Research and Development (R&D) hhceco (the hhc Concept + ecosystem) Management Policy IR Library Financial Data Stock & Bond Information Sustainability Management Initiatives for Improving Access to Medicines Environment Society Governance ESG Data & Report Corporate Information Corporate Governance Business Activities Oita University and the Usuki City Medical Association announced today that they have entered into a joint research agreement to verify the relationship between changes in cognitive function and daily physical condition of elderly drivers and their driving ability people are returning their driver's licenses because of age-related concerns about their physical condition and driving ability This is leading to a decline in quality of life due to the inconvenience of transportation in daily life This joint research agreement will be conducted with the aim to maintain and improve the safety and health of elderly drivers by constantly monitoring their daily physical condition and their state while driving providing safety and peace of mind suited to each individual driver thereby realizing a society with zero accidents where their families and local residents can also live with peace of mind the physical examinations and some of the cognitive function tests will be conducted at the Usuki City Medical Association Citizen’s Health Management Center will mainly be administering cognitive function tests Cognitive function tests include imaging and neuropsychological tests for clinical diagnosis a digital tool for self-assessment of brain health developed by Eisai*1 is to be used which will enable measurement of the subjects’ daily physical condition data at the Usuki City Medical Association Cosmos Hospital the subject’s driving ability (driving cognitive behavior and driving operation) will be measured using a tool that utilizes research technology developed by Honda to monitor driver behavior and conditions*2 This will allow us to examine how human health data and daily physical condition relate to driving ability This joint research is expected to enable the monitoring of drivers’ daily physical condition and driving behavior in order to detect and notify them of poor physical condition and to provide safe driving advice and health promotion advice in accordance with changes in the physical condition and driving ability of each individual Eisai Oita University and Usuki City Medical Association will continue to work on the creation of new solutions to provide safety and peace of mind suited to each individual utilizing the results of this joint research Subject: 100 people aged 65 or older living in Usuki City *1 “NouKNOW” (non-medical equipment) is a self-checking tool of brain health (brain performance) developed by Eisai based on the algorithm created by Cogstate (Headquarters: Australia) for which Eisai holds the rights for exclusive development and commercialization worldwide. This digital tool allows users to self-assess independently evaluating psychomotor function and working memory in a short time frame (approx.15 minutes) through a simple card test using PC or other devices For more information about “NouKNOW”, please visit https://nouknow.jp/ (Japanese only) a simple and easy to use automobile driving simulator developed for a wider-range of users based on the concept of “enabling anyone to experience and learn driving skills while driving various traffic situations on-screen with fun” by leveraging know-how Honda accumulated through its development of automobile driving simulators will be improved and then be used to measure the subjects’ driving behavior abilities related to driving such as cognitive behavior will be measured with an original program For more information about Honda Safety Navi https://www.honda.co.jp/safetyinfo/simulator/safetynavi/ Eisai'shhcConcept Innovation Sustainability About Eisai News Release Contact Us This website uses cookies to enhance your browsing experience. 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Read more the surroundings are characterized by mountainous terrain and scattered fields and houses the concept behind the design is to utilise the topography and difference in levels of the site going down from the mountains all images courtesy of kenta eto architects the architect has designed the shape of the building not to disturb the impressive landscape but instead to be an extension of the environment and topography the house appears as a slope that is inclined to about 24 degrees allowing a person to climb directly up from ground level the slow gradient allows you to sit or lie down and admire the pastoral mountain scenery master bedroom and wet area are concentrated on the first floor and the hobby room and kid’s room are arranged on the second the southern edge where the slope goes down has a large opening that connects the inside and outside in a courtyard space the conventional post and beam structural method has been used as the main element the timber eaves which form the sloping roof are expressed within the interior resulting in an honest approach to the architecture the goal by kenta eto architects is to create a home where human and environmental scales blend together harmoniously designboom has received this project from our ‘DIY submissions‘ feature, where we welcome our readers to submit their own work for publication. see more project submissions from our readers here. AXOR presents three bathroom concepts that are not merely places of function but destinations in themselves — sanctuaries of style Located in the southeastern part of Oita Prefecture Usuki is a town with a cultural atmosphere the first Buddha sculpture in Japan and the first sculpture in Kyushu to be designated a national treasure Fascinated by the pottery culture preserved in the unique atmosphere of Usuki Usuki City in Oita Prefecture is a town with a rich natural environment and a variety of history and culture including a castle town represented by the Niouza Historical Road it is widely known as a “food town” with products from the sea and the mountains in which people have preserved and improved on traditions the town was recognized as a member of the Food Culture Division of the UNESCO Creative Cities Network for 2021 in recognition of the food culture that has been preserved Usuki was certified as a member of the Food Culture Division of the UNESCO Creative Cities Network and Komine (Miyazaki) were invited to Usuki to make ceramics and porcelain for the Usuki clan president of the “USUKIYAKI Laboratory,” has focused his attention on this mysterious ceramic culture Usami first encountered pottery when he was in art school He always wanted to combine art and pottery which was his major since he was still a student where he took over his family’s restaurant serving local cuisine he came to know that there was pottery in his hometown that was dying out “I would like to combine my pottery skills with it and make Usuki’s unique brand even one step forward he also wanted to revive Usuki’s ceramic culture that had ceased to exist so he established the “USUKIYAKI Laboratory” in 2015 with his friends who had been making pottery in Oita The institute was born out of the desire to renew the pottery culture of Usuki that once existed which ceased to exist after only a dozen years was locally called “Suehiro-yaki” or “Sarayama-yaki” because the kiln at that time was located in the Suehiro Zempoji area (commonly known as Sarayama) The first “Suehiro (Sarayama) Pottery” Usami encountered was a small bowl just right for ice cream The moment he saw the chrysanthemum-shaped white porcelain rinka where the spirit of “frugality and thrift” has been nurtured since ancient times and the simple but elegant white porcelain rinka were intuitively suited to the image of the bowls they wanted to produce Usami named the series “Usukiyaki” with his desire to develop a series of white porcelain ring and ridge flowers with traditional motifs of chrysanthemums and lotuses and his wish for the revitalization of the local community of Usuki The motif of “Usuki Pottery” is the rich nature in the town of Usuki The inspiration comes from various things such as flowers and grass and landscapes consisting of the sea and mountains The matte white color with beautiful shadows and shadows and designs with modern arrangements of traditional motifs such as chrysanthemums and lotuses which have taken root in Usuki since ancient times Based on the few remaining materials and existing works the pieces are made by a combination of katauchi molding in which a mold is made by placing a raw clay sheet on a plaster mold and transferring it to the mold Usukine-yaki vessels are completed with a handmade texture The use of a matte glaze gives the vessels a soft and comfortable feel when you hold them in your hands the “USUKIYAKI Laboratory” uses limited resources with great care and spares no effort aiming to create products that people will use for a long time are only completed when both “makers” and “users” carefully nurture them The people behind “USUKIYAKI” are a group of professionals not only in ceramics but also in various other fields The studio started with a small number of people but now the number of staff has increased to two locations: “USUKIYAKI Laboratory” and “Atelier Sarayama” The work is completed by a division of labor between locals we would not be able to increase the number of craftsmen so we looked for a way to divide the