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Seismic isolation is widely used in several countries, and the number of seismically isolated buildings has increased rapidly in recent decades. Seismic isolation extends the natural period of a building to decrease the absolute acceleration and seismic force. As there is a trade-off between the absolute acceleration and displacement, a soft layer results in a large displacement for a large seismic wave, but the hard one causes the large absolute acceleration even for a small seismic wave. The restoring force of a Duffing spring is given by the third and first orders of the displacement. This spring has been applied to protect a building from large earthquake waves. However, the influence of the coefficient of the Duffing spring that determines the dynamic characteristics of the system has not been clarified. Thus, a used Duffing spring may not be appropriate for seismic resistance. Moreover, most studies are based on analytical methods, and the advantages of the Duffing isolation have not been verified in an actual system. To address these problems, this paper reveals the influence of the coefficient of the Duffing spring on structural responses to seismic waves. Moreover, this paper devised a way to implement a Duffing spring for seismic isolation and carried out experiments to verify the validity in actual systems. The experimental results presented that the Duffing spring was effective in protecting a building in actual systems.

Seismic isolation is widely used in several countries, and the number of seismically isolated buildings has increased rapidly in recent decades. Seismic isolation extends the natural period of a building to decrease the absolute acceleration and seismic force. As there is a trade-off between the absolute acceleration and displacement, a soft layer results in a large displacement for a large seismic wave, but the hard one causes the large absolute acceleration even for a small seismic wave. The restoring force of a Duffing spring is given by the third and first orders of the displacement. This spring has been applied to protect a building from large earthquake waves. However, the influence of the coefficient of the Duffing spring that determines the dynamic characteristics of the system has not been clarified. Thus, a used Duffing spring may not be appropriate for seismic resistance. Moreover, most studies are based on analytical methods, and the advantages of the Duffing isolation have not been verified in an actual system. To address these problems, this paper reveals the influence of the coefficient of the Duffing spring on structural responses to seismic waves. Moreover, this paper devised a way to implement a Duffing spring for seismic isolation and carried out experiments to verify the validity in actual systems. The experimental results presented that the Duffing spring was effective in protecting a building in actual systems.

Seismic isolation is widely used in several countries, and the number of seismically isolated buildings has increased rapidly in recent decades. Seismic isolation extends the natural period of a building to decrease the absolute acceleration and seismic force. As there is a trade-off between the absolute acceleration and displacement, a soft layer results in a large displacement for a large seismic wave, but the hard one causes the large absolute acceleration even for a small seismic wave. The restoring force of a Duffing spring is given by the third and first orders of the displacement. This spring has been applied to protect a building from large earthquake waves. However, the influence of the coefficient of the Duffing spring that determines the dynamic characteristics of the system has not been clarified. Thus, a used Duffing spring may not be appropriate for seismic resistance. Moreover, most studies are based on analytical methods, and the advantages of the Duffing isolation have not been verified in an actual system. To address these problems, this paper reveals the influence of the coefficient of the Duffing spring on structural responses to seismic waves. Moreover, this paper devised a way to implement a Duffing spring for seismic isolation and carried out experiments to verify the validity in actual systems. The experimental results presented that the Duffing spring was effective in protecting a building in actual systems.

Oxidative metabolism in mitochondria regulates cellular differentiation and gene expression through intermediary metabolites and reactive oxygen species. Its role in kidney development and pathogenesis is not completely understood. Here we inactivated ubiquinone-binding protein QPC, a subunit of mitochondrial complex III, in two types of kidney progenitor cells to investigate the role of mitochondrial electron transport in kidney homeostasis. Inactivation of QPC in sine oculis-related homeobox 2 (SIX2)-expressing cap mesenchyme progenitors, which give rise to podocytes and all nephron segments except collecting ducts, resulted in perinatal death from severe kidney dysplasia. This was characterized by decreased proliferation of SIX2 progenitors and their failure to differentiate into kidney epithelium. QPC inactivation in cap mesenchyme progenitors induced activating transcription factor 4-mediated nutritional stress responses and was associated with a reduction in kidney tricarboxylic acid cycle metabolites and amino acid levels, which negatively impacted purine and pyrimidine synthesis. In contrast, QPC inactivation in ureteric tree epithelial cells, which give rise to the kidney collecting system, did not inhibit ureteric differentiation, and resulted in the development of functional kidneys that were smaller in size. Thus, our data demonstrate that mitochondrial oxidative metabolism is critical for the formation of cap mesenchyme-derived nephron segments but dispensable for formation of the kidney collecting system. Hence, our studies reveal compartment-specific needs for metabolic reprogramming during kidney development.

