorated and prevented the development of metabolic disorders, such as obesity and diabetes mellitus. In the present study, we demonstrated that berberine, a naturally occurring compound, stimulated FGF21 expression in brown adipose tissue (BAT). Furthermore, the up-regulated expression of FGF21 in brown adipocytes in response to berberine was due, at least in part, to the activation of the AMP-activated protein kinase pathway. We also found that berberine reversed high-fat diet-induced obesity concomitant with its regulation of the expression of Fgf21 and the core clock component brain and muscle Arnt-like 1 (Bmal1) in BAT. Berberine significantly up-regulated the gene expression and production of FGF21 in a dose-dependent manner in C3H10T1/2 brown adipocytes. Furthermore, the knockdown of Bmal1 prevented the up-regulated expression of FGF21 in response to berberine in C3H10T1/2 brown adipocytes, suggesting that Bmal1 links the regulatory mechanisms of FGF21 in response to berberine. The present results suggest that berberine stimulates the expression of FGF21 by modulating molecular clock Bmal1 in BAT, which may, in turn, attenuate diet-induced obesity. They also indicate the potential of berberine as a therapeutic agent for obesity and obesity-associated metabolic disorders related to circadian misalignments. [ABSTRACT FROM AUTHOR]

Abstract Retinoic acid receptor-related orphan receptor (ROR) α has been implicated in various physiological functions, including the immune system, inflammation, and circadian rhythms. In the present study, the synthetic RORα/γ agonist SR1078 stimulated the production and gene expression of fibroblast growth factor 21 (FGF21) in C2C12 myotubes. FGF21, a member of the FGF family, plays important roles in the regulation of peripheral glucose tolerance and lipid metabolism and improves metabolic health. The mRNA expression and secretion of FGF21 was significantly weaker in Rora -silenced cells than in cells transfected with non-targeting control siRNA. SR1078 significantly up-regulated C/EBP homologous protein (CHOP), an established marker of ER stress, in a dose-dependent manner in C2C12 myotubes, while CHOP expression was decreased in Rora -silenced C2C12 cells, suggesting that RORα is involved in the regulation of FGF21 expression and stimulates ER stress in C2C12 myotubes. The naturally occurring compound baicalein up-regulated FGF21 expression and secretion in C2C12 myotubes. Additionally, the up-regulation of CHOP mRNA and protein expression was observed in C2C12 myotubes after the baicalein treatment. Furthermore, the knockdown of RORα prevented the augmentation of FGF21 and up-regulation of CHOP in response to baicalein in C2C12 cells. Collectively, these results suggest that baicalein stimulates the ER stress response and FGF21 expression through an RORα-dependent mechanism in C2C12 myotubes, and indicate the potential of baicalein as an effective anti-obesity therapy via its ability to enhance FGF21 production. [ABSTRACT FROM AUTHOR]