labor and we settled on the current method of “katauchi” (mold making) who started the institute with the desire to create pottery work in Usuki is expanding the base of craftsmen’s activities by dividing the workload Usukine-yaki is a simple yet elegant dishware that adds color to dishes We are happy if Usukine-yaki is useful as a tool for spreading awareness of Usuki’s food,” says Usami Usuki is a town that has established a soil cultivation center and produces compost for organic vegetables many young farmers from all over Japan have moved to Usuki Usami is introducing the taste of Usuki to people through “USAMI,” a local cuisine restaurant that offers creative dishes using locally grown organic vegetables and “Sarayama Tea Room,” where seasonal sweets and authentic Chinese tea can be enjoyed “A vessel comes alive only when it is used to serve food The institute’s belief is that “a vessel is a frame for a dish Usuki ware is born from people’s daily life and is used in their daily life Usukine-yaki” is not only white and beautiful but also has multifaceted charms such as its simplicity and usability that can be blended into any lifestyle “The most important thing I want to convey through ‘Usuki Pottery’ is to make people interested in the town of Usuki and visit there What he wants to convey most through “Usuki Pottery” is that he wants people to be interested in the town of Usuki and to visit the place called Usuki While the number of visitors to Usuki decreased during the Corona Disaster after 2020 Although the timing was just right for them to consider overseas expansion they found that they could display and ship their products and communicate with customers online without having to visit they were so busy making orders that they were unable to fulfill their original wish of having people come to their hometowns and actually touch and see the vessels while they were selling them This experience led him to seek a place not only for a store but also for a place where people can have a relaxing experience of eating and he completed “USUKI SARAYAMA,” a space for experiencing food and tableware The space consists of a gallery where Usuki ware is exhibited and sold an atelier where visitors can experience molding and metal-joining and observe the production process where visitors can experience “making Various events are held throughout the year where visitors can enjoy dishes and seasonal meals creating a warm and welcoming place for new communication with customers Usami’s heart is always filled with the desire to “promote Usuki The origin of his activities is the encouragement he received from people from Oita and Usuki all over the world when he started “Usuki Pottery” which carries the feelings of people who love and live with Usuki will continue to be connected to the world Oita Prefecture is home to clusters of Buddha images carved into rock and known for their delicate and elegant forms The expressive countenances of the “Usuki Stone Buddhas,” designated as a National Treasure bring peace to the hearts of those who view them No article or any part there of may be reproduced without the express permission of the Cabinet Office. Copyright inquiries should be made through this form. © 2009 Cabinet Office, Government of Japan Japanese yard takeover creates chemical tanker giant. Japanese specialist chemical tanker builder Fukuoka Shipbuilding has acquired more than 90% of the shares in compatriot yard Usuki Shipbuilding. Both are privately owned yards located on the western island of Kyushu and specialize in building stainless steel chemical tankers. Usuki is building chemical tankers up to 20,000 dwt and Fukuoka up to 36,000 dwt. Both yards have filled their orderbooks through to 2020. Facebook Twitter LinkedIn YouTube Instagram Your data on TradeWinds TradeWinds is part of DN Media Group AS From November 1st DN Media Group is responsible for controlling your data on TradeWinds We use your data to ensure you have a secure and enjoyable user experience when visiting our site. You can read more about how we handle your information in our privacy policy DN Media Group is the leading news provider in the shipping, seafood, and energy industries, with a number of English- and Norwegian-language news publications across a variety of sectors. Read more about DN Media Group here TradeWinds is part of NHST Global Publications AS and we are responsible for the data that you register with us and the data we collect when you visit our websites We use cookies in a variety of ways to improve your experience such as keeping NHST websites reliable and secure personalising content and ads and to analyse how our sites are being used For more information and how to manage your privacy settings please refer to our privacy and cookie policies Metrics details Nonsense-mediated mRNA decay (NMD) is a cellular mechanism that eliminates mRNAs that harbor premature translation termination codons (PTCs) we investigated the effects of environmental stresses (oxidative stress and endoplasmic reticulum (ER) stress) on NMD activity Methylmercury (MeHg) was used to cause oxidative stress and thapsigargin to stress the ER evidenced by upregulation of NMD-sensitive mRNAs and a decrease in UPF1 phosphorylation was observed in MeHg-treated myogenic cells Mild ER stress amplified NMD suppression caused by MeHg To elucidate the cause of stress-induced NMD suppression the role of the phospho-eIF2α/ATF4 pathway was investigated Knockdown and non-phosphorylatable eIF2α-transfection studies demonstrated the critical role of phospho-eIF2α-mediated repression of translation in mild ER stress-induced NMD suppression NMD suppression was also observed in phospho-eIF2α-deficient cells under mild ER stress Mechanistic target of rapamycin suppression-induced inhibition of cap-dependent translation and downregulation of the NMD components UPF1 were probably involved in stress-induced NMD suppression Our results indicate that stress-induced NMD suppression has the potential to affect the condition of cells and phenotypes of PTC-related diseases under environmental stresses by stabilizing NMD-targeted gene expression The underlying mechanism is the induction of integrated stress responses phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) accumulation of activating transcription factor 4 (ATF4) and upregulation of stress-related proteins We hypothesized that environmental stresses suppressing NMD might thereby affect the expression of truncated proteins that arise from PTCs NMD and the change in NMD that occurs upon exposure to stresses in the central nervous system are not clear yet Our results demonstrated that environmental stresses induce NMD suppression in aforementioned cells suggesting that this may be a mechanism through which these stresses affect cellular condition We further investigated the mechanism of NMD suppression induced by mild ER stress using mutant cells expressing non-phosphorylatable eIF2α We demonstrated that phospho-eIF2α-mediated repression of translation plays a critical role and that mechanistic target of rapamycin (mTOR) suppression-induced inhibition of cap-dependent translation and eIF4A3 are also involved in environmental stress-induced NMD suppression These results indicated that NMD suppression varied in the different cell types and conditions Effects of depleting NMD effectors on NMD-sensitive and NMD-non-sensitive isoform mRNA expression under mild ER stress (a,c) RT-qPCR analysis of NMD-sensitive mRNA of Hnrnpl_NMD (a) and Tra2b_NMD (c) Total RNA was extracted from untreated cells or following treatment with 0.2 μg/ml TPG for 16 h The histogram depicts Hnrnpl_NMD or Tra2b_NMD mRNA normalized to Actb mRNA presented as the fold-increase over non-pretreated NS siRNA-transfectants Values shown are the mean ± SE of three separate experiments ***Significantly different from TPG-untreated cells by one-way ANOVA followed by Bonferroni’s multiple comparison test (p < 0.001) ###Significantly different from NS siRNA-transfectants by one-way ANOVA followed by Bonferroni’s multiple comparison test (p < 0.001) (b,d) RT-qPCR analysis of mRNA of NMD-non-sensitive Hnrnpl (b) or Tra2b (d) isoform using the same data set of NMD-sensitive isoform mRNA of panel a or c to determine expression under mild ER stress The histogram depicts each mRNA normalized to Actb mRNA presented as the fold-increase over non-pretreated NS siRNA-transfectants These results confirmed that phosphorylation of eIF2α plays a role in NMD suppression under mild ER stress significant upregulation of Hnrnpl_NMD mRNA and downregulation of phospho-UPF1 were also observed in the TPG-treated mutant SA cells compared to SA cells that were not treated with TPG These results suggested that NMD suppression might be also induced by factors other than phospho-eIF2α-mediated translation suppression in SA cells exposed to mild ER stress although a reduction in the expression of UPF1 and eIF4A3 induced by mild ER stress might also contribute to NMD suppression (d) Effect of mTOR activator MHY1485 (MHY) on NMD activity Expression of Snhg1 mRNA was evaluated by RT-qPCR Total RNA was extracted from SA cells 16 h after exposure to 0.2 μg/ml TPG SA cells were treated with the indicated concentration of MHY for 3 h before RNA extraction The histogram depicts Snhg1 mRNA normalized to Actb mRNA presented as the fold-increase over MHY- and TPG-untreated control ###Significantly different from TPG-treated MHY-non-treated cells