Oxidative metabolism in mitochondria regulates cellular differentiation and gene expression through intermediary metabolites and reactive oxygen species. Its role in kidney development and pathogenesis is not completely understood. Here we inactivated ubiquinone-binding protein QPC, a subunit of mitochondrial complex III, in two types of kidney progenitor cells to investigate the role of mitochondrial electron transport in kidney homeostasis. Inactivation of QPC in sine oculis-related homeobox 2 (SIX2)-expressing cap mesenchyme progenitors, which give rise to podocytes and all nephron segments except collecting ducts, resulted in perinatal death from severe kidney dysplasia. This was characterized by decreased proliferation of SIX2 progenitors and their failure to differentiate into kidney epithelium. QPC inactivation in cap mesenchyme progenitors induced activating transcription factor 4-mediated nutritional stress responses and was associated with a reduction in kidney tricarboxylic acid cycle metabolites and amino acid levels, which negatively impacted purine and pyrimidine synthesis. In contrast, QPC inactivation in ureteric tree epithelial cells, which give rise to the kidney collecting system, did not inhibit ureteric differentiation, and resulted in the development of functional kidneys that were smaller in size. Thus, our data demonstrate that mitochondrial oxidative metabolism is critical for the formation of cap mesenchyme-derived nephron segments but dispensable for formation of the kidney collecting system. Hence, our studies reveal compartment-specific needs for metabolic reprogramming during kidney development.

Oxidative metabolism in mitochondria regulates cellular differentiation and gene expression through intermediary metabolites and reactive oxygen species. Its role in kidney development and pathogenesis is not completely understood. Here we inactivated ubiquinone-binding protein QPC, a subunit of mitochondrial complex III, in two types of kidney progenitor cells to investigate the role of mitochondrial electron transport in kidney homeostasis. Inactivation of QPC in sine oculis-related homeobox 2 (SIX2)-expressing cap mesenchyme progenitors, which give rise to podocytes and all nephron segments except collecting ducts, resulted in perinatal death from severe kidney dysplasia. This was characterized by decreased proliferation of SIX2 progenitors and their failure to differentiate into kidney epithelium. QPC inactivation in cap mesenchyme progenitors induced activating transcription factor 4-mediated nutritional stress responses and was associated with a reduction in kidney tricarboxylic acid cycle metabolites and amino acid levels, which negatively impacted purine and pyrimidine synthesis. In contrast, QPC inactivation in ureteric tree epithelial cells, which give rise to the kidney collecting system, did not inhibit ureteric differentiation, and resulted in the development of functional kidneys that were smaller in size. Thus, our data demonstrate that mitochondrial oxidative metabolism is critical for the formation of cap mesenchyme-derived nephron segments but dispensable for formation of the kidney collecting system. Hence, our studies reveal compartment-specific needs for metabolic reprogramming during kidney development.

Oxidative metabolism in mitochondria regulates cellular differentiation and gene expression through intermediary metabolites and reactive oxygen species. Its role in kidney development and pathogenesis is not completely understood. Here we inactivated ubiquinone-binding protein QPC, a subunit of mitochondrial complex III, in two types of kidney progenitor cells to investigate the role of mitochondrial electron transport in kidney homeostasis. Inactivation of QPC in sine oculis-related homeobox 2 (SIX2)-expressing cap mesenchyme progenitors, which give rise to podocytes and all nephron segments except collecting ducts, resulted in perinatal death from severe kidney dysplasia. This was characterized by decreased proliferation of SIX2 progenitors and their failure to differentiate into kidney epithelium. QPC inactivation in cap mesenchyme progenitors induced activating transcription factor 4-mediated nutritional stress responses and was associated with a reduction in kidney tricarboxylic acid cycle metabolites and amino acid levels, which negatively impacted purine and pyrimidine synthesis. In contrast, QPC inactivation in ureteric tree epithelial cells, which give rise to the kidney collecting system, did not inhibit ureteric differentiation, and resulted in the development of functional kidneys that were smaller in size. Thus, our data demonstrate that mitochondrial oxidative metabolism is critical for the formation of cap mesenchyme-derived nephron segments but dispensable for formation of the kidney collecting system. Hence, our studies reveal compartment-specific needs for metabolic reprogramming during kidney development.

