Kyoto, Japan
Kyoto, Japan

Doshisha University , also referred to as Dodai , is a private university in Kyoto City, Japan. Established in 1875, it is one of the oldest private institutions of higher learning in Japan, and has approximately 30,000 students enrolled on four different campuses in Kyoto. It is one of the Japanese "Global 30" universities and one of the "Kankandoritsu," a group of the four leading private universities in the Kansai region of western Japan.Doshisha was founded by Joseph Hardy Neesima as "Doshisha English School", and in 1920 it was granted university status. The university now encompasses 14 faculties and 16 graduate schools with numerous affiliated institutions including Doshisha Women's College of Liberal Arts. Wikipedia.

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Exercise has numerous health-promoting effects in humans; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine selenoprotein P (SeP) causes exercise resistance through its muscle receptor low-density lipoprotein receptor–related protein 1 (LRP1). SeP-deficient mice showed a 'super-endurance' phenotype after exercise training, as well as enhanced reactive oxygen species (ROS) production, AMP-activated protein kinase (AMPK) phosphorylation and peroxisome proliferative activated receptor γ coactivator (Ppargc)-1α (also known as PGC-1α; encoded by Ppargc1a) expression in skeletal muscle. Supplementation with the anti-oxidant N-acetylcysteine (NAC) reduced ROS production and the endurance capacity in SeP-deficient mice. SeP treatment impaired hydrogen-peroxide-induced adaptations through LRP1 in cultured myotubes and suppressed exercise-induced AMPK phosphorylation and Ppargc1a gene expression in mouse skeletal muscle—effects which were blunted in mice with a muscle-specific LRP1 deficiency. Furthermore, we found that increased amounts of circulating SeP predicted the ineffectiveness of training on endurance capacity in humans. Our study suggests that inhibitors of the SeP–LRP1 axis may function as exercise-enhancing drugs to treat diseases associated with a sedentary lifestyle. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Sakurai Y.,Kyoto University | Takahashi S.,Doshisha University
European Journal of Neuroscience | Year: 2013

The aim of this study was to examine the potential ability of neuronal groups to enhance their activities by conditioning without behaviors. We employed a method of neuronal operant conditioning in which increments in the firing rates and synchrony of closely neighboring neurons in the motor cortex and hippocampus were rewarded in the absence of behaviors. Rats were trained to engage in a free-operant task in which nose-poke behaviors were rewarded in session 1, and firing rates and synchrony above preset criteria were rewarded in sessions 2 and 3, respectively. The firing rates of motor cortical and hippocampal neuron groups were found to increase rapidly in session 2 similarly to the nose-poke behavior in session 1. Placing contingency of reward on firing synchrony resulted in selective enhancement of firing synchrony of only hippocampal neurons in session 3. Control experiments revealed that the enhancement of neuronal firing was not attributable to increments of superstitious behaviors or excitation caused by reward delivery. Analysis of the firing rates and synchrony of individual neurons and neuron pairs in each group revealed that the firing rates and synchrony of some but not all neurons and neuron pairs increased in each group. No enhancement was observed in any neurons and neuron pairs recorded by neighboring electrodes not used for conditioning. These results suggest that neuronal operant conditioning enhances the firing rates and synchrony of only some neurons in small restricted areas. The present findings are expected to contribute to further research into neurorehabilitation and neuroprosthesis. We examined the ability of closely neighboring groups of neurons in the motor cortex and hippocampus to enhance their activities by neuronal operant conditioning. The firing rates of motor cortical and hippocampal neuron groups increased rapidly and contingency of reward on firing synchrony resulted in selective enhancement of firing synchrony of only hippocampal neuron pairs. The conditioning enhanced the firing rates and synchrony of only some neurons and neuron pairs in each group. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Yao L.,Max Planck Institute for Biophysical Chemistry | Sakaba T.,Max Planck Institute for Biophysical Chemistry | Sakaba T.,Doshisha University
Proceedings of the National Academy of Sciences of the United States of America | Year: 2012

Although Ca 2+/calmodulin has been suggested to play a role during endocytosis, it remains unknown if binding of Ca 2+ to calmodulin is essential for initiating endocytosis or if this interaction only has a modulatory effect on endocytosis. In this study, using timeresolved capacitance measurements at the rat calyx of Held synapse, the role of calmodulin in endocytosis was examined. Our results demonstrate that blocking calmodulin with an inhibitory peptide, which interfers with the binding of calmodulin to downstream targets, slowed the rate of endocytosis, but only when accompanied by high Ca 2+ influx. In response to a short train of action potential-like stimulation, blocking calmodulin had no effect on endocytosis. Furthermore, we have identified conditions in which inhibition of calmodulin fails to affect the rate of endocytosis, but nevertheless retards recruitment of synaptic vesicles to the fast-releasing vesicle pool responsible for synchronous release. The results indicate that calmodulin facilitates endocytosis in an activity-dependent manner but is not mandatory for endocytosis, and suggest that calmodulin modulates an endocytotic intermediate process, which in turn affects synaptic vesicle recruitment and membrane fission.