by one-way Welch’s t-test (p < 0.001) The findings suggested that the mTORC1 pathway plays a role in NMD suppression in mutant non-phosphorylatable eIF2α-transfectants under mild ER stress possibly by the inhibition of cap-dependent mRNA translation repression of translation caused by eIF2α phosphorylation played a critical role in NMD suppression under the two environmental stresses it was not an exclusive factor because upregulation of NMD target Hnrnpl_NMD mRNA and decreased p-UPF1 were also observed in phospho-eIF2α-deficient SA cells under mild ER stress Summary of the interactions among causative factors for mild ER stress-induced NMD suppression stable cell line transfected with wild-type eIF2α plasmid Phospho-eIF2α-mediated translation suppression plays a critical role for mild ER stress-induced NMD suppression and eIF4A3 are involved in the inhibition of NMD stable cell line transfected with mutant eIF2α-SA plasmid Suppression of NMD in the preconditioned mutant SA cell line is due to mTOR suppression-induced inhibition of cap-dependent translation The foregoing suggest that stress-induced NMD suppression has the potential to affect the condition of cells under environmental stress by stabilizing NMD-targeted gene expression we demonstrate that environmental stresses suppress NMD in three cell types Phospho-eIF2α-mediated repression of translation plays a critical role We also revealed the involvement of mTOR suppression-induced inhibition of cap-dependent translation and downregulation of NMD components UPF1 and eIF4A3 in stress-induced NMD suppression MHY1485 (Sigma-Aldrich) stock was dissolved in dimethylsulfoxide MHY1485 was treated for 3 h for RNA analysis and for 5 h for protein analysis Blots were stripped in the stripping buffer including 62.5 mM Tris-HCl (pH 6.8) the membrane was reused for re-probing with other antibodies Densitometric quantification of the immunoblots was performed using NIH Image software and All Star Negative Control siRNA were purchased from Qiagen Transfections of synthetic siRNAs were carried out with Lipofectamine RNAiMAX (Thermo Fisher Scientific) and the cells were analyzed 48 h after transfection The results were confirmed in more than three independent experiments Statistical analyses were conducted using Graph Pad PRISM 5.0 (GraphPad Software) Data were analyzed by one-way ANOVA followed by Bonferroni’s multiple comparison test or one-way Welch’s t-test for dual comparison A difference was considered statistically significant when p < 0.05 Holbrook, J. 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Frontiers in genetics 3, 127, https://doi.org/10.3389/fgene.2012.00127 (2012) Download references This work was partly supported by the Japan Society for the Promotion of Science KAKENHI [25460402 to FU Kyoko Aoyagi for eIF2α plasmid construction Yokohama City University School of Medicine The experiments were conceived and designed by F.U performed the experiments and analyzed the data Reagents/materials/analysis tools were contributed by F.U. The authors declare no competing interests Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-018-38015-2 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Japanese tanker owner Sansho Kaiun has placed an order at compatriot shipyard Usuki for the construction of two 19,700 dwt product tankers the two vessels are scheduled for delivery in 2022 Sansho Kaiun specialises in the operation of small product tankers VesselsValue data shows the company currently owns a fleet of 25 small product tankers with a total capacity of 447,300 dwt Don't have an account? Please upgrade your browser to improve your experience If you're an adventurous foodie with exacting standards these 8 Michelin-starred fugu specialist restaurants might just be what you need From listening bars to neighbourhood restaurants explore all the top recommendations from Chishuru’s Adejoké Bakare One of the most prominent chefs serving Indian cuisine talks India and his New York these splurge-worthy hotels have the design and prestige to rival even that most historic of city landmarks The first hotel on this list is just 20 minutes from Florence From vineyards to infinity pools and farm-to-table restaurants every one of these 14 Tuscan classics is within two hours of the city The stylish siblings share their haute address book Why choose between a luxurious stay and a world-class meal when you can have both These MICHELIN Key hotels in Japan and Thailand are home to MICHELIN-Starred restaurants offering the perfect blend of impeccable hospitality and cuisine With just enough time to plan a trip before cherry blossom season this spring we're taking a closer look at one of the best hotels in Kyoto Discover unique ways to experience Tokyo’s winter charm—from glittering lights to gourmet delights—according to a local a dessert-focused restaurant earned a MICHELIN Star Chef Koichi Katsumata redefines fine dining through an eight-course dessert experience proving that sweets can be just as sophisticated as savory cuisine Actor and idol Yuta Tamamori shares his favorite Tokyo addresses with MICHELIN from third-wave coffee spots to serene hotel restaurants MICHELIN Guide inspectors sample an endless procession of dishes a dish lands on their tables that is simply unforgettable The popular belief about the MICHELIN Guide is that it’s all about the stars Bib Gourmand awarded restaurants are adored by their many diners because these restaurants offer satisfaction beyond what you’d expect for the price we present a list of thirteen restaurants that will be joining our Tokyo Selection SÉZANNE is newly awarded Three MICHELIN Stars in the 18th edition of the MICHELIN Guide Tokyo One restaurant newly awarded Two MICHELIN Stars and 13 restaurants newly receive One MICHELIN Star The MICHELIN Green Star highlights the eco-friendly initiatives of one new restaurant Three Special Awards presented to talented professional including the debut of the Sommelier Award in Japan Our inspector shares their notes on the French-Japanese restaurant’s dishes these restaurants showcase the best of Tokyo’s culinary scene room #3419 at the Park Hotel Tokyo is one of the boldest in the city Non-members can add the privileges at checkout through our 30 day free trial By continuing I accept the Terms & Condition and Privacy Policy. I would like to receive Newsletter from MICHELIN Guide Save lists of your favorite restaurants & hotels Professor Toyonobu Usuki of the Faculty of Science and Technology conducts research on amino acids synthesis and analysis for diagnosing chronic lung disease he has techniques for extracting active ingredients from plant waste he discusses the potential of naturally occurring substances and the rewarding aspects of engaging in research that benefits society My research area covers natural products chemistry a subfield of organic chemistry that encompasses all substances created by organisms One of the molecules I am particularly focused on is “desmosine” a beautiful amino acid found abundantly in human skin I determined to research desmosine after meeting Professor Gerard M a key figure in chronic obstructive lung disease (COPD) research when I was researching at Columbia University in the US COPD is characterized by shortness of breath and reduced lung functionality due to permanent lung damage While the number of COPD sufferers is increasing globally early detection of the disease remains problematic Professor Turino told me that levels of desmosine increase in COPD patients with permanent lung damage—and that this increase could possibly be used for diagnosing COPD Since the body only generates a minute amount of desmosine precise measurement requires the use of a synthetic form called an isotopically labelled compound The synthetic compound has the same chemical structure as naturally occurring desmosine it accurately indicates the desmosine content Professor Turino encouraged me to try creating this isotopically compound which had yet to be created by anyone anywhere in the world I succeeded in creating the world’s first synthetic desmosine compound; since then I have also managed to chemically synthesize many related chemical compounds including isotopic desmosine I am preparing to carry out new research with clinicians and private enterprises aimed at using this synthetic desmosine to diagnose COPD and other diseases characterized by elastin degradation Another area of my research centers on extracting polyphenols from plants Polyphenols exert antioxidants and anti-aging properties which are used in cosmetics and health foods we should be able to broaden their scope of applications Using deep eutectic solvents and other special solvents we have developed methods for extracting polyphenols contained in the leaves of sweet potatoes and polyphenols contained in “kabuchii”—a type of citrus fruit native to Okinawa The sweet potato polyphenols have been productized in the form of sweet potato leaf tea; for the kabuchii polyphenols we have commenced joint research with cosmetics manufacturers with the aim of using them in cosmetics I begin my research by drawing up a plan of the process from start to goal—perhaps a better way of putting it is that I use existing information to “predict” what will happen as a scientist I experiment by mixing different ingredients and reagents in flasks and beakers these experiments never follow the path I predicted—80 percent of my experiments end in failure Yet this is