The clock system has been identified as one of the major mechanisms controlling cellular functions. Circadian clock gene oscillations also actively participate in the functions of various cell types including bone-related cells. Previous studies demonstrated that clock genes were expressed in bone tissue and also that their expression exhibited circadian rhythmicity. Recent findings have shown that sympathetic tone plays a central role in biological oscillations in bone. Adrenergic receptor (AR) signaling regulates the expression of clock genes in cancellous bone. Furthermore, α-AR signaling in osteoblasts is known to negatively regulate the expression of bone morphogenetic protein-4 (Bmp4) by up-regulating nuclear factor IL-3 (Nfil3)/e4 promoter-binding protein 4 (E4BP4). The ablation of α-AR signaling also increases the expression of the Bmp4 gene in bone. The findings of transient overexpression and siRNA experiments have supported the involvement of the transcription factor CCAAT/enhancer-binding protein delta (C/EBPδ, Cebpd) in Nfil3 and Bmp4 expression in MC3T3-E1 cells. These findings suggest that the effects of Cebpd are due to the circadian regulation of Bmp4 expression, at least in part, by the up-regulated expression of the clock gene Nfil3 in response to α-AR signaling in osteoblasts. Therefore, AR signaling appears to modulate cellular functionality through the expression of clock genes that are circadian rhythm regulators in osteoblasts. The expression of clock genes regulated by the sympathetic nervous system and clock-controlled genes that affect bone metabolism are described herein. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that the sensory nervous system is involved in bone metabolism. However, the mechanism of communication between neurons and osteoblasts is yet to be elucidated. In this study, we investigated the signaling pathways between sensory neurons of the dorsal root ganglion ( DRG) and the osteoblast-like MC3T3-E1 cells using an in vitro coculture system. Our findings indicate that signal transduction from DRG-derived neurons to MC3T3-E1 cells is suppressed by antagonists of the AMPA receptor and the NK1 receptor. Conversely, signal transduction from MC3T3-E1 cells to DRG-derived neurons is suppressed by a P2X7 receptor antagonist. Our results suggest that these cells communicate with each other by exocytosis of glutamate, substance P in the efferent signal, and ATP in the afferent signal. [ABSTRACT FROM AUTHOR]

Background and Purpose: The sympathetic nervous system regulates bone remodelling, in part, through ß2 -adrenoceptor signalling. However, the physiological role of α1 -adrenoceptor signalling in bone in vivo remains unclear. Therefore, to obtain a deeper understanding of bone remodelling by the sympathetic nervous system, we investigated the role of α1B -adrenoceptor signalling in bone metabolism.Experimental Approach: Prazosin, a nonspecific α1 -adrenoceptor antagonist, was administered for 2 weeks in C57BL6 mice, and efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of bone formation by fluorescent labelling of bone. We also compared the bone phenotype of α1B -adrenoceptor null mice (α1B (-/-) ) with that of wild-type littermates.Key Results: We demonstrated that the systemic administration of prazosin decreased bone formation. In addition, α1B -adrenoceptor-deficient mice had a lower bone mass due to decreased bone formation but did not exhibit any changes in bone-resorbing activity. Furthermore, stimulation with phenylephrine, a non-specific α1 -adrenoceptor agonist, increased the expression of the transcriptional factor CCAAT/enhancer-binding protein δ (Cebpd) in MC3T3-E1 osteoblastic cells. The overexpression of Cebpd induced cellular proliferation in MC3T3-E1 cells, whereas the silencing of Cebpd suppressed it.Conclusions and Implications: Taken together, these results suggested that α1B -adrenoceptor signalling is required for bone formation and regulated cellular proliferation through a mechanism relevant to the up-regulation of Cebpd in osteoblasts and, thus, provide new evidence for the physiological importance of α1B -adrenoceptor signalling in bone homeostasis. [ABSTRACT FROM AUTHOR]