Oxidative metabolism in mitochondria regulates cellular differentiation and gene expression through intermediary metabolites and reactive oxygen species. Its role in kidney development and pathogenesis is not completely understood. Here we inactivated ubiquinone-binding protein QPC, a subunit of mitochondrial complex III, in two types of kidney progenitor cells to investigate the role of mitochondrial electron transport in kidney homeostasis. Inactivation of QPC in sine oculis-related homeobox 2 (SIX2)-expressing cap mesenchyme progenitors, which give rise to podocytes and all nephron segments except collecting ducts, resulted in perinatal death from severe kidney dysplasia. This was characterized by decreased proliferation of SIX2 progenitors and their failure to differentiate into kidney epithelium. QPC inactivation in cap mesenchyme progenitors induced activating transcription factor 4-mediated nutritional stress responses and was associated with a reduction in kidney tricarboxylic acid cycle metabolites and amino acid levels, which negatively impacted purine and pyrimidine synthesis. In contrast, QPC inactivation in ureteric tree epithelial cells, which give rise to the kidney collecting system, did not inhibit ureteric differentiation, and resulted in the development of functional kidneys that were smaller in size. Thus, our data demonstrate that mitochondrial oxidative metabolism is critical for the formation of cap mesenchyme-derived nephron segments but dispensable for formation of the kidney collecting system. Hence, our studies reveal compartment-specific needs for metabolic reprogramming during kidney development.

Primary cilia influence cell activity, and thus have a unique role in maintaining cell proliferation and differentiation. In atopic dermatitis (AD) and psoriasis, areas of skin inflammation exhibit dysregulated keratinocyte homeostasis. The role of primary cilia in these conditions remains unclear. The objectives of this study is to elucidate the incidence of primary cilia in skin inflammation and the potential mechanism underlying the dysregulation of keratinocytes. Primary cilia were observed using immunofluorescence staining. Normal skin samples were compared with skin samples from patients with AD or psoriasis in terms of cilia numbers and length. The effect of cytokine stimulation on ciliogenesis in keratinocytes was analysed using a primary keratinocyte culture. IFT88, an important ciliary intraflagellar protein, was blocked in Th2 and Th17 cytokines-stimulated keratinocytes. These effects were analysed with quantitative polymerase chain reaction and Western blot. Significant increases in ciliated cells were observed in AD and psoriasis skin samples compared with normal skin samples. The stimulation of keratinocytes using Th2 and Th17 cytokines modulated the formation of primary cilia. The amount of IFT88 in the primary cilia associated with the phosphorylation of JNK, but not p38, in keratinocytes stimulated with interleukin-13, 17A and 22. An increase of ciliated cells in the epidermis may impair keratinocyte differentiation under stress conditions caused by inflammation in both AD and psoriasis patients., identifier:1600-0625

BACKGROUND:There have been no reports describing how cervical reconstruction surgery affects global spinal alignment (GSA). OBJECTIVE:To elucidate the effects of cervical reconstruction for GSA through a retrospective multicenter study. METHODS:Seventy-eight patients who underwent cervical reconstruction surgery for cervical kyphosis were divided into a Head-balanced group (n = 42) and a Trunk-balanced group (n = 36) according to the values of the C7 plumb line (PL). We also divided the patients into a cervical sagittal balanced group (CSB group, n = 18) and a cervical sagittal imbalanced group (CSI group, n = 60) based on the C2 PL-C7 PL distance. Various sagittal Cobb angles and the sagittal vertical axes were measured before and after surgery. RESULTS:Cervical alignment was improved to achieve occiput-trunk concordance (the distance between the center of gravity [COG] PL, which is considered the virtual gravity line of the entire body, and C7 PL < 30 mm) despite the location of COG PL and C7PL. A subsequent significant change in thoracolumbar alignment was observed in Head-balanced and CSI groups. However, no such significant change was observed in Trunk-balanced and CSB groups. We observed 1 case of transient and 1 case of residual neurological worsening. CONCLUSION:The primary goal of cervical reconstruction surgery is to achieve occiput-trunk concordance. Once it is achieved, subsequent thoracolumbar alignment changes occur as needed to harmonize GSA. Cervical reconstruction can restore both cervical deformity and GSA. However, surgeons must consider the risks and benefits in such challenging cases.

