642 results on '"Masahiro Nakajima"'
Search Results
2. Clinical study for the characteristics and treatment of masticatory muscle tendon-aponeurosis hyperplasia
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Tomoko Fujii, Kenji Kakudo, Rio Min, Masahiro Watanabe, Tomokazu Motohashi, Yuichi Shoju, Hirohito Kubo, Yuichi Ohnishi, and Masahiro Nakajima
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Otorhinolaryngology ,Surgery ,Oral Surgery ,Pathology and Forensic Medicine - Published
- 2022
3. Does postoperative masticatory training for prognathism contribute to functional improvement?
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Rio Min, Tomokazu Motohashi, Yuichi Shoju, Hirohito Kubo, and Masahiro Nakajima
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Otorhinolaryngology ,Surgery ,Oral Surgery ,Pathology and Forensic Medicine - Published
- 2022
4. Analysis of factors affecting postoperative relapse after bilateral saggital split osteotomy for mandibuler set back
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Akio Himejima, Masahiro Nakajima, Tomoko Fujii, Tomokazu Motohashi, Yuichi Shoju, Yuichi Ohnishi, Kentaro Okuno, and Tomio Iseki
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Otorhinolaryngology ,Surgery ,Oral Surgery ,Pathology and Forensic Medicine - Published
- 2022
5. Novel glycoside hydrolase family enzymes fromEscherichia coliare associated with osmo-regulated periplasmic glucan synthesis
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Sei Motouchi, Kaito Kobayashi, Hiroyuki Nakai, and Masahiro Nakajima
- Abstract
Most Gram-negative bacteria synthesize osmo-regulated periplasmic glucans (OPG) in the periplasm or extracellular space. Many pathogens lose their pathogenicity by knocking outopgG, an OPG-related gene indispensable for OPG synthesis. However, the biochemical functions of OpgG and OpgD, a paralog of OpgG, have not been elucidated. In this report, structural and functional analyses of OpgG and OpgD fromEscherichia colirevealed that these proteins are β-1,2-glucanases with remarkably different activity, establishing a new glycoside hydrolase family. Furthermore, a reaction mechanism with an unprecedentedly long proton transfer pathway is proposed for OpgD. The conformation of the region that forms the reaction pathway differs noticeably between OpgG and OpgD, which explains the observed low activity of OpgG. The findings enhance our understanding of OPG biosynthesis and provide insights into functional diversity for this novel enzyme family.
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- 2023
6. β-1,2-Glucans and associated enzymes
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Masahiro Nakajima
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Genetics ,Animal Science and Zoology ,Cell Biology ,Plant Science ,Molecular Biology ,Biochemistry ,Ecology, Evolution, Behavior and Systematics - Published
- 2022
7. Author response for 'Identification of a functional susceptibility variant for adolescent idiopathic scoliosis that upregulates <scp>EGR1</scp> ‐mediated UNCX expression'
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null Yoshiro Yonezawa, null Long Guo, null Hisaya Kakinuma, null Nao Otomo, null Soichiro Yoshino, null Kazuki Takeda, null Masahiro Nakajima, null Toshiyuki Shiraki, null Yoji Ogura, null Yohei Takahashi, null Yoshinao Koike, null Shohei Minami, null Koki Uno, null Noriaki Kawakami, null Manabu Ito, null Ikuho Yonezawa, null Kei Watanabe, null Takashi Kaito, null Haruhisa Yanagida, null Hiroshi Taneichi, null Katsumi Harimaya, null Yuki Taniguchi, null Hideki Shigematsu, null Takahiro Iida, null Satoru Demura, null Ryo Sugawara, null Nobuyuki Fujita, null Mitsuru Yagi, null Eijiro Okada, null Naobumi Hosogane, null Katsuki Kono, null Kazuhiro Chiba, null Toshiaki Kotani, null Tsuyoshi Sakuma, null Tsutomu Akazawa, null Teppei Suzuki, null Kotaro Nishida, null Kenichiro Kakutani, null Taichi Tsuji, null Hideki Sudo, null Akira Iwata, null Tatsuya Sato, null Satoshi Inami, null Masaya Nakamura, null Morio Matsumoto, null Chikashi Terao, null Kota Watanabe, null Hitoshi Okamoto, and null Shiro Ikegawa
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- 2022
8. Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression
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Yoshiro Yonezawa, Long Guo, Hisaya Kakinuma, Nao Otomo, Soichiro Yoshino, Kazuki Takeda, Masahiro Nakajima, Toshiyuki Shiraki, Yoji Ogura, Yohei Takahashi, Yoshinao Koike, Shohei Minami, Koki Uno, Noriaki Kawakami, Manabu Ito, Ikuho Yonezawa, Kei Watanabe, Takashi Kaito, Haruhisa Yanagida, Hiroshi Taneichi, Katsumi Harimaya, Yuki Taniguchi, Hideki Shigematsu, Takahiro Iida, Satoru Demura, Ryo Sugawara, Nobuyuki Fujita, Mitsuru Yagi, Eijiro Okada, Naobumi Hosogane, Katsuki Kono, Kazuhiro Chiba, Toshiaki Kotani, Tsuyoshi Sakuma, Tsutomu Akazawa, Teppei Suzuki, Kotaro Nishida, Kenichiro Kakutani, Taichi Tsuji, Hideki Sudo, Akira Iwata, Tatsuya Sato, Satoshi Inami, Masaya Nakamura, Morio Matsumoto, Chikashi Terao, Kota Watanabe, Hitoshi Okamoto, and Shiro Ikegawa
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Endocrinology, Diabetes and Metabolism ,Orthopedics and Sports Medicine - Abstract
Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).
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- 2022
9. Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use
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Tatsuya Sato, Yuki Taniguchi, Morio Matsumoto, Yohei Takahashi, Katsumi Harimaya, Mitsuru Yagi, Katsuki Kono, Ryo Sugawara, Koki Uno, Akira Iwata, Ikuyo Kou, Yukihide Momozawa, Masaru Koido, Kazuhiro Chiba, Kotaro Nishida, Masaya Nakamura, Kazuki Takeda, Masahiro Nakajima, Tsutomu Akazawa, Yoji Ogura, Nao Otomo, Taichi Tsuji, Kenichiro Kakutani, Kazuo Kaneko, Hiroshi Taneichi, Manabu Ito, Yuta Kochi, Noriaki Kawakami, Takahiro Iida, Toshiaki Kotani, Wei Chiao Chang, Hideki Shigematsu, Teppei Suzuki, Kota Watanabe, Eijiro Okada, Shohei Minami, Nobuyuki Fujita, Shiro Ikegawa, Haruhisa Yanagida, Chikashi Terao, Yoichiro Kamatani, Michiaki Kubo, Takashi Kaito, Naobumi Hosogane, Satoshi Inami, Satoru Demura, Kei Watanabe, Hsing Fang Lu, Tsuyoshi Sakuma, and Hideki Sudo
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Oncology ,medicine.medical_specialty ,Adolescent ,Cobb angle ,business.industry ,Endocrinology, Diabetes and Metabolism ,Genome-wide association study ,Odds ratio ,Heritability ,Twin study ,Genetic correlation ,Bone and Bones ,Decile ,Scoliosis ,Risk Factors ,Internal medicine ,medicine ,Humans ,Female ,Orthopedics and Sports Medicine ,Kyphosis ,business ,Body mass index ,Genome-Wide Association Study - Abstract
Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10-40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10-10 ) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10-8 ), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10-4 ). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).