the standard way of carrying out experimental chemistry research—persisting with your experiments I am motivated by a desire to benefit society I hope that my research into desmosine will contribute to medicine and that the techniques I have developed for extracting polyphenols from plant waste will contribute to Sustainable Development Goals (SDGs) I am also concurrently working on several other multi-year research projects I will continue devoting myself to research so that I can produce as many beneficial results as possible I first read Kokoro when I was a high school student which comprises a long confessional letter written by “Sensei,” was astonishing I wish to astound the world with a similarly jaw-dropping narrative arc in my research too—this is something I think about all the time The Knot- Nexus of Knowledge by Sophia Professors Exploring the potential of natural products chemistry and Usuki City Medical Association hereby announce the commencement of a cohort study using Usuki City as a demonstration site This joint study will attempt to develop Japan’s first diagnostic workflow for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) that uses blood biomarkers In accordance with “Guidelines for Proper Use of Cerebrospinal Fluid and Blood Biomarkers in Dementia”*1 this study aims to demonstrate the utility of blood biomarkers and improve the early diagnosis of Alzheimer’s disease within a coordinated system of medical care that encompasses primary care physicians and specialists who are members of dementia-related medical societies which is said to account for more than 60 % of dementia cases a protein thought to cause AD) starts aggregating in the brain around 20 years before AD onset Positron emission tomography (amyloid PET) and cerebrospinal fluid (CSF) testing are used to estimate the degree of Aβ accumulation in the brain but only a limited number of facilities are capable of performing these investigations and the high cost of testing and physical stress involved due to the invasiveness of these investigations also pose a challenge The increased use of blood biomarkers is expected to reduce the burden on patients Usuki City Medical Association will recruit applicants (50 years and older) who wish to participate in the study Primary care physicians affiliated with Usuki City Medical Association will perform simple cognitive function tests on applicants and select around 200 people with suspected MCI or mild dementia Specialists affiliated with Usuki City Medical Association Cosmos Hospital (Cosmos Hospital) will then take an in-depth medical history and perform more detailed cognitive function tests before making a final selection of 100 subjects with MCI or mild dementia who are suspected of having Alzheimer’s disease Shimadzu will be responsible for analyzing and evaluating blood biomarker data obtained using Shimadzu’s Amyloid MS CL system for measuring amyloid peptides in blood (Amyloid MS CL)*2 Primary care physicians affiliated with Usuki City Medical Association and specialists affiliated with Cosmos Hospital will present and explain test results to participants evaluate the psychological impact of these results and provide ongoing medical care as needed detailed cognitive function tests will be performed a self-assessed measurement of brain health will be performed using the “NouKNOW”*3 tool developed by Eisai Aβ accumulation will be checked by amyloid PET and the utility of blood biomarkers will be verified Eisai will use its expertise in dementia research to propose ideas and assist with study planning and provide advice on methods of analyzing and reviewing test results and psychological impact All four parties will combine findings from evaluating the clinical performance of blood biomarkers and the psychological effects of disclosing test results to ascertain the acceptability of blood biomarkers under actual clinical conditions the four parties aim to establish a new diagnostic workflow for Alzheimer’s disease that is based on blood biomarkers and includes primary care physicians the four parties are committed to building an ecosystem that improves the early detection of Alzheimer’s disease and to developing social infrastructure that allows those concerned and their families to live in peace and security Labour and Welfare Grants for Scientific Research https://www.neurology-jp.org/guidelinem/pdf/dementia_biomarker.pdf *2 Amyloid MS CL is a product that measures amyloid peptides (the main component of amyloid plaques which are a characteristic feature of Alzheimer’s disease) in the blood and provides biomarker data related to amyloid beta levels Amyloid MS CL was the first product to measure amyloid peptides with a mass spectrometric technique to be approved for use as a medical device in Japan *3 “NouKNOW” (non-medical equipment) is a tool developed by Eisai for the self-assessment of brain health (brain performance) “NouKNOW” was developed based on an algorithm created by Cogstate Ltd (Headquarters: Australia) for which Eisai holds the exclusive rights for development and commercialization worldwide “NouKNOW” uses common playing cards displayed on a PC or similar device to test brain response time “NouKNOW” are registered trademarks of Eisai Please visit the website for further details https://nouknow.jp/ Phone: +81-75-823-1110 Phone: +81-3-3817-5120 Phone: +81-97-586-5814 Phone: +81-972-63-0099 Volume 10 - 2019 | https://doi.org/10.3389/fphys.2019.00759 Muscle atrophy can be caused by unloading stress such as microgravity environments or cast immobilization Therapies for such disuse muscle atrophy and their underlying mechanisms are incompletely understood we investigated the therapeutic effects of local vibration stimulation on immobilization-induced skeletal muscle atrophy A rat model was made by placing the left hindlimb in a cast for 1 week leading to oxidative myofiber atrophy without myopathic changes in soleus skeletal muscle 15 min) to the plantar fascia of the atrophic hindlimb was performed once a day using a hand-held vibration massager after removal of a cast at the end of the immobilization period and quantitative analysis of the cross-sectional areas of soleus myofibers was performed The results revealed that vibration induced significant recovery from disuse muscle atrophy compared with untreated immobilized samples vibration treatment suppressed the fiber transition from slow to fast fiber types compared with vibration-untreated immobilized samples Western blotting analyses of mechanical stress-induced factors revealed that the expression of mechano-growth factor (MGF) was decreased in untreated immobilized soleus muscle whereas vibration stimulation restored their expression No change in the level of phosphorylation of YAP1Ser127 was observed leading to no change in p-YAP1/YAP1 ratio in vibration-treated immobilized soleus muscle The results indicate that vibration stimulus is effective to restore immobilization-induced inactivation of YAP1 pathway was enhanced in vibration-treated immobilized soleus muscle vibration stimuli restored immobilization-induced downregulation of the paired box transcription factor a critical factor for regenerative myogenesis in muscle satellite cells Our results indicate that cyclic vibration stimuli are effective in activating satellite cells and facilitate recovery from immobilization-induced oxidative myofiber atrophy through upregulation of MGF and YAP1 these immobilized rat models are useful for investigation of the mechanisms and treatment of disuse skeletal muscle atrophy caused by weightlessness Our results demonstrate that local vibration stimulation of the plantar fascia facilitates recovery from immobilization-induced oxidative myofiber atrophy We further demonstrate that the therapeutic effects of vibration stimuli may be attributable to upregulation of the mechanical stress-induced factors which can induce expression of the paired box transcription factor (PAX7) an indispensable factor for regenerative myogenesis in muscle satellite cells Only left limbs were immobilized for 1 week; the contralateral (right) limb was not treated and served as a control Vibration therapy was initiated at the end of the immobilization period Vibration therapy was performed for 15 min once a day This study was carried out in accordance with the recommendations of National Institute for Minamata Disease The Committee on Animal Experimentation of the National Institute for Minamata Disease approved the experimental protocol The condition of plaster casts was checked daily and changed when they were loosened or tightened Left hind limbs were fixed in the extended position and animals had free access to food and water (A) Rats were wrapped in a cloth and dangled on a wooden frame to relax their muscle tone (arrow) (B) The head of a hand-held vibration massager was manually applied to the sole of only the left foot The peripheral parts of muscle specimens were immediately frozen in liquid nitrogen and stored at −80°C for biochemical studies. Western blotting was performed as previously described (Fujimura and Usuki, 2015, 2017) the samples were sonicated for 5 s in tissue lysis buffer (T-PER Mammalian Protein Extraction Reagent; Pierce Biotechnology USA) containing Protease Inhibitor Cocktail and Phosphatase Inhibitor Cocktail 2 and 3 (Sigma-Aldrich The samples were centrifuged (14,000 g for 1 h) The protein content was determined using the DC Protein Assay Kit II (Bio-Rad