Research team head, Research team member, Collaborator, Publisher, 本研究では実験用イメージング画像 (μCT) において解析可能である骨梁構造データを、医用イメージング画像 (MDCT) から評価可能とする計測系を確立する。これにより現在臨床において主流となっている骨密度評価法 (DEXA) に代わる、新たな骨密度・骨強度評価方法を確立する。さらに、本手法により得られた骨密度・骨強度と整形外科インプラントの設置強度の関係を調べることで、医用画像よりインプラント設置強度を予測する手法を開発する。また歯科におけるインプラント設置強度評価法を応用することで、手術中にインプラント強度を評価できる計測手法を確立する。 Resonance frequency analysis (RFA) has been used in dentistry to evaluate implant stability, but not in orthopaedics. The aim of this study was to use RFA to analyse pedicle screw stability and examine its relationship with micro-CT parameters. Biomechanical test materials : the implant stability quotient (ISQ) calculated from RFA was preserved in high-density materials, unlike traditional test forces (insertion torque and pull-out strength) with repeat screw insertion and create ‘loosening’. Human vertebrae: Traditional test forces showed the strongest correlations with BS/TV (insertion torque: R=0.681, pull-out strength: R=0.689). ISQ showed the strongest correlations with the number of branch points of the cancellous bone network: N.Nd/TV(R=0.533). Stepwise forward regression analysis showed that the predictions of traditional test forces improved when combined with BS/TV and pedicle diameter. The prediction of ISQ improved when combined with N.Nd/TV and pedicle length., 研究種目 : 基盤研究 (B) (一般) 研究期間 : 2016～2018 課題番号 : 16H03174 研究分野 : バイオメカニクス

BACKGROUND:There have been no reports describing how cervical reconstruction surgery affects global spinal alignment (GSA). OBJECTIVE:To elucidate the effects of cervical reconstruction for GSA through a retrospective multicenter study. METHODS:Seventy-eight patients who underwent cervical reconstruction surgery for cervical kyphosis were divided into a Head-balanced group (n = 42) and a Trunk-balanced group (n = 36) according to the values of the C7 plumb line (PL). We also divided the patients into a cervical sagittal balanced group (CSB group, n = 18) and a cervical sagittal imbalanced group (CSI group, n = 60) based on the C2 PL-C7 PL distance. Various sagittal Cobb angles and the sagittal vertical axes were measured before and after surgery. RESULTS:Cervical alignment was improved to achieve occiput-trunk concordance (the distance between the center of gravity [COG] PL, which is considered the virtual gravity line of the entire body, and C7 PL < 30 mm) despite the location of COG PL and C7PL. A subsequent significant change in thoracolumbar alignment was observed in Head-balanced and CSI groups. However, no such significant change was observed in Trunk-balanced and CSB groups. We observed 1 case of transient and 1 case of residual neurological worsening. CONCLUSION:The primary goal of cervical reconstruction surgery is to achieve occiput-trunk concordance. Once it is achieved, subsequent thoracolumbar alignment changes occur as needed to harmonize GSA. Cervical reconstruction can restore both cervical deformity and GSA. However, surgeons must consider the risks and benefits in such challenging cases.

This paper presents a mechanical model for predicting the behavior of elastomeric seismic isolation bearings subject to combined end rotations and shear deformation. The mechanical model consists of a series of axial springs at the top, mid-height and bottom of the bearing to vertically reproduce asymmetric bending moment distribution in the bearings. The model can take into account end rotations of the bearing, and the overall rotational stiffness includes the effect of the variation of vertical load on the bearing and the imposed shear deformation. Static bending tests under various combinations of vertical load and shear deformation were performed to identify the mechanical characteristics of bearings. The test results indicate that bearing rotational stiffness increases with increasing vertical load but decreases with increasing shear deformation. Simulation analyses were conducted to validate the new mechanical model. The results of analyses using the new model show very good agreement with experimental observations. A series of seismic response analyses were performed to demonstrate the dynamic behavior of top-of-column isolated structures, a configuration where the end rotations of isolation bearings are typically expected to be larger. The results suggest that the end rotations of elastomeric bearings used in practical top-of-column isolated structures do not reduce the stability limit of isolation system.

This paper presents a mechanical model for predicting the behavior of elastomeric seismic isolation bearings subject to combined end rotations and shear deformation. The mechanical model consists of a series of axial springs at the top, mid-height and bottom of the bearing to vertically reproduce asymmetric bending moment distribution in the bearings. The model can take into account end rotations of the bearing, and the overall rotational stiffness includes the effect of the variation of vertical load on the bearing and the imposed shear deformation. Static bending tests under various combinations of vertical load and shear deformation were performed to identify the mechanical characteristics of bearings. The test results indicate that bearing rotational stiffness increases with increasing vertical load but decreases with increasing shear deformation. Simulation analyses were conducted to validate the new mechanical model. The results of analyses using the new model show very good agreement with experimental observations. A series of seismic response analyses were performed to demonstrate the dynamic behavior of top-of-column isolated structures, a configuration where the end rotations of isolation bearings are typically expected to be larger. The results suggest that the end rotations of elastomeric bearings used in practical top-of-column isolated structures do not reduce the stability limit of isolation system.

