Details: cache-fra-eddf8230111-FRA 1746516654 3151387377 a biopharmaceutical company traded on the NASDAQ Global Market (Nasdaq:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875) focused on development of novel anti-inflammatory treatments for neurodegenerative diseases provides shareholders a corporate update in the following Letter to Stockholders from CEO Yuichi Iwaki MediciNova has been clear in its mission to deliver new treatment options to the patients suffering with unmet medical needs we have been steadfast in our commitment to both further our science in partnership with some of the greatest minds across the United States and to do so in a way that preserves capital and provides optimal value to shareholders as it provides the Company with non-dilutive funding as we collaborate to continue to develop MN166 for ALS without incurring the expenses associated with an additional clinical trial The six-month trial is being conducted with 17 institutions all under the aegis of the lead institution and funded entirely by the NIH and without the added expenses of contract research organizations (CROs) our Company-sponsored Phase 2/3 trial of MN166 for ALS We believe that the combination of the two trials allow us to more completely investigate MN166 in a significantly larger patient population the NIH-funded trial is also very much in line with our corporate strategy which is to choose a small number of trials on which to focus our resources and identify partners and other funding sources to ensure that additional programs are conducted and yet our cash reserves are minimally impacted Another current example of this strategy is an ongoing clinical trial of MN-166 in Long COVID which is being funded and conducted under the aegis of Health Canada MediciNova is providing study drug and some administrative support the Canadian government is largely responsible for most other aspects of the trial Health Canada will turn the results over to the Company at which time it will be in a position to then apply for approval under that indication to Health Canada We anticipate that there may be advantages in the regulatory process in Canada resulting from the partnership We have several additional programs that are being overseen by both U.S that follow this model of partnering with prestigious institutions and government agencies to conduct and sponsor clinical trials Our responsibilities are usually limited to providing study drug in most of these cases along with administrative and trial design support we consider our core programs those for which we have direct fiscal responsibility as well as the emerging glioblastoma program such as the above mentioned Long COVID and others for which we only provide study drug and guidance – but almost never cash – are easy ways for us to create revenue over time We will provide additional information on that award in the coming weeks The global landscape is in a state of perpetual flux our aspiration is to cultivate a society where every individual can attain lifelong health and enjoy a prosperous and fulfilling life we are committed to fostering sustainable growth and we believe that this approach is essential to manage cash while driving multiple programs through a complicated global development and regulatory landscape We also understand that our story may be perceived as complex I hope that laying out this approach has gone some distance to help clarify our story we also recently announced that our Chief Business Officer has also assumed the role of managing our communications We believe it is essential that current and future investors understand the nuances of our company two-way communications to ensure clarity and transparency Transparency is all the more important as we are the only dual-listed biopharmaceutical company listed both at NASDAQ market and Tokyo Stock Exchange which presents the challenge of ensuring that all of our shareholders from both markets are up to date We are very excited about the future at MediciNova and anticipate providing status updates regularly beginning in the coming weeks we remain grateful to those shareholders who have shown their loyalty over the years and look forward to welcoming new shareholders to the fold is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory MN-166 (ibudilast) and MN-001 (tipelukast) with multiple mechanisms of action and strong safety profiles MediciNova has 11 programs in clinical development two of which are the Company’s primary focus is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 statements regarding the future development and efficacy of MN-166 These forward-looking statements may be preceded by or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include risks of obtaining future partner or grant funding for development of MN-166 and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development risks and uncertainties inherent in clinical trials expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors product development and commercialization risks the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development the risk of delays or failure to obtain or maintain regulatory approval risks associated with the reliance on third parties to sponsor and fund clinical trials risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected the risk of increased cost and delays due to delays in the commencement completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials and the timing of expected filings with the regulatory authorities MediciNova's collaborations with third parties the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission including its annual report on Form 10-K for the year ended December 31 2023 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K Undue reliance should not be placed on these forward-looking statements MediciNova disclaims any intent or obligation to revise or update these forward-looking statements INVESTOR CONTACT:David H. Crean, Ph.D.Chief Business OfficerMediciNova, Incinfo@medicinova.com 12 Apr 2025 05:00:00 GMT?.css-1txiau5-AnswerContainer{color:var(--GlobalColorScheme-Text-secondaryText2);}Montedio Yamagata won 1–0 over Iwaki FC on Sat Predicted lineups are available for the match a few days in advance while the actual lineup will be available about an hour ahead of the match The current head to head record for the teams are Iwaki FC 1 win(s) Have scored 4 goals in their last 5 matches Haven't scored in their last 2 matches Who won between Iwaki FC and Montedio Yamagata on Sat 12 Apr 2025 05:00:00 GMT?Montedio Yamagata won 1–0 over Iwaki FC on Sat 12 Apr 2025 05:00:00 GMT.InsightsHave scored 4 goals in their last 5 matches Iwaki FC is playing home against Montedio Yamagata on Sat This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page The Mitsubishi Chemical Group (hereafter “MCG Group”) has decided to discontinue the manufacture of products at Mitsubishi Chemical Corporation’s (MCC) Onahama Plant and Shinryo Corporation’s (Shinryo) Iwaki Plant MCC’s Onahama Plant began operations in September 1937 as Japan Hydrogen Industrial Co. (later Nippon Kasei Chemical Company Limited) while Shinryo’s Iwaki Plant was established in October 2020 as a result of the transfer and integration of a number of MCC’s products and the former Onahama Distillery’s business into Shinryo The two plants have been engaged in the manufacture of various chemical products have undertaken initiatives to streamline operations and attract new business in response to drastic changes in the market environment securing profitability at these plants has become extremely difficult MCG Group promotes business portfolio transformation based on the three criteria for business selection (consistent with the Vision and potential for growth) set out in the New Medium-Term Management Plan 2029 that was announced in November 2024 As a result of reviewing MCC’s Onahama Plant and Shinryo’s Iwaki Plant in line with these criteria MCG has decided to discontinue manufacturing at these two plants in stages Location            34 Takayama Location           312-5 Takayama MCG Group will support the employees of these plants by reassigning them within the group and providing outplacement support etc The manufacturing of products from these plants will be discontinued in stages starting in March 2026 and fully terminated by the end of March 2027 Search Companies editorial@fibre2fashion.com POIPU — Representatives from the Iwaki Sunshine Marathon blistered the 26-mile Kauai Marathon to take the first two places in the full marathon phase of the event, which is celebrating its 15th year. Saki Shimada, of Japan, was met at the Kauai Marathon finish line by her mother, Atsuko Shimada, on Sunday, Sept. 1, 2024. Saki was the top overall finisher of the full marathon. Seiya Waragai and Saki Shimada waited for the Kauai Marathon results at Koloa Landing Resort on Sunday, Sept. 1, 2024. Waimea High School Class of 1988 Kauai Marathon finishers Esta Lumabao, Robbyn Silva and Carolyn Jardin enjoyed the shade of a parked truck at the finish line on Sunday, Sept. 1, 2024. Saki Shimada, listing Tsurumi-ku, Hokkaido, Japan, as her city, was the top overall full marathon finisher, crossing the line in a time of 3 hours, 5 minutes and 52 seconds. Shimada was also the first female finisher in the full marathon. Seiya Waragai, listing Tsurumi-ku, Yokohama-shi, Japan, as his city, followed in second overall finish at 3:11.14. (function(d,s,n){var js,fjs=d.getElementsByTagName(s)[0];js=d.createElement(s);js.className=n;js.src="//player.ex.co/player/bdc806f4-0fc1-40a1-aff0-a3d5239c169c";fjs.parentNode.insertBefore(js,fjs);}(document,"script","exco-player")); This is the second consecutive year that Iwaki Marathon runners finished in the top two spots after Shinya Ohashi finished first in the 2023 Kauai Marathon in a 2:29:34 run. Mirai Homma was the first female record-setting finisher, third overall, on a 2:59:37 run. Shimada and Waragai came to the Kauai Marathon as second place winners of the Iwaki Marathon after Homma and Ohashi repeated as winners, and officials decided to send the second place finishers to Kauai. First Kauai finisher for the full marathon crossed the line third overall, as Justin Deforge of Kapaa stopped the timer at 3:20:16, nearly three minutes ahead of Brian Alter of Los Angeles. “This year was a sellout,” said Kauai Marathon founder Jeff Sacchini. “We must’ve had about 2,500 runners on the course. We were at more than 2,300 at registration close, but we didn’t want to turn away the additional 150 or so that came in. Thanks to the community support — we had more than 700 local residents running, the community checks are going to look good.” CJ Albertson of Fresno, Californa, topped the Half Marathon, finishing the 13-mile trek at 1:05:53, just six seconds faster than multi-year Kauai Marathon winner Tyler McCandless, who stopped the clocks at 1:05:59 before taking the microphone to announce marathon winners. McCandless was also a Kauai Marathon representative to the Iwaki Marathon. Make a Lei, Give a Lei, Wear a Lei was the theme of this year’s annual Kauai Museum Lei... During two recesses, House Majority Leader Sean Quinlan (D, Waialua-Haleiwa-Punaluu) strod... Members of the Waimea High School girls football team arrived home on Sunday from the 2025... Your email address will not be published. Required fields are marked * the young rally superstar is bringing the sideways a host of Nineties Japanese motoring heroes The young Finn and two-time WRC champion was “greatly influenced