Recent studies reported that serotonin (5-hydroxytryptamine, 5-HT) may be an endogenous paracrine and/or autocrine factor that is used for intercellular communication in bone cells and between multiple organs regulating bone homeostasis. In the present study, we showed that the administration of MDL11939, a selective 5-HT 2A receptor antagonist, reduced bone mass in mice. The loss of bone mass in MDL11939-treated mice was associated with impaired bone formation in vivo , as demonstrated by the lower expression of osterix ( Osx ) and osteocalcin than that in vehicle-treated mice. On the other hand, no significant differences were observed in osteoclast numbers between MDL11939- and vehicle-treated mice. The pharmacological blockade of 5-HT 2A receptor signaling significantly decreased alkaline phosphatase activity in osteoblastic cells. In addition, the knockdown of the 5-HT 2A receptor by a siRNA treatment decreased Osx , but not Runx2 gene expression in MC3T3-E1 cells. These results suggest that 5-HT 2A receptor signaling mediated bone mass by regulating osteoblast differentiation. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH)-related protein (PTHrP), regulated by Indian hedgehog and acting through the PTH/PTHrP receptor (PPR), is crucial for normal cartilage development. These observations suggest a possible role of PPR signaling in the postnatal growth plate; however, the role of PPR signaling in postnatal chondrocytes is unknown. In this study, we have generated tamoxifeninducible and cartilage-specific PPR KO mice to evaluate the physiological role of PPR signaling in postnatal chondrocytes. We found that inactivation of the PPR in chondrocytes postnatally leads to accelerated differentiation of chondrocytes, followed by disappearance of the growth plate. We also observed an increase of TUNEL-positive cells and activities of caspase-3 and caspase-9 in the growth plate, along with a decrease in phosphorylation of Bad at 5er155 in postnatal PPR KO mice. Administration of a low-phosphate diet, which prevents apoptosis of chondrocytes, prevented the disappearance of the growth plate. Taken together, these observations suggest that the major consequences of PPR activation are similar in both the fetal and postnatal growth plates. Moreover, chondrocyte apoptosis through the activation of a mitochondrial pathway may be involved in the process of premature disappearance of the growth plate by postnatal inactivation of the PPR in chondrocytes. [ABSTRACT FROM AUTHOR]

Abstract: In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT2 receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT2A and 5-HT2C receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT2A receptor specific antagonist. Moreover, both DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT2A receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells. [Copyright &y& Elsevier]

For the rationalization of lightning protection design of distribution lines, it is important to clarify the behavior of distribution lines when direct or nearby lightning occurs. Because of the lower insulation level than for transmission lines, in studies on lightning protection design of distribution lines, not only direct lightning strokes but also induced voltages caused by nearby strokes must be taken into account. Thus, it is necessary to grasp the frequency of occurrence on lightning phenomena around distribution lines. For this aim, lightning phenomena on TEPCO's distribution lines in use had been continuously observed for 6 years (1996 to 2001). The observation was carried out in a composite way, using still cameras and sensor for acquisition of lightning surge waveform data. Through the observation, new phenomena about lightning performance on distribution lines in the field became apparent. In some cases, in spite of a direct strike to the line, flashover did not occur. This fact means that the distribution line has a certain level of lightning resistance. Moreover, it was confirmed that AC following current generated between both ends of insulator disappeared naturally. These results are interesting discoveries that can be useful in estimating the fault ratio precisely. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 157(1): 10–19, 2006; Published online in Wiley InterScience (http://www.interscience.wiley.com). DOI 10.1002/eej.20164 [ABSTRACT FROM AUTHOR]

Because of the lower insulation level than for transmission lines, in this study on lightning protection design of distribution lines, not only direct lightning strokes but also induced voltages caused by nearby strokes must be taken into account. Thus, it is necessary to grasp the frequency of occurrence of lightning phenomena around distribution lines. For this aim, lightning phenomena on TEPCO's distribution lines in use were continuously observed for 6 years (1996 to 2001). Through this observation, new interesting statistical data that can be a useful basis for rationalization of lightning protection design of distribution lines were obtained. Two hundred and four lightning strokes were observed through the six-year period. Probability of occurrence of a direct stroke was 22% (45 direct strokes were obtained). The fact that in 47% of direct strokes the electric outage did not occur is very interesting. Moreover, the value of surge discharge current of the arrester in the case of nearby stroke is the basis for conventional theory of grounding system. Therefore, statistical analysis of ZnO discharging current in the case of nearby strokes was carried out. As a result, in the case of nearby strokes, 5% value of cumulative frequency of discharging current is 0.5 kA. This value is half the conventional data. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 155(2): 8–16, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20180 [ABSTRACT FROM AUTHOR]