Hirano T.,Kyoto University | Kawaguchi S.-Y.,Doshisha University
Frontiers in Cellular Neuroscience | Year: 2014

Purkinje cells receive both excitatory and inhibitory synaptic inputs and send sole output from the cerebellar cortex. Long-term depression (LTD), a type of synaptic plasticity, at excitatory parallel fiber-Purkinje cell synapses has been studied extensively as a primary cellular mechanism of motor learning. On the other hand, at inhibitory synapses on a Purkinje cell, postsynaptic depolarization induces long-lasting potentiation of GABAergic synaptic transmission. This synaptic plasticity is called rebound potentiation (RP), and its molecular regulatory mechanisms have been studied. The increase in intracellular Ca2+ concentration caused by depolarization induces RP through enhancement of GABAA receptor (GABAAR) responsiveness. RP induction depends on binding of GABAAR with GABAAR associated protein (GABARAP) which is regulated by Ca2+/calmodulindependent kinase II (CaMKII). Whether RP is induced or not is determined by the balance between phosphorylation and de-phosphorylation activities regulated by intracellular Ca2+ and by metabotropic GABA and glutamate receptors. Recent studies have revealed that the subunit composition of CaMKII has significant impact on RP induction. A Purkinje cell expresses both α- and β-CaMKII, and the latter has much higher affinity for Ca2+/calmodulin than the former. It was shown that when the relative amount of α- to β-CaMKII is large, RP induction is suppressed. The functional signicicance of RP has also been studied using transgenic mice in which a peptide inhibiting association of GABARAP and GABAAR is expressed selectively in Purkinje cells. The transgenic mice show abrogation of RP and subnormal adaptation of vestibulo-ocular reclex (VOR), a type of motor learning. Thus, RP is involved in a certain type of motor learning © 2014 Hirano and Kawaguchi.

Hori T.,Doshisha University | Hori T.,Okinawa Institute of Science and Technology | Takahashi T.,Doshisha University | Takahashi T.,Okinawa Institute of Science and Technology
Neuron | Year: 2012

After releasing neurotransmitter, synaptic vesicles are retrieved by endocytosis and recycled via fast and slow pathways to be reused for synaptic transmission. To maintain the synaptic efficacy, vesicles must be refilled with neurotransmitter during recycling. However, the refilling speed estimated in isolated or reconstructed vesicles is, thus far, too slow to fill up vesicles within the period of recycling. Here, we re-examined the vesicle refilling rate directly at central glutamatergic synapses in slices, using simultaneous presynaptic and postsynaptic whole-cell recording combined with caged glutamate photolysis. After washing out vesicular glutamate, refilling of vesicles with uncaged glutamate caused a recovery of EPSCs with a time constant of 15 s that varied depending upon temperature, age, and cytosolic Cl- concentrations. This time constant is faster than that of the slow recycling pathway (∼30 s) after clathrin-mediated endocytosis but is much too slow to fill up vesicles replenished through fast recycling pathways (<1 s).

Midorikawa M.,Doshisha University | Sakaba T.,Doshisha University
Neuron | Year: 2015

Synaptic vesicles are tethered to the active zone where they are docked/primed so that they can fuse rapidly upon Ca2+ influx. To directly study these steps at a CNS presynaptic terminal, we used total internal reflection fluorescence (TIRF) microscopy at the live isolated calyx of Held terminal and measured the movements of single synaptic vesicle just beneath the plasma membrane. Only a subset of vesicles within the TIRF field underwent exocytosis. Following exocytosis, new vesicles (newcomers) approached the membrane and refilled the release sites slowly with a time constant of several seconds. Uniform elevation of the intracellular Ca2+ using flash photolysis elicited an exocytotic burst followed by the sustained component, representing release of the readily releasable vesicles and vesicle replenishment, respectively. Surprisingly, newcomers were not released within a second of high Ca2+. Instead, already-tethered vesicles became release-ready and mediated the replenishment. Our results reveal an important feature of conventional synapses. © 2015 Elsevier Inc.