by the famous manga throughout his youth” (which was… yesterday?) and had long dreamed of haring up a scary mountain pass mostly sideways. And in this project pulled together by Initial D and Red Bull, Kalle’s got his work cut out. He was set the task of drifting up a pass on Mount Iwaki that’s never been done before. And along the 69 corners he’d be viewing through the side windows, he’d have to drift past Japan’s drift heroes. Including: Yoshitatsu Kaneda in an R34 Skyline, Toshimitsu Masuda in a 180SX, Hokuto Matsuyama in a Toyota Chaser JZX100, Yusuke Kusaba in a Mk2 JZX90, Liberty Walk founder Wataru Kato in that very special LB-Works Ferrari F40, Manabu Orido in a GR86, and… ‘Takumi Fujiwara’ in the classic Toyota AE86. Sort of. The driver in the video has had Fujiwara’s manga-likeness digitally overlaid onto his face so Kalle can challenge him and… yeah, look, it’s best not to pull on too many of these threads. Basically: rally superstar takes on sub-zero-cool Japanese drift cars up a glorious Japanese mountain with lots of sideways. “Drifting on a mountain road like this has been a dream of mine for quite a while,” Kalle said. “And being able to do it here in Japan with these amazing landscapes is amazing. “I have liked it a lot.” Hit go below to see how much he liked it. Thank you for subscribing to our newsletter. Look out for your regular round-up of news, reviews and offers in your inbox. Get all the latest news, reviews and exclusives, direct to your inbox. Look out for your regular round-up of news No money from the licence fee was used to create this website The profits we make from it go back to BBC programme-makers to help fund great new BBC programmes BBC is a trademark of the British Broadcasting Corporation Colombia Methanol Market Analysis: Industry Market Size Copyright © ChemAnalyst - 2020 | Terms & Conditions | Privacy Policy Today's print edition Home Delivery Some municipalities in northeastern Japan are ending the storage of personal items — such as photographs and cell phones — that were collected after the Great East Japan Earthquake in March 2011 and have yet to be returned to their owners Miyagi and Fukushima prefectures that were hit hardest by the disaster 11 have already stopped holding such items a Jiji Press survey found.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); the Fukushima town of Namie closed its exhibition of such personal items in March 2021 citing related costs and a decline in the number of items returned to owners The remaining 20 municipalities continue storing the personal items A city official said that the number of people coming to collect their belongings is decreasing reflecting the changing attitudes of the people affected by the disaster The Iwate city of Kamaishi is also considering ending its storage of such items at the end of March 2026 When asked what is needed to continue storing collected personal items 16 municipalities cited the need for storage and display space Nine municipalities expressed the desire to continue storing the items with the town of Otsuchi in Iwate stating that the project is "necessary to prevent the disaster from being forgotten." In a time of both misinformation and too much information quality journalism is more crucial than ever.By subscribing Your subscription plan doesn't allow commenting. To learn more see our FAQ Sponsored contents planned and edited by JT Media Enterprise Division I didn't want to go back home for the summer to work at the local grocery I applied for a bunch of environmental internships and got a fisheries internship in Colorado I had no prior experience or any interest in fish I knew I wanted to continue to work in natural sciences I feel like many of the skills I learned in school I can still apply in a natural science setting I enjoy being and working outside in nature because it not only keeps me active but I can really connect my work to the physical It’s also nice to not be behind a screen all day." "I monitor and collect water quality data in freshwater streams at national parks in the San Francisco Bay Area Network (SFAN) I calibrate my water quality instrument for accurate measurements and gather all the appropriate gear needed I spend about half the day driving and hiking to beautiful streams recording water chemistry readings (temperature I am in a bit of a time crunch because the samples I take are time-sensitive But there are times during sampling where I get to stare around at nature and just be where I am I process these samples and analyze them for bacteria I also recheck the instrument again to ensure accuracy It is cool that my job allows me to physically go out and see which stream the samples came from It's very rewarding to see the entire process and connect the data to the watershed Every month I get to visit the same streams and basically perform a routine health check!" We [SFAN] monitor and collect these data to assess watershed health through streams Monthly monitoring and data collecting creates long-term datasets which allows us to know a stream's baseline status Deviations from this baseline can reveal important trends Collecting these data are extremely important when considering how climate change might be impacting freshwater streams water with higher temperatures can hold less oxygen negatively impacting fish such as salmon." "One thing I'm proud of in my career is still having the connections I've made from former jobs Many of my previous bosses and coworkers have become my mentors and friends Forming those relationships was extremely important in my early career since the beginning was all seasonal jobs I realized how important it was for me to keep an open mind I think keeping an open mind and having a good work ethic can take you far in this field Download the NPS app to navigate the parks on the go The Food and Drug Administration (FDA) on Wednesday announced that almost all produce from five Japanese prefectures affected by the 2011 Fukushima Dai-ichi nuclear power plant disaster would now be allowed into Taiwan The only items that would still be blocked from being imported into the nation are those that are still banned from being circulated in Japan the meat of wild birds and other wild animals and koshiabura” (foraged vegetables) would now be permitted to enter Taiwan along with the other produce permitted since 2022 All food items imported from the five prefectures must be accompanied by radiation and origin certificates and undergo batch-by-batch inspections FDA Deputy Director-General Lin Chin-fu (林金富) said The amendment to the regulations permitting the imports was made known to the public 60 days ago to allow for feedback The FDA did not receive any comments of note during the period dairy products and baby food imports from areas outside the five prefectures would only be required to present origin certificates Radiation certification would no longer be necessary Taiwan banned all food imports from the five prefectures for almost 11 years following the disaster in Fukushima Forestry and Fisheries Tetsushi Sakamoto said he “welcomes the move as a positive step toward promoting the recovery of disaster-hit areas.” The ministry statement said it would continue to push for all remaining restrictions to be lifted “The Japanese government has used multiple opportunities to assure the Taiwan authorities of the safety of our products based on scientific evidence but we will continue our persistent efforts so that import restrictions such as certificate submission can be scrapped swiftly,” it said Sapporo saw its first snow of the season eight days earlier than usual and 22 days earlier than last year observed snowfall 12 days earlier than a usual year and 25 days earlier than last year TOKYO – The first snow of the season was observed in Sapporo and some parts of Aomori Prefecture on Sunday morning as temperatures dropped in many areas of northern and eastern Japan According to the Japan Meteorological Agency’s Sapporo Regional Headquarters “There were still lots of greenery when I climbed the mountain last week,” said a woman in her 30s who came from Sapporo to climb it “But I was able to enjoy the red and yellow autumn leaves as well as the snow today.” the first snowfall of the season was also observed on Mt which operates the Tsugaru Iwaki Skyline toll expressway snow was observed 13 days later than last year snow had accumulated on the eighth station of the 1,625-meter-high mountain on Sunday The company said that snow had also built up between the ninth station and the summit the Aomori Local Meteorological Observatory said that it had observed the first snowcap of the season on the Hakkoda Mountains in Aomori Prefecture one day earlier than last year but one day later than in a usual year At the Sukayu Onsen hot spring resort in Aomori City tourists and others were seen admiring the contrast between the snow and autumn leaves According to the Japan Meteorological Agency’s weather advisory office a powerful cold spell brought snow to the mountain peaks An official from the local meteorological office visually confirmed the first snowcap 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 Your browser does not support JavaScript, or it is disabled．Please check the site policy for more information Fukushima Prefecture—A weed described as “the worst alien species on the planet” has been discovered for the first time in the northeastern Tohoku region has already caused headaches in western Japan where the rapidly reproducing species has impeded river improvement and farm work “We need to rein in the spread,” said an official with the Fukushima prefectural pest control center Agriculture is the main industry of the prefecture and local officials are calling on the public to immediately report sightings of suspicious weeds Alligatorweed grows to more than 1 meter tall and branches out in large numbers The weed’s roots can extend for more than 50 centimeters It can form dense mats and drive out native species Clusters of alligatorweed can also block drainage systems a colony of alligatorweed took root and clogged drainage pipes on Lake Biwako causing them to fall and resulting in a drop in the harvest Alligatorweed was first confirmed in Japan in 1989 according to the Fukushima prefectural government the weed has spread to many regions in western Japan the Environment Ministry designated alligatorweed as an invasive alien species that poses a threat to local ecology and agricultural produce The weed is considered particularly harmful because it not only has strong reproductive power but it can also thrive both on land and in water The weed’s swift spread along the Shin-Tonegawa river in Ibaraki Prefecture forced authorities in the central and local governments to set up a taskforce to fight the harmful plant a resident spotted the suspicious weed in a waterway of a rice paddy and reported it to the prefectural government in June Prefectural officials asked the National Agriculture and Food Research Organization to analyze and identify the species It was confirmed as alligatorweed in early August The weed has not yet been found in other parts of Fukushima Prefecture The prefecture’s pest control station swiftly issued an alert calling for all-out efforts to exterminate the invasive plant The prefecture asked farmers to place fine-meshed nets on feed water inlets of rice fields and to thoroughly clean their agricultural equipment because use of the machines could disperse the stems and roots of alligatorweed many prefectures are struggling to exterminate the plant due to its ability to quickly replicate local workers go to great lengths to tackle the problem They remove the weeds with a heavy machinery The Fukushima prefectural government has chosen not to disclose where the alien weed was discovered It wants to prevent curious people from visiting the site and unknowingly spreading the species to other regions through tiny alligatorweed pieces attached to their clothes Survey warns mountaineers to avoid carrying in invasive plants Rare species in Fukushima raise hopes for end to radiation rumors Okayama dangles popular snack to round up invasive ants 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 Copyright © The Asahi Shimbun Company. All rights reserved. No reproduction or republication without written permission. 