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- 2021
10. Gasdermin D–mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma
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Ryota Yamagishi, Fumitaka Kamachi, Masaru Nakamura, Shota Yamazaki, Tomonori Kamiya, Masaki Takasugi, Yi Cheng, Yoshiki Nonaka, Yoshimi Yukawa-Muto, Le Thi Thanh Thuy, Yohsuke Harada, Tatsuya Arai, Tze Mun Loo, Shin Yoshimoto, Tatsuya Ando, Masahiro Nakajima, Hayao Taguchi, Takamasa Ishikawa, Hisaya Akiba, Sachiko Miyake, Masato Kubo, Yoichiro Iwakura, Shinji Fukuda, Wei-Yu Chen, Norifumi Kawada, Alexander Rudensky, Susumu Nakae, Eiji Hara, and Naoko Ohtani
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Pore Forming Cytotoxic Proteins ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Immunology ,General Medicine ,Phosphate-Binding Proteins ,Interleukin-33 ,肝星細胞 ,Mice ,制御性T細胞 ,Hepatic Stellate Cells ,Tumor Microenvironment ,肝がん ,Animals ,Humans ,Obesity ,SASP因子 ,リポタイコ酸 ,Cellular Senescence ,細胞老化随伴分泌現象 - Abstract
研究グループは、肝臓に移行した腸内細菌叢の成分であるリポタイコ酸が、肝がん微小環境を変化させてがんの増殖進展を促進するSASP(Senescence-associated secretory phenotype、細胞老化随伴分泌現象)因子を老化肝星細胞から放出させるメカニズムを明らかにしました。がんの組織はがん細胞そのものだけでなく、線維芽細胞や免疫細胞など、様々な種類の細胞種が集まって「がん微小環境」を構成しています。進行したがん組織の微小環境ではがん細胞周囲の細胞ががんの増殖を助長していると考えられています。本グループは、脂肪肝を素地とする肝がん微小環境では、肝星細胞と呼ばれる線維芽細胞が細胞老化を引き起こしており、「細胞老化随伴分泌現象(SASP)」という様々な分泌因子を放出する現象が生じ、その分泌因子(SASP因子)ががんの増殖を促進することを以前から見出していました。しかしこれまでにSASP因子の放出メカニズムについては明らかにされていませんでした。本研究では高脂肪食摂取による肥満誘導性肝がんのマウスモデルを用い、老化肝星細胞の細胞膜上にガスダーミンDというタンパク質が酵素切断されて生じたN末端側の部分(以降GSDMD-Nと略記)が集合して形成される小孔を介して、SASP因子に含まれるサイトカインIL-1βとIL-33が細胞の外部に放出されることを明らかにしました。また、高脂肪食摂取マウスでは、腸管バリアが脆弱化しており、肝臓にグラム陽性腸内細菌の細胞壁成分であるリポタイコ酸が蓄積していました。さらに、蓄積したリポタイコ酸は老化肝星細胞にトル様受容体2(TLR2)を介した刺激を入れ続け、酵素切断で生じたGSDMD-Nによる細胞膜上の小孔形成とそれに続くIL-33やIL-1βの放出を促進していることもわかりました。老化肝星細胞から放出されたIL-33は、その受容体ST2が陽性の制御性T細胞(Treg細胞)に作用し、がんの増殖を促進させることがわかりました。また、GSDMD-NはヒトのNASH(Non-alcoholic steatohepatitis)肝がんの腫瘍部にある肝星細胞でもその存在が認められました。これらの結果から、ガスダーミンDによる小孔形成を阻害する薬剤は肝がんの予防や治療につながる可能性があります。, Long-term senescent cells exhibit a secretome termed the senescence-associated secretory phenotype (SASP). Although the mechanisms of SASP factor induction have been intensively studied, the release mechanism and how SASP factors influence tumorigenesis in the biological context remain unclear. In this study, ...
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- 2022
11. Regional Revitalization from the View Point of Local Human Resource Development
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Satoshi NAKAMURA, Tadayuki MIYACHI, Toyokazu KUBOTA, Masahiro NAKAJIMA, Masahiko KIKUCHI, Shuichi NAKAGAWA, Masaya NAKATSUKA, and Kazunobu TSUTSUI
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- 2021
12. [Review] Structures and Functions of β-1,2-Glucan-associated Enzymes and Proteins
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Masahiro Nakajima
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chemistry.chemical_classification ,Enzyme ,chemistry ,Biochemistry ,General Medicine ,Glucan - Published
- 2021
13. Study on Environmental Characteristics of Agricultural Watercourses Supporting Children's Play in Areas 30 Years after the Water Environment Improvement Program
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Masahiro Nakajima, Masayuki Nitta, Takuto Fujimori, and Mitsuru Ohira
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Thesaurus (information retrieval) ,Engineering ,Agriculture ,business.industry ,Environmental resource management ,Water environment ,business - Published
- 2019
14. The Effects of the Cooperation among Members on the Activities in the 'Local Vitalization Cooperators' Project
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Masahiro Nakajima, Yoshiki Kuwabara, and Sae Takeuchi
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Process management ,Work (electrical) ,Business - Published
- 2019
15. Bone Regeneration by Dedifferentiated Fat Cells Using Composite Sponge of Alfa-Tricalcium Phosphate and Gelatin in a Rat Calvarial Defect Model
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Nobuhito Tsumano, Hirohito Kubo, Rie Imataki, Yoshitomo Honda, Yoshiya Hashimoto, and Masahiro Nakajima
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Fluid Flow and Transfer Processes ,Technology ,QH301-705.5 ,Process Chemistry and Technology ,Physics ,QC1-999 ,General Engineering ,rat calvarial defect ,animal study ,Engineering (General). Civil engineering (General) ,alfa-tricalcium phosphate ,Computer Science Applications ,Chemistry ,bone regeneration ,dedifferentiated fat cells ,General Materials Science ,TA1-2040 ,Biology (General) ,Instrumentation ,QD1-999 - Abstract
Mechanical and resorbable scaffolds are in high demand for stem cell-based regenerative medicine, to treat refractory bone defects in craniofacial abnormalities and injuries. Multipotent progenitor cells, such as dedifferentiated fat (DFAT) cells, are prospective sources for regenerative therapies. Herein, we aimed to demonstrate that a composite gelatin sponge (α-TCP/GS) of alfa-tricalcium phosphate (α-TCP) mixed with gelatin scaffolds (GS), with/without DFATs, induced bone regeneration in a rat calvarial defect model in vivo. α-TCP/GS was prepared by mixing α-TCP and 2% GS using vacuum-heated methods. α-TCP/GS samples with/without DFATs were transplanted into the model. After 4 weeks of implantation, the samples were subjected to micro-computed tomography (μ-CT) and histological analysis. α-TCP/GS possessed adequate mechanical strength; α-TCP did not convert to hydroxyapatite upon contact with water, as determined by X-ray diffraction. Moreover, stable α-TCP/GS was formed by electrostatic interactions, and verified based on the infrared peak shifts. μ-CT analyses showed that bone formation was higher in the α-TCP/GS+ DFAT group than in the α-TCP/GS group. Therefore, the implantation of α-TCP/GS comprising DFAT cells enhanced bone regeneration and vascularization, demonstrating the potential for healing critical-sized bone defects.
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- 2021
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16. Reconstruction of a system for using and managing agricultural irrigation water stock through 'critical succession'
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Masayuki Nitta and Masahiro Nakajima
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Agricultural irrigation ,business.industry ,Environmental resource management ,Ecological succession ,business ,Assistant professor ,Stock (geology) - Abstract
Professor Masahiro Nakajima and Assistant Professor Masayuki Nitta are collaborating on a project that focuses on the reconstruction of a system that utilises and manages agricultural irrigation water stocks through maintenance and innovation. Their focus for the project is Japanese communities.