Tsukagoshi K.,Doshisha University
Analytical Sciences | Year: 2014

The author herein reviews a specific microfluidic behavior exhibited by mixed-solvent solutions in a microspace, coined as the tube radial distribution phenomenon (TRDP). The specific fluidic behavior was observed in the following solution systems: ternary water-hydrophilic/hydrophobic organic solvents, water-surfactant, water-ionic liquid, and fluorous/organic solvents. When the mixed homogeneous solutions were delivered into a microspace under certain conditions, the solvent molecules were radially distributed in the microspace, generating inner and outer phases with a kinetic liquid-liquid interface. The TRDP was fundamentally evaluated by fluorescence microscopy, phase diagrams construction, and the elution behaviors of solutes in a capillary tube. A TRDP-based capillary chromatography, referred to as tube radial distribution chromatography (TRDC), where the outer phase serves as a pseudo-stationary phase under laminar flow conditions, has been developed as one of the applications of TRDP. We have also investigated TRDP-based extraction, chemical reaction, and mixing processes, coined as tube radial distribution extraction (TRDE), tube radial distribution reaction (TRDR), and tube radial distribution mixing (TRDM), respectively. The concept and experimentalfindings regarding TRDP, TRDC, TRDE, TRDR, and TRDM are described in this review. © 2014 The Japan Society for Analytical Chemistry.

Kouzu M.,Doshisha University | Hidaka J.-S.,Doshisha University
Fuel | Year: 2012

Vegetable oil is one of the biomass resources generated from carbon dioxide and water with the aid of photosynthesis, and is converted into an alternative to fossil diesel fuel by transesterifying with methanol. The eco-friendly fuel, termed as "Biodiesel", is manufactured with the help of alkali hydroxide, but its homogeneous catalysis gives rise to some technological problems: a massive amount of wastewater, soap formation and so on. Therefore, much interest has been taken in utilizing the heterogeneous catalysis of solid base for biodiesel production. Calcium oxide (CaO) is a candidate for the solid base catalyst from an economical point of view. In the present work, we reviewed CaO catalyst for the vegetable oil transesterification on the basis of a variety of the concerning research papers. After catalytic properties of the basic sites generated on CaO were described preliminarily, a mechanism on the vegetable oil transesterification catalyzed by CaO was explained. Then, procedure to prepare the active CaO catalyst, its deactivation occurring under the reacting condition and modification of CaO catalyst were discussed. Finally, the practical use of CaO catalyst for industrial biodiesel production was studied with pointing out the required future works. © 2011 Elsevier Ltd. All rights reserved.

Hanabusa K.,Doshisha University
Renewable and Sustainable Energy Reviews | Year: 2012

The aim of this paper is to show the influence of the 107th OPEC Ordinary Meeting (meeting) and investigates the relationships between oil prices and economic activities, using an exponential generalized autoregressive conditional heteroskedasticity (EGARCH) and a vector autoregressive (VAR) model from 1991 to 2008 in Japan. We find that levels and volatilities of oil prices increase after the meeting. We examine the effects of it on Japanese economic activities, employing a Granger-causality test and data before and after it. The empirical result reveals that each price of regular gasoline and diesel has information to be useful to predict the economy after the meeting. On the other hand, volatilities of regular gasoline and diesel price have information to predict the inflation and economic growth before the meeting, respectively. After the meeting, however, these volatilities change to be useful to predictive both inflation and economic growth. Thus, we conclude that the decision of meeting is related to not only the domestic oil prices, but also the macroeconomy. © 2011 Elsevier Ltd. All rights reserved.

Kawaguchi S.-Y.,Doshisha University | Sakaba T.,Doshisha University
Neuron | Year: 2015

An axon is thought to faithfully conduct action potentials to its terminals. However, many features of the axon and axon terminals, especially at inhibitory synapses, remain unknown. By directly recording from the axon and terminal of a cultured cerebellar Purkinje cell (PC), we demonstrate that low membrane excitability of axon terminals shapes synaptic output. Simultaneous measurements of presynaptic capacitance and evoked IPSCs revealed PC axon terminals contained large readily releasable synaptic vesicles that exhibited a low release probability. Nevertheless, IPSCs evoked by stimulating a PC soma underwent frequency-dependent depression. Direct axonal recordings showed that high-frequency action potentials were faithfully conducted over axonal bifurcations but were attenuated around terminals. Sparse Na+ channels relative to enriched voltage-gated K+ channels in terminals caused short-term depression of IPSCs by reducing Ca2+ influx. Together with confirmation in slice recordings, our findings reveal a presynaptic mechanism that shapes short-term synaptic depression without depleting releasable vesicles. © 2015 Elsevier Inc.

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