05 Apr 2025 04:30:00 GMT?.css-1txiau5-AnswerContainer{color:var(--GlobalColorScheme-Text-secondaryText2);}Ventforet Kofu won 1–0 over Iwaki FC on Sat The current head to head record for the teams are Ventforet Kofu 1 win(s) Ventforet Kofu and Iwaki FC have drawn their last 3 matches against each other Have scored 5 goals in their last 5 matches Haven't kept a clean sheet in 6 matches Who won between Ventforet Kofu and Iwaki FC on Sat 05 Apr 2025 04:30:00 GMT?Ventforet Kofu won 1–0 over Iwaki FC on Sat 05 Apr 2025 04:30:00 GMT.InsightsHave scored 8 goals in their last 5 matches Ventforet Kofu is playing home against Iwaki FC on Sat The operator of Japan's Spa Resort Hawaiians said Monday that it has received an acquisition proposal from U.S which operates the Hawaii-themed hot springs theme park in Iwaki in a two-stage tender offer estimated at up to some ¥14 billion.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); Joban Kosan's board expressed support for the first round of offer and recommended that shareholders tender their shares Spa Resort Hawaiians originally opened in 1966 as "Joban Hawaiian Center." The 2006 Japanese film "Hula Girls," which was about the story of when the resort first opened Spa Resort Hawaiians had struggled with falling tourist demand following the COVID-19 pandemic leaving Joban Kosan with a fourth straight year of net loss in the year that ended in March 2022 Joban Kosan thinks that support from Fortress will help Spa Resort Hawaiians improve its aging facilities to attract more people Fortress acquired the Phoenix Seagaia Resort complex in the city of Miyazaki investment fund bought Japanese department store operator Sogo & Seibu The Fukushima prefectural government said Monday it will stop providing temporary housing for evacuees of the two towns hosting the crisis-hit Fukushima Daiichi nuclear power plant at the end of March 2026 The move comes as living conditions are expected to improve for residents of the municipalities of Okuma and Futaba who fled their homes following the meltdowns triggered by the devastating earthquake and tsunami in 2011 thanks in part to the completion of public housing 966 people were living in 593 temporary accommodations which comprise prefabricated homes in Koriyama in central Fukushima and rented out private properties across 26 prefectures The prefecture has already terminated such housing programs for evacuees of other municipalities in the prefecture Prefectural officials plan to survey residents on their prospects of securing residence and provide support such as real estate introductions as needed Japan completes 7th round of Fukushima treated water discharge To have the latest news and stories delivered to your inbox Simply enter your email address below and an email will be sent through which to complete your subscription Please check your inbox for a confirmation email Thank you for reaching out to us.We will get back to you as soon as possible The trial will confirm the efficacy of the drug candidate for the treatment of cutaneous warts KinoPharma in partnership with IWAKI SEIYAKU has started a Phase II clinical trial of a drug candidate to treat cutaneous warts The clinical trial aims to evaluate the drug candidate’s efficacy The decision to start the Phase II clinical trial was made after confirming the drug’s safety in humans and animals The companies have also submitted a notification of clinical trial to the Pharmaceuticals and Medical Devices Agency (PMDA) the two companies have been working on the development of an ointment based on KinoPharma’s new concept of HPV antiviral drugs targeting human host factors The new ointment formulation is proposed to be an optimal delivery method to treat for HPV infection on the skin and mucous membranes the collaboration was expanded with the signing of a co-development and commercialisation agreement to advance the clinical development for the treatment of cutaneous warts Don’t let policy changes catch you off guard Stay proactive with real-time data and expert analysis Cutaneous warts are small proliferative non-cancerous lesions (benign tumours) of the skin They are a type of infection caused by the HPV the treatment includes cryotherapy using liquid nitrogen It requires repeated procedures and usually causes pain HPV infection is known to cause several diseases such as reproductive organ (cervical cancer) and upper aerodigestive tract (oropharyngeal cancer) More than 100 different types of HPV have been identified Give your business an edge with our leading industry insights View all newsletters from across the GlobalData Media network FUKUSHIMA (Jiji Press) — Fossils of insects found in amber excavated from a geological formation dating back to the Late Cretaceous period in the city of Iwaki have been identified as a new species of false fairy wasp please disable the ad blocking feature and reload the page This website uses cookies to collect information about your visit for purposes such as showing you personalized ads and content By clicking “Accept all,” you will allow the use of these cookies Users accessing this site from EEA countries and UK are unable to view this site without your consent The finding was published in the international journal of the Paleontological Society of Japan in July by a joint research team including a member from the Fukushima Museum were found almost perfectly preserved in the amber from the formation dating back 86.3 million to 88 million years The team stressed the importance of the finding in understanding the ecology of insects that were alive at the time The fossils were found at the Tamayama Formation’s Futaba Group in the Fukushima Prefecture city of Iwaki many fossils of dinosaurs and other prehistoric animals have been found found the fossil-containing amber over 20 years ago went without undergoing academic analysis for a long time Suzuki donated the amber to the research team The team found the insects trapped inside to be a new species of the genus Archaeromma in the family Mymarommatidae considering that features on their heads and wings were not found in other fossils of 10 Archaeromma species already known in the world The new species was named Archaeromma chisatoi The chairman of a noodle manufacturer in Iwaki Suzuki has spent 60 years or so digging for fossils The new false fairy wasp marks the third time a new species of a creature was named after him “I’d like to thank my family for supporting my excavations.” a research team member from the Fukushima Museum “We hope that the discoveries help us unravel the origins of a symbiotic relationship between plants and insects that has continued to this day,” Inose said Our weekly ePaper presents the most noteworthy recent topics in an exciting © 2025 The Japan News - by The Yomiuri Shimbun An International Atomic Energy Agency (IAEA) team caught fish off Fukushima Prefecture on Wednesday in an ocean survey following the discharges of treated water from the Fukushima No 1 nuclear power plant in the northeastern Japan prefecture The fish and other samples including horse mackerel and sea bream were landed at a fishing port in Iwaki before being processed for testing to be conducted respectively by the IAEA and analysis organizations in Japan and third-party countries including China to measure the concentrations of radioactive materials The IAEA will compare and evaluate the results to enhance reliability.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); The IAEA investigation team will prepare minced samples of six types of fish including flounder caught earlier this month and send them to the analysis organizations The third-country research bodies designated by the IAEA also included those of South Korea and Switzerland a similar survey was conducted by the IAEA and third-party countries to examine marine products off Fukushima the Chinese government said that it will resume imports of Japanese fishery products in stages if the IAEA expands the scope of its monitoring and the safety is confirmed But it is uncertain when China will remove its import ban introduced last year in response to the first release of the treated water from the meltdown-stricken Tokyo Electric Power Company Holdings nuclear plant into the Pacific "We want people to confirm that Japanese fishery products are safe and consume them without worry," said a Fisheries Agency official who was present during the collection of marine products Wednesday "We hope people from overseas will understand that the monitoring is appropriate." Real Salt Lake have been fairly quiet so far in their preparations for Preseason presented by Advocare but they're riding the wave all the way to Hawaii to play in the Pacific Rim Cup with their first match coming against Japanese side Iwaki FC on Friday evening RSL have unsurprisingly welcomed the trip to Hawaii although they been putting in the work even with the trip to an island paradise RSL head coach Mike Petke admits a recent session was one he'll remember a long time “When I look back on my five years as a head coach, this is one of my favorite days,” Petke said to RSL's website.  “I didn’t see it coming. After the long travel getting to the field that was interesting – to say the least – the guys put it in. We not only reached our objectives but we were able to add a couple more that we didn’t anticipate. And it was perhaps one of my longest sessions as a coach.  