Bakhtiyor Nosirov,1 Joël Billaud,1 Alexis Vandenbon,2 Diego Diez,3 Edward Wijaya,1 Ken J Ishii,4,5 Shunsuke Teraguchi,3 Daron M Standley1,6 1Systems Immunology Lab, 2Immuno-Genomics Research Unit, 3Quantitative Immunology Research Unit, 4Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Suita, 5Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka, 6Lab of Integrated Biological Information, Institute for Virus Research Kyoto University, Kyoto, Japan Purpose: Evidence suggests that circulating serum microRNAs (miRNAs) might preferentially target immune-related mRNAs. If this were the case, we hypothesized that immune-related mRNAs would have more predicted serum miRNA binding sites than other mRNAs and, reciprocally, that serum miRNAs would have more immune-related mRNA targets than non-serum miRNAs.Materials and methods: We developed a consensus target predictor using the random forest framework and calculated the number of predicted miRNA–mRNA interactions in various subsets of miRNAs (serum, non-serum) and mRNAs (immune related, nonimmune related).Results: Immune-related mRNAs were predicted to be targeted by serum miRNA more than other mRNAs. Moreover, serum miRNAs were predicted to target many more immune-related mRNA targets than non-serum miRNAs; however, these two biases in immune-related mRNAs and serum miRNAs appear to be completely independent.Conclusion: Immune-related mRNAs have more miRNA binding sites in general, not just for serum miRNAs; likewise, serum miRNAs target many more mRNAs than non-serum miRNAs overall, regardless of whether they are immune related or not. Nevertheless, these two independent phenomena result in a significantly larger number of predicted serum miRNA–immune mRNA interactions than would be expected by chance. Keywords: biomarker, posttranscriptional regulation, random forest, target prediction

Purpose: Evidence suggests that circulating serum microRNAs (miRNAs) might preferentially target immune-related mRNAs. If this were the case, we hypothesized that immune-related mRNAs would have more predicted serum miRNA binding sites than other mRNAs and, reciprocally, that serum miRNAs would have more immune-related mRNA targets than non-serum miRNAs., Materials and Methods: We developed a consensus target predictor using the random forest framework and calculated the number of predicted miRNA–mRNA interactions in various subsets of miRNAs (serum, non-serum) and mRNAs (immune related, nonimmune related)., Results: Immune-related mRNAs were predicted to be targeted by serum miRNA more than other mRNAs. Moreover, serum miRNAs were predicted to target many more immune-related mRNA targets than non-serum miRNAs; however, these two biases in immune-related mRNAs and serum miRNAs appear to be completely independent., Conclusion: Immune-related mRNAs have more miRNA binding sites in general, not just for serum miRNAs; likewise, serum miRNAs target many more mRNAs than non-serum miRNAs overall, regardless of whether they are immune related or not. Nevertheless, these two independent phenomena result in a significantly larger number of predicted serum miRNA–immune mRNA interactions than would be expected by chance.

Cancer cells contain a small population of cancer stem cells or cancer initiating cells, which can be enriched in the side population (SP) after fluorescence activated cell sorting. To examine the members of the ADAM, ADAMTS and MMP gene families related to phenotypes of the SP and the main population (MP), we screened the expression of all the members in the propagated SP and MP of A549 lung adenocarcinoma cells, and found that the relative expression ratio of ADAM23 in the MP to the SP is most highly increased, but none of them are increased in the SP. A similar result on the ADAM23 expression was obtained with another cell line, Calu-3 cells. Overexpression of ADAM23 inhibited colony formation, cell adhesion and migration, and knockdown of ADAM23 by shRNA showed the reverse effects. ADAM23-mediated suppression of colony formation, cell adhesion and migration was greatly reduced by treatment with neutralizing anti-ADAM23 antibody, anti-αvβ3 integrin antibody and/or ADAM23 disintegrin peptide. Expression of cancer stem cell-related genes, including AKRC1/2, TM4SF1 and NR0B1, was increased by knockdown of ADAM23. In addition, lung metastasis of A549 transfectants with different levels of ADAM23 expression was negatively regulated by the ADAM23 expression levels. Our data provide evidence that ADAM23 plays a role in suppression of cancer cell progression through interaction with αvβ3 integrin, and suggest that downregulation of ADAM23 in SP cells may contribute toward providing a cancer stem cell phenotype by facilitating the activity of integrin αvβ3., 博士（医学）・乙第1382号・平成28年9月28日, © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association., This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is noncommercial and no modifications or adaptations are made.

Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater and leads to neurological disturbances. We previously showed that familial SEDAC is caused by FOXC2 mutation; however, the causal gene of sporadic SEDAC has not been identified. To identify the causal gene of sporadic SEDAC, we performed whole exome sequencing for 12 subjects with sporadic SEDAC and identified heterozygous HOXD4 loss-of-function mutations in three subjects. HOXD4 haplo-insufficiency causes SEDAC and a transcriptional network containing HOXD4 and FOXC2 is involved in the development of the dura mater and the etiology of SEDAC.

Engineering Test Satellite-6 (ETS-6), known as Kiku-6, was launched at 16:50 (Japan time) on 28 August 1994. Although the satellite was inserted into orbit more or less according to plan, the firing of the apogee engine for orbital maneuvering failed completely, and the satellite was consequently positioned to assume an elliptical orbit. Thereafter, the secondary propulsion subsystem inserted the satellite into a 3-day circled subrecurrent orbit in order to conduct as many communication experiments as possible, and to minimize the effects of radiation on the experimental equipment by bypassing the Van Allen belts. This paper will report on the characteristics of all orbits where ETS-6 was positioned and on its operating status., NASDA Conference Publication, 宇宙開発事業団会議報告

Although failure of ETS-6 apogee engines threatened intersatellite communication experiments, the efforts of the all involved could bring fruitful results. (1) It was confirmed that functions and performance of KSA, FLCE and SIC were normally maintained in orbit by the initial checkout after launch and subsequent experiments with the DSS. (2) Furthermore, it was verified that SIC had compatibility with EUST at DSS. For comprehensive capability of ETS-6 as an intersatellite communication system, the Japan's first orbital experiments were successful with NASA's UARS so that cooperative support operation was more feasible. From these results, it was determined that the initial objectives were achieved; confirmation and verification of the basic technology necessary for the development of future DRTSS. Finally, sincere thanks are expressed to everyone in and out of the work groups that participated in this intersatellite communication experiments, the members of the ESA compatibility test, and NASA, especially the operation management staff of the UARS for their great support., NASDA Conference Publication, 宇宙開発事業団会議報告

Research team head, Research team member, Publisher, マウス脊髄損傷に対するマウス及びヒトiPS細胞由来神経幹細胞(iPSC-NS/PC)移植を行い、移植前にin vitroで安全なクローンを選別すれば、移植後に腫瘍形成はみられず、運動機能回復を促進することが明らかになった。さらに前臨床研究の最終段階として、サル脊髄損傷に対するヒトiPSC-NS/PC移植を行い、その安全性および有効性を確認した。安全性の評価を事前に十分行えば、ヒトiPSC-NS/PCは脊髄損傷に対する細胞移植療法における細胞供給源として有用である。, 研究種目 : 基盤研究(B) 研究期間 : 2009～2011 課題番号 : 21390426 研究分野 : 医歯薬学 科研費の分科・細目 : 外科系臨床医学・整形外科学

To evaluate the responses to the spring phytoplankton bloom, short-term changes in population structure and vertical distribution of mesopelagic copepods (Gaetanus simplex, Gaidius variabilis, Pleuromamma scutullata, Paraeuchaeta elongata, P. birostrata, Heterorhabdus tanneri and Heterostylites major) were studied in the Oyashio region. Samples were collected with a 60 mu m mesh VMPS from 9 strata between 0 and 1000 m both day and night on five occasions during March-April 2007. All the species except Heterorhabdidae species performed reproduction during the spring phytoplankton bloom, while no recruitment to copepodid stages was detected because the newly born individuals were eggs or nauplii. The shallower-living species, G. simplex, P. scutullata and P. elongata had nocturnal ascent did l vertical migration (DVM). While suspension feeding copepods cease DVM after 11 April (P. scutullata) or 23 April (G. simplex), carnivorous P. elongata continued DVM over the study period. Since the gut contents of G. simplex showed a nocturnal increment even in the period of no DVM (23 and 29 April), they might be feeding at depth without DVM. Thus, the cessation of DVM in mesopelagic suspension feeding copepods would be induced by the increase of sinking particles (e.g. food for suspension feeders) during the spring phytoplankton bloom. (C) 2012 Elsevier Ltd. All rights reserved.