Laboratories The cell lysates (20 μg protein) were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on a 10% gel (Tefco Japan) and transferred to nitrocellulose membranes (GE Healthcare The membranes were then subjected to the following antibody probes: anti-MGF (Millipore USA); anti-IGF-I (Santa Cruz Biotechnology and anti-phospho-p70 S6 kinase (Cell Signaling Technologies); and anti-β-actin (Sigma-Aldrich) Myofiber cross-sectional areas were measured using the Flovel Filing System (FLOVEL Co including a total of 200 myofibers [50 myofibers per field (×200)] were measured in each rat CCO-stained skeletal muscle specimen PAX7-positive nuclei and MYH2-positive type IIa fibers were counted in the four fields (×200) more than 300 myofibers were counted for each sample Data were analyzed by one-way ANOVA followed by Bonferroni’s multiple comparison test or one-way Welch’s t test for dual comparison A difference was considered statistically significant when p < 0.05 Non-grouping scattered atrophic angulated fibers were also detected in both types of skeletal muscles These findings indicate that immobilization with a cast for 1 week induced rat oxidative myofiber-specific atrophy Effects of immobilization for 1 week on skeletal muscle (A) Cytochrome c oxidase (CCO) activity immunostaining in soleus and EDL muscle samples from an immobilized limb (upper panel) and contralateral control samples (lower panel) Representative photographs were selected for each of the three samples Most soleus muscle myofibers were CCO activity-rich oxidative myofibers Immobilization for 1 week induced CCO-active oxidative myofiber atrophy in soleus skeletal muscle compared with a contralateral non-immobilized muscle of the same rat (B) Quantitative analysis of myofiber cross-sectional areas Cross-sectional areas of myofibers in immobilized limb samples were significantly smaller (48.4 ± 3.3%) than those of contralateral non-immobilized soleus muscle from the same rat Cross-sectional areas of EDL muscle from immobilized foot were not significantly different from those of contralateral non-immobilized EDL muscle from the same rat ###Significantly different from the non-immobilized contralateral control (p < 0.001) (C) Hematoxylin and eosin (H&E) staining A representative photograph was selected for each of the four samples or angulated fibers were observed in either soleus or EDL muscle samples (D) Immunostaining with an anti-myosin 2 (MYH2) antibody in soleus and EDL muscles Some MYH2-positive myofibers were detected in both immobilized and contralateral non-immobilized soleus skeletal muscle from the same rat (E) Quantitative analysis of MYH2-positive myofibers in soleus muscle The proportion of type IIa fiber in soleus muscle was varied among individuals Fiber transition by immobilization for 1 week to IIa was not statistically different (F) Immunostaining with an anti-myosin 4 (MYH4) antibody in soleus and EDL muscles MYH4-positive myofibers were detected in neither immobilized nor contralateral non-immobilized soleus skeletal muscle from the same rat To investigate the therapeutic effect of mechanical stimulation vibration stimulus to the plantar fascia of an atrophic limb was performed for 2 weeks using a hand-held vibration massager after the removal of plaster casts at the end of immobilization period Effects of vibration therapy for 2 weeks on immobilization-induced oxidative myofiber atrophy (A) Hematoxylin and eosin (H&E) staining An increase in the interstitial area was observed in the non-vibration group (right panel) Representative photographs were selected for each of the four samples (B,C) Immunostaining for CCO activity in soleus (B) and EDL (C) muscles Representative photographs of vibration-treated (left panels) were selected for each of the four samples Vibration therapy caused a recovery effect on soleus skeletal muscle atrophy (D,E) Quantitative analysis of the cross-sectional areas of myofibers in soleus (D) and EDL (E) muscle The cross-sectional areas (% contralateral control) of vibration-treated immobilized limb samples were significantly larger (81.5 ± 1.7%) than those in vibration-untreated immobilized limbs (61.7 ± 2.3%) Cross-sectional areas (% contralateral control) of vibration-treated immobilized limb samples in EDL muscle were not significantly different from those in vibration-untreated EDL muscle The cross-sectional areas of soleus or EDL muscle after a 1-week immobilization were also shown in each figure ###Significantly different from vibration-untreated immobilized muscle by one-way Welch’s t test (p < 0.005) (F) Immunostaining with an anti-myosin 2 (MYH2) antibody in soleus muscle An increase in MYH2-positive myofibers was detected in immobilized muscle compared to contralateral non-immobilized soleus skeletal muscle from the same rat (G) Quantitative analysis of MYH2-positive myofibers in soleus muscle Fiber transition to IIa was statistically different in Im + non-Vib group but not in Im + Vib group The fiber transition to type IIa in soleus muscle was statistically suppressed in Im + Vib group compared to that in Im + non-Vib group Data are represented as the mean ± SEM (n = 4) ***Significantly different from non-immobilized contralateral control muscle by a one-way ANOVA followed by Bonferroni’s multiple comparison test (p < 0.001) #Significantly different from vibration-untreated immobilized rats by a one-way ANOVA followed by Bonferroni’s multiple comparison test (p < 0.05) Although we examined the expression of phospho-4EBP1 and phospho-p70 S6 kinase both of which are factors involved in the mTOR pathway we did not observe any change in the expression of these factors Western blot analyses of soleus and EDL muscle extracts non-immobilized vibration-untreated control rat; 2) Im immobilized vibration-untreated rat; 3) Im + Vib (A) Western blot analyses of factors related to muscle growth and atrophy Images are representative of four independent experiments Prepared muscle samples were analyzed using the indicated antibody probes Cropped blots are shown; all gels were run under the same experimental conditions (B) Densitometric quantification of the bands shown in (A) or PAX7 normalized to those of β-actin represented as the percentage increase over non-immobilized contralateral control samples from the same rat **Significantly different from non-immobilized contralateral control muscle by a one-way ANOVA followed by Bonferroni’s multiple comparison test (p < 0.01) ##Significantly different from vibration-untreated immobilized rats by a one-way ANOVA followed by Bonferroni’s multiple comparison test (#p < 0.05 Photographs are representative of four independent experiments (D) Densitometric quantification of the bands shown in (C) The histogram depicts the levels of YAP1 normalized to those of β-actin and p-YAP1 or p-AKT levels normalized to those of YAP1 Values are the means ± SEM (n = 4) (E,F) Comparison of the basic level of MGF (F) Densitometric quantification of the bands shown in (E) The histogram depicts the level of the indicated protein expression normalized to β-actin (MGF and PAX7) or YAP1 (p-YAP1) represented as the percentage increase over soleus muscle from the same rat ##Significantly different from EDL muscle by one-way Welch’s t test (p < 0.01) the results indicated that vibration stimuli restored immobilization-induced inactivation of YAP1 pathway which regulates cell growth and cell cycle progression was suppressed in (Im + non-Vib) soleus muscle whereas it was restored after vibration stimuli phosphorylation of AKT did not alter in response to vibration therapy these changes were not observed in EDL muscle The basic level of MGF, YAP1, IGF-I, or PAX7 was compared between soleus and EDL muscles (Figures 6E,F) Quantification analysis indicated that the levels of MGF and IGF-I and p-YAP1/YAP1 ratio were significantly higher in soleus muscle than those in EDL muscle whereas the level of PAX7 was not significantly different between them Immunohistochemistry analysis of soleus skeletal muscle with an anti-PAX7 (A) Effects of immobilization for 1 week on the PAX7 expression in satellite cells PAX7-positive satellite cells are indicated by arrows (B) Quantitative analysis of cross-sectional areas PAX7-positive nuclei were counted in four fields (×200) The histogram depicts PAX7-positive nuclei per 100 myofibers Numbers of PAX7-positive satellite cells were significantly lower in samples from limbs immobilized for 1 week than those in samples from contralateral non-immobilized soleus muscle ###Significantly different from non-immobilized contralateral control by one-way Welch’s t test (p < 0.001) (C) Immunostaining of an immobilized limb sample (upper panel) and a contralateral control (lower panel) with an anti-PAX7 antibody Vibration stimuli induced PAX7-positive satellite cells (arrow) in the immobilized muscle vibration-treated immobilized muscle; Im + non-Vib (D) Quantitative analysis of cross-sectional areas in soleus muscle Numbers of PAX7-positive satellite cells were significantly higher in soleus muscle in Im + Vib group than those in samples from Im + non-Vib group ##Significantly different from vibration-untreated muscle by one-way Welch’s t test (p < 0.01) These findings indicate that the mechanisms underlying the therapeutic effects of vibration stimuli on disuse atrophy involve the induction of MGF indicating that MGF has an important role in inducing generation of PAX7-positive satellite cells and recovery from