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Takahashi T.,Suntory Institute for Bioorganic Research | Ohnishi H.,Japan National Institute of Advanced Industrial Science and Technology | Ohnishi H.,Kyoto University | Sugiura Y.,Keio University | And 13 more authors.
FEBS Journal | Year: 2014

Non-neuronal acetylcholine (ACh) is predicted to function as a local cell signaling molecule. However, the physiological significance of the synthesis of non-neuronal ACh in the intestine remains unclear. Here, experiments using crypt-villus organoids that lack nerve and immune cells in culture led us to suggest that endogenous ACh is synthesized in the intestinal epithelium to evoke growth and differentiation of the organoids through activation of muscarinic ACh receptors (mAChRs). The extracts of the cultured organoids showed a noticeable capacity for ACh synthesis that was sensitive to a potent inhibitor of choline acetyltransferase. Imaging MS revealed endogenous ACh localized in the epithelial layer in mouse small intestinal epithelium in vivo, suggesting that there are non-neuronal resources of ACh. Treatment of organoids with carbachol downregulated the growth of organoids and the expression of marker genes for epithelial cells. On the other hand, antagonists for mAChRs enhanced the growth and differentiation of organoids, indicating the involvement of mAChRs in regulating the proliferation and differentiation of Lgr5-positive stem cells. Collectively, our data provide evidence that endogenous ACh released from intestinal epithelium maintains homeostasis of intestinal epithelial cell growth and differentiation via mAChRs in mice. © 2014 FEBS.


Seki F.,Keio University | Seki F.,Central Institute for Experimental Animals | Hikishima K.,Keio University | Hikishima K.,Central Institute for Experimental Animals | And 9 more authors.
Frontiers in Neuroanatomy | Year: 2013

Naked mole-rats have a variety of distinctive features such as the organization of a hierarchical society (known as eusociality), extraordinary longevity, and cancer resistance; thus, it would be worthwhile investigating these animals in detail. One important task is the preparation of a brain atlas database that provide comprehensive information containing multidimensional data with various image contrasts, which can be achievable using a magnetic resonance imaging (MRI). Advanced MRI techniques such as diffusion tensor imaging (DTI), which generates high contrast images of fiber structures, can characterize unique morphological properties in addition to conventional MRI. To obtain high spatial resolution images, MR histology, DTI, and X-ray computed tomography were performed on the fixed adult brain. Skull and brain structures were segmented as well as reconstructed in stereotaxic coordinates. Data were also acquired for the neonatal brain to allow developmental changes to be observed. Moreover, in vivo imaging of naked mole-rats was established as an evaluation tool of live animals. The data obtained comprised three-dimensional (3D) images with high tissue contrast as well as stereotaxic coordinates. Developmental differences in the visual system were highlighted in particular by DTI. Although it was difficult to delineate optic nerves in the mature adult brain, parts of them could be distinguished in the immature neonatal brain. From observation of cortical thickness, possibility of high somatosensory system development replaced to the visual system was indicated. 3D visualization of brain structures in the atlas as well as the establishment of in vivo imaging would promote neuroimaging researches towards detection of novel characteristics of eusocial naked mole-rats. © 2013 Seki, Hikishima, Nambu, Okanoya, Okano, Sasaki, Miura and Okano.


Motoyoshi K.,Tohoku University | Tajima A.,Tohoku University | Higuchi T.,Tohoku University | Yabu H.,Tohoku University | And 2 more authors.
Soft Matter | Year: 2010

This paper reports static and dynamic control of the phase separation structures of polymer blended nanoparticles. The phase separated nanoparticles were prepared from various combinations of polymers by evaporating good solvents from the polymer blended solutions after adding poor solvents into the solutions. Transmission electron microscope observation of the nanoparticles shows that two types of phase separation structures were formed in them. One is Janus type structure and another is core-shell type structure. When the difference of the Flory-Huggins solubility parameter (δ) between two blended polymers is large, one polymer having a higher δ value encapsulated another polymer. As a result, a core-shell type structure is formed. On the other hand, when the difference of δ value is small, both moieties of polymer are exposed to the poor solvent, and then, a Janus structure is formed. Moreover, when the thermoresponsive polymer was blended with a hydrophobic polymer, a Janus type or core-shell structure was formed by changing the preparation temperature. The core-shell type structure was transformed to a Janus type structure by heating the nanoparticles. This control and transformation of structures of nanoparticles can be applied to nano-sensing devices, switching devices and drug delivery systems. © 2011 The Royal Society of Chemistry.