To evaluate the responses to the spring phytoplankton bloom, short-term changes in population structure and vertical distribution of mesopelagic copepods (Gaetanus simplex, Gaidius variabilis, Pleuromamma scutullata, Paraeuchaeta elongata, P. birostrata, Heterorhabdus tanneri and Heterostylites major) were studied in the Oyashio region. Samples were collected with a 60 mu m mesh VMPS from 9 strata between 0 and 1000 m both day and night on five occasions during March-April 2007. All the species except Heterorhabdidae species performed reproduction during the spring phytoplankton bloom, while no recruitment to copepodid stages was detected because the newly born individuals were eggs or nauplii. The shallower-living species, G. simplex, P. scutullata and P. elongata had nocturnal ascent did l vertical migration (DVM). While suspension feeding copepods cease DVM after 11 April (P. scutullata) or 23 April (G. simplex), carnivorous P. elongata continued DVM over the study period. Since the gut contents of G. simplex showed a nocturnal increment even in the period of no DVM (23 and 29 April), they might be feeding at depth without DVM. Thus, the cessation of DVM in mesopelagic suspension feeding copepods would be induced by the increase of sinking particles (e.g. food for suspension feeders) during the spring phytoplankton bloom. (C) 2012 Elsevier Ltd. All rights reserved.

To evaluate the responses to the spring phytoplankton bloom, short-term changes in population structure and vertical distribution of mesopelagic copepods (Gaetanus simplex, Gaidius variabilis, Pleuromamma scutullata, Paraeuchaeta elongata, P. birostrata, Heterorhabdus tanneri and Heterostylites major) were studied in the Oyashio region. Samples were collected with a 60 mu m mesh VMPS from 9 strata between 0 and 1000 m both day and night on five occasions during March-April 2007. All the species except Heterorhabdidae species performed reproduction during the spring phytoplankton bloom, while no recruitment to copepodid stages was detected because the newly born individuals were eggs or nauplii. The shallower-living species, G. simplex, P. scutullata and P. elongata had nocturnal ascent did l vertical migration (DVM). While suspension feeding copepods cease DVM after 11 April (P. scutullata) or 23 April (G. simplex), carnivorous P. elongata continued DVM over the study period. Since the gut contents of G. simplex showed a nocturnal increment even in the period of no DVM (23 and 29 April), they might be feeding at depth without DVM. Thus, the cessation of DVM in mesopelagic suspension feeding copepods would be induced by the increase of sinking particles (e.g. food for suspension feeders) during the spring phytoplankton bloom. (C) 2012 Elsevier Ltd. All rights reserved.

Research team head, Research team member, Publisher, 研究種目 : 基盤研究(C) 研究期間 : 2008～2010 課題番号 : 20591329 研究分野 : 皮膚科 科研費の分科・細目 : 内科系臨床医学・皮膚科学, 落葉状天疱瘡は全身の皮膚に水疱、びらんをきたす自己免疫疾患であるが、自己抗体が抗原に結合してから水疱発生までの機序は明らかではない。本研究では正常ヒト皮膚器官培養にクローン化した抗体を局所注射し、経時的に超微細組織変化を観察した。病原性抗体注射後2時間後にはデスモソームの減少が見られ、22時間後にはデスモソームの消失と細胞離開が見られた。デスモソームの数が減少することによる細胞離開の経路が存在することが推察された。

Cerebral malaria is the most severe complication of Plasmodium falciparum infection in humans and the pathogenesis is still unclear. Using the P. berghei ANKA infection model of mice, we investigated a potential involvement of Nlrp3 and the inflammasome in the pathogenesis of cerebral malaria. Nlrp3 mRNA expression was upregulated in brain endothelial cells after exposure to P. berghei ANKA. Although ??-hematin, a synthetic compound of the parasites heme polymer hemozoin, induced the release of IL-1?? in macrophages through Nlrp3, we did not obtain evidence for a role of IL-1?? in vivo . Nlrp3 knock-out mice displayed a delayed onset of cerebral malaria; however, mice deficient in caspase-1, the adaptor protein ASC or the IL-1 receptor succumbed as WT mice. These results indicate that the role of Nlrp3 in experimental cerebral malaria is independent of the inflammasome and the IL-1 receptor pathway.

The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di-guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor kappaB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid-sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand.

The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di-guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor kappaB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid-sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand.