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- 2020
17. Large-scale preparation of β-1,2-glucan using quite a small amount of sophorose
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Kaito Kobayashi, Masahiro Nakajima, Hayao Taguchi, Hiroyuki Nakai, Tadahisa Iwata, Satoshi Kimura, and Hiroki Aramasa
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0301 basic medicine ,beta-Glucans ,Scale (ratio) ,Sophorose ,Applied Microbiology and Biotechnology ,Biochemistry ,Phosphates ,Substrate Specificity ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Glucans ,Molecular Biology ,Glucan ,chemistry.chemical_classification ,Chromatography ,030102 biochemistry & molecular biology ,Hydrolysis ,Organic Chemistry ,Sucrose phosphorylase ,General Medicine ,Acceptor ,Kinetics ,030104 developmental biology ,chemistry ,Glucosyltransferases ,Biotechnology - Abstract
A large amount of β-1,2-glucan was produced enzymatically from quite a small amount of sophorose as an acceptor material through three synthesis steps using a sucrose phosphorylase and a 1,2-β-oligoglucan phosphorylase. The first synthesis step was performed in a 200 μL of a reaction solution containing 5 mM sophorose and 1.0 M sucrose. β-1,2-Glucan in a part of the resultant solution was hydrolyzed to β-1,2-glucooligosaccharides by a β-1,2-glucanase. The second synthesis was performed in 25 times the volume for the first synthesis. The hydrolysate solution (1% volume of the reaction solution) was used as an acceptor. After treatment with the β-1,2-glucanase again, the third synthesis was performed 200 times the volume for the second synthesis (1 L). The reaction yield of β-1,2-glucan at each synthesis was 93%, 76% and 91%. Finally, more than 140 g of β-1,2-glucan was synthesized using approximately 20 μg of sophorose as the starting acceptor material. Abbreviations: DPs: degrees of polymerization; SOGP: 1,2-β-oligoglucan phosphorylase; Sopns: β-1,2-glucooligosaccharides with DP of n; Glc1P: α-glucose 1-phosphate; SucP: sucrose phosphorylase from Bifidobacterium longum subsp. longum; SGL: β-1,2-glucanase; CaSGL: Chy400_4174 protein; TLC: thin layer chromatography; GOPOD: glucose oxidase/peroxidase; PGM: phosphoglucomutase; G6PDH: glucose 6-phosphate dehydrogenase
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- 2019
18. A population-based study identifies an association of THBS2 with intervertebral disc degeneration
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Masatoshi Teraguchi, Hiroshi Hashizume, Hiroshi Yamada, Shiro Ikegawa, Munehito Yoshida, Tsuyoshi Deguchi, Noriko Yoshimura, Toru Akune, Shu Tanaka, Masahiro Nakajima, and M. Nojima
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Male ,0301 basic medicine ,medicine.medical_specialty ,Population ,Biomedical Engineering ,Single-nucleotide polymorphism ,Intervertebral Disc Degeneration ,Degeneration (medical) ,Logistic regression ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Rheumatology ,Internal medicine ,medicine ,Humans ,Orthopedics and Sports Medicine ,education ,Association (psychology) ,Aged ,Aged, 80 and over ,030203 arthritis & rheumatology ,education.field_of_study ,business.industry ,Intervertebral disc ,Odds ratio ,Middle Aged ,Cross-Sectional Studies ,030104 developmental biology ,medicine.anatomical_structure ,Female ,Thrombospondins ,business ,Body mass index - Abstract
To clarify the genetic mechanisms underlying intervertebral disc degeneration (IDD), we examined the associations between single-nucleotide polymorphisms (SNPs) and indicated as coefficient of interaction term (IDD) in a general population in Japan.This was a cross-sectional study. In 1,605 participants, C2-3 to L5/S1 in the total spine magnetic resonance imaging (MRI) were evaluated using the Pfirrmann's scoring system. Disc scores of 4 and 5 were defined as IDD. Eight SNPs in eight genes associated with IDD were examined at each disc level, considering the non-genetic risk factors of age, sex, and body mass index (BMI).The highest odds ratio was found for rs9406328 in the THBS2 gene at disc level T12-L1 (OR 1.27, 95%CI 1.05 to 1.53), and this association was strengthened after adjustment for age using logistic regression (OR 1.37, 95%CI 1.12 to 1.67). Among participants aged50 years and 50-59, the average IDD score in those with 2 risk alleles of rs9406328 was markedly higher than in those with 0 or 1 risk allele, and the difference is much wider than the elderly participants. It indicates the genetic effect of rs9406328 is stronger in the younger age groups. Finally, multiple linear regression analyses of the association between rs9406328 and IDD, adjusted for age, sex, and BMI at each disc level, showed a statistical interaction between age and the number of risk alleles at C7-T1, T3-4 and T4-T5 as well as T12-L1.CONCLUSION: The association between rs9406328 in THBS2 and IDD was replicated. The contributions of genetic and environmental factors to IDD differed by disc level.
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- 2019
19. Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese
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Taichi Tsuji, Tsuyoshi Sakuma, Hideki Sudo, Haruhisa Yanagida, Kota Watanabe, Kotaro Nishida, Mitsuru Yagi, Kazuhiro Chiba, Shohei Minami, Takahiro Iida, Masaya Nakamura, Tsutomu Akazawa, Manabu Ito, Hiroshi Taneichi, Nobuyuki Fujita, Hsing Fang Lu, Noriaki Kawakami, Chikashi Terao, Yukihide Momozawa, Tatsuya Sato, Yoichiro Kamatani, Toshiaki Kotani, Kazuki Takeda, Morio Matsumoto, Nao Otomo, Ikuho Yonezawa, Teppei Suzuki, Ryo Sugawara, Shiro Ikegawa, Yohei Takahashi, Katsumi Harimaya, Eijiro Okada, Kenichiro Kakutani, Ikuyo Kou, Akira Iwata, Satoru Demura, Naobumi Hosogane, Koki Uno, Hideki Shigematsu, Masahiro Nakajima, Kei Watanabe, Satoshi Inami, Yoji Ogura, Takashi Kaito, Katsuki Kono, Yuki Taniguchi, and Michiaki Kubo
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0301 basic medicine ,Male ,Adolescent ,Science ,Quantitative Trait Loci ,General Physics and Astronomy ,Genome-wide association study ,02 engineering and technology ,Quantitative trait locus ,Biology ,Genome-wide association studies ,General Biochemistry, Genetics and Molecular Biology ,Article ,Body Mass Index ,03 medical and health sciences ,Sex Factors ,Asian People ,Japan ,Humans ,Genetic Predisposition to Disease ,lcsh:Science ,Bone ,Genetic association ,Genetics ,Multidisciplinary ,Disease genetics ,General Chemistry ,Heritability ,021001 nanoscience & nanotechnology ,Phenotype ,Uric Acid ,030104 developmental biology ,Scoliosis ,Meta-analysis ,Etiology ,lcsh:Q ,Female ,0210 nano-technology ,Body mass index ,Genome-Wide Association Study - Abstract
Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS., Adolescent idiopathic scoliosis (AIS) is a common pediatric disease leading to spinal deformities. Here, the authors report GWAS followed by genome-wide meta-analysis in up to 79,211 Japanese individuals, identifying 20 genetic loci for AIS, 14 of which were previously unreported, and perform in vitro validation for rs1978060.
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- 2019
20. How can Researchers Approach to the Sustainable Rural-urban Interchange Activities?
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Masahiro Nakajima
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- 2019
21. Determination of sterigmatocystin in foods in Japan: method validation and occurrence data
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Yaeko Shichinohe, Tomoharu Fujiyoshi, Shigeki Hashiguchi, Takahiro Ohnishi, Masahiro Nakajima, Tomoya Yoshinari, Masaru Taniguchi, Yoshiko Sugita-Konishi, Yukiko Hara-Kudo, Masaki Kosugi, Hiroshi Takeuchi, and Masumi Waki
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0301 basic medicine ,Sterigmatocystin ,Health, Toxicology and Mutagenesis ,Food Contamination ,Occurrence data ,Toxicology ,03 medical and health sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Japan ,Tandem Mass Spectrometry ,Lc ms ms ,Mycotoxin ,Chromatography ,Chemistry ,Public Health, Environmental and Occupational Health ,Reproducibility of Results ,04 agricultural and veterinary sciences ,General Chemistry ,General Medicine ,Contamination ,040401 food science ,030104 developmental biology ,Food Analysis ,Chromatography, Liquid ,Food Science - Abstract
A survey of the contamination of foods by sterigmatocystin (STC) was performed by an analytical method based on LC-MS/MS. STC was extracted from samples with acetonitrile/water (85/15, v/v) and then purified with immunoaffinity columns. The method was validated by a small-scale inter-laboratory study using spiked wheat samples. Mean recoveries of STC were 100.3% and 92.5% from two samples spiked at 0.5 and 5.0 µg/kg, respectively. A total of 583 samples were analysed between 2016 and 2018, and STC was detected in 19.9% of all samples at0.05 μg/kg (limit of quantification). The foods that were contaminated by STC were wheat flour, Job's tears products, rye flour, rice, buckwheat flour, white sorghum, barley products, azuki bean and corn flour. STC was not found in beer or wine. The occurrence of STC in domestic wheat flour (44.4%), Job's tears products (41.7%) and rye flour (29.9%) accounted for the three highest values. The highest mean concentrations were obtained for Job's tears products (0.3 μg/kg) and rye flour (0.3 μg/kg). The maximum contamination level was present in a sample of rye flour (7.1 μg/kg). Although the contamination levels were low, these results indicate that STC frequently contaminates Japanese retail foods. A continuous survey is required to assess exposure to STC in Japan.