Hiraishi K.,Tohoku University | Masuhara A.,Tohoku University | Kasai H.,Tohoku University | Kasai H.,Precursory Research for Embryonic Science and Technology | And 2 more authors.
Japanese Journal of Applied Physics | Year: 2010

We report the optical and electrical properties of Cu-TCNQ (TCNQ = 7,7',8,8'-tetracyanoquinodimethane) nanocrystals (NCs) fabricated by previously reported chemical reduction reprecipitation methods. The size of the resulting NCs ranges from 50 nm to 10 μm along the long axis. Raman experiment, X-ray photoelectron spectroscopic experiment, and elemental analysis reveal that these NCs have few TCNQ dianions due to the excess amount of Cu. The absorption of interband transition in the near-infrared region shows a blue shift, and the band gap increases with decreasing NC size. The obtained NCs show high electric conductivity, compared with typical Cu-TCNQ microcrystals, and multistep switching due to the existence of TCNQ dianions. © 2010 The Japan Society of Applied Physics.


Yamamoto H.M.,Japan Institute for Molecular Science | Yamamoto H.M.,RIKEN | Yamamoto H.M.,Precursory Research for Embryonic Science and Technology | Nakano M.,Tohoku University | And 8 more authors.
Nature Communications | Year: 2013

In state-of-the-art silicon devices, mobility of the carrier is enhanced by the lattice strain from the back substrate. Such an extra control of device performance is significant in realizing high-performance computing and should be valid for electric-field-induced superconducting (SC) devices, too. However, so far, the carrier density is the sole parameter for field-induced SC interfaces. Here we show an active organic SC field-effect transistor whose lattice is modulated by the strain from the substrate. The soft organic lattice allows tuning of the strain by a choice of the back substrate to make an induced SC state accessible at low temperature with a paraelectric solid gate. An active three-terminal Josephson junction device thus realized is useful both in advanced computing and in elucidating a direct connection between filling-controlled and bandwidth-controlled SC phases in correlated materials. © 2013 Macmillan Publishers Limited.


News Article | March 18, 2016
Site: www.greencarcongress.com

« DOE announces $3M for 2nd round of HPC4Mfg for industry access to high performance computing | Main | IEEE publishes three updated standards to support connected vehicle development » Scientists at Tokyo Institute of Technology, in collaboration with colleagues in Japan, have demonstrated the first electrochemical reaction based on hydride ions in an oxide-based solid-state cell for potential next-generation batteries. A paper on their work is published in the journal Science. Ionic transport has been studied extensively over the years for energy devices such as fuel cells and batteries using Li+, H+, Ag+, Cu+, F–, and O2– as ionic charge carriers. The conduction of hydride ions, H–, is also attractive, the team notes in their paper. In contrast to proton conduction that takes place widely in oxides and other systems, pure H– conduction has been verified only for a few hydrides of alkaline earth metals such as BaH . Unfortunately, utilization of the hydrides is difficult because of their structural inflexibility, which makes control of the lattice structure to create smooth transport pathways and control of the conducting hydride ion content difficult. Using an oxyhydride solid state cell, the researchers have now demonstrated pure H- conduction in an oxide for the first time. Metal hydrides tend to have an inflexible lattice, which makes H– transport difficult, so the researchers turned to oxyhydrides where oxygen and hydrogen share the same lattice sites. Another challenge is the high electron-donating properties of H-, which means that the electrons will dissociate from the H- to produce protons and electrons, giving rise to electron rather than hydride-ion transport. As a result the team sought a system containing cations that were more electron-donating than the H-. Genki Kobayashi and Ryoji Kanno from Tokyo Tech collaborated with colleagues from the Institute for Molecular Science, Japan Science and Technology Agency, Tokyo Institute of Technology, Kyoto University and High Energy Accelerator Research Organization (KEK) in Japan. They examined how the structure of their oxyhydride compounds changed with composition and synthesis conditions. They also studied characteristics of the electronic structure that suggested an ionic Li-H bond in the compound—the existence of H– in the oxides. They then used La LiHO in an orthorhombic structural phase (o-La LiHO ) as an electrolyte in a cell with titanium anode and titanium hydride cathodes. Phase changes at the electrodes by the discharge were consistent with a Ti-H phase diagram suggesting hydride-ion transport. In a Perspective on the work by Kobayashi et al., published in the same issue of Science, Shu Yamaguchi of The University of Tokyo observed that: Kobayashi et al. report a material with pure H− conductivity (and yet an electronic insulator) in an oxyhydride system, which has been a “last frontier” in solid state ionics. … The result … is just the beginning of a new materials science of H− conductivity in oxyhydride systems that will require further elaboration of the underlying mechanisms, as well as potential applications of the extremely reducing H− ion in chemical synthesis. A drawback of the current material is its chemical reactivity in oxidizing atmospheres, but this disadvantage may be overcome by various techniques, like surface protection coatings. These explorations of H− conductors now leave the question of what will be the next last frontier for solid state ionics. This research was supported by Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), and Grant-in-Aid for Scientific Research on Innovative Areas from the Japan Society for the Promotion of Science (JSPS).