By using a synthetic photosensitive amphiphile containing azobenzene (KAON12), we developed a method for the photo-manipulation of lipid membrane morphology, in which the shape of a vesicle can be switched by light. Cell-sized liposomes are prepared from KAON12 and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We conducted real-time observations of vesicular transformation in the photo-sensitive liposome by phase-contrast microscopy, and found that membrane budding transitions could be controlled by light. These transformations can be interpreted in terms of the change in the effective membrane surface area due to photoisomerization of the constituent molecules. We discuss the mechanism by considering the elastic free energy of the membranes., identifier:https://dspace.jaist.ac.jp/dspace/handle/10119/9555

By using a synthetic photosensitive amphiphile containing azobenzene (KAON12), we developed a method for the photo-manipulation of lipid membrane morphology, in which the shape of a vesicle can be switched by light. Cell-sized liposomes are prepared from KAON12 and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We conducted real-time observations of vesicular transformation in the photo-sensitive liposome by phase-contrast microscopy, and found that membrane budding transitions could be controlled by light. These transformations can be interpreted in terms of the change in the effective membrane surface area due to photoisomerization of the constituent molecules. We discuss the mechanism by considering the elastic free energy of the membranes.

Research team head, Research team member, publisher, 研究種目：基盤研究(B) 研究期間：2007～2008 課題番号：19390400 研究分野：医歯薬学 科研費の分科・細目：外科系臨床医学・整形外科学, 本研究により、神経堤幹細胞は成体に至るまで胚葉を超えて各組織に潜伏しており、骨髄等において胚葉転換と表現されている組織幹細胞の多くが実は神経堤由来である可能性が示唆された。臨床応用を考えた場合、神経堤幹細胞は患者の組織から採取することが可能であり、倫理的問題や免疫拒絶反応を回避でき、さらに正常組織から回収するため腫瘍化の可能性も低く、脊髄損傷に対する自家細胞移植の新しい細胞供給源として有用と考えられる。

Fusulininan foraminifera are one of the most important index fossils from the late early Carboniferous to the Permian in having worldwide distribution and short stratigraphic range. But, in accordance with an increase of size and complexity of shells the areal distribution was successively more localized, and at the end of the Middle Permian the larger fusulines represented by the Verbeekinidae and the Schwagerininae of the Fusulinidae were almost extinguished....

The Permian limestone in west Cambodia is well known for its yield of a rich fauna of marine invertebrates. The stratigraphical and paleontological studies of the Permian limestone have been published by D_EPRAT (1912, 1913), M_ANSUY (1913, 1914), G_UBLER (1935a, b), D_ELPEY (1941-1942), S_KINNER and W_ILDE (1954), S_AURIN (1959), V_IEN (1959), C_HI-T_HUAN (1961), F_ONTAINE (1961, 1965, 1967), S_ERRA (1966), I_SHII and N_OGAMI (1964), I_SHII (1966), and by I_SHII, K_ATO and N_AKAMURA (1969)....

Fusulininan foraminifera are one of the most important index fossils from the late early Carboniferous to the Permian in having worldwide distribution and short stratigraphic range. But, in accordance with an increase of size and complexity of shells the areal distribution was successively more localized, and at the end of the Middle Permian the larger fusulines represented by the Verbeekinidae and the Schwagerininae of the Fusulinidae were almost extinguished....

The Permian limestone in west Cambodia is well known for its yield of a rich fauna of marine invertebrates. The stratigraphical and paleontological studies of the Permian limestone have been published by D_EPRAT (1912, 1913), M_ANSUY (1913, 1914), G_UBLER (1935a, b), D_ELPEY (1941-1942), S_KINNER and W_ILDE (1954), S_AURIN (1959), V_IEN (1959), C_HI-T_HUAN (1961), F_ONTAINE (1961, 1965, 1967), S_ERRA (1966), I_SHII and N_OGAMI (1964), I_SHII (1966), and by I_SHII, K_ATO and N_AKAMURA (1969)....

This limestone yields many fossils belonging to the Bivalvia, Gastropoda, Coelenterata, Porifera, Fusulinids etc. Mr.K.S.T_OONG of the Geological Survey Malaya and Dr.D.J.G_OBBETT of the University of Malaya have been working on the limestone....

In the winter 1966, the Committee for Southeast Asia Studies of the Osaka City University sent its 5th Scientific Expedition team to Southeast Asia. Three geologists, I_SHII, K_ATO and N_OGAMI jointly carried out field study in Sarawak, Pahang, Perak, Kedah and Perlis states of Malaysia....

Near Kodiang railway station in Kedah, Northwest Malaya several limestone hills are distributed above the plain. They are called Bukit Hantu, Bt. Kechil, Bt. Kalong, Bt. Kodiang, Bt. Kechil, Bt. Mutong and Bt. Kepelu, respectively, from the southwest to the northeast....

Between Temerloh and Maran in Pahang, Malaya there are two Middle Permian limestone localities. The one is located near the Jengka Pass (loc. M40) and the other is at the Kompong Awah Quarry (loc. M36)....