But it was a great vibe and a great atmosphere. The guys responded and it was awesome.” Iwaki is a provincial team located in Iwaki Currently in the Japanese regional leagues the club has aspirations to reach the J-League one day who appears to be a Japanese-American dual national which partially ascends Mount Iwaki stratovolcano and is notable for its steep gradient and 69 hairpin turns The road ascends 806 meters over an average gradient of 8.66% The Tsugaru Iwaki Skyline has been considered one of the most dangerous mountain roads in the world With its 14 spectral bands from the visible to the thermal infrared wavelength region and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet) ASTER images Earth to map and monitor the changing surface of our planet ASTER is one of five Earth-observing instruments launched Dec The instrument was built by Japan's Ministry of Economy A joint U.S./Japan science team is responsible for validation and calibration of the instrument and data products The broad spectral coverage and high spectral resolution of ASTER provides scientists in numerous disciplines with critical information for surface mapping and monitoring of dynamic conditions and temporal change Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface temperature mapping of soils and geology; and measuring surface heat balance science team is located at NASA's Jet Propulsion Laboratory The Terra mission is part of NASA's Science Mission Directorate More information about ASTER is available at http://asterweb.jpl.nasa.gov/. NASA Airborne Sensor’s Wildfire Data Helps Firefighters Take Action News. NASA Takes to the Air to Study Wildflowers News. Next-Generation Water Satellite Maps Seafloor From Space News. NASA’s EZIE Launches on Mission to Study Earth’s Electrojets News. NASA Analysis Shows Unexpected Amount of Sea Level Rise in 2024 News. NASA-ISRO Mission Will Map Farmland From Planting to Harvest News. NASA Awards Launch Service Task Order for Mission to Study Storm Formation News. NASA Uses New Technology to Understand California Wildfires News. NASA-Led Study Pinpoints Areas Sinking, Rising Along California Coast News. NASA Radar Imagery Reveals Details About Los Angeles-Area Landslides JAPANESE Metrics details Mechanosensitive biological nanomachines such as motor proteins and ion channels regulate diverse cellular behaviour Combined optical trapping with single-molecule fluorescence imaging provides a powerful methodology to clearly characterize the mechanoresponse structural dynamics and stability of such nanomachines this system requires complicated experimental geometry and is limited by low data-acquisition efficiency Here we develop a programmable DNA origami nanospring that overcomes these issues We apply our nanospring to human myosin VI and demonstrate nanometre-precision single-molecule fluorescence imaging of the individual motor domains (heads) under force We observe force-induced transitions of myosin VI heads from non-adjacent to adjacent binding which correspond to adapted roles for low-load and high-load transport Our technique extends single-molecule studies under force and clarifies the effect of force on biological processes but it is technically difficult to apply due to a number of factors caused by large-scale devices that use a high-power infrared beam to trap microspheres including low throughput (that is only one biomolecule can be analysed at a time) and complicated experimental geometry preparation and optics that minimize dye photobleaching induced by the infrared trapping beam the use of fluorescent quantum dots (QDs) or gold nanoparticles (GNPs) to circumvent dye bleaching issues is problematic due to their attraction to the trapping beam’s focus point SMF imaging of myosin heads in the presence of load is required; however combined OT and SMF imaging was difficult to implement for the study of molecular machines; therefore dark-field microscopy and electron microscopy without complicated optics or geometries Here we demonstrate SMF imaging of single- and double-colour QDs attached to the heads of myosin VI dimers tagged with our nanospring and also the tug-of-war between myosin VI and myosin V (opposite directional motors) We find force and ADP synergistically trigger transitions from hand-over-hand to inchworm-like movement of myosin VI and stalling in the adjacent binding state thus providing insights into the mechanism of the physiological dual function of myosin VI as a vesicle transporter and anchor (b) A gel-shift assay confirmed the labelling of oligos and DNA-induced dimerization myosin VI monomer labelled with 21 mer oligo (myosin VI-21 mer oligo); lane 3 myosin VI monomer labelled with 42 mer oligo (myosin VI-42 mer oligo); lane 4 myosin VI-21 mer oligo mixed with myosin VI-42 mer oligo The black arrowhead indicates a dimer fraction (c) Myosin VI tethered to a two-helix bundle (2HB) nanospring moves unidirectionally along actin against the load of the nanospring (d) Visualization of the stretch/compression dynamics of the nanospring by myosin VI at 2 mM ATP+100 μM ADP The kymograph shows repetitive stretching and compressing of the TAMRA-labelled nanospring (e) Trajectory of the centre position of the fluorescence image of the nanospring (orange circles) to measure the spring extension from which the force was calculated (grey circles) (f) Averaged force–velocity curve at 2 mM ATP+100 μM ADP Velocities at 0 pN force were measured by tracking myosin VI-NS in the absence of immobile myosin II (open circle Stall over 2 s were included in the analysis The red line marks a a Gaussian function fit (2.1±0.6 pN (mean±s.d.)) To observe the stepping dynamics of myosin VI under tension, we designed a myosin VI–nanospring complex (myosinVI-NS; Fig. 2c) where one end of the nanospring was attached to a DNA-coupled myosin VI dimer via the nanospring capture domain on the myosin VI 42-mer oligo whereas the other end of the nanospring was attached to an immobilized myosin II dimer which was chemically inactivated by N-ethylmaleimide and labelled with ssDNA Immobile myosin II strongly binds to actin filaments in the presence of ATP and plays a role in fixing myosinVI-NS on the actin filament (a) Typical trajectory for dual colour imaging of tug-of-war between myosin V and VI at 2 mM ATP+100 μM ADP which indicates myosin V motion; orange circles Black triangles indicate detachment events (b) Detachment frequency during tug-of-war for myosin V (red) and myosin VI (orange) (c) Trajectories of a QD (red circles) attached to the head of a myosin VI the centre position of a TAMRA nanospring (orange circles) and two times the displacement of the centre position of the TAMRA nanospring (grey line) at 2 mM ATP+100 μM ADP (d–f) Trajectories at 2 mM ATP and 0 pN (d) The red Gaussian fits in g represent step sizes at 2 mM ATP and 1–2 pN load (−41.8±15 42.5±11 and 72.1±11 nm) and in h at 2 mM ATP+100 μM ADP and 1–2 pN load (−38.0±13 short (red) and backward (dark green) steps at different loads and ADP concentrations estimated from the Gaussian fits our results show a transition in the myosin VI step size distribution in response to ADP and load (a) Typical trajectory of QDs attached to both heads showing hand-over-hand steps and inchworm-like steps (dashed-line box) (b) Typical trajectory of QDs attached to both heads in the stall state (dashed-lined box) The grey and light grey bars indicate the binding state of myosin VI onto actin (grey (c,d) Distance between heads at stalled state (c) and at unloaded state (d) The distribution fit to three Gaussian functions (solid and broken lines) with peaks at 37±9.3 nm The peak around 0 nm is interpreted as a convolution of positive and negative distances for the adjacent binding state The combination of our DNA nanospring technology with SMF imaging reveals that higher forces induce a transition from hand-over-hand to inchworm-like motion in myosin VI the adjacent binding state was observed to be predominant at stall force which is consistent with myosin VI anchoring in the cell These two stepping patterns (or bound states) and the transition between them can only be distinguished by independent tracking of the two head domains under load The results demonstrate that our DNA nanospring system can reveal the force-dependent functional changes of molecular machines This mechanism is consistent with our observation of a transition to inchworm-like stepping under load with physiological ADP The programmability of nanospring–motor protein complexes could also be the basis for nanoactuators to study other mechanosensory proteins or be used as components for synthetic nanoscale devices that require dynamic buildup of mechanical potential energy To fold the spring, 10 nM of scaffold was mixed with 100 nM of core staples (Supplementary Data) Oligos were obtained from Hokkaido System Science or IDT The folding reaction was carried out in Folding buffer (5 mM Tris pH 8.0 1 mM EDTA and 2–30 mM MgCl2) with rapid heating to 80 °C and cooling in single degree increments to 60 °C over 2 h followed by additional cooling in single degree increments to 25 °C over another 2 h The folded nanospring was purified by agarose gel electrophoresis. Structures were loaded into 2% agarose gels and run at 50 V for 3 h in TBE buffer (45 mM Tris, 45 mM boric acid and 1 mM EDTA) supplemented with 11 mM MgCl2. The highest migration bands (see Supplementary Fig. 2) were excised crushed and spun through a Freeze and Squeeze column (Bio-Rad) for 10 min at 20,000 g and 4 °C The purified nanospring was adsorbed for 5 min onto glow discharged formvar- and carbon-coated copper grids stained for 1 min with 2% uranyl formate and 25 mM NaOH Images were acquired at 80 kV under low-dose conditions in a Tecnai T12 equipped with a LaB6 filament and a 4k × 4k CCD (charge-coupled device) camera The nominal magnification was × 50,000 for a pixel size of 3.66 Å at the sample level To estimate the force-extension curve of the nanospring, biotin-modified staples and digoxigenin (DIG)-modified staples (Supplementary Data) were added to the 100 nM core staples which were then folded to attach biotin and DIG at opposite ends of the nanospring Carboxylate-modified polystyrene beads (0.2 μm in diameter Invitrogen) were crosslinked to anti-DIG polyclonal antibody (Roche) and BSA using the Polylink Protein Coupling Kit (Polysciences One microlitre of anti-DIG antibody-coated beads (∼3 nM) and 10 μl of nanospring (∼1 nM) were mixed and incubated for 1 h on ice before use in an optical tweezers assay The chamber was observed by our microscope after 5 min We estimated the fix point of bead-NS on the glass surface as the mean value of the probability density distribution of the bead position Human myosin Va complementary DNA (Kazusa Product ID ORK07567) was truncated at Gly924 lever arm domain (IQ1-6) and a small part of the coiled-coil domain (11 a.a. HaloTag (Promega) was attached at the N-terminal via a linker (15 a.a. For oligo labelling and protein purification SNAP-tag (NEB) and 6 × His-tag were attached at the C-terminal via linkers (2 a.a. This Halo-hMyosinVa-SNAP-His fragment and the human calmodulin gene (Met1-Lys149 Kazusa Product ID ORK01403) were introduced downstream of the PH and p10 promoters of the Baculovirus expression vector pFastBac Dual Human myosin VI cDNA (Kazusa Product ID ORK01080) was truncated at Ala1021 medial and most of the distal tail domain (41 a.a. IQAEVEAQLARQKEEESQQQAVLEQER RDRELALR IAQSEA) HaloTag was attached at the N-terminal via a linker (15 a.a. This Halo-hMyosinVI-SNAP-His fragment and the human calmodulin gene (Met1-Lys149 Monomeric forms of myosin V and VI were expressed and purified as follows Recombinant viruses for myosin V or VI heavy chain and calmodulin were produced by homologous recombination using the Bac-to-Bac Baculovirus Expression System (Life Technologies) Sf9 insect cells were maintained in a monolayer culture in ventilated 175 cm2 flasks at 28 °C with 10% fetal bovine serum and 1 × Antibiotic-Antimycotic liquid/Sf-900 II SFM (Life Technologies) After 60 h of incubation for recombinant proteins expression cells were collected by centrifugation at 6,000 g for 5 min and stored at −80 °C Frozen cells were suspended and sonicated in 2 ml Lysis buffer (30 mM Tris–HCl pH 8.0 5 mM ATP and 10 mM 2-mercaptoethanol) containing Complete EDTA-free protease inhibitors cocktail tablet (Roche Diagnostics) per flask of cells After ultracentrifugation at 35,000 g for 20 min soluble fractions were mixed with pre-washed 100 μl Ni-NTA Agarose (QIAGEN) for 40 min 10 mM 2-mercaptoethanol and 20 mM imidazole pH 8.0) was added into the column Myosin was eluted by Elution buffer (20 mM Tris–HCl pH 8.0 10 mM 2-mercaptoethanol and 300 mM imidazole pH 8.0) and myosin V or VI recombinants were obtained (0.3–1 mg ml−1) Oligo labelling reactions were performed just after His-tag affinity purification. Amine-modified