In order to elucidate mechanisms underlying modulation by static magnetism of the cellular functionality and/or integrity in the brain, we screened genes responsive to brief magnetism in cultured rat hippocampal neurons using differential display analysis. We have for the first time cloned and identified Ntan1 (amidohydrolase for N-terminal asparagine) as a magnetism responsive gene in rat brain. Ntan1 is an essential component of a protein degradation signal, which is a destabilizing N-terminal residue of a protein, in the N-end rule. In situ hybridization histochemistry revealed abundant expression of Ntan1 mRNA in hippocampal neurons in vivo. Northern blot analysis showed that Ntan1 mRNA was increased about three-fold after 3 h in response to brief magnetism. Brief magnetism also increased the transcriptional activity of Ntan1 promoter by luciferase reporter assay. Brief magnetism induced degradation of microtubule-associated protein 2 (MAP2) without affecting cell morphology and viability, which was prevented by a selective inhibitor of 26S proteasome in hippocampal neurons. Overexpression of Ntan1 using recombinant Ntan1 adenovirus vector resulted in a marked decrease in the MAP2 protein expression in hippocampal neurons. Our results suggest that brief magnetism leads to the induction of Ntan1 responsible for MAP2 protein degradation through ubiquitin–proteasome pathway in rat hippocampal neurons. [ABSTRACT FROM AUTHOR]

Brief exposure for 15 min to static magnetic filed at 100 mT led to marked but transient potentiation of binding of a radiolabeled probe for activator protein-1 (AP1) in immature cultured rat hippocampal neurons with high expression of growth-associated protein-43. Immunoblotting and supershift analyses revealed that brief exposure to static magnetic field increased AP1 DNA binding through expression of Fra-2, c-Jun, and Jun-D proteins in immature cultured hippocampal neurons. Significantly less potent increases were seen in both intracellular free Ca2+ concentration and AP1 binding following the addition of N-methyl-d-aspartate in these immature neurons exposed to magnetism 24 h before. These results suggest that brief exposure to weak static magnetic field may lead to desensitization of NMDA receptor channels through modulation of de novo synthesis of particular inducible target proteins at the level of gene transcription by the AP1 complex expressed in the nucleus of immature cultured rat hippocampal neurons. [Copyright &y& Elsevier]

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcriptional factor belonging to the basic helix-loop-helix-Per-Ahr/Arnt-Sim family. In this study, we evaluated the AhR agonistic activities of 12 xanthones isolated from the roots of M. cochinchinensis var. gerontogea using HepG2 cells transfected with pX4TK–Luc reporter plasmids. Gerontoxanthone B (GXB) showed the most potent activity at a concentration of 10 μM, and the activity was inhibited by AhR antagonists such as GNF-351. GXB also increased cytochrome P450 1A1 mRNA and protein levels in HepG2 cells. Similar to the AhR agonist 2,3,7,8-tetrachlorodibenzo- p -dioxin, however, GXB suppressed the IL-1β-induced mRNA level of SAA1 , an acute-phase response gene that is up-regulated AhR-dependently but XRE-independently. Thus, GXB shows XRE-dependent transcriptional activity and XRE-independent activity involving AhR. [ABSTRACT FROM AUTHOR]

Three new isocoumarins and two new phthalides, tubakialactones A–E ( 1 – 5 ), together with three known polyketides including ( R )-3,4-dihydro-4-hydroxyl-6,8-dimethoxy-4-methyl-3-methylene-1 H -2-benzopyran-1-one ( 6 ), (−)-5,7-dimethoxy-3-methyl-1(3 H )-isobenzofuranone ( 7 ), and isosclerone ( 8 ) were found in the endophytic fungus Tubakia sp. ECN-111 isolated from the leaves of Houttuynia cordata . The chemical structures of the new compounds were determined by spectroscopic analyses, including extensive 2D-NMR experiments. The absolute configuration of 3 and 7 was determined by optical rotation and circular dichroism. [ABSTRACT FROM AUTHOR]