immobilization-induced soleus skeletal muscle atrophy Our findings suggest that cyclic vibration stimuli (90 Hz once a day) are useful to induce the expression of YAP1 leading to the recovery of muscular atrophy we further demonstrate the therapeutic effects of vibration therapy on immobilization-induced oxidative myofiber atrophy Our data show that vibration-induced upregulation of MGF and YAP1 contributes to the activation of PAX7-positive satellite cells leading to recovery from oxidative myofiber atrophy The device we used in this study was a commercial hand-held vibration massager that could generate an effective frequency of 90 Hz we believe that it could be widely used to facilitate recovery from disuse-induced skeletal muscle atrophy No datasets were generated or analyzed for this study This study was not exempted from the Committee on Animal Experimentation of the National Institute for Minamata Disease and FU conceived and designed the experiments and IH contributed materials and analysis tools The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest Noriko Hirata for excellent technical assistance in the histochemical studies and Ms Kaori Nakahara for excellent assistance in administering immobilization Myonuclear number and myosin heavy chain expression in rat soleus single muscle fibers after spaceflight Alterations in muscle mass and contractile phenotype in response to unloading models: role of transcriptional/pretranslational mechanisms Skeletal muscle wasting with disuse atrophy is multi-dimensional: the response and interaction of myonuclei A new device combining mechanical stimulation of plantar sole and Achilles' tendon to alleviate the consequences of muscle deconditioning Effects of cutaneous receptor stimulation on muscular atrophy developed in hindlimb unloading condition Muscle biopsy: a modern approach 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digitorum longus and soleus muscles of the adult rat PubMed Abstract | Google Scholar PAX7 is required for the specification of myogenic satellite cells Characterization of the mammalian YAP (yes-associated protein) gene and its role in defining a novel protein module Atrophy of the soleus muscle by hindlimb unweighting Vibration therapy of the plantar fascia improves spasticity of the lower limbs of a patient with fetal-type Minamata disease in the chronic stage CrossRef Full Text | Google Scholar Three case reports of successful vibration therapy of the plantar fascia for spasticity due to cerebral palsy-like syndrome The effect of methylmercury on skeletal muscle in the rat: a histopathological study Mechanisms for fiber-type specificity of skeletal muscle atrophy The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation The hippo pathway: regulators and regulations Okita M and Higuchi I (2019) Local Vibration Stimuli Induce Mechanical Stress-Induced Factors and Facilitate Recovery From Immobilization-Induced Oxidative Myofiber Atrophy in Rats Received: 28 February 2019; Accepted: 31 May 2019; Published: 20 June 2019 Copyright © 2019 Usuki, Fujimura, Nakamura, Nakano, Okita and Higuchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Fusako Usuki, ZnVzdWtpMjNAZ21haWwuY29t; dXN1a2lAbmltZC5nby5qcA== Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish Looprider charts their own path through Tokyo's aural map of genre pigeonholes By Patrick St. Michel The musical geography of Tokyo has long been divided up by neighborhoods You go to Koenji if you are looking for artists on the punk or experimental side Shimokitazawa houses rock bands often flirting with the mainstream those neat boundaries between styles seem to have dissolved vocalist and guitarist for the band Looprider 20 years ago I would have said the ‘Koenji sound’ was punk or hardcore,” he says following band practice in the very neighborhood we are discussing “But after [live venue] 20000V burned down Now Koenji is all over the place.” He and bandmate Sean McGee point to venues leaning towards shoegaze visual-kei and even idol music as examples of this shift Looking at the live house offerings of other districts a four-piece started by Aoki as a solo project a few years back that eventually grew to include McGee on drums bassist Hideaki Usuki and guitarist Haruka Sato is a band apt for this moment in Tokyo’s independent rock scene and diving into crusty hardcore on their sophomore release This refusal to stay in just one spot has now resulted in Umi a single 25-minute-long-song featuring double drumming and sudden melodic shifts that has more in common with post-rock than what they’ve done before If many indie outfits in Tokyo tend to fall in common patterns Looprider’s latest opts to go in a completely different direction “I don’t think we try to fit anywhere either I think we have the ability to sort of have one foot in And people in different scenes tend to like us where we bring people in from different places.” This desire to follow his own desires emerged after a previous band Aoki was in focused too much on a specific niche recording everything on his own until he felt comfortable with what he was creating on the street in Nishi-Ogikubo,” Aoki says on his first encounter with McGee a music journalist and the founder of Call And Response Records and eventually decided to recruit a bass player for their full-length debut My Electric Fantasy “I put up ads looking for a bassist and guitarist,” Aoki says and that’s how Usuki and Sato became part of Looprider they tackled their most ambitious project yet: the 25-minute-song Umi “I had always wanted to make a really long instrumental It’s 25 minutes long because most bands in Tokyo I thought it would be interesting to have a set where we play one song and we are done.” Umi came together over a focused two week period new for a group that previously worked in spurts The addition of another drummer—something Aoki had long wanted to explore—also presented new challenges we are trying to make two parts work together,” McGee says The end result is one of the more intriguing releases to come from an independent Tokyo rock band in recent memory Aoki can think of groups who have done concept albums—Umi boasts a loose concept about the origin of life and evolution another departure for a group that previously said their songs don’t have intentional meaning—but can’t recall anyone else trying something like this nor can I think of one that managed to make one biggie-sized number sound (with its constant shifts) so intriguing artists in Tokyo get bogged down in their own little corner of the city playing shows to the same people and oftentimes settling on the same sounds at least on a geographic front—areas of the city are open to different styles coming in though artists favoring other genres might not be inclined to check out something outside their comfort zone shows what can happen when one lets sonic borders blur You come up with something genuinely novel and different Next challenge for them—making good on Umi’s central conceit and playing the whole thing live in one go They’ll give it a whirl on March 29 at Shindaita Fever Even if you aren’t big on the Setagaya scene From purple sweet potatoes to wild horse sightings here’s how to make the most of Okinawa’s tropical escape Explore the best local brands shaping Tokyo’s fashion scene From vintage clothing to Hawaiian-themed goods here’s what’s worth checking out before it’s gone From buying and registering a bike to key rules of the road Collagen staples for beauty and health in Japan Our handpicked list of the best events going on this month and the untold tales of Japan’s queer community Everything you need to know before and during a natural disaster Stay up to date with Tokyo news and events Look out for your first newsletter in your inbox soon We help you navigate a myriad of possibilities Sign up for our newsletter for the best of the city By entering your email address you agree to our Terms of Use and Privacy Policy and consent to receive emails from Time Out about news, events, offers and partner promotions. Tokyo Adapted from James Clavell’s eponymous 1975 novel, FX’s limited series 'Shogun' on Disney+ throws viewers into the complex and turbulent world of Japan’s Sengoku or ‘Warring States’ period (1467-1615) This historical drama vividly portrays the power struggles and cultural clashes between feudal Japan and the Western world through the perspective of John Blackthorne Blackthorne becomes deeply entangled in the deadly political intrigue of local samurai lords The series, which concluded its ten-episode run recently, has been celebrated as one of the best shows of 2024 praised for its excellent acting and meticulous attention to detail Despite being filmed entirely in Vancouver the set design and authenticity are remarkable thanks to a talented team of set designers and VFX specialists who collaborated with historians and Japanese experts to ensure cultural and historical accuracy its characters are based on real figures from early 17th century Japan formidable warlords and samurai defined an enthralling era we’ll take a closer look at the true events and places in Japan that inspired the story behind ‘Shogun’ – places you can still visit today RECOMMENDED: Places in Japan that look like scenes from 'Spirited Away' Photo: Wayusuke/Photo ACThe story begins with English navigator John Blackthorne (Cosmo Jarvis) in poor condition as his ship and crew are marooned on the coast of a small Japanese fishing village Blackthorne’s character is based on the story of William Adams a navigator who was the first Englishman to reach Japan In the new series adaptation of ‘Shogun’ and in James Clavell’s original novel the village that Blackthorne washes up to is a place called Ajiro in Izu province aka the real Miura Anjin (as he's known in Japan) an area that was known as Bungo at the time The small fishing village of Ajiro made an ideal setting for Clavell’s story as it was perfectly situated halfway between Edo-Tokyo and Osaka if you want the real samurai locale depicted in the opening episode of the series you should plan a trip to Oita prefecture instead Records indicate that Adams originally landed on Kuroshima The town celebrates the anniversary of the arrival of his ship every year and exhibits a model of the vessel at Usuki City Hall built in 1562 and pivotal in the town's history endured numerous power struggles and wars over the ensuing years Despite changing hands among various clans and warlords some remnants of the castle still stand today As referenced in Clavell's novel and the 'Shogun' series adaptation the complex had a strong Christian influence for a time with records by Portuguese missionary Luis Frois relating that there were many Christian facilities built near the castle and even a chapel within the castle itself.  