DNA oligos (Hokkaido System Science) (Oligo A*, B*, C* and D* in Supplementary Data) were linked to the SNAP substrate and 25 μM of BG-oligonuculeotides was labelled with ∼1 μM myosin V or VI containing an C-terminal SNAPf tag (NEB) in His tag affinity Elution buffer for 30 min at room temperature Oligo-labelled myosin V and VI were purified by actin filament affinity ∼1 μM oligo-labelled monomeric myosin V or VI was mixed and incubated for 30 min at 4 °C The efficiencies of labelling the oligos to and the dimerization of myosin VI were estimated by a gel-shift assay (4–15% gradient gel Biorad) and determined as >90 and >30% Qdot 565 amine-derivatized polyethylene glycol (PEG) conjugates (4 μM; Life Technologies) was mixed with 50 mM HaloTag succinimidyl Ester (O4) ligand (Promega) and incubated for 1 h at room temperature Excess HaloTag ligand was removed three times by gel filtration (Micro BIO-SPIN P-6 Biorad) and the HaloTag ligand-QD conjugation was stored at 4 °C Myosin VI dimer (2 μl; ∼500 nM) was mixed with 1 μl HaloTag ligand-QD conjugation (∼2 μM) and incubated for 3 h on ice before use for single-molecule imaging experiments myosin VI monomer was used when mixing with QD ∼500 nM oligo-labelled monomeric myosin VI with Qdot 565 or 655 was mixed together and incubated for 30 min at 4 °C to form DNA-hybridized myosin VI dimers labelled with different colour QDs For the myosin-NS conjugation, handle staples (Supplementary Data) were added to the 100 nM core staples which were then folded to attach optional 21 bp ssDNA to both ends of the nanospring One microlitre of DNA-hybridized myosin dimer or immobile myosin II (0.5∼1 μM) with anti-handle oligos was mixed with 10 μl of nanospring (∼10 nM condensed by ultrafiltration (Amicon Ultra 100 K Merck Millipore)) and incubated for 30 min on ice To avoid nonspecific interactions of myosin-NS with the glass surface, a glass coverslip was coated with functional PEG according to Schroeder et al.47 with some modifications coverslips were cleaned with a plasma cleaner for 10 min (FEMTO The coverslips were then soaked in freshly prepared 2% (3-Aminopropyl) trimethoxysilane (KBM-603 Shin-etsu Chemical) in acetone for 45 min with gentle shaking at room temperature and rinsed with ddH2O Coverslips were dried and 30 μl of PEG solution (100 mg ml−1 (PEG 5000 (ME-0500HS NOF Corp.)=100:10:1) in freshly prepared 0.1 M bicarbonate buffer pH 8.3) was put between a pair of coverslips and incubated for 3 h 20 μl of sulfodisuccinimidylartrate (Solteck Ventures) solution (30 mg ml−1 in freshly prepared 1 M bicarbonate buffer pH 8.3) was put between a pair of coverslips and incubated for 45 min dried and stored at −80 °C in a vacuum desiccator with desiccant Ten microlitres of myosin-NS or myosin-QDs-NS diluted 10 or 100 times in Motility buffer was flowed into the cell The chamber was sealed with nail polish and observed immediately Single-molecule imaging and analysis of the nanosprings or QDs was performed using TIRFM Illumination was provided by 488 nm laser light (OBIS 488LS-100 Coherent) or 640 nm laser light (OBIS 640LX-75 The fluorescence of TAMRA labelled with nanospring or Qdot 565 labelled with myosin was passed through a dichroic mirror (FF552-Di02 or FF506-Di03 Semrock) and emission filter (FF01-585/29 or FF01-562/40 the fluorescence of Cy3 and ATTO647N labelled with nanospring or Qdot 565/655 labelled with myosin was passed through a dichroic mirror (FF01-577/690-25 or FF552-Di02) and a dual-view apparatus (Hamamatsu) equipped with dichroic mirrors (DML630 nm or DML 600 nm and emission filters (FF01-585/29 or FF01-562/40 and FF655/15 Semrock) were put in front of the EMCCD camera (Andor TAMRA-labelled nanosprings and QDs showing smooth processive motions were chosen for the analysis and a sufficient data set was collected from multiple preparations (flow chambers) to estimate the fit values multicolour fluorescent beads (Ultra Rainbow Fluorescent particles Spherotech) stuck on a coverslip were used as fiducial markers for each imaging channel An alignment grid by the fluorescent beads was created with a piezo stage (Physik Instrumente 3CD) and the fiducial registration error for each marker was calculated by MATLAB software and estimated to be <7 nm over 12 h which ensured sufficient stability during the single-molecule experiments To quantify the number of myosin VI attached to a nanospring 10 μM HaloTag TMR ligand (Promega) was labelled with ∼1 μM myosin VI during the labelling process of 21-mer BG-oligo Labelling efficiency was spectrophotometrically estimated to be >95% The TMR and 21-mer oligo-labelled myosin VI was mixed with 42-mer oligo-labelled myosin VI and incubated for 30 min at 4 °C to form myosin dimers Myosin-NS was prepared as described in Myosin-nanospring (myosin-NS) conjugation section and purified with Sephacryl S-500 HR resin (GE Healthcare) twice The resulting myosin-NS was diluted in Motility buffer flowed into the cell and observed by TIRFM The force–velocity relation and the precision of the nanospring extension were determined using Origin 8.5 (Origin Lab.) individual displacements obtained from tracking a fluorescently labelled nanospirng were averaged to reduce Brownian noise Line fits were made to successive 1 s time segments and the velocity for each segment was determined as well as the mean force during the segment Data points were clustered at fixed intervals of force and the average velocities were plotted against average force of the force includes the error from the force-extension curve (average standard deviation is 0.19 pN at 0–2 pN range) The force–velocity curve was constructed from 38 processive motions The authors declare that the data supporting the findings of this study are available within the article and its Supplementary Information files or are available from the authors upon request A programmable DNA origami nanospring that reveals force-induced adjacent binding of myosin VI heads Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Myosin I can act as a molecular force sensor Mechanosensitive channels in bacteria: signs of closure Actin filaments function as a tension sensor by tension-dependent binding of cofilin to the filament The minimal cadherin-catenin complex binds to actin filaments under force Local force and geometry sensing regulate cell functions Direct observation of kinesin stepping by optical trapping interferometry Single myosin molecule mechanics: piconewton forces and nanometre steps Nonlinear elasticity and an 8-nm working stroke of single myosin molecules in myofilaments Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization Repetitive shuttling of a motor protein on DNA Single-molecule observations of neck linker conformational changes in the kinesin motor protein Simultaneous observation of individual ATPase and mechanical events by a single myosin molecule during interaction with actin coincident optical trapping and single-molecule fluorescence Fluorescence-force spectroscopy maps two-dimensional reaction landscape of the holliday junction Interlaced optical force-fluorescence measurements for single molecule biophysics Self-assembly of DNA into nanoscale three-dimensional shapes Folding DNA into twisted and curved nanoscale shapes Unconventional myosins in inner-ear sensory epithelia Loss of myosin VI reduces secretion and the size of the Golgi in fibroblasts from Snell’s waltzer mice The mechanism of myosin VI translocation and its load-induced anchoring Uncoated endocytic vesicles require the unconventional myosin for rapid transport through actin barriers Robust mechanosensing and tension generation by myosin VI Switch between large hand-over-hand and small inchworm-like steps in myosin VI Myosin VI must dimerize and deploy its unusual lever arm in order to perform its cellular roles Video imaging of walking myosin V by high-speed atomic force microscopy Long single alpha-helical tail domains bridge the gap between structure and function of myosin VI Cargo binding induces dimerization of myosin VI Dynein achieves processive motion using both stochastic and coordinated stepping Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization Walking to work: roles for class V myosins as cargo transporters Myosin VI is a processive motor with a large step size Class VI myosin moves processively along actin filaments backward with large steps Simultaneous observation of the lever arm and head explains myosin VI dual function Single molecule high-resolution colocalization of Cy3 and Cy5 attached to macromolecules measures intramolecular distances through time An in vitro assay reveals essential protein components for the ‘catch’ state of invertebrate smooth muscle Mechanics of Motor Proteins and the Cytoskeleton Sinauer Associates Processive steps in the reverse direction require uncoupling of the lead head lever arm of myosin VI Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport Direct observation of intermediate states during the stepping motion of kinesin-1 Tug-of-war in motor protein ensembles revealed with a programmable DNA origami scaffold Rapid prototyping of 3D DNA-origami shapes with caDNAno Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures Mechanochemical coupling in actomyosin energy transduction studied by in vitro movement assay Preparation of myosin and its subfragments from rabbit skeletal muscle Sliding movement of single actin filaments on one-headed myosin filaments Brownian search-and-catch mechanism for myosin-VI steps Spontaneous detachment of the leading head contributes to myosin VI backward steps Download references We thank colleagues of the Riken Quantitative Biology Center and T Karagiannis for helpful comments on the manuscript This work was supported by Grant-in-Aid for Scientific Research on Innovative Areas (20118009 Grant-in-Aid for challenging Exploratory Research (24654139 Department of Biological Chemistry and Molecular Pharmacology Wyss Institute for Biologically Inspired Engineering Center for Information and Neural Networks conceived the idea and planned the experiments performed the single-molecule experiments and analysed the data discussed the experimental results with T.Y The authors declare no competing financial interests Supplementary Figures 1-7 and Supplementary References (PDF 633 kb) Handles and Anti-handles for nanospring (XLSX 23 kb) A 200 nm fluorescent bead tagged with a nanospring (right bead) was optically trapped at the fixed trap center and the cover glass was moved by a piezo-driven stage (triangle wave The displacement of the cover glass was calculated using a fluorescent bead stuck on the cover glass (left bead) The fluorescence image was recorded by an EMCCD camera at a 30 Hz recording rate A nanospring was fluorescently labeled by thirteen TAMRA-labeled staple strands and immobile myosin II and single myosin VI were attached to the ends Non-fluorescent actin filaments were adsorbed on the cover glass and the nanospring-motor protein complex was tethered to the actin via immobile myosin IIs Myosin VI tethered with the nanospring moved processively along actin filaments and the stretch/compression dynamics of a fluorescently labeled nanospring could be seen by TIRF microscopy (10 Hz frame rate Both ends of a nanospring were fluorescently labeled and attached to single myosin V and VI molecules (Cy3 for myosin VI indicated by dark green; ATTO647N for myosin V Dual-color imaging was done by TIRF microscopy and the two imaging channels were co-localized by SHREC (10 Hz frame rate A myosin VI monomer was labeled with Qdot (Q565) via HaloTag at the N-terminal head domain and dimerized with a non-labeled myosin VI monomer via DNA hybridization The resulting dimer moved processively along actin filaments and the fluorescence image was observed using TIRF microscopy (30 Hz frame rate Qdot (Q655)-labeled myosin VI (indicated by red) was tethered to an actin filament via a TAMRA-labeled nanospring (indicated by dark yellow) and the fluorescence image was observed by TIRF microscopy (10 Hz frame rate Download citation 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 Fresh arrest warrants were served to five suspects Friday over the murder of a man whose body was found last December in a suitcase in the Tama River near Tokyo arrested last month on suspicion of abandoning the body 46-year-old video content creator Tadayuki Hara according to the new warrants.