- Published
- 2019
22. Identification, characterization, and structural analyses of a fungal endo-β-1,2-glucanase reveal a new glycoside hydrolase family
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Hiroki Matsunaga, Tohru Terada, Yuta Takahashi, Fumio Sugawara, Hayao Taguchi, Hiroyuki Nakai, Koichi Abe, Tetsuro Yamashita, Hiroki Aramasa, Masahiro Nakajima, Megumi Narukawa-Nara, Takashi Kamakura, Shinji Kamisuki, Naohisa Sugimoto, Shiro Komba, Akimasa Miyanaga, and Nobukiyo Tanaka
- Subjects
0301 basic medicine ,Glycoside Hydrolases ,Sophorose ,Stereochemistry ,Mutant ,Biochemistry ,Substrate Specificity ,Enzyme catalysis ,Fungal Proteins ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Complementary DNA ,Hydrolase ,Glycoside hydrolase ,Molecular Biology ,Soil Microbiology ,chemistry.chemical_classification ,030102 biochemistry & molecular biology ,Cell Biology ,Enzyme structure ,030104 developmental biology ,Enzyme ,Talaromyces ,chemistry ,Enzymology - Abstract
endo-β-1,2-Glucanase (SGL) is an enzyme that hydrolyzes β-1,2-glucans, which play important physiological roles in some bacteria as a cyclic form. To date, no eukaryotic SGL has been identified. We purified an SGL from Talaromyces funiculosus (TfSGL), a soil fungus, to homogeneity and then cloned the complementary DNA encoding the enzyme. TfSGL shows no significant sequence similarity to any known glycoside hydrolase (GH) families, but shows significant similarity to certain eukaryotic proteins with unknown functions. The recombinant TfSGL (TfSGLr) specifically hydrolyzed linear and cyclic β-1,2-glucans to sophorose (Glc-β–1,2-Glc) as a main product. TfSGLr hydrolyzed reducing-end–modified β-1,2-gluco-oligosaccharides to release a sophoroside with the modified moiety. These results indicate that TfSGL is an endo-type enzyme that preferably releases sophorose from the reducing end of substrates. Stereochemical analysis demonstrated that TfSGL is an inverting enzyme. The overall structure of TfSGLr includes an (α/α)(6) toroid fold. The substrate-binding mode was revealed by the structure of a Michaelis complex of an inactive TfSGLr mutant with a β-1,2-glucoheptasaccharide. Mutational analysis and action pattern analysis of β-1,2-gluco-oligosaccharide derivatives revealed an unprecedented catalytic mechanism for substrate hydrolysis. Glu-262 (general acid) indirectly protonates the anomeric oxygen at subsite −1 via the 3-hydroxy group of the Glc moiety at subsite +2, and Asp-446 (general base) activates the nucleophilic water via another water. TfSGLr is apparently different from a GH144 SGL in the reaction and substrate recognition mechanism based on structural comparison. Overall, we propose that TfSGL and closely-related enzymes can be classified into a new family, GH162.
- Published
- 2019
23. Chronological Analysis of Residents' Activities and Sustainable Management of Neighbourhood Associations in Temporary Housing Complexes
- Author
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Masahiro Nakajima, Hikaru Shiota, and Yu Kanbara
- Subjects
Geography ,Sustainable management ,Socioeconomics ,Neighbourhood (mathematics) - Published
- 2018
24. Analysis of Factors Influencing Place Attachment in Rural Areas
- Author
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Sae Shinzato, Mitsuyoshi Ando, and Masahiro Nakajima
- Subjects
Geography ,Place attachment ,Rural area ,Socioeconomics - Published
- 2018
25. Study on Interannual Changes in the Management System for Irrigation-based Environmental Stocks
- Author
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Yuki Miyakawa, Jun Iwamoto, Masayuki Nitta, and Masahiro Nakajima
- Subjects
Irrigation ,Geography ,Settlement (structural) ,Management system ,Water resource management - Published
- 2018
26. Service Actual Conditions of Local Vitalization Cooperators Out-migrated Following Completion of the Service
- Author
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Masahiro Nakajima and Yoshiki Kuwabara
- Subjects
Service (business) ,Focus (computing) ,Process management ,Business - Published
- 2018
27. Enzymatic control and evaluation of degrees of polymerization of β-(1→2)-glucans
- Author
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Nobukiyo Tanaka, Hiroyuki Nakai, Tadahisa Iwata, Satoshi Kimura, Masahiro Nakajima, Kaito Kobayashi, and Hayao Taguchi
- Subjects
chemistry.chemical_classification ,Chromatography ,Sucrose ,beta-Glucosidase ,Biophysics ,Cell Biology ,Biochemistry ,Acceptor ,Polymerization ,Glycogen phosphorylase ,chemistry.chemical_compound ,Enzyme ,chemistry ,Molecular Biology ,Glucans ,Phosphorolysis - Abstract
β-(1 → 2)-Glucans can be synthesized by 1,2-β-oligoglucan phosphorylase using β-(1 → 2)-glucooligosaccharides as acceptors and α- d -glucose 1-phosphate as a donor. Using phosphorolysis of sucrose as a source of α- d -glucose 1-phosphate, we generated β-(1 → 2)-glucans with degrees of polymerization (DPs) up to approximately 280. Average DPs up to approximately 1000 were obtained using β-(1 → 2)-glucan with average DP of 160 as an acceptor and pure α- d -glucose 1-phosphate as a donor. A colorimetric assay of the β-glucosidase activity against the β-(1 → 2)-glucan products was used to determine their DPs.
- Published
- 2021
28. Effects of Three-Dimensional Culture of Mouse Calvaria-Derived Osteoblastic Cells in a Collagen Gel with a Multichannel Structure on the Morphogenesis Behaviors of Engineered Bone Tissues
- Author
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Kei Nagao, Masahiro Nakajima, Saki Yahata, Toshio Fukuda, and Kazuya Furusawa
- Subjects
Materials science ,biology ,Haversian canal ,Biomedical Engineering ,Morphogenesis ,Calvaria ,Bone tissue ,Biomaterials ,medicine.anatomical_structure ,Tissue engineering ,medicine ,Biophysics ,Dentin ,Osteocalcin ,biology.protein ,Biomedical engineering ,Biomineralization - Abstract
Bone has a complex hierarchical structure that contributes to its superior mechanical properties. Therefore, reproducing the complex hierarchical structure of bone tissue is a promising strategy to construct functional engineered bone tissues. In this study, we aimed to reproduce this complex hierarchical structure by developing a method for the three-dimensional culture of MC3T3-E1 osteoblastic cells in a collagen gel with a multichannel structure (MCCG), which mimics the parallel arrangement of Haversian canals in bone tissue. MCCG was homogeneously calcified via the biomineralization properties of MC3T3-E1s. Confocal laser scanning microscopy revealed that MCCG could support the growth and proliferation of MC3T3-E1 cells in the deeper parts of the engineered bone tissue and that the cells formed a toroidal structure on the channel surface and a network-like structure in the gel matrix region. Furthermore, quasi-quantitative measurement of osteocalcin and dentin matrix protein 1 expression indicated the coexistence of two types of cells with different morphologies and differentiation phenotypes. Thus, three-dimensional culture of MC3T3-E1 cells in MCCG yielded engineered tissues mimicking the hierarchical structures of bone tissues. Engineered bone tissues with a biomimetic hierarchical structure could be used as a model system for investigating bone metabolism and evaluating the efficacy of novel drugs.
- Published
- 2021
29. Author response for 'Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use'
- Author
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Nao Otomo, Hiroshi Taneichi, Yoji Ogura, Shiro Ikegawa, Haruhisa Yanagida, Morio Matsumoto, Hsing Fang Lu, Chikashi Terao, Satoru Demura, Kazuo Kaneko, Koki Uno, Akira Iwata, Wei Chiao Chang, Takahiro Iida, Ryo Sugawara, Hideki Shigematsu, Tsutomu Akazawa, Yukihide Momozawa, Tatsuya Sato, Kei Watanabe, Naobumi Hosogane, Yoichiro Kamatani, Teppei Suzuki, Kota Watanabe, Yohei Takahashi, Manabu Ito, Yuki Taniguchi, Michiaki Kubo, Yuta Kochi, Toshiaki Kotani, Satoshi Inami, Kazuki Takeda, Tsuyoshi Sakuma, Eijiro Okada, Ikuyo Kou, Noriaki Kawakami, Hideki Sudo, Shohei Minami, Taichi Tsuji, Nobuyuki Fujita, Takashi Kaito, Masaya Nakamura, Kotaro Nishida, Katsuki Kono, Masaru Koido, Kenichiro Kakutani, Katsumi Harimaya, Masahiro Nakajima, Mitsuru Yagi, and Kazuhiro Chiba
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Medicine ,Idiopathic scoliosis ,Polygenic risk score ,business - Published
- 2021
30. Characterization and structural analyses of a novel glycosyltransferase acting on the β-1,2-glucosidic linkages
- Author
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Kaito Kobayashi, Hisaka Shimizu, Nobukiyo Tanaka, Kouji Kuramochi, Hiroyuki Nakai, Masahiro Nakajima, and Hayao Taguchi
- Subjects
Kinetics ,Glucosides ,Glycoside Hydrolases ,Glucosyltransferases ,Glycosyltransferases ,Cell Biology ,Molecular Biology ,Biochemistry ,Substrate Specificity - Abstract
The IALB_1185 protein, which is encoded in the gene cluster for endo-β-1,2-glucanase homologs in the genome of Ignavibacterium album, is a glycoside hydrolase family (GH) 35 protein. However, most known GH35 enzymes are β-galactosidases, which is inconsistent with the components of this gene cluster. Thus, IALB_1185 is expected to possess novel enzymatic properties. Here, we showed using recombinant IALB_1185 that this protein has glycosyltransferase activity toward β-1,2-glucooligosaccharides, and that the kinetic parameters for β-1,2-glucooligosaccharides are not within the ranges for general GH enzymes. When various aryl- and alkyl-glucosides were used as acceptors, glycosyltransfer products derived from these acceptors were subsequently detected. Kinetic analysis further revealed that the enzyme has wide aglycone specificity regardless of the anomer, and that the β-1,2-linked glucose dimer sophorose is an appropriate donor. In the complex of wild-type IALB_1185 with sophorose, the electron density of sophorose was clearly observed at subsites -1 and +1, whereas in the E343Q mutant-sophorose complex, the electron density of sophorose was clearly observed at subsites +1 and +2. This observation suggests that binding at subsites -1 and +2 competes through Glu102, which is consistent with the preference for sophorose as a donor and unsuitability of β-1,2-glucooligosaccharides as acceptors. A pliable hydrophobic pocket that can accommodate various aglycone moieties was also observed in the complex structures with various glucosides. Overall, our biochemical and structural data are indicative of a novel enzymatic reaction. We propose that IALB_1185 be redefined β-1,2-glucooligosaccharide:d-glucoside β-d-glucosyltransferase as a systematic name and β-1,2-glucosyltransferase as an accepted name.