Near the castle’s western moat lies the Nioza Historical Road where beautifully preserved buildings that housed samurai over 400 years ago can still be visited Photo: Ken Cheung/UnsplashShortly after his arrival in Japan Adams was sent to Osaka on the orders of Tokugawa Ieyasu (Ieyasu was the model for Toranaga has a rich history tied closely to the tumultuous period of the country’s unification in the late 16th century Construction of the fortress began in 1583 under Toyotomi Hideyoshi Osaka Castle was not only an architectural marvel but also a symbol of Toyotomi power featuring immense stone walls and a five-storey main keep.The period from 1599 to 1602 was crucial for Osaka Castle as the stronghold transitioned from the hands of the Toyotomi clan to becoming a focal point in the power struggle that ensued after Hideyoshi's demise and regents were appointed to govern in his stead This era was marked by intrigue and plotting among Japan’s powerful daimyos who would eventually establish his shogunate after defeating the Toyotomi forces was an impressive fortress built during the Warring States period by the warlord Oda Nobunaga who was the first samurai to unite Japan and is the model for the Kuroda character in ‘Shogun’ it later becomes the residence of Akechi Jinsai and his family after they pledge their loyalty to Kuroda The castle is portrayed as not just a military stronghold but also a lavish home where Kuroda and Akechi's daughters They spend their days engaging in educational activities and training in martial arts within the castle’s opulent gardens.Both in ‘Shogun’ and in real life Azuchi Castle was strategically located atop a mountain overlooking a lake symbolising its builder’s immense power with a striking tower adorned with black lacquer and colourful embellishments This architectural marvel stood as a testament to power and to the aesthetic sensibilities of its era making it a significant cultural and political landmark in Japan’s history Very little of the original castle remains at its site high on a hill overlooking Lake Biwa in Shiga prefecture but a reproduction of the keep can be taken in at Ise Sengoku Village Photo: Kattyan/PixtaIn ‘Shogun’s’ fictional portrayal Osaka serves as a major trading hub with the presence of the iconic Portuguese Black Ship – a deviation from actual history as European trade with Japan at the time was centred on Nagasaki the Portuguese Black Ship sailed annually from Macao to Nagasaki chosen for its protected bay and proximity to China – significantly closer than Osaka the city of Osaka was located inland along the Yodo River necessitating large sea-bound vessels to anchor at Denpo Cargo was then transferred to smaller ships that travelled upstream to the city This setup reflected the logistical challenges of the time as Japan did not have modern ports with wharves small boats were used to move goods and passengers to the land from large ships anchored offshore transformed dramatically under the governance of Tokugawa Ieyasu who was given the area during his rivalry with the Taiko amidst Japan's power struggles Tasked with establishing a new stronghold after failing to defeat the Taiko Ieyasu converted Edo from a swampy region into a burgeoning city (which later became present-day Tokyo) its potential as a major urban and trading hub became evident Unlike the opulent castles of Azuchi or Osaka reflecting Ieyasu’s focus on strategic growth rather than lavish decoration This utilitarian approach extended to the city's infrastructure prioritizing economic and defensive capabilities The former site of Edo Castle is now occupied by the Tokyo Imperial Palace, where the Japanese royal family resides. Most of the grounds are off limits to visitors, but you can join a guided tour of a few inner structures if you apply in advance. Photo: Ziggy Mars/ShutterstockTravel off the beaten track to these storybook villages, Edo-era towns with geisha (not Kyoto!) and seaside retreats Photo: Dayo Adepoju/UnsplashAside from culture and tradition Japan also offers some of the world's most spectacular landscapes Thanks for subscribing! Look out for your first newsletter in your inbox soon! facebooktwitterpinterestinstagramAbout us Create your free account to receive personalised content alerts and Re:action our weekly newsletter of the top chemical science stories handpicked from a range of magazines journals and websites alongside insight and analysis from our expert editorial team Tell us what you think. Take part in our reader survey By Holly Sheahan2011-08-25T08:43:00+01:00 Isolating Tamiflu starting material from Ginkgo biloba trees could avoid future Tamiflu shortages Japanese scientists have discovered a new way of obtaining shikimic acid the compound needed to make the influenza drug Tamiflu They found that the acid could be extracted and isolated from the leaves of the Ginkgo biloba tree using an ionic liquid Tamiflu (oseltamir phosphate) hit the headlines in 2005 for its effectiveness against H5N1 a strain of the influenza virus known as bird flu Tamiflu inhibits neuraminidase - an enzyme that enables the virus to be released from the host cell - and prevents the virus from reproducing Oseltamir phosphate is synthesised via a multistep process developed by pharmaceutical company Roche and uses shikimic acid as the starting material Shikimic acid is normally obtained from star anise But the shortage of star anise caused Roche problems a few years ago when the demand for Tamiflu peaked during the H1N1 - swine flu - pandemic in 2009 Shikimic acid extracted from Ginkgo biloba leaves using ionic liquids can be used to make Tamiflu extracted shikimic acid by stirring Ginkgo biloba leaves at 150  degrees Celsius in an ionic liquid which allowed the shikimic acid to be separated and isolated. Ginkgo biloba is mainly found in China and has a long history in Chinese medicine Shikimic acid has been obtained from other plants and been made by genetically modified bacteria but these methods have not given as high a yield as Usuki’s method ’Since the yield from gingko is quite close to the one from star anise the gingko leaves are an interesting raw material,’ says Volkmar Jordan an expert in obtaining natural substances from plants at M?nster University of Applied Sciences Usuki hopes that his technique will be used commercially but the problem is the cost of building the plants for the extraction-isolation part,’ he says Jordan adds: ’The processing of the used ionic liquid and of the raw material residues must be developed before the technique can be applied in industrial scale processes.’  Usuki plans to isolate other natural products from Ginkgo biloba which may have potential uses in improving blood circulation and have been linked to improved memory.   Site powered by Webvision Cloud Your browser does not support JavaScript, or it is disabled．