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); and Nishitaka's boyfriend Shuhei Iwaki The new warrants allege that the five conspired to strangle Hara in an apartment in Tokyo's Ota Ward between the night of Dec 15 last year and the early hours of the next day All five except the mother have mostly admitted to the allegations against them According to Kanagawa Prefectural Police sources Nishitaka and Iwaki were living in the apartment Hara is known to have entered the apartment but his whereabouts after that were unknown Hara and Nishitaka had some problems after breaking up last September adding that the five are suspected of planning and committing the murder The Kanagawa police arrested the five on May 25 this year for allegedly abandoning the victim's body in a riverside area in Ota Ward on the Tama River The suitcase containing the body was found by a person who was fishing in the river in Kawasaki later that month Metrics details Age-related hearing loss (ARHL) is a complex multifactorial disorder and in human suggest that oxidative stress and mitochondrial disturbance play an important role in the pathoetiology of ARHL Mitochondrial DNA (mtDNA) haplogroups are populations with genetically similar traits and they have been reported to affect the mitochondrial function of oxidative phosphorylation To gain further insights into the relationships between mitochondrial haplotypes and the susceptibility to cochlear aging we aimed to elucidate how the differences in mtDNA haplogroups may affect ARHL development in Japanese general population as the same mtDNA haplogroup can show either a negative or positive effect on systemic co-morbidities of ARHL that appear later in life A total of 1167 participants of the Iwaki Health Promotion Project were surveyed in 2014 A total of 698 subjects aged 30 to 65 years were included in the statistical analysis and the hearing loss group consisted of 112 males (40.3%) and 111 females (26.4%) Multiple logistic regression analysis showed that the male subjects belonging to haplogroup A had a significantly increased risk of hearing loss whereas the female subjects belonging to haplogroup N9 had a significantly decreased risk of hearing loss These results suggested that the mtDNA haplogroup may be an indicator for future risk of morbidity associated with ARHL it is suggested that people over 30 years of age experience hearing loss at high frequencies which may lead to tissue dysfunction in all somatic systems we aimed to elucidate how the differences in mtDNA haplogroups affect the development of ARHL in Japanese population There were 698 individuals aged 30 to 64 years; 33 data-deficient individuals 58 individuals with a history of ear disease and 378 young and elderly individuals were excluded from our analyses Data collection and genetic analysis in the present study and the Iwaki Health Promotion Project were approved by the Ethics Committee of Hirosaki University School of Medicine (authorization numbers: 2014-014 and all subjects provided written informed consent before participating in the project To obtain the participants’ lifestyle information we used a self-administered questionnaire and conducted face-to-face interviews to determine the medical history The pack-years (number of cigarette packs per day × years of smoking) for smoking habit was also calculated Venous blood samples were obtained early morning with the participants on an empty stomach to examine hemoglobin A1c (HbA1c) high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC) average hearing thresholds at 4000 and 8000 Hz were used for analysis The subjects with average hearing at 4000 and 8000 Hz greater than 25 dB were included in the hearing loss group and the remaining subjects were included in the control group The characteristics of the subjects (males and females) and the hearing loss and control groups for each gender were compared using Student’s t-test and chi-square test A comparison of specific mtDNA haplogroup prevalence was performed using the chi-square test Risk factors influencing high-frequency hearing loss were evaluated using the multiple logistic regression analysis separately for males and females The dependent variable was the presence or absence of high-frequency hearing loss each of the 12 haplogroups were added to the independent variable Test results with p < 0.05 were regarded as statistically significant All statistical analyses were performed using IBM SPSS Statistics (version 25.0; IBM Corp. The characteristics of our subjects by gender are shown in Table 1a The 698 subjects comprised 278 males (39.8%) and 420 females (60.2%) The number of subjects in the hearing loss group was 112 (40.3%) for males and 111 (26.4%) for females and the prevalence of hearing loss was significantly higher in males than in females the average age was significantly lower in males and dyslipidemia were significantly higher in males The characteristics of subjects in the hearing loss and control groups for each gender are shown in Table 1b and diabetes were significantly higher in the hearing loss group than in the control group the average age and prevalence of hypertension were significantly higher in the hearing loss group than in the control group Distribution of the mtDNA haplogroups in the subjects in question (n = 698) is shown as a percentage of each haplogroup in individuals with hearing loss (HL) and control groups All variables were examined using chi-square statistics Statistical significance was set at p < 0.05 For mtDNA haplogroups with a significant difference Haplogroup M7b was not significantly associated with hearing in this analysis For the purpose of detecting early hearing loss with aging subjects aged only 30‒64 years were enrolled and average hearing thresholds at higher frequencies were used for analysis in the present study The evaluation of hearing at high frequencies may be useful as a screening method for ARHL in young individuals the present study did not show a significant correlation between the hearing loss at high frequency and haplogroup D4b after considering confounding factors The difference may come from the differences in the subjects and the definition of hearing loss for detecting early hearing loss with aging The results of the present study indicated that dyslipidemia did not significantly lead to the progression of hearing loss Because the subjects of the present study were relatively younger dyslipidemia might not result in hearing loss The other variables did not influence hearing loss in the present study This may be explained by that the effect of the disease on hearing loss may be less pronounced than that in the elderly These considerations are uncertain and further detailed studies might be necessary to clarify the association between risk factors and hearing loss multivariate analyses after considering confounding factors were performed to investigate the association between any mtDNA haplogroup and ARHL development The results indicated that males in mtDNA haplogroup A were more likely to develop ARHL than males in other haplogroups and females in haplogroup N9 were less likely to develop ARHL than females in other haplogroups This suggested that the mtDNA haplogroup may be an indicator for future risk of morbidity associated with ARHL Current concepts in age-related hearing loss: Epidemiology and mechanistic pathways Estimates of the size of the hearing-impaired elderly population in Japan and 10-year incidence of hearing loss by age based on data from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) Prevalence of hearing loss in older adults in beaver dam Wisconsin: The epidemiology of hearing loss study Age-related hearing loss: Gender differences Age effect on hearing: a study on Japanese Gender-specific hearing loss in German adults aged 18 to 84 years compared to US-American and current European studies Cisplatin and aminoglycoside antibiotics: hearing loss and its prevention Association of nutritional factors with hearing loss Association of midlife hypertension with late-life hearing loss Hearing loss in type 2 diabetes in association with diabetic neuropathy Mitochondrial dysfunction and oxidative stress in aging and cancer A Mitochondrial paradigm of metabolic and degenerative diseases and cancer: A dawn for evolutionary medicine May “Mitochondrial Eve” and Mitochondrial haplogroups play a role in neurodegeneration and Alzheimer’s diseases Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese males Mitochondrial haplogroup A is a genetic risk factor for atherothrombotic cerebral infarction in Japanese females MitoSuite: a graphical tool for human mitochondrial genome profiling in massive parallel sequencing Mitochondrial genome variation in eastern Asia and the peopling of Japan Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals Mitochondrial DNA haplogroup A decreases the risk of drug addiction but conversely increases the risk of HIV-1 infection in Chinese addicts Mitochondrial haplogroups associates with lifestyle-related diseases and longevity in the Japanese population Mitochondrial DNA haplogroup associated with hereditary hearing loss in a Japanese population Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey Race and sex difference in age-related hearing loss: The Health Hearing loss in the elderly: an epidemiologic study of the Framingham Heart Study Cohort Modifiable determinants of hearing impairment in adults Prevalence of hazardous occupational noise exposure and hearing protection usage among a representative sample of working Canadians Hearing sensitivity in order adults: association with cardiovascular risk factors in the health The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors Download references This work was supported by the JST COI (grant number JPMJCE1302) The authors would like to thank all their coworkers for their skillful contributions to data collection and management Hirosaki University Graduate School of Medicine Research Institute of Bio-System Informatics Center of Innovation Research Initiatives Organization Hirosaki University COI Research Initiative Organization 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/s10038-022-01011-6 today held a ceremony at its Iwaki Plant in Fukushima Prefecture to mark five years since the Great East Japan Earthquake that devastated the area Nissan also further underlined its ongoing commitment to the region by donating e-NV200 electric vehicles to the prefecture and Iwaki City Nissan President and CEO Carlos Ghosn said: "Five years ago this plant was heavily damaged by the Great East Japan Earthquake I visited just two weeks after and saw cracked floors and collapsed engine and casting