This paper presents the fundamental surge phenomenon when a step voltage is applied to a horizontal line above the ground which has branch feeders. We study line current and voltage at joint with the method of moments that calculates electromagnetic field in frequency domain. It is widely noted that the current reflection factor changes to a third at the junction of the same three lines in conventional transmission line theory based on TEM wave, and the stepwise current reflected appears overlapping to the incident current. On the other hand, the reflected current from the joint shows the inductive characteristic or the capacitive one depending on the angle between lines, which varies gradually and not stepwise in our numerical analysis considering TM wave. The time characteristic of the voltage at joint depends on the angles also, and the peak voltage slightly exceeds the voltage by the transmission line theory. These phenomena are caused by the electromagnetic coupling between the main line and branch lines. In addition to the computer simulations, we measured the currents in the reduced-scale model lines and the results show the validity of our analysis regarding changes of the reflected current depending on the angles. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(2): 1–8, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10176 [ABSTRACT FROM AUTHOR]

An image sensor with an in-pixel demodulation function for detecting modulated light is proposed and demonstrated. The pixel has two floating diffusion regions, one of which stores charges produced by static illumination, and the other stores charges produced by both static and modulated illumination. By subtracting the two outputs, images produced only by the modulated illumination can be obtained. Based on the proposed circuit, an image sensor with 64 × 64 pixels is fabricated using a 0.6 µm two-poly three-metal CMOS technology. Using this sensor, we successfully demonstrate the extraction of the modulated component of images under constant illumination conditions. In addition, for the application of motion capture, we demonstrate that a marker, which is a modulated light source, can be extracted from a captured image under several light conditions by using this sensor. Finally, means of improving the characteristics of charge transfer efficiency are discussed. [ABSTRACT FROM AUTHOR]

Abstract The prevalence of obesity and its associated diseases is increasing worldwide, and the therapeutic potential of increasing energy expenditure through differentiation or activation of beige adipocytes has attracted much interest. Therefore, we explored naturally occurring compounds that induce beige adipocytes by screening for activity to induce mRNA expression of uncoupling protein 1 (UCP1) in stromal vascular fraction (SVF) cells cultured in beige adipocyte differentiation medium. Through screening, p -synephrine, a compound isolated from Citrus unshiu Marcov., was found to be an active compound that increased UCP1 mRNA expression in a dose-dependent manner from a concentration of 3.12 µM, which induced morphological changes specific for beige adipocytes. Similar effects were also observed in SVF cells prepared from db/db obese mice. While investigating the underlying mechanism of p -synephrine-induced beige adipocyte differentiation, we found that the effects of p- synephrine were abolished by the β3-adrenoceptor antagonist SR58894. Intriguingly, p -synephrine increased UCP1 mRNA levels in SVF cells cultured in beige adipocyte differentiation medium lacking insulin to an extent different from those by the β-agonist isoprenaline. Furthermore, phosphatidylinositol 3-kinase inhibitor LY294002 decreased isoprenaline-induced UCP1 mRNA levels in the early phase of beige adipocyte differentiation and p -synephrine-induced UCP1 mRNA levels in fully differentiated beige adipocytes. Thus, p -synephrine appears to elicit signals via β3-adrenoceptor combined with some part of the insulin signaling pathway, finally resulting in efficient stimulation of beige adipocyte differentiation with the support of certain beige adipocyte differentiation-inducing factors. The present results suggest the potential of p -synephrine for prophylaxis and treatment of obesity and its associated diseases. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system is known to regulate osteoclast development. However, the involvement of α2-adrenergic receptors (α2-ARs) in osteoclastogenesis is not well understood. In the present study, their potential role in osteoclastogenesis was investigated. Guanabenz, clonidine and xylazine were used as agonists of α2-ARs, while yohimbine and idazoxan were employed as antagonists. Using RAW264.7 pre-osteoclast and primary bone marrow cells, the mRNA expression of the osteoclast-related genes nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K was evaluated following induction with receptor activator of nuclear factor κB ligand (RANKL). TRAP staining was also conducted to assess effects on osteoclastogenesis in mouse bone marrow cells in vitro. Administration of 5-20 μM guanabenz (P<0.01, for RANKL-only treatment), 20 μM clonidine (P<0.05, for RANKL-only treatment) and 20 μM xylazine (P<0.05, for RANKL-only treatment) attenuated RANKL-induced upregulation of NFATc1, TRAP and cathepsin K mRNA. Furthermore, the reductions in these mRNAs by 10 μM guanabenz and 20 μM clonidine in the presence of RANKL were attenuated by 20 μM yohimbine or idazoxan (P<0.05). The administration of 5-20 μM guanabenz (P<0.01, for RANKL-only treatment) and 10-20 μM clonidine (P<0.05, for RANKL-only treatment) also decreased the number of TRAP-positive multi-nucleated osteoclasts. Collectively, the present study demonstrates that α2-ARs may be involved in the regulation of osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Diaporthols A ( 1 ) and B ( 2 ), two diphenyl ether derivatives, were isolated from cultures of an endophytic fungus Diaporthe sp. ECN-137 obtained from the leaves of Phellodendron amurense . The structures of 1 and 2 were determined by extensive spectroscopic analyses, and the structure of 2 was confirmed by X-ray crystallographic analysis. Compounds 1 and 2 showed anti-migration activities in TGF-β1-elicited MDA-MB-231 breast cancer cells at a concentration of 20 μM. [ABSTRACT FROM AUTHOR]