Okuyama-Uchimura F.,Nara Institute of Science and Technology | Komai S.,Nara Institute of Science and Technology | Komai S.,Precursory Research for Embryonic Science and Technology | Komai S.,Japan Science and Technology Agency
Perception | Year: 2016

In contrast to the previously held notion that mice have a weak visual system, it is now generally accepted that mice can perceive rather complicated figures in various contexts such as in cognitive experiments and in social settings. Here, we show that mice could even be capable of perceiving a visual illusion—subjective contours. This illusion requires the visual system to compensate for a lack of visual information in compressed 2D images on the retina. In this experiment, we trained mice to respond appropriately to a rectangle-shaped rewarded figure of specific orientation in a two-choice visual discrimination task with a touchscreen monitor. In Transfer Test 1, mice could discriminate illusory rectangle-shaped figures significantly as compared with a figure, which did not induce illusory figures. In Transfer Test 2, the choice rate of targets decreased with imperfect illusory figures, which produced weak perception of rotated or deficient inducers. Moreover, in Transfer Test 3, mice could not discriminate the low-resolution illusory figure, which also induced weak perception. These results demonstrated the possibility that mice might be useful for investigating fundamental properties of the neural visual system. © 2015, © The Author(s) 2015.


Mizuhashi K.,Osaka Bioscience Institute | Mizuhashi K.,Kyoto University | Kanamoto T.,Osaka University | Ito M.,Nagasaki University | And 9 more authors.
Development Growth and Differentiation | Year: 2012

In vertebrate bone formation, the functional mechanisms of transcription factors in osteoblastic differentiation have been relatively well elucidated; however, the exact roles of cell-extrinsic molecules are less clear. We previously identified human and mouse Obif, an osteoblast induction factor, also known as Tmem119, which encodes a single transmembrane protein. OBIF is predominantly expressed in osteoblasts in mouse. While exogenous Obif expression stimulated osteoblastic differentiation, knockdown of Obif inhibits the osteoblastic differentiation of pre-osteoblastic MC3T3-E1 cells. In order to investigate an in vivo role of OBIF in bone formation, we generated Obif-deficient mice by targeted gene disruption. Analyses of micro-computed tomography (mCT) revealed that Obif -/- mice exhibit significantly reduced cortical thickness in the mid-shaft of the femur at postnatal day 14 (P14). Furthermore, progressive bone hypoplasia is observed after 8weeks. The expression levels of osteoblast marker genes, Collagen 1a1, Osteopontin, Runx2, and Osterix, in the calvaria were decreased in Obif -/- mice at P4. These data indicate that Obif plays an essential role in bone formation through regulating osteoblastogenesis. © 2012 The Authors. Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.


Shichita T.,Keio University | Shichita T.,Precursory Research for Embryonic Science and Technology | Sakaguchi R.,Keio University | Sakaguchi R.,Japan Science and Technology Agency | And 4 more authors.
Frontiers in Immunology | Year: 2012

Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. In this review, we focus on the post-ischemic inflammation triggered by infiltrating immune cells, macrophages, and T lymphocytes. Brain ischemia is a sterile organ, but injury-induced inflammation is mostly dependent on Toll-like receptor (TLR) 2 andTLR4. Some endogenousTLR ligands, high mobility group box 1 (HMGB1) and peroxiredoxin family proteins, in particular, are implicated in the activation and inflammatory cytokine expression in infiltrating macrophages. Following macrophage activation, T lymphocytes infiltrate the ischemic brain and regulate the delayed phase inflammation. IL17-producing γδT lymphocytes induced by IL-23 from macrophages promote ischemic brain injury, whereas regulatory T lymphocytes suppress the function of inflammatory mediators. A deeper understanding of the inflammatory mechanisms of infiltrating immune cells may lead to the development of novel neuroprotective therapies. © 2012 Shichita, Sakaguchi, Suzuki and Yoshimura.


Yamada T.,University of Tokyo | Tani Y.,University of Tokyo | Nakanishi H.,University of Tokyo | Taguchi R.,University of Tokyo | And 5 more authors.
FASEB Journal | Year: 2011

Acute inflammation in healthy individuals is self-limiting and has an active termination program. The mechanisms by which acute inflammation is resolved are of interest. In murine zymosan-induced peritonitis, we found that eosinophils are recruited to the inflamed loci during the resolution phase of acute inflammation. In vivo depletion of eosinophils caused a resolution deficit, namely impaired lymphatic drainage with reduced appearance of phagocytes carrying engulfed zymosan in the draining lymph node, and sustained numbers of polymorphonuclear leukocytes in inflamed tissues. Liquid chromatography-tandem mass spectrometry-based lipidomics of the resolving exudates revealed that locally activated eosinophils in the resolution phase produced proresolving mediators, including protectin D1 (PD1) from docosa-hexaenoic acid. The resolution deficit caused by eosinophil depletion was rescued by eosinophil restoration or the administration of PD1. Eosinophils deficient in 12/15-lipoxygenase could not rescue the resolution phenotype. The present results indicate that mouse eosinophils and eosinophil-derived lipid mediators, including PD1, have a role in promoting the resolution of acute inflammation, expanding the roles of eosinophils in host defense and resolution. © FASEB.

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