production lines It was clear that we faced a huge challenge in bringing this plant back on line But thanks to the fighting spirit of our workers—and the strong support we received from Fukushima Prefecture and Iwaki City—we were back to full operations two months after the earthquake we reached a significant milestone when Iwaki produced its seven millionth engine This step forward would not have been possible without the ongoing support of local leaders and community members." Ghosn presented one e-NV200 each to Fukushima Prefecture Governor Masao Uchibori and Iwaki City Mayor Toshio Shimizu The vehicles will serve the prefecture's Aquamarine Fukushima aquarium and the city's Iwaki Lalamew shopping center a tsunami hit the Onahama area where the aquarium and shopping center are located Although both facilities have been since been restored visitor numbers are 30 percent lower than before the disaster Nissan's donation of the zero-emission vehicles will help the facilities' operations flourish again Besides using the vehicle for transportation Aquamarine Fukushima will take advantage of the e-NV200's electricity-supply function to power a mobile aquarium Iwaki Lalamew's e-NV200 will transport goods and supply electricity to events the e-NV200 can work as a power source by discharging electricity from its battery It shows how owning an EV can strengthen a community's ability to recover in times of disaster Under the strong leadership of Uchibori-san and Shimizu-san I hope this region will promote the many other benefits of electric vehicles "Nissan remains committed to restoration efforts across Tohoku We are proud and grateful to be part of the Iwaki and Fukushima communities and we look forward to building a bright future together." Nissan is a global full-line vehicle manufacturer that sells more than 60 models under the Nissan the company sold more than 5.3 million vehicles globally manufactures and markets the world's best-selling all-electric vehicle in history Japan manages operations in six regions: ASEAN & Oceania; Africa Middle East & India; China; Europe; Latin America and North America and has been partnered with French manufacturer Renault under the Renault-Nissan Alliance since March 1999 Futoshi Mori / Yomiuri Shimbun Senior Writer Iwaki City in Fukushima Prefecture is full of such delights The city was hit hard by the Great East Japan Earthquake and the pandemic but tourists are finally starting to return some might head to the city’s Onahama district for a bowl of Yamatonbi’s “Iwaki sunshine ramen” (¥980) a local ramen dish filled with the bounty of the Iwaki area The young proprietor and his wife are as cheerful as the sunshine that bathes Iwaki and they are passionate in their commitment to their hometown’s recovery I boarded the Hitachi limited express train on the Joban Line from Tokyo Station and alighted at Izumi Station The famous Spa Resort Hawaiians is one stop further a short trip toward the mountains from Yumoto Station about a 15-minute taxi ride from Izumi Station two-story shop and residence with red nobori banners reading “Ramen” and a brighter red chochin lantern hanging at the entrance In one corner of the property stands a small shrine that mourns broken renge ramen spoons A plaque explains that money donated here is used to run a children’s cafeteria that provides free or low-cost meals and a friendly environment for children in the area A shrine on the premises to mourn broken renge ramen spoons A white noren curtain hangs over the shop entrance greeted me cheerfully with a “Welcome!” The seating area and kitchen are spacious After I purchased “Iwaki sunshine ramen” from the ticket machine at the entrance “The soup is made from an underutilized fish called kanagashira,” Mami told me It was reddish and resembled the high-end sea robin but there is not much to eat on it and it’s difficult to cook we collaborated with Iwaki City to create a local ramen using such underutilized fish.” bought at auction at the local fishing port but supermarkets have recently begun selling it Shuta pours soup that has been heated up into a bowl The finished ramen was served in front of me in a white bowl with a red saucer The small colorful arare (rice crackers) sprinkled on top of the ramen further added to the cheery ambiance But it’s hardly any wonder once you hear the reason “We have a license to bid on fish at the Iwaki Fishing Port Auction,” Shuta said “And immediately after securing fish at auction I clean them up with salt and water and make soup in a large zundo pot I almost exclusively use kanagashira.” There’s no beating fresh fish Fish caught off the coast of Fukushima are known as “Joban-mono,” a brand of fish that is known for its freshness one serving of soup makes use of two kanagashira The soup is divided up between small bags and frozen for individual servings then heated and served when the ramen is ordered Thin noodles made with hot spring water from Iwaki Yumoto Onsen The soup is not the only thing they are particular about The noodles are custom-made by a local noodle producer using hot spring water from the Iwaki Yumoto Onsen The water is said to give the noodles a more expansive feel White soy sauce is used as the kaeshi sauce for this ramen and white forms the basis of the overall color scheme Combined with the red and white of the bowls with which you can enjoy three separate umami flavors as the temperature of the soup changes Thin noodles with whole wheat flour are used for the standard ramen and are topped with a beautiful naruto fish cake produced by a local company The soup is made with homemade niboshi (dried fish) and a unique blend of soy sauce from three breweries in the cities of Iwaki Shirakawa and Fukushima in Fukushima Prefecture Added to this is the umami of kombu seaweed and shiitake mushrooms Toppings include two kinds of homemade braised pork and chicken chashu as well as picture-perfect naruto fish cake is used in cup noodles and accounts for a massive share of the national market Kitakata and Shirakawa are famous for their ramen when the Magariyamas started their ramen shop in Iwaki the couple had been thinking about creating a local ramen and in 2019 they launched a project in collaboration with the city of Iwaki to create one The city’s condition was that underutilized fish and the Yumoto Onsen be used to promote the city the Magariyamas came up with a kanagashira broth and noodles made using the hot spring water which they began offering the following year but customers and children who visited the shop filled out request cards A ticket machine button with a picture of “Iwaki sunshine ramen” Shuta studied at a university in Tokyo and after graduating went straight to work for a midsize construction company the company’s scope was in fact quite broad and Shuta was assigned to its food and beverage department where he worked on the company’s related businesses It was during this time that the Great East Japan Earthquake struck in 2011 Shuta felt a strong desire to aid in the reconstruction of his hometown so he quit the company and returned in 2016 Although he had little experience with ramen “I was what is called a raota [ramen otaku] so I had my own favorite flavors.” A ramen shop was the ideal way for him to put to work his love of ramen and the restaurant management experience he had gained while working for the company was a high school student at the time of the earthquake and though she afterward went to study in Tokyo she too eventually returned to her hometown “I wanted to help out with the rebuilding of Iwaki,” she explained She became a tourism ambassador for the city and carried out PR at various locations She also works as a model and belongs to the agency that produces the magazine “Fukushima Bishojo Zukan” (“Beautiful Girl Pictorial Book”) in which young women in Fukushima become faces of the recovery effort through their upbeat and energetic messages Mami and Shuta met in their hometown and opened a ramen shop in the city in 2017 I couldn’t even use a kitchen knife by myself.” But after getting married Now she goes to fish auctions by herself decked out in rubber boots and brings home tens of kilograms of fish with aching muscles The couple has been working hard together to run their ramen shop they moved into their current location in a brand new building The official “Hula City Iwaki” logo is displayed in the shop as a sign of support for the city A paper place mat describing the shop’s approach to ramen “Iwaki sunshine ramen” is also available online which had been very cheap when they first started has recently started to be sold in supermarkets and the price has gone up “There are days when I get outbid and am unable to buy it,” she added as it proves that the value of the fish has increased and it is now seen as an edible rather than thrown away “Kanagashira can be caught all over in Japan so I want more and more people to know and eat it and I also want people to know about our Iwaki sunshine ramen,” says Mami The shop name Yamatonbi combines the character “yama,” meaning mountain from the couple’s family name and “tonbi,” meaning black kite — a type of bird common to Iwaki “Tonbi are birds that can stay airborne for a long time We would like to keep our shop going and help carry the recovery of the local community for a long time There are concerns in the local community now about reputational damage that could come from the release of treated water from the Fukushima No.1 nuclear power plant we will continue to use ingredients from Iwaki and support the area’s rebuilding,” Shuta said resolutely Information about the shop is available on Instagram https://www.instagram.com/iwaki.ramen.yamatonbi/  It’s a serious battle for both the cook and the diner There are many ramen restaurants in Japan that have a tremendous passion for ramen and I’d like to introduce to you some of these passionate establishments making the best of my experience of enjoying cuisine from both Japan and around the world Non-human theatre both provokes and comforts in a post-Fukushima world it is difficult to reflect on 9/11 without mass disquietude for many Japanese 3/11 is not merely another day the Tōhoku earthquake and tsunami—better known today as the Fukushima Daiichi Nuclear Power Plant Disaster—rippled along the Northeastern coastline of the island country This unprecedented triple attack included a magnitude 9.0 earthquake that moved Japan eight feet east a 9.8-foot tsunami that killed over 15,000 people and a Level-7 nuclear melt-through of three nuclear vessels might be said to have created an almost complete tabula rasa In addition to the earthquake and tsunamis radiation extinguishes another intangible dimension: time Considering that Plutonium 239 has a half-life (the period in which 50 percent of nuclides will have undergone nuclear decay) of 24,110 years nuclear aftermaths indeed seem to defy a human conception of time Unfortunately humanity’s sense of emergency does not last for 20,000 years for good reason: If we were to continue to dwell at length in the same level of hypertension the repercussions of Fukushima seem invisible (unless you’re near the epicenter) Prime Minister Abe Shinzō unabashedly declared before the International Olympic Committee that Fukushima is “under control,” an assurance that was probably crucial to Japan winning the 2020 Olympics Ostensibly the country has regained its peace yet one must never forget that this peace is only a palimpsest resting upon a constant effort to silence anxieties That’s why for some