Please check the site policy for more information At a day service center for elderly individuals in Usuki a sports drink seemed like a prudent beverage on a summer day 13 elderly citizens got sick after gobbling the mixture of sports drink powder and water from a kettle An analysis revealed copper in the kettle fur or flaky deposits of calcium salts that accumulate on the bottom and sides had dissolved into the beverage and caused the acute poisoning The case is among a succession that have been reported where people become ill after consuming water and food in this world’s most hygienic country is consumers’ lowered awareness of the issue tap water was boiled and then cooled before mixed with the sports drink powder The finished beverage was distributed to the facility’s users ranging in age from 77 to 96 following bathing on the morning of July 6 those sickened reportedly complained of such conditions as nausea and loose bowels the local public health center examined the drink and detected 200 milligrams of copper per liter in it Although the kettle was made of stainless steel fur had accumulated in the 10-year-old vessel turning blackish in a section in the kettle according to the results of the health center’s inspections A tiny amount of copper in tap water that formed the fur in the kettle is thought to have dissolved in the acidic sports drink a professor emeritus of medicine at Tokyo Medical and Dental University who has surveyed water quality in 90 countries all over the world described the case as being “unlikely” to occur under normal conditions As only an extremely small volume of copper can be found in tap water the metal’s residue is easily washed away from dishes it is rare that tap water is identified as the cause of poisoning Efforts to improve the quality of water supplied for consumption started around the beginning of the Meiji Era (1868-1912) since cholera spread through water during the Edo Period (1603-1867) Tap water in Japan is now deemed as boasting “one of the world’s safest qualities.” noted that mineral water is better for “direct consumption.” Fujita said although Japan’s water contains a smaller amount of chlorine for sterilization than the safety guidelines of the World Health Organization (WHO) and thus could not have significant negative health effects different hardness levels are better for consumers with varying conditions “Those with diabetes and increased blood pressure should choose harder water while soft water is better for children and others,” Fujita said One can easily suffer from food poisoning when health conditions are not good.” soy sauce and umeboshi were traditionally actively used to stop microorganisms from proliferating in foodstuffs But consumers are currently said to have little awareness of food poisoning “People have lower awareness of protecting themselves as salt-reduced products are pitched amid the health boom and advanced logistics systems are introduced,” said Makoto Kanauchi a professor of environmental adaptation at Miyagi University Kanauchi recommended ingredients be heated and miso and salt added to prevent foods from rotting during the summer 13,000 individuals became ill after consuming foods last year About half were infected with the norovirus a fish parasite known as anisakis has been confirmed as the cause of a growing number of poisoning cases Food poisoning can also occur even when consuming items generally viewed as safe children who ate harvested potatoes at an elementary school in Takarazuka bottle gourd and other cucurbitaceous plants sometimes boast significantly high bitterness levels leading to vomiting and other health-related problems Hydrangea leaves are poisonous though they resemble perilla in appearance so one should pay careful attention when using the leaves for decoration People increasingly often carry their own shopping bags with them as store operators now charge for plastic bags to cut down on plastic waste As juice from meat and fish could allow bacilli that may cause poisoning to proliferate reusable shopping bags should be washed frequently Kanauchi pointed out that as consumers increasingly take food products out during the novel coronavirus pandemic they should take precautions such as not buying at shops that sell food outdoors for many hours on hot days Information on the latest cherry blossom conditions Please right click to use your browser’s translation function.) A series based on diplomatic documents declassified by Japan’s Foreign Ministry Here is a collection of first-hand accounts by “hibakusha” atomic bomb survivors chefs and others involved in the field of food introduce their special recipes intertwined with their paths in life A series about Japanese-Americans and their memories of World War II In-house News and Messages No reproduction or republication without written permission Please view the main text area of the page by skipping the main menu. The page may not be displayed properly if the JavaScript is deactivated on your browser Japanese version Koei Tecmo has revealed new details on the downloadable beta demo for its upcoming action RPG Nioh The beta demo will be available via the PlayStation Store from August 23 until September 6 after which time the demo will be disabled to-be-revealed “Mark of the Conqueror” downloadable content as well as the new “Mark of the Strong” downloadable content Here’s the full overview of the demo Following the overwhelming success of the Alpha Demo in April—as well as the community’s generous feedback—the Nioh Beta Demo will incorporate a number of gameplay changes made with fans in mind which will be immediately noticeable upon their return to the village of Usuki This first stage of the demo will offer new challenges and the opportunity to once again fight for the mysterious Mark of the Conqueror DLC Warriors who conquered Usuki and procured the DLC during the Alpha Demo won’t be left wanting as they will receive a set of weapons and more starting money These champions will also have the opportunity to play through the new Nakatsu stage without having to clear Usuki again The new Nakatsu stage leads protagonist William along a treacherous mountain path to a deep cave where he must prevail against human and supernatural enemies alike—including the seductive Hinoenma a dangerous Yokai under the guise of a beautiful woman Defeating the Nakatsu stage will award players with the Mark of the Strong DLC which will be available when the game launches The experience gained from the trials of Usuki and Nakatsu should equip the most skilled players for an even more challenging undertaking: the Twilight mission battle against stronger enemies and new fearsome creatures The Beta Demo will also feature a selection of new weapons including the long-range hand cannon rifle and a fresh selection of Katanas (including dual-wielded Katanas) Axes and Hammers which will provide new options to suit any gameplay style players will get a taste of Onmyo magic and Ninjutsu elements of combat which add bonuses to William’s attack and can invoke special techniques to provide various effects to better prepare players for the trials that await a Training Dojo has been added to the demo This tutorial stage has been implemented to teach newcomers how to fight with a katana the most basic yet refined of weapon choices The Training Dojo will be available from the beginning of the demo Koei Tecmo has released a new set of screenshots taken directly from the beta demo alongside a selection of character art illustrating a pair of enemies protagonist William will have to face Nioh is in development exclusively for PlayStation 4 Watch the trailer below. View the screenshots at the gallery Reproduction in whole or in part in any form or medium without acknowledgment of Gematsu is prohibited Use of this site is governed by all applicable laws Website by 44 Bytes Emerging tanker player Truong Phat Loc Shipping (TPL) has been linked as the buyer of the Yellow Ray a small 19,900 dwt chemical tanker built in 2003 at Usuki Zosensho in Japan No price was reported for the sale however VesselsValue.com says the vessel is worth about $15.5m TPL will continue to be active in the sales and purchase market as the company’s plan is to have 20 vessels with a total deadweight of more than 300,000 dwt of chemical vessels and capacity of 200,000 cu m of LPG carriers by 2017 This purchase doubled the company’s fleet size in the VLGC sector Starved and brutally beaten by their captors hundreds of emaciated servicemen were found by Allied troops following the fall of Japan in 1945 Photographers were brought in to take pictures of the PoWs to be used as evidence for any potential war crimes trial The images show gaunt and haggard men whose bodies were reduced to skin and bone Others were snapped wearing false legs having undergone amputations brought about either from being tortured or through contracting tropical diseases There are images showing some of the most sadistic Japanese guards including the notorious camp chief Lieutenant Usuki Another depicted is Sergeant Seiichi Okada He carried out water torture on the detainees which included pumping gallons of water into their mouths through a hose and then jumping on their swollen stomachs They were later convicted of war crimes and we hanged prints of the photographs could be purchased at the time by the PoWs from the Far East section of the Returned British Prisoners of War Association An album of almost 50 of the images has now been made available for sale at auction "Some of the images are quite horrific. You hear stories of the brutal treatment many PoWs suffered at the hands of the Japanese but it's not often you see the horrors. "They do give you an idea of what these men went through. An album of almost 50 of the images has now been made available for sale at auction(Image: CandTAuctions/BNPS)‌"A lot of men suffered terrible ordeals and beatings which resulted in limbs being damaged and deformed. "One of these pictures show a large group of them with artificial limbs. "It is a very interesting and rare grouping." During the war, Japan failed to follow the Geneva Convention rules of war governing prisoner treatment which led to tens of thousands of Allied PoWs enduring barbaric conditions in which they were starved, brutalised and used as forced labor. The images are being sold with a pre-sale estimate of £100 on September 18(Image: CandTAuctions/BNPS)One of the most notorious examples was the construction of the Burma or Death Railway. Of the 60,000 Allied servicemen forced to work on the railroad, more than 12,000 died from maltreatment, sickness and starvation. The images are being sold with a pre-sale estimate of £100 on September 18.