Serine racemase (SR) is responsible for the biosynthesis of D-serine (D-Ser), an endogenous co-agonist for the glycine (Gly)-binding site on N-methyl-D-aspartate (NMDA) receptors, from L-Ser in the brain. We have previously demonstrated high expression of SR by chondrocytes in cartilage. In this study, we attempted to elucidate the possible functional role of D-Ser in chondrogenesis. Expression of mRNA and corresponding protein was seen for SR in cultured rat costal chondrocytes, while the addition of L-Ser significantly increased intracellular and extracellular levels of D-Ser. In organotypic cultured mouse embryonic metatarsals isolated before vascularization, SR mRNA was highly localized in hypertrophic and calcified chondrocytes. Exposure to D-Ser not only suppressed several chondrocytic maturation markers, including alkaline phosphatase (ALP) activity, Ca2+ accumulation, nodule formation, and osteopontin expression, in rat chondrocytes, but also delayed chondral mineralization in mouse metatarsals. Either NMDA or Gly alone significantly increased Ca2+ accumulation in cultured chondrocytes, whereas D-Ser significantly prevented Ca2+ accumulation by Gly, but not by NMDA. Gly alone also significantly increased gene transactivation by the introduction of runt-related transcription factor-2 (Runx2) in COS7 cells transfected with NR1 and NR3A subunits, while D-Ser significantly prevented the increase by Gly without affecting the promoter activity of Runx2. In both cultured chondrocytes and metatarsals from NR1-null mice, significant decreases were seen in ALP activity and chondral mineralization, respectively. These results suggest that D-Ser may negatively regulate cellular differentiation through inhibiting NMDA receptors composed of NR1 and NR3A subunits in a manner related to Runx2 transcriptional activity in chondrocytes. J. Cell. Physiol. 220: 756–764, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Recently, the total number of distributed generators (DGs) such as photovoltaic generation system and wind turbine generation system connected to an actual distribution network has increased drastically. The distribution network connected to many distributed generators must be operated keeping reliability of power supply, power quality, and loss minimization. In order to accomplish active distribution network operation to take advantage of many connections of DGs, a new coordinated operation of distribution system with many connections of DGs is necessary. In this paper, the authors propose a coordinated operation of distribution network system connected to many DGs by using newly proposed sectionalizing switch control, sending voltage control, and computation of available DG connection capability. In order to check the validity of the proposed coordinated operation of distribution system, numerical simulations using the proposed coordinated distribution system operation are carried out in a practical distribution network model. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(3): 46–57, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20655 [ABSTRACT FROM AUTHOR]