people in Japan (and the rest of the world) the Fukushima nuclear catastrophe was absent to begin with: out of sight Owing to this simultaneous absence and presence many Japanese are impelled to broach uncharted domain—that is they are compelled to seek a new language to aptly express their uncertainties to rebuild collective values that could mend divided narratives and to construct a new way of life that is not merely situated prior to but is always aligned with death and fictional safeguards—naturally becomes a useful testbed Not that theatre has taken what may seem the most obvious reaction and approach: an ecocritical theatre demanding a full cessation of the 54 nuclear power plants in Japan or a head-on political theatre rigidly questioning the legal liabilities of Tokyo Electric Power Company Instead a gradual yet sturdy “non-human” turn has been evident theatremakers have become noticeably more attracted to cyborgs human actors perform roles of anthropomorphized non-human beings One could argue that this is just another form of the techno-animistic imagination prevalent in Japan since long before 3/11 But what must be noted here is that the rationales underpinning this turn toward the non-human have shifted in subtle yet interesting ways after Fukushima Japan is considered by many to be a trailblazer of industrial robots and futuristic imagination From the mangas of Osamu Tezuka’s Astro Boy (1952) and Mitsutru Yokoyama’s Ironman 28 (1956) ideal human-robot kinships have been dreamt of by boys most of these robots were designed to serve humans as part of a better society In this unthinkingly human-centric register robots were acknowledged to be essentially inferior to humans; that’s why Atom always longed to be treated like a human child this human-robot hierarchy has been subtly inverted Forced to realize how easily destructible their social bonds are and how physically vulnerable their bodies could be many Japanese theatremakers have created androids who “act” onstage as symbols of indestructible immortality—a thing humans have yearned for half-eternally Oriza Hirata—playwright, director, leader of Seinendan (Youth group) Theatre Company and a usual suspect in Francophone theatre festivals—is generally considered the forerunner of Japanese robot theatre Hirata has created eight robot theatre productions including robotic versions of Kenji Miyazawa’s Night on the Galactic Railroad (2013) and the Hamburg State Opera’s Stilles Meer (Silent Sea 2016) in which a robot (Robovie-R3 by Vstone) appears as a nuclear power plant worker Hirata even sometimes talks about a near future in which human actors could be completely replaced by androids “They could act in any language; travel cheaply; never get sick; and never complain.” In his post-3/11 robot theatre productions Hirata sheds light on the concepts of immortality and integrity In his android version of Chekhov’s Three Sisters (2012) the Fukazawa sisters live in a rural town with a formerly thriving robot industry created an android of his youngest daughter though we later learn that she is still alive but has become a hikikomori—a social recluse.) While the older sisters visit their father’s grave to commemorate his death because “death does not concern” her; mortality is a purely abstract concept in her mind Meanwhile other family members seem agonized by the impending death of their community in the face of a declining birthrate and fading hope overall—an almost prophetic vision of a near-future Japan And while they dodge the gloomy topic around the dinner table Next to this logically impeccable and immortal robot humans come to seem increasingly more fragile This Three Sisters forces the post-Fukushima audience to question whether or not they are hiding behind a veil of escapism; indeed they might even envy the fearless “human integrity” so well represented by the android shrewd observers may begin to feel that accepting faults and failures might be the crux of humanity Hirata’s Three Sisters demands that we reconsider what is putatively morally “human.” director-playwright Shū Matsui has been questioning the validity of several key concepts of Western humanism seem to run against harmony-oriented Japanese norms But it wasn’t until the 3/11 catastrophe that Matsui clearly imagined a non-human theatrical universe favoring collectivism over individualism In Forgetting the Future (Mirai o wasureru a character called Shimada Burio (the name is a spoof on the Japanese word for “embryo”) is presented as the world’s first cockroach-human hybrid In addition to fluently speaking a human language Burio can also talk through a Deleuzian language of “molecular vibration and scraping,” enabling him to go beyond the formal limits of communication that inevitably draw a boundary between the subject and the object When facing vulnerable situations like the aftermath of 3/11 Matsui proposes that people must cease prioritizing cognitive functions to enjoy a non-linguistic and non-logical form of unity which he calls “environmental symbiosis.” We must learn to herd with others like critters to avoid untoward confrontations in an already calamitous situation as they may be only onerous abstractions that needlessly complicate our already intractable lives the writer-director with the theatre company called chelfitsch (a coinage meant to evoke a child attempting to say the English word “selfish”) is among the leading theatre artists in Japan He initially received acclaim for voicing the uncertainties of the economically vulnerable Lost Generation in productions using “super-real” colloquial Japanese speech matched with ungainly yet eloquent body movements In 2007 Okada ventured into the international theatre circuit when he was invited to the Kunstenfestivaldesarts in Brussels to present Five Days in March (Sangatsu no itsuka kan) he has expanded his theatrical vision beyond the solipsistic aesthetics of super-real Japanese after living in the suburbs of the metropolis for 38 years He felt that after the disaster he could no longer “identify” himself with Tokyo even considering the capital city “something already over or already lost—at least for me.” His worldview thus changed Okada could not help but change the “reality” in his stagecraft Okada was interested in writing about present reality after the catastrophe he became increasingly interested in fiction—or “alternative realities.” He also looked back to a 600-year-old theatre tradition: In trying to give voice to someone (family he adopted the structure of the dream noh (mugen noh) in which the protagonists (shite) are most often resentful or regretful dead spirits He’s written three plays responding to the Fukushima disaster: Time’s Journey Through a Room (Heya o nagareru jikan no tabi 2013)—a three-hander in which the protagonist is the wife of a 30-something man who now fancies another woman the audience does not know that the protagonist is actually dead as she is the one narrating the proceedings describing the minutest details of everyday life as if to never forget the life she had led After providing her tranquil yet unyieldingly articulate monologue she presses her husband as to whether he remembers the same details she does The production seems to find Okada divided between narratives of remembering and forgetting We humans could not survive a single day if we remembered all the details of the past the act of forgetting implies their complete disappearance theatremakers have begun to feel the obligation to reconsider not only the politics of humans but also those of the dead Okada has said that “the ghost is a great invention of humans,” a way for us to give body to our imaginations and to our struggles with the past Whether looking to the future through androids and hybrid bugs or veering toward the past through the visions of ghosts Japanese theatre artists are imagining a time well beyond the lifespan of a single human being The 3/11 catastrophe may not have changed Japanese society for the better but it has surely stirred the imaginations of theatre directors and playwrights—and audiences The non-human turn in post-Fukushima theatre is a clear embodiment of the ways Japanese artists feel responsible for giving voice not only to those who survived but also to the dead and the unborn a scholar of Japanese modern and contemporary theatre and performance CORRECTION: An earlier version of this story misspelled Tōhoku as Thoku Support American Theatre: a just and thriving theatre ecology begins with information for all. Please join us in this mission by joining TCG which entitles you to copies of our quarterly print magazine and helps support a long legacy of quality nonprofit arts journalism ©2025 Theatre Communications Group Each gift is a stitch in the tapestry that celebrates our resilience Donate to TCG! The Iwaki City Coal and Fossil Museum (Horuru) in Fukushima Prefecture is set to celebrate its 40th anniversary in October the museum showcases numerous ancient fossils and offers educational and fun experiences for families The museum stands on land that was once an ancient ocean where many fossils have been unearthed The most notable discovery made here was one in 1968 by Tadashi Suzuki who found the fossil of a new genus of plesiosaur on a riverbank.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); as it overturned the common belief that dinosaur and elasmosaurus fossils could not be found in Japan," Suzuki Metrics details Multicentric Castleman disease (MCD) is a heterogeneous lymphoproliferative disorder It is characterized by inflammatory symptoms and interleukin (IL)-6 contributes to the disease pathogenesis Human herpesvirus 8 (HHV-8) often drives hypercytokinemia in MCD although the etiology of HHV-8-negative MCD is idiopathic (iMCD) A distinct subtype of iMCD that shares a constellation of clinical features including thrombocytopenia (T) and organomegaly (O) has been reported as TAFRO-iMCD however the differences in cytokine profiles between TAFRO-iMCD and iMCD have not been established We retrospectively compared levels of serum interferon γ-induced protein 10 kDa (IP-10) and other cytokines between 11 cases of TAFRO-iMCD patients with TAFRO-iMCD had significantly higher serum IP-10 and tended to have lower PDGF-AA levels than the other 2 groups and vascular endothelial growth factor-A were elevated in both TAFRO-iMCD and iMCD Elevated serum IP-10 is associated with inflammatory diseases including infectious diseases There was a strong correlation between high serum IP-10 and the presence of TAFRO-iMCD suggesting that IP-10 might be involved in the pathogenesis of TAFRO-iMCD These findings suggest that elevated serum IL-6 might not be a primary pathological driver of the proinflammatory hypercytokinemia observed in patients with TAFRO-iMCD to identify the cytokine profile associated with TAFRO-iMCD we compared serum cytokine profiles between patients with non-HHV-8-associated MCD including TAFRO-iMCD and plasma cell iMCD (iMCD-NOS) the 6 cases that were positive for reticulin fibrosis were classified as MF-1 and had a very loose network of reticulin fibers Bone marrow samples were not available for the iMCD-NOS cases; therefore the status of reticulin fibrosis could not be evaluated Detailed laboratory data are presented in Table 1 Patients with TAFRO-iMCD and iMCD-NOS commonly demonstrated microcytic anemia Serum procalcitonin (PCT) levels for all 3 cases of TAFRO-iMCD were high (median patients in the TAFRO-iMCD group had severe thrombocytopenia and elevated serum ALP without polyