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Objectives Orthodontic tooth movement (OTM) increases sympathetic and sensory neurological markers in periodontal tissue. However, the relationship between the sympathetic and sensory nervous systems during OTM remains unclear. Therefore, the present study investigated the relationship between the sympathetic and sensory nervous systems activated by OTM using pharmacological methods. Materials and Methods We compared the effects of sympathectomy and sensory nerve injury during OTM in C57BL6/J mice. Capsaicin (CAP) was used to induce sensory nerve injury. Sympathectomy was performed using 6-hydroxydopamine. To investigate the effects of a β-agonist on sensory nerve injury, isoproterenol (ISO) was administered to CAP-treated mice. Furthermore, to examine the role of the central nervous system in OTM, the ventromedial hypothalamic nucleus (VMH) was ablated using gold thioglucose. Results Sensory nerve injury and sympathectomy both suppressed OTM and decreased the percent of the alveolar socket covered with osteoclasts (Oc.S/AS) in periodontal tissue. Sensory nerve injury inhibited increases in OTM-induced calcitonin gene-related peptide (CGRP) immunoreactivity (IR), a marker of sensory neurons, and tyrosine hydroxylase (TH) IR, a marker of sympathetic neurons, in periodontal tissue. Although sympathectomy did not decrease the number of CGRP-IR neurons in periodontal tissue, OTM-induced increases in the number of TH-IR neurons were suppressed. The ISO treatment restored sensory nerve injury-inhibited tooth movement and Oc.S/AS. Furthermore, the ablation of VMH, the centre of the sympathetic nervous system, suppressed OTM-induced increases in tooth movement and Oc.S/AS. Conclusions The present results suggest that OTM-activated sensory neurons contribute to enhancements in osteoclast activity and tooth movement through sympathetic nervous signalling. [ABSTRACT FROM AUTHOR]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]