Okazaki, Japan
Okazaki, Japan

Aichi Gakuin University is a private university in Aichi Prefecture, Japan. It has campuses at the city of Nisshin, Aichi and Chikusa-ku, Nagoya.The predecessor of the school was founded in 1876 , and it was chartered as a university in 1953. Wikipedia.


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News Article | April 8, 2016
Site: www.rdmag.com

A group of scientists at Nagoya University has succeeded in discovering AMOR, a sugar chain molecule that increases the fertilization efficiency in plants. AMOR was found to be responsible for activating pollen tubes to lead to fertilization. Moreover, through the collaboration between biologists and chemists, the group has synthesized a disaccharide, i.e. a double sugar, which exhibits the same properties as AMOR. This discovery is expected to lead to advances in research to improve plant fertilization efficiency as well as carbohydrate chemistry for plants. Nagoya, Japan - Dr. Akane Mizukami and Professor Tetsuya Higashiyama of the JST-ERATO Higashiyama Live-Holonics Project and the Institute of Transformative Bio-Molecules (ITbM) of Nagoya University, and their colleagues have reported their new findings on April 8, 2016, in Current Biology, on their success in identifying a sugar chain that activates pollen tubes to respond to attractant molecules that promote fertilization in plants. When pollen grains (male reproductive organ) germinate at the tip of the pistil (female reproductive organ), a pollen tube grows through the pistil. There have been many reports that suggest the presence of a compound that is present inside the pistil, which activates the pollen tube to respond to attractant molecules for fertilization, i.e. like a love potion sent out by the female organ to attract the male organ towards them. However, the actual nature of this substance has been a mystery up to now. Using Torenia fournieri as a model plant, Higashiyama's group and his colleagues have succeeded for the first time in identifying the activator for pollen tubes. This activator consists of arabinogalactan, which is a sugar chain specific for plants. The group named it as Activation Molecule for Response-Capability (AMOR), taken from the Latin word meaning "love" and "cupid", thus illustrating its function to bring female and male organs together, to promote fertilization in plants. In their study, the group also reported that the two sugar units at the terminus of AMOR were the active component responsible for pollen tube activation towards attractant molecules. Thus, through the collaboration with synthetic chemists, Dr. Jiao Jiao and Dr. Junichiro Yamaguchi, the team synthesized a disaccharide that consists of methyl-glucuronic acid and galactose linked together. They found that the newly synthesized molecule activates the pollen tube to respond to attractant molecules, and lead to successful fertilization. "We are excited to demonstrate for the first time, that this terminus disaccharide, which is characteristic to sugar chains in plants, is responsible for the signaling between plant cells," said Higashiyama, project leader of the ERATO project and a Professor/Vice-Director at ITbM, Nagoya University. "This could lead to the development of new methods to improve the plant fertilization efficiency and open a new avenue for carbohydrate research in plant biology using synthetic chemistry approaches." For fertilization to occur in seed plants (angiosperms), it is necessary for pollen grains to pollinate at the pistil, followed by germination and growth of a pollen tube through the pistil, with final delivery of the sperm cells to the ovules that contain the egg cells. Upon passing through the pistil, the pollen tube receives various substances, such as plant hormones and glycoproteins. In mammals, a phenomenon called sperm capacitation, which is where the sperm becomes activated by substances originating from the female organs, has been known for a long time. Thus, there has been much research ongoing to uncover its molecular mechanism. Similarly in plants, there have been reports on a phenomenon where pollen tubes receive attractant molecules that are produced from the two synergid cells located next to the egg cells, in order to grow their tubes towards the egg cells and lead to fertilization. However, the molecular mechanism on how pollen tubes become capable of responding to attractant molecules has not been uncovered. "In this research, I have used Torenia fournieri plants to develop new experiments to test which factors cause the pollen tubes to gain response capability towards attractant molecules," said Akane Mizukami, currently an assistant professor at the Aichi Gakuin University, who mainly conducted the biological assay. Torenia fournieri is unique in that the egg apparatus, containing the egg cell and the two synergid cells, protrudes from the ovule. "By using this method to measure the activities in various parts of the Torenia flower, we found AMOR, the molecule which enabled pollen tubes to gain the ability to respond to attractant molecules produced by the synergid cells," describes Mizukami. Through the purification of AMOR, the group found that AMOR contains a sugar chain called arabinogalactan, which is characteristic for plants. Furthermore, by using a digestive enzyme specific for cutting the arabinogalactan sugar chain at various sections, the group was able to identify that a disaccharide moiety containing a methyl-glucuronic acid unit located at the terminus of arabinogalactan, was essential for AMOR's activity. The organic chemists in the group then synthesized the disaccharide moiety on the terminus of arabinogalactan. "Although I can now say it is easy, at the beginning when I joined this project, I struggled a lot to synthesize and isolate the sugar compounds, because I was not exactly an expert in sugar chemistry, and it was a new research field for me," said Jiao Jiao, a postdoctoral researcher in Professor Kenichiro Itami's lab at ITbM, Nagoya University. "I also find many organic chemists have the same feeling that sugar compounds are difficult to handle, especially when handling them in isolation." "It took me about three months to obtain the desired compound with a confirmed structure and good purity. The synthesis of this small sugar molecule was really like a total synthetic project. My mentor, Junichiro Yamaguchi (Associate Professor at Nagoya University) was an expert for making natural products, and he designed the synthetic route initially," continues Jiao. "We discussed and modified the procedure to make it better and better both in selectivity and yield. I guess the three months for me was really a precious time for studying new chemistry and getting a good experience for my future." Interestingly, when the β-linkage isomer of the synthesized methyl-glucuronosyl galactose disaccharide was added to the culture, the pollen tube was attracted to the attractant molecule. "This shows that this particular disaccharide was the key structure for AMOR activity," explains Mizukami. Other synthesized derivatives of the disaccharide were also added to the culture to see its effect on pollen tube response capability towards attractant molecules. The group also found that the methyl group on the methyl-glucuronic acid unit and the β-linkage between the two sugars was also necessary for attraction of the pollen tube. "This behavior of pollen tubes indicates that they are clearly recognizing the specific structure of the disaccharide." This new study has revealed the presence of AMOR, the sugar molecule responsible for controlling the pollen tube's response capability towards attractant molecules, which is an ability that is essential for plant fertilization to succeed. The arabinogalactan sugar chain is commonly present in the cell wall of plants and is known to be involved in various signaling pathways within the cell. However, effective analytical methods to identify the active sites on the sugar chain have not been well established and the exact role of the sugar chain structure has not been fully clarified up to now. Through the combination of a biological approach using various sugar-digesting enzymes and a chemical approach using synthetic sugars, the group succeeded in uncovering the active functional site on the plant's sugar chain. In addition, it was the first time that a specific sugar chain structure that is part of the extracellular matrix in plants, has been identified as a bioactive species that functions in the signaling pathway between cells. "The interdisciplinary research between biology and chemistry has been absolutely fantastic," speaks Jiao. "I feel super fun to talk and discuss about research with biologists. We share a different knowledge of science, experimental techniques and so on. We never feel shy to ask some "stupid" question because we are not only collaborators but also like friends or teachers to each other. I definitely want to and am looking forward to such kind of collaboration again in the near future," she continues. "This research is an outcome of a fantastic fusion between my colleagues, which include biologists in my lab, chemists in the Itami lab, as well as the Molecular Structure Center at ITbM," said Higashiyama. "I believe that the result of this collaboration not only sheds light on the long sought mystery of arabinogalactan sugar chains but will also advance the understanding of the yet to be resolved signaling pathway between cells involving sugar chains."