- Published
- 2022
31. Malignant mesothelioma metastatic to the oral region and latest topics (Review)
- Author
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Tomokazu Motohashi, Tomoko Fujii, Masahiro Watanabe, Tsukasa Sakamoto, Masahiro Nakajima, Hirohito Kubo, and Yuichi Ohnishi
- Subjects
Cancer Research ,business.industry ,Incidence (epidemiology) ,Cancer ,Review ,medicine.disease ,medicine.disease_cause ,Molecular medicine ,Asbestos ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,Neoplasm ,030211 gastroenterology & hepatology ,Mesothelioma ,business - Abstract
Malignant mesothelioma (MM) is a rare neoplasm with poor prognosis that usually develops after exposure to asbestos, and is characterised by aggressive local invasion and metastatic spread. While metastasis to the oral cavity is very rare, a total of 23 cases of MM metastasising to the oral cavity were identifed. Among those, the tongue was the most common site of metastasis (39.1%), and frequently involved the epithelioid MM cell type. Recent studies have elucidated the mechanisms underlying the development of MM. Chronic inflammation has been implicated in promoting MM growth and was shown to play a key role by driving the release of high mobility group box protein 1 following asbestos deposition. Inherited heterozygous germline mutations in the deubiquitylase BRCA-associated protein 1 were shown to increase the incidence of MM in some families. Infection by the simian virus 40 was also found to be associated with the occurrence of MM. Moreover, the increasing incidence rates of MM, together with its propensity to metastasise to the oral cavity, indicate that clinicians and pathologists should be highly aware of this disease. Furthermore, identification of novel serum biomarkers would enable better screening and treatment of MM, and improve the survival outcomes.
- Published
- 2020
32. Curcumin inhibits epithelial‑mesenchymal transition in oral cancer cells via c‑Met blockade
- Author
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Yuichi Ohnishi, Hirohito Kubo, Hiroyuki Hamada, Tsukasa Sakamoto, Li Zhengguang, Hiroki Yasui, and Masahiro Nakajima
- Subjects
0301 basic medicine ,Cancer Research ,C-Met ,Oncogene ,Chemistry ,Cancer ,Articles ,medicine.disease ,stomatognathic diseases ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Cancer stem cell ,030220 oncology & carcinogenesis ,Cancer cell ,medicine ,Curcumin ,Cancer research ,Hepatocyte growth factor ,Epithelial–mesenchymal transition ,medicine.drug - Abstract
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. OSCC cells are highly invasive, a characteristic that involves epithelial-mesenchymal transition (EMT); the conversion of immotile epithelial cells into motile mesenchymal cells. EMT is involved in the progression of various types of cancer by promoting tumour cell scattering and conferring to these cells cancer stem cell (CSC)-like characteristics, such as self-renewal. Hepatocyte growth factor (HGF) signalling plays an important role in EMT induction and, therefore, contributes to cell invasion and metastasis in cancer. Due to its potential chemopreventative and anti-tumour activities, curcumin has attracted much interest and has been shown to act as a potent EMT inhibitor in various types of cancer. However, at present, the potential effects of curcumin on HGF-induced EMT in OSCC have not been investigated. Here, we demonstrated that HGF signalling could induce EMT in the HSC4 and Ca9-22 OSCC cell lines via the HGF receptor c-Met and downstream activation of the pro-survival ERK pathway. Notably, curcumin inhibited HGF-induced EMT and cell motility in HSC-4 and Ca9-22 cells via c-Met blockade. Therefore, these findings establish curcumin as a candidate drug for OSCC treatment. Furthermore, curcumin was able to effectively inhibit the HGF-induced increase in the levels of vimentin by downregulating the expression of phosphorylated c-Met, an ERK. In conclusion, the results of the present study demonstrated that curcumin was able to reverse HGF-induced EMT, possibly by inhibiting c-Met expression in oral cancer cells, providing a strong basis for the development of novel approaches for the treatment of oral cancer.
- Published
- 2020
33. Synthesis of three deoxy-sophorose derivatives for evaluating the requirement of hydroxy groups at position 3 and/or 3’ of sophorose by 1,2-β-oligoglucan phosphorylases
- Author
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Masahiro Nakajima, Shiro Komba, Hiroki Aramasa, Nobukiyo Tanaka, Hiroyuki Nakai, Wakako Tsuzuki, and Hayao Taguchi
- Subjects
Models, Molecular ,0301 basic medicine ,Phosphorylases ,Sophorose ,Protein Conformation ,Stereochemistry ,Biochemistry ,Analytical Chemistry ,03 medical and health sciences ,Glycogen phosphorylase ,chemistry.chemical_compound ,Moiety ,Amino Acid Sequence ,Protecting group ,Glucans ,Deoxygenation ,Trichoderma reesei ,Trichoderma ,chemistry.chemical_classification ,030102 biochemistry & molecular biology ,biology ,Organic Chemistry ,Leaving group ,Stereoisomerism ,General Medicine ,biology.organism_classification ,Furanose ,030104 developmental biology ,chemistry ,Enzyme Induction - Abstract
Sophorose (Sop2) is known as a powerful inducer of cellulases in Trichoderma reesei, and in recent years 1,2-β-D-oligoglucan phosphorylase (SOGP) has been found to use Sop2 in synthetic reactions. From the structure of the complex of SOGP with Sop2, it was predicted that both the 3-hydroxy group at the reducing end glucose moiety of Sop2 and the 3′-hydroxy group at the non-reducing end glucose moiety of Sop2 were important for substrate recognition. In this study, three kinds of 3- and/or 3′-deoxy-Sop2 derivatives were synthesized to evaluate this mechanism. The deoxygenation of the 3-hydroxy group of D-glucopyranose derivative was performed by radical reduction using a toluoyl group as a leaving group. The utilization of a toluoyl group that plays two roles (a leaving group for the deoxygenation and a protecting group for a hydroxy group) resulted in efficient syntheses of the three target compounds. The NMR spectra of the two final compounds (3-deoxy- and 3,3′-dideoxy-Sop2) suggested that the glucose moiety of the reducing end of Sop2 can easily take on a furanose structure (five-membered ring structure) by deoxygenation of the 3-hydroxy group of Sop2. In addition, the ratio of the five- and six-membered ring structures changed depending on the temperature. The SOGPs exhibited remarkably lower specific activity for 3′-deoxy- and 3,3′-dideoxy-Sop2, indicating that the 3′-hydroxy group of Sop2 is important for substrate recognition by SOGPs.