Probability distribution of surge discharging current of arresters provided a basis for conventional theory of grounding systems. In order to rationalize the grounding systems, it is necessary to grasp the statistical data of lightning surges on distribution lines caused by direct lightning strokes and indirect lightning strokes. Lightning phenomena on TEPCO's distribution lines had been continuously observed for the rationalization of lightning protection design of distribution lines. The observation had been carried out with still cameras and monitoring sensors of lightning surges. This makes it possible to discover new interesting facts that can be useful for rationalization of lightning protection design of distribution lines. Cumulative frequency distribution of conventional data is close to that of ZnO discharging current in the case of direct strokes and indirect strokes through TEPCO's observation. Moreover, to verify the cumulative current distribution in concrete poles, the authors have compared the cumulative distribution of current through ground lines with that of current through ground lines and concrete poles. The results show that the distribution of current through ground lines and concrete poles is larger than that of current through only ground lines for high currents exceeding 1 kA. This fact suggests that lightning surge current flows not only in ground lines but also in concrete poles. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 165(2): 36–44, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20468 [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21) acts as an endocrine factor, playing important roles in the regulation of energy homeostasis, glucose and lipid metabolism. It is induced by diverse metabolic and cellular stresses, such as starvation and cold challenge, which in turn facilitate adaptation to the stress environment. The pharmacological action of FGF21 has received much attention, because the administration of FGF21 or its analogs has been shown to have an anti-obesity effect in rodent models. In the present study, we found that 3- O -acetyloleanolic acid, an active constituent isolated from the fruits of Forsythia suspensa , stimulated FGF21 production concomitant with the up-regulation of a transcription factor, nuclear receptor Nr4a1, in C2C12 myotubes. Additionally, significant increases in mFgf21 promoter activity were observed in C2C12 cells overexpressing TGR5 receptor in response to 3- O -acetyloleanolic acid treatment. Treatment with the p38 MAPK inhibitor SB203580 was effective at suppressing these stimulatory effects of 3- O -acetyloleanolic acid. Pretreatment with SB203580 also significantly repressed FGF21 mRNA abundance and FGF21 secretion in C2C12 myotubes after 3- O -acetyloleanolic acid stimulation, suggesting that p38 activation is required for the induction of FGF21 by ligand-activated TGR5 in C2C12 myotubes. These findings collectively indicated that TGR5 receptor signaling drives FGF21 expression via p38 activation, at least partly, by mediating Nr4a1 expression. Thus, the novel biological function of 3- O -acetyloleanolic acid as an agent having anti-obesity effects is likely to be mediated through the activation of TGR5 receptors. [Display omitted] • 3- O -acetyloleanolic acid, an active constituent isolated from the fruits of Forsythia suspensa , stimulated FGF21 in C2C12 myotubes. • TGR5 receptor signaling drives FGF21 expression via p38 activation. • Up-regulation of Nr4a1 after stimulation with 3- O -acetyloleanolic acid regulates FGF21. • Biological function of 3- O -acetyloleanolic acid as an agent having anti-obesity effects is likely mediated through the activation of TGR5. [ABSTRACT FROM AUTHOR]

In order to rationalize the lightning protection design of distribution lines, lightning phenomena on TEPCO's distribution lines were continuously observed. The observations were carried out with still cameras and lightning surge monitoring sensors. The results elucidate the lightning performance of distribution lines. For example, direct lightning strokes are the major cause of the present distribution line faults. This fact suggests that it is important to investigate observation data on direct lightning strokes. The observation data were analyzed by means of a direct lightning analysis model. The calculated waveforms were compared with the measured waveforms on distribution lines. The probability distributions of the surge currents and voltages were calculated by the Monte Carlo method. These results provide new data on lightning performance. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 91(10): 28– 37, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10164 [ABSTRACT FROM AUTHOR]