Kondo H.,Aichi Gakuin University | Takeuchi S.,Aichi Gakuin University | Togari A.,Aichi Gakuin University
American Journal of Physiology - Endocrinology and Metabolism | Year: 2013

Sympathetic signaling regulates bone resorption through receptor activator of nuclear factor-κB ligand (RANKL) expression via the β-adrenergic receptor (β-AR) on osteoblasts. Reactive oxygen species (ROS) are known as one type of osteoclast regulatory molecule. Here we show that an antioxidant, α-lipoic acid (α-LA), treatment prevent the β-adrenergic signaling-induced bone loss by suppressing osteoclastogenesis, and sympathetic signaling directly regulates osteoclastogenesis through β2-AR expressed on osteoclasts via intracellular ROS generation. In an in vitro study, the β-AR agonist isoprenaline increased intracellular ROS generation in osteoclasts prepared from bone marrow macrophages (BBMs) and RAW 264.7 cells. Isoprenaline enhanced osteoclastogenesis through β2-AR expressed on BMMs and RAW 264.7 cells. The antioxidant α-LA inhibited isoprenaline-enhanced osteoclastogenesis. Isoprenaline increased the expression of osteoclast-related genes such as nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1, tartrate-resistant acid phosphatase, and cathepsin K on osteoclasts. α-LA also inhibited isoprenaline-induced increases of these gene expressions. These in vitro results led to the hypothesis that β-adrenergic signaling directly stimulates osteoclastogenesis via ROS generation. In an in vivo study, isoprenaline treatment alone caused oxidative damage in local bone and reduced bone mass because of an increase in bone resorption, and, in α-LA-treated mice, isoprenaline did not increase tibial osteoclast number even though the RANKL-to-osteoprotegerin ratio increased. These in vitro and in vivo results indicate that β-adrenergic signaling, at least in part, directly stimulates osteoclastogenesis through β2-AR on osteoclasts via ROS generation. © 2013 the American Physiological Society.