- Published
- 2018
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34. Screening of known disease genes in congenital scoliosis
- Author
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Kota Watanabe, Ryo Sugawara, Yuki Taniguchi, Noriaki Kawakami, Shohei Minami, Hiroshi Taneichi, Koki Uno, Morio Matsumoto, Toshiaki Kotani, Yoji Ogura, Shiro Ikegawa, Shuji Mizumoto, Naomichi Matsumoto, Noriko Miyake, Shuhei Yamada, Hideki Shigematsu, Ikuyo Kou, Nao Otomo, Kei Watanabe, Masahiro Nakajima, Kazuki Takeda, Ikuho Yonezawa, Masaya Nakamura, and Hideki Sudo
- Subjects
Male ,0301 basic medicine ,Heterozygote ,Adolescent ,Mutation, Missense ,LFNG ,spondylocostal dysostosis ,medicine.disease_cause ,Compound heterozygosity ,Bioinformatics ,03 medical and health sciences ,Genetics ,medicine ,Humans ,Missense mutation ,Genetic Testing ,congenital scoliosis ,Child ,Molecular Biology ,Genetics (clinical) ,Exome sequencing ,Mutation ,business.industry ,Glycosyltransferases ,Original Articles ,medicine.disease ,Spondylocostal dysostosis ,Vertebra ,030104 developmental biology ,medicine.anatomical_structure ,Scoliosis ,Dysplasia ,Original Article ,whole‐exome sequencing ,Female ,T-Box Domain Proteins ,business - Abstract
Background Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5–1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of remaining CS is unknown. Methods We recruited 78 CS patients without TBX6 mutations and major comorbidities, and investigated the genes previously reported to be associated with CS and congenital vertebral malformations by whole‐exome sequencing. Results We identified the compound heterozygous missense variants in LFNG in one patient. No likely disease‐causing variants were identified in other patients, however. LFNG encodes a GlcNAc‐transferase. The LFNG variants showed loss of their enzyme function. Conclusions A LFNG mutation is reported in a case of spondylocostal dysostosis (SCD), a skeletal dysplasia with severe malformations of vertebra and rib. The CS patient with LFNG mutations had multiple vertebral malformations including hemivertebrae, butterfly vertebrae, and block vertebrae, and rib malformations. LFNG mutations may cause a spectrum of phenotypes including CS and SCD. The current list of known disease genes could explain only a small fraction of genetic cause of CS.
- Published
- 2018
35. [Evolving Digital Imaging]
- Author
-
Masahiro Nakajima
- Subjects
Diagnostic Imaging ,Thesaurus (information retrieval) ,Information retrieval ,Computer science ,Digital imaging ,Image Processing, Computer-Assisted ,Humans ,General Medicine - Published
- 2019
36. [Review] Functions and Structures of β-1,2-Glucan-related Enzymes and Proteins
- Author
-
Masahiro Nakajima and Hayao Taguchi
- Subjects
General Medicine - Published
- 2018
37. Characterization and Structural Analysis of a Novel exo-Type Enzyme Acting on β-1,2-Glucooligosaccharides from Parabacteroides distasonis
- Author
-
Kaito Kobayashi, Yuta Takahashi, Hiroyuki Nakai, Naohisa Sugimoto, Masahiro Nakajima, Nobukiyo Tanaka, Akimasa Miyanaga, Hayao Taguchi, and Hisaka Shimizu
- Subjects
0301 basic medicine ,beta-Glucans ,030106 microbiology ,Protein domain ,Oligosaccharides ,Chitinophaga pinensis ,Crystallography, X-Ray ,medicine.disease_cause ,Polysaccharide ,Biochemistry ,03 medical and health sciences ,Bacterial Proteins ,Protein Domains ,Symbiosis ,Hydrolase ,medicine ,chemistry.chemical_classification ,biology ,Bacteroidetes ,Chemistry ,biology.organism_classification ,Molecular Docking Simulation ,030104 developmental biology ,Enzyme ,Parabacteroides distasonis ,Glucosidases ,Bacteria - Abstract
β-1,2-Glucan is a polysaccharide produced mainly by some Gram-negative bacteria as a symbiosis and infectious factor. We recently identified endo-β-1,2-glucanase from Chitinophaga pinensis ( CpSGL) as an enzyme comprising a new family. Here, we report the characteristics and crystal structure of a CpSGL homologue from Parabacteroides distasonis, an intestinal bacterium (BDI_3064 protein), which exhibits distinctive properties of known β-1,2-glucan-degrading enzymes. BDI_3064 hydrolyzed linear β-1,2-glucan and β-1,2-glucooligosaccharides with degrees of polymerization (DPs) of ≥4 to produce sophorose specifically but did not hydrolyze cyclic β-1,2-glucan. This result indicates that BDI_3064 is a new exo-type enzyme. BDI_3064 also produced sophorose from β-1,2-glucooligosaccharide analogues that have a modified reducing end, indicating that BDI_3064 acts on its substrates from the nonreducing end. The crystal structure showed that BDI_3064 possesses additional N-terminal domains 1 and 2, unlike CpSGL. Superimposition of BDI_3064 and CpSGL complexed with ligands showed that R93 in domain 1 overlapped subsite -3 in CpSGL. Docking analysis involving a β-1,2-glucooligosaccharide with DP4 showed that R93 completely blocks the nonreducing end of the docked β-1,2-glucooligosaccharide. This indicates that BDI_3064 employs a distinct mechanism of recognition at the nonreducing end of substrates to act as an exo-type enzyme. Thus, we propose 2-β-d-glucooligosaccharide sophorohydrolase (nonreducing end) as a systematic name for BDI_3064.
- Published
- 2018
38. Susceptibility Genes for Ossification of the Posterior Longitudinal Ligament of the Spine―The Discovery and Future Prospects―
- Author
-
Masahiro Nakajima
- Subjects
Spine (zoology) ,business.industry ,Medicine ,Ossification of the posterior longitudinal ligament ,Susceptibility gene ,Anatomy ,business - Published
- 2018
39. Tapered Microfluidic for Continuous Micro-Object Separation Based on Hydrodynamic Principle
- Author
-
Masahiro Nakajima, Masaru Takeuchi, Mohd Ridzuan Ahmad, Yasuhisa Hasegawa, and Ida Laila Ahmad
- Subjects
Effective size ,Materials science ,Sedimentation (water treatment) ,business.industry ,Microfluidics ,010401 analytical chemistry ,Separation (aeronautics) ,Biomedical Engineering ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Finite element method ,0104 chemical sciences ,Volumetric flow rate ,chemistry.chemical_compound ,chemistry ,Hydrodynamics ,Fluid dynamics ,Polystyrenes ,Optoelectronics ,Polystyrene ,Electrical and Electronic Engineering ,0210 nano-technology ,business - Abstract
Recent advances in microfluidic technologies have created a demand for a simple and efficient separation intended for various applications such as food industries, biological preparation, and medical diagnostic. In this paper, we report a tapered microfluidic device for passive continuous separation of microparticles by using hydrodynamic separation. By exploiting the hydrodynamic properties of the fluid flow and physical characteristics of micro particles, effective size based separation is demonstrated. The tapered microfluidic device has widening geometries with respect to specific taper angle which amplify the sedimentation effect experienced by particles of different sizes. A mixture of 3- μ m and 10- μ m polystyrene microbeads are successfully separated using 20° and 25° taper angles. The results obtained are in agreement with three-dimensional finite element simulation conducted using Abaqus 6.12. Moreover, the feasibility of this mechanism for biological separation is demonstrated by using polydisperse samples consists of 3- μ m polystyrene microbeads and human epithelial cervical carcinoma (HeLa) cells. 98% of samples purity is recovered at outlet 1 and outlet 3 with flow rate of 0.5–3.0 μ l/min. Our device is interesting despite adopting passive separation approach. This method enables straightforward, label-free, and continuous separation of multiparticles in a stand-alone device without the need for bulky apparatus. Therefore, this device may become an enabling technology for point of care diagnosis tools and may hold potential for micrototal analysis system applications.
- Published
- 2017
40. Molecularly-targeted therapy for the oral cancer stem cells
- Author
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Hiroki Yasui, Yuichi Ohnishi, Masami Nozaki, and Masahiro Nakajima
- Subjects
0301 basic medicine ,Molecularly-targeted therapy ,medicine.medical_treatment ,Cetuximab ,Review Article ,Lapatinib ,Metastasis ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Growth factor receptor ,Cancer stem cell ,medicine ,Epidermal growth factor receptor ,skin and connective tissue diseases ,General Dentistry ,neoplasms ,biology ,business.industry ,Cancer stem cells ,medicine.disease ,Metastatic breast cancer ,Sphere formation ,lcsh:RK1-715 ,030104 developmental biology ,Oral squamous cell carcinoma ,lcsh:Dentistry ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,business ,medicine.drug - Abstract
Summary: Human cancer tissues are heterogeneous in nature and become differentiated during expansion of cancer stem cells (CSCs). CSCs initiate tumorigenesis, and are involved in tumor recurrence and metastasis. Furthermore, data show that CSCs are highly resistant to anticancer drugs. Cetuximab, a specific anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is used in cancer treatment. Although development of resistance to cetuximab is well recognized, the underlying mechanisms remain unclear. Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR)/ErbB2, has antiproliferative effects and is used to treat patients with ErbB2-positive metastatic breast cancer. In this review, cetuximab and lapatinib-resistant oral squamous cell carcinoma (OSCC) cells proliferation and migration signal transduction passway is discussed by introducing our research. Keywords: Cancer stem cells, Cetuximab, Lapatinib, Epidermal growth factor receptor, Oral squamous cell carcinoma, Molecularly-targeted therapy, Sphere formation
- Published
- 2017
41. The Regional Social System that Supports the Safety of Children’s Diverse Water Play around Rivers
- Author
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Masayuki Nitta, Masahiro Nakajima, and Yutaro Senga
- Subjects
03 medical and health sciences ,0302 clinical medicine ,030503 health policy & services ,030212 general & internal medicine ,0305 other medical science ,Psychology - Published
- 2017
42. Study on the Relationship between Activities and Personal Networks of Community-Reactivating Cooperator Squad
- Author
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Masahiro Nakajima and Yoshiki Kuwabara
- Published
- 2017
43. Compensation of matrix effects in gas chromatography–mass spectrometry analysis of pesticides using a combination of matrix matching and multiple isotopically labeled internal standards
- Author
-
Masahiro Nakajima, Miki Katsuhara, and Tomoyuki Tsuchiyama
- Subjects
Agricultural commodity ,Chromatography ,Matching (graph theory) ,Chemistry ,010401 analytical chemistry ,Organic Chemistry ,Pesticide Residues ,Food Contamination ,Residual matrix ,General Medicine ,Pesticide ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Gas Chromatography-Mass Spectrometry ,0104 chemical sciences ,Analytical Chemistry ,Compensation (engineering) ,Matrix (chemical analysis) ,Isotope Labeling ,Statistical analysis ,Pesticides ,Gas chromatography–mass spectrometry ,Food Analysis - Abstract
In the multi-residue analysis of pesticides using GC-MS, the quantitative results are adversely affected by a phenomenon known as the matrix effect. Although the use of matrix-matched standards is considered to be one of the most practical solutions to this problem, complete removal of the matrix effect is difficult in complex food matrices owing to their inconsistency. As a result, residual matrix effects can introduce analytical errors. To compensate for residual matrix effects, we have developed a novel method that employs multiple isotopically labeled internal standards (ILIS). The matrix effects of ILIS and pesticides were evaluated in spiked matrix extracts of various agricultural commodities, and the obtained data were subjected to simple statistical analysis. Based on the similarities between the patterns of variation in the analytical response, a total of 32 isotopically labeled compounds were assigned to 338 pesticides as internal standards. It was found that by utilizing multiple ILIS, residual matrix effects could be effectively compensated. The developed method exhibited superior quantitative performance compared with the common single-internal-standard method. The proposed method is more feasible for regulatory purposes than that using only predetermined correction factors and is considered to be promising for practical applications.
- Published
- 2017
44. CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1
- Author
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Noboru Taniguchi, Hiroki Tawaratsumida, Kazuki Oishi, Hiroyuki Tominaga, Ichiro Kawamura, Shiro Ikegawa, Shingo Maeda, Go Jokoji, Masahiro Nakajima, Eiji Taketomi, and Toshiro Ijuin
- Subjects
ITS, insulin/transferrin/selenium ,MSC, mesenchymal stem cell ,Cell Cycle Proteins ,mRNA splicing ,Biochemistry ,Mice ,Osteogenesis ,TGF, transforming growth factor ,GFP, green fluorescent protein ,Agc1, aggrecan ,Gene knockdown ,DMEM, Dulbecco's modified Eagle's medium ,RNA-Binding Proteins ,PTHrP, parathyroid-hormone-related protein ,Cell Differentiation ,SOX9 Transcription Factor ,Transfection ,SNP, single nucleotide polymorphism ,Protein-Tyrosine Kinases ,Cell biology ,medicine.anatomical_structure ,chondrocyte ,Models, Animal ,eQTL, expression quantitative trait loci ,cell cycle ,Chondrogenesis ,IHC, immunohistochemistry ,Research Article ,cell division cycle 5-like (CDC5L) ,SDS, sodium dodecyl sulfate ,RNA Splicing ,PCNA, proliferating cell nuclear antigen ,Type II collagen ,WST, water-soluble tetrazolium ,CDC5L, cell division cycle 5-like ,Biology ,Chondrocyte ,Cell Line ,Chondrocytes ,FBS, fetal bovine serum ,medicine ,Wee1 ,Animals ,Humans ,IF, immunofluorescence ,GWAS, genome-wide association study ,Collagen Type II ,Molecular Biology ,Endochondral ossification ,Aggrecan ,Cartilage ,TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling ,Cell Biology ,COL II, type II collagen ,OPLL, ossification of the posterior longitudinal ligament ,ossification of the posterior longitudinal ligament (OPLL) - Abstract
Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common pathological condition that causes intractable myelopathy and radiculopathy, mainly the result of an endochondral ossification-like process. Our previous genome-wide association study identified six susceptibility loci for OPLL, including the cell division cycle 5-like (CDC5L) gene region. Here, we found CDC5L to be expressed in type II collagen-producing chondrocyte-like fibroblasts in human OPLL specimens, as well as in differentiating ATDC5 chondrocytes. Cdc5l siRNA transfection in murine chondrocytes decreased the expression of the early chondrogenic genes Sox9 and Col2a1, diminished the cartilage matrix production, and enhanced the expression of parathyroid-hormone-related protein (a resting chondrocyte marker). We also showed that Cdc5l shRNA suppressed the growth of cultured murine embryonal metatarsal cartilage rudiments and that Cdc5l knockdown suppressed the growth of ATDC5 cells. Fluorescence-activated cell sorting analysis revealed that the G2/M cell cycle transition was blocked; our data showed that Cdc5l siRNA transfection enhanced expression of Wee1, an inhibitor of the G2/M transition. Cdc5l siRNA also decreased the pre-mRNA splicing efficiency of Sox9 and Col2a1 genes in both ATDC5 cells and primary chondrocytes; conversely, loss of Cdc5l resulted in enhanced splicing of Wee1 pre-mRNA. Finally, an RNA-binding protein immunoprecipitation assay revealed that Cdc5l bound directly to these target gene transcripts. Overall, we conclude that Cdc5l promotes both early chondrogenesis and cartilage growth and may play a role in the etiology of OPLL, at least in part by fine-tuning the pre-mRNA splicing of chondrogenic genes and Wee1, thus initiating the endochondral ossification process.
- Published
- 2021
45. Microchip device with parallel operation for bacterial chemotactic analysis
- Author
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Tatsuo Arai, Zhiqin Wang, Masahiro Nakajima, Toshio Fukuda, and Masaru Kojima
- Subjects
0301 basic medicine ,Microchannel ,Motile bacteria ,Materials science ,biology ,Metals and Alloys ,Chemotaxis ,Nanotechnology ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,biology.organism_classification ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Microscopic observation ,03 medical and health sciences ,Microelectrode ,030104 developmental biology ,Microscopy ,Materials Chemistry ,Electrical and Electronic Engineering ,0210 nano-technology ,Biological system ,Instrumentation ,Bacteria - Abstract
In this study, we developed a novel microchip device system that enables the analysis of a large amount of bacterial chemotaxis data, which is one of the most fundamental behaviors of bacteria. Chemotaxis involves sensing of chemical gradients and behavioral adjustment by bacteria. In the proposed system, we conducted parallel analysis of bacterial chemotaxis without microscopic observation. We first confirmed that a simple microchannel could be used to analyze bacterial chemotaxis by microscopy. Next, we developed a system involving the photolithography technique and sputtering, and counted bacterial numbers without microscopic observation by measuring the capacitance between the two microelectrodes. Furthermore, we developed an integrated microchip for bacterial chemotactic analysis and successfully analyzed motile bacteria with single and parallel operation. This device may achieve large-scale analysis by parallel operation and may be useful for high-throughput analysis of unknown bacterial chemotaxis for identifying new attractants and repellents.
- Published
- 2017
46. Multi-Layered Channel Patterning by Local Heating of Hydrogels
- Author
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Masahiro Nakajima, Akiyuki Hasegawa, Yasuhisa Hasegawa, Masaru Takeuchi, Toshio Fukuda, Tomoyuki Oya, and Akihiko Ichikawa
- Subjects
0301 basic medicine ,Control and Optimization ,Materials science ,Fabrication ,Biomedical Engineering ,02 engineering and technology ,Substrate (electronics) ,law.invention ,03 medical and health sciences ,Tissue engineering ,Artificial Intelligence ,law ,parasitic diseases ,business.industry ,Mechanical Engineering ,technology, industry, and agriculture ,021001 nanoscience & nanotechnology ,Computer Science Applications ,Human-Computer Interaction ,Microelectrode ,030104 developmental biology ,Control and Systems Engineering ,Self-healing hydrogels ,Optoelectronics ,Computer Vision and Pattern Recognition ,Photolithography ,0210 nano-technology ,business ,Voltage ,Communication channel - Abstract
In this letter, we conducted a new method to fabricate channels inside cell structures for tissue engineering applications. A cell-embedded hydrogel is locally melted to fabricate channels inside cell structures. The fabricated channels can be used as vascular-like networks to supply nutrition and oxygen to cells, or patterning another types of cells inside the cell structures. Microelectrodes were prepared as heaters on a glass substrate by photolithography techniques. The channel patterning was conducted using the microelectrodes. The channel width and height are controlled by the heating duration when the applied voltage to the microelectrodes is constant. The multi-layered channel fabrication was achieved by repeating melting-filling hydrogel. Patterning of different cell types in hydrogel was conducted using liver cells and fibroblast cells. The proposed method can fabricate vascular-like channels in cell structures to achieve in vitro 3-D co-culture cell systems.