Abstract: We have previously identified Ntan1 as a magnetism response gene by differential display screening in cultured rat hippocampal neurons. Ntan1 mRNA was ubiquitously expressed in all the mouse tissues examined but relatively abundant in brain, retina and testis. Ntan1 mRNA expression was detectable in the embryonic 12-day mouse brain and gradually increased with ageing. In situ hybridization analysis showed high localization of Ntan1 mRNA in pyramidal cell layer of CA region and granular cell layer of dentate gyrus in the hippocampus, and Purkinje and granular cell layers in the cerebellum, respectively. Ntan1 mRNA expression was significantly increased about two-fold 12h after brief exposure for 15min to magnetism at 100mT with a gradual decrease thereafter in cultured mouse hippocampal neurons. When embryonic 12-day-old or newborn mice were successively exposed to magnetic fields at 100mT for 2h, four times per day until the postnatal seventh day, Ntan1 mRNA was significantly increased about 1.5–2-fold in the hippocampus in vivo. The mice exposed to magnetic fields under the same condition showed significantly decreased locomotor activity. These results suggest that magnetic exposure affects higher order neural functions through modulation of genes expression. [Copyright &y& Elsevier]

Abstract: We investigated the effect of 5-HT receptor antagonists on mechanical hyperalgesia observed in a neuropathic pain rat model prepared by chronic constriction injury of the sciatic nerve. NAN-190, a 5-HT1A receptor antagonist, (−)-pindolol, a 5-HT1A/1B receptor antagonist, and tropisetron, a 5-HT3/4 receptor antagonist, did not affect the pain threshold in the hyperalgesic hind limb to the same extent as in the normal hind limb. However, sarpogrelate and ketanserin, 5-HT2A receptor antagonists, significantly elevated the pain threshold in the hyperalgesic hind limb, but not in the normal hind limb. In spite of its high affinity for the 5-HT2A receptor, methysergide only slightly elevated the pain threshold in the hyperalgesic hind limb. Pre-treatment with methysergide significantly antagonized the inhibitory effect of sarpogrelate on hyperalgesia. Furthermore, the 5-HT2A receptor specific binding activity of 3H-ketanserin determined for the hyperalgesic hind limb did not differ from that of the normal hind limb. From these results, we propose that the 5-HT2A receptor in the hyperalgesic hind paw function as an agonist-independent active receptor following constriction of the sciatic nerve, and that sarpogrelate and ketanserin act as inverse agonists of this receptor and suppress its activation. Methysergide may act as a neutral antagonist that blocks the effect of inverse agonists on the 5-HT2A receptor. [Copyright &y& Elsevier]

Rat cortical neurons cultured for 3 days in vitro were loaded with the fluorescent indicator fluo-3 for assessment of intracellular free calcium ion (Ca[sup 2+]) concentrations with the aid of a confocal laser-scanning microscope. In the absence of added MgCI[sub 2], the addition of NMDA induced a rapid but sustained increase in the number of fluorescent neurons in a concentration-dependent manner at a concentration range of 1-100 µM with the increase by KCI being transient. The addition of FeCI[sub 2], but not FeCI[sub 3], markedly inhibited the increase by NMDA in a reversible manner at concentrations of 10-200 µM, without affecting that by KCI. Extensive analyses revealed clear differentiation between inhibitions by ferrous iron and other channel blockers known to date. The inhibition by FeCI[sub 2] was completely prevented by the addition of two different iron chelators. Exposure to NMDA alone did not lead to cell death in immature cultured neurons, however, while further addition of FeCI[sub 2] invariably induced neuronal cell death 24 h after exposure. These results give support to our previous proposal that NMDA receptor complex may contain a novel site sensitive to blockade by ferrous iron in rat brain. [ABSTRACT FROM AUTHOR]