Hirai T.,Aichi Gakuin University | Tanaka K.,Aichi Gakuin University | Togari A.,Aichi Gakuin University
Journal of Cell Science | Year: 2014

The sympathetic nervous system modulates bone remodeling and mediates the expression of core clock genes in part through the badrenergic receptor (β-AR) in osteoblasts. In this study, we show that in MC3T3-E1 osteoblastic cells that isoproterenol (Iso), a nonselective β-AR agonist, upregulated the transcriptional factor Nfil3, and induced rhythmic mRNA expression of prostaglandinendoperoxide synthase 2 (Ptgs2, also known as Cox2). The rhythmic effects of Iso on Ptgs2 expression were mediated by interplay between the Per2 and Bmal1 clock genes in osteoblasts. In addition, Ptgs2 was significantly decreased in bone after continuous Iso treatment. Overexpression of Nfil3 decreased Ptgs2 expression in MC3T3-E1 cells. Knockdown of Nfil3 upregulated the expression of Ptgs2 in MC3TC-E1 cells, indicating that Nfil3 negatively regulated Ptgs2 in osteoblasts. Furthermore, Iso acutely induced the expression Nfil3 and increased the binding of Nfil3 to the Ptgs2 promoter in MC3T3-E1 cells. These results suggest that Isomediated induction of Nfil3 in osteoblasts regulates the expression of Ptgs2 by driving the expression of circadian clock genes. These findings provide new evidence for a physiological role of circadian clockwork in bone metabolism. © 2014. Published by The Company of Biologists Ltd.


Muramatsu T.,Aichi Gakuin University
Expert Opinion on Therapeutic Targets | Year: 2012

Introduction: Malaria is one of the most serious infectious diseases at the beginning of the twenty-first century. Various membrane proteins are present in Plasmodium falciparum, the principal malaria pathogen. Among them, P. falciparum reticulocyte-binding protein homolog 5 (PfRh5) is indispensable for erythrocyte invasion, and has become a promising vaccine target. Basigin (CD147, EMMPRIN) has been identified as the erythrocyte receptor of PfRh5, and shown to be essential for the invasion of multiple strains of the pathogen. Areas covered: Fundamental information on basigin is fully described, including structure as a member of the immunoglobulin superfamily and function based on its interactions with external molecules and with proteins within the same membrane. The involvement of basigin in many diseases such as cancer and inflammatory diseases is also described, the implication being that anti-basigin therapy might be helpful to treat certain illnesses. Finally, PfRh5 as a vaccine candidate is covered, and its interaction with basigin is evaluated. Expert opinion: The identification of basigin, a well-characterized membrane protein, as a receptor essential for malaria infection will contribute significantly to prevention and treatment of malaria. As an example, anti-basigin therapy can be considered an alternative approach to the treatment of drug-resistant malaria. © 2012 Informa UK, Ltd.


Nishikawa K.,Aichi Gakuin University | Duncan M.J.,Forsyth Institute
Journal of Bacteriology | Year: 2010

Porphyromonas gingivalis, a Gram-negative oral anaerobe, is strongly associated with chronic adult periodontitis, and it utilizes FimA fimbriae to persistently colonize and evade host defenses in the periodontal crevice. The FimA-related gene cluster (the fim gene cluster) is positively regulated by the FimS-FimR two-component system. In this study, comparative analyses between fimbriate type strain ATCC 33277 and fimbria-deficient strain W83 revealed differences in their fimS loci, which encode FimS histidine kinase. Using a reciprocal gene exchange system, we established that FimS from W83 is malfunctional. Complementation analysis with chimeric fimS constructs revealed that W83 FimS has a defective kinase domain due to a truncated conserved G3 box motif that provides an ATP-binding pocket. The introduction of the functional fimS from 33277 restored the production, but not polymerization, of endogenous FimA subunits in W83. Further analyses with a fimA-exchanged W83 isogenic strain showed that even the fimbria-deficient W83 retains the ability to polymerize FimA from 33277, indicating the assembly of mature FimA by a primary structure-dependent mechanism. It also was shown that the substantial expression of 33277-type FimA fimbriae in the W83 derivative requires the introduction and expression of the functional 33277 fimS. These findings indicate that FimSR is the unique and universal regulatory system that activates the fim gene cluster in a fimA genotype-independent manner. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Muramatsu T.,Aichi Gakuin University
Proceedings of the Japan Academy Series B: Physical and Biological Sciences | Year: 2010