- Published
- 2017
47. Biochemical and structural analyses of a bacterial endo-β-1,2-glucanase reveal a new glycoside hydrolase family
- Author
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Takatoshi Arakawa, Hiroki Matsunaga, Tetsuro Yamashita, Naohisa Sugimoto, Takanori Nihira, Shinji Kamisuki, Koichi Abe, Masahiro Nakajima, Shinya Fushinobu, Yuta Takahashi, Hayao Taguchi, Akimasa Miyanaga, and Hiroyuki Nakai
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,Gram-negative bacteria ,030102 biochemistry & molecular biology ,biology ,Stereochemistry ,Active site ,Cell Biology ,Glucanase ,biology.organism_classification ,Biochemistry ,Enzyme structure ,03 medical and health sciences ,030104 developmental biology ,Enzyme ,chemistry ,Hydrolase ,Extracellular ,biology.protein ,Glycoside hydrolase ,Molecular Biology - Abstract
β-1,2-Glucan is an extracellular cyclic or linear polysaccharide from Gram-negative bacteria, with important roles in infection and symbiosis. Despite β-1,2-glucan's importance in bacterial persistence and pathogenesis, only a few reports exist on enzymes acting on both cyclic and linear β-1,2-glucan. To this end, we purified an endo-β-1,2-glucanase to homogeneity from cell extracts of the environmental species Chitinophaga arvensicola, and an endo-β-1,2-glucanase candidate gene (Cpin_6279) was cloned from the related species Chitinophaga pinensis. The Cpin_6279 protein specifically hydrolyzed linear β-1,2-glucan with polymerization degrees of ≥5 and a cyclic counterpart, indicating that Cpin_6279 is an endo-β-1,2-glucananase. Stereochemical analysis demonstrated that the Cpin_6279-catalyzed reaction proceeds via an inverting mechanism. Cpin_6279 exhibited no significant sequence similarity with known glycoside hydrolases (GHs), and thus the enzyme defines a novel GH family, GH144. The crystal structures of the ligand-free and complex forms of Cpin_6279 with glucose (Glc) and sophorotriose (Glc-β-1,2-Glc-β-1,2-Glc) determined up to 1.7 A revealed that it has a large cavity appropriate for polysaccharide degradation and adopts an (α/α)6-fold slightly similar to that of GH family 15 and 8 enzymes. Mutational analysis indicated that some of the highly conserved acidic residues in the active site are important for catalysis, and the Cpin_6279 active-site architecture provided insights into the substrate recognition by the enzyme. The biochemical characterization and crystal structure of this novel GH may enable discovery of other β-1,2-glucanases and represent a critical advance toward elucidating structure-function relationships of GH enzymes.
- Published
- 2017
48. Three-dimensional hepatic lobule-like tissue constructs using cell-microcapsule technology
- Author
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Masahiro Nakajima, Masaru Takeuchi, Chengzhi Hu, Zeyang Liu, Yasuhisa Hasegawa, Qiang Huang, and Toshio Fukuda
- Subjects
0301 basic medicine ,Materials science ,Alginates ,Cell number ,Cell ,Biomedical Engineering ,Capsules ,02 engineering and technology ,Biochemistry ,Cell Line ,Biomaterials ,03 medical and health sciences ,Glucuronic Acid ,Tissue engineering ,Spheroids, Cellular ,Materials Testing ,medicine ,Animals ,Polylysine ,Secretion ,Lobules of liver ,Molecular Biology ,Tissue Scaffolds ,Hexuronic Acids ,Spheroid ,General Medicine ,Cells, Immobilized ,021001 nanoscience & nanotechnology ,Liver, Artificial ,In vitro ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Liver ,Rat liver ,0210 nano-technology ,Biotechnology ,Biomedical engineering - Abstract
The proper functioning of the liver and tissues containing hepatocytes greatly depends upon the intricate organization of the cells. Consequently, controlling the shape of three-dimensional (3D) cellular constructs is an important issue for in vitro applications of fabricated artificial livers. However, the precise control of tissue shape at the microscale cannot be achieved with various commonly used 3D tissue-engineered building units, such as spheroids. Here, we present the fabrication of hepatic lobule-shaped microtissue (HLSM) containing rat liver (RLC-18) cells. By using cell-microcapsule technology, RLC-18 cells were encapsulated in the core region of poly-l-lysine-alginate microcapsules. After 14days of long-term cultivation, RLC-18 cells self-assembled into HLSM, and the cells fully occupied the microcapsule. By monitoring the cell number and albumin secretion during culture and characterizing the dimensions of the fabricated tissue, we demonstrated that the HLSM showed higher hepatic function as compared with normal cell spheroids. We also showcased the assembly of these microtissues into a 3D four-layered hepatic lobule model by a facile micromanipulation method. Our technology for fabricating 3D multilayer hepatic lobule-like, biofunctional tissue enables the precise control of tissue shape in three dimensions. Furthermore, these constructs can serve as tissue-engineered building blocks for larger organs and cellular implants in clinical treatment.
- Published
- 2017
49. Compound Heterozygosity for Null Mutations and a Common Hypomorphic Risk Haplotype inTBX6Causes Congenital Scoliosis
- Author
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Noriaki Kawakami, Masaya Nakamura, Eri Imagawa, Morio Matsumoto, Toshiaki Kotani, Masahiro Nakajima, Ikuyo Kou, Aritoshi Iida, Hideki Sudo, Yukuto Yasuhiko, Shiro Ikegawa, Noriko Miyake, Yoji Ogura, Kazuki Takeda, Kota Watanabe, and Naomichi Matsumoto
- Subjects
Male ,0301 basic medicine ,Heterozygote ,Adolescent ,DNA Mutational Analysis ,Single-nucleotide polymorphism ,Locus (genetics) ,030105 genetics & heredity ,Biology ,Compound heterozygosity ,Congenital Abnormalities ,03 medical and health sciences ,Loss of Function Mutation ,Genetics ,medicine ,Humans ,Missense mutation ,Allele ,Child ,Genetics (clinical) ,Haplotype ,medicine.disease ,Spondylocostal dysostosis ,Pedigree ,Radiography ,Phenotype ,030104 developmental biology ,Haplotypes ,Scoliosis ,Child, Preschool ,Female ,Chromosome Deletion ,T-Box Domain Proteins ,Hemivertebrae ,Chromosomes, Human, Pair 16 - Abstract
Congenital scoliosis (CS) occurs as a result of vertebral malformations and has an incidence of 0.5-1/1,000 births. Recently, TBX6 on chromosome 16p11.2 was reported as a disease gene for CS; about 10% of Chinese CS patients were compound heterozygotes for rare null mutations and a common haplotype defined by three SNPs in TBX6. All patients had hemivertebrae. We recruited 94 Japanese CS patients, investigated the TBX6 locus for both mutations and the risk haplotype, examined transcriptional activities of mutant TBX6 in vitro, and evaluated clinical and radiographic features. We identified TBX6 null mutations in nine patients, including a missense mutation that had a loss of function in vitro. All had the risk haplotype in the opposite allele. One of the mutations showed dominant negative effect. Although all Chinese patients had one or more hemivertebrae, two Japanese patients did not have hemivertebra. The compound heterozygosity of null mutations and the common risk haplotype in TBX6 also causes CS in Japanese patients with similar incidence. Hemivertebra was not a specific type of spinal malformation in TBX6-associated CS (TACS). A heterozygous TBX6 loss-of-function mutation has been reported in a family with autosomal-dominant spondylocostal dysostosis, but it may represent a spectrum of the same disease with TACS.
- Published
- 2017
50. EVALUATION METHOD AND CONSTRUCTION MANAGEMENT INDEX ABOUT FLATNESS OF CONCRETE GROUNDWORK FROM A VIEWPOINT OF FOOT TOUCH
- Author
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Shintaro Fukuda, Takeshi Yokoi, Yutaka Yokoyama, and Masahiro Nakajima
- Subjects
Foot (prosody) ,Construction management ,Engineering ,Engineering drawing ,Index (economics) ,business.industry ,Flatness (systems theory) ,Architecture ,Evaluation methods ,Building and Construction ,business - Published
- 2017
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