Midkine is a heparin-binding cytokine or a growth factor with a molecular weight of 13 kDa. Midkine binds to oversulfated structures in heparan sulfate and chondroitin sulfate. The midkine receptor is a molecular complex containing proteoglycans. Midkine promotes migration, survival and other activities of target cells. Midkine has about 50% sequence identity with pleiotrophin. Mice deficient in both factors exhibit severe abnormalities including female infertility. In adults, midkine is expressed in damaged tissues and involved in the reparative process. It is also involved in inflammatory reactions by promoting the migration of leukocytes, induction of chemokines and suppression of regulatory T cells. Midkine is expressed in a variety of malignant tumors and promotes their growth and invasion. Midkine appears to be helpful for the treatment of injuries in the heart, brain, spinal cord and retina. Midkine inhibitors are expected to be effective in the treatment of malignancies, rheumatoid arthritis, multiple sclerosis, renal diseases, restenosis, hypertension and adhesion after surgery. © 2010 The Japan Academy.


Lee J.Y.,Aichi Gakuin University
The Journal of toxicological sciences | Year: 2013

We examined the alteration of gene expression in HK-2 human proximal tubular cells exposed to cadmium (Cd) using DNA microarray analysis. Cd increased the expression of 30 genes, including 7 genes coding for heat shock proteins, more than 2.0-fold and decreased the expression of 21 genes, including transcription-related genes, such as AP2B1, HOXA7, HOXA9 and TCEB2, less than 0.5-fold prior to the appearance of cytotoxicity in HK-2 cells.


Morita Y.,Aichi Gakuin University | Tomida J.,Aichi Gakuin University | Kawamura Y.,Aichi Gakuin University
Frontiers in Microbiology | Year: 2013

Infections caused by Pseudomonas aeruginosa often are hard to treat; inappropriate chemotherapy readily selects multidrug-resistant P. aeruginosa. This organism can be exposed to a wide range of concentrations of antimicrobials during treatment; learning more about the responses of P. aeruginosa to antimicrobials is therefore important. We review here responses of the bacterium P. aeruginosa upon exposure to antimicrobials at levels below the inhibitory concentration. Carbapenems (e.g., imipenem) have been shown to induce the formation of thicker and more robust biofilms, while fluoroquinolones (e.g., ciprofloxacin) and aminoglycosides (e.g., tobramycin) have been shown to induce biofilm formation. Ciprofloxacin also has been demonstrated to enhance the frequency of mutation to carbapenem resistance. Conversely, although macrolides (e.g., azithromycin) typically are not effective against P. aeruginosa because of the pseudomonal outer-membrane impermeability and efflux, macrolides do lead to a reduction in virulence factor production. Similarly, tetracycline is not very effective against this organism, but is known to induce the type-III secretion system and consequently enhance cytotoxicity of P. aeruginosa in vivo. Of special note are the effects of antibacterials and disinfectants on pseudomonal efflux systems. Sub-inhibitory concentrations of protein synthesis inhibitors (aminoglycosides, tetracycline, chloramphenicol, etc.) induce the MexXY multidrug efflux system. This response is known to be mediated by interference with the translation of the leader peptide PA5471.1, with consequent effects on expression of the PA5471 gene product. Additionally, induction of the MexCD-OprJ multidrug efflux system is observed upon exposure to sub-inhibitory concentrations of disinfectants such as chlorhexidine and benzalkonium. This response is known to be dependent upon the AlgU stress response factor. Altogether, these biological responses of P. aeruginosa provide useful clues for the improvement and optimization of chemotherapy in order to appropriately treat pseudomonal infections while minimizing the emergence of resistance. © 2014 Morita, Tomida and Kawamura.


Patent
Aichi Gakuin University and Permelec Electrode Ltd. | Date: 2015-06-17

A method for treating an implant material having excellent biocompatibility, particularly, a method and an apparatus for treating a dental implant material. A method and an apparatus for treating an implant material having excellent biocompatibility, in which a surface-roughened implant material containing titanium and a titanium alloy is immersed in electrolyzed ozone water, and the electrolyzed ozone water is held at normal temperature, thereby preventing contamination due to adsorption of carbide on the surface of the implant material and imparting hydrophilicity.


Patent
Matsutani Chemical Industry Co. and Aichi Gakuin University | Date: 2010-09-10

A bone filling material comprising sintered titanium dioxide and dextrin and a method for reconstructing bone defects which comprises filling the bone defects in an animal with the bone filling material. The bone filling material of the invention has excellent cell compatibility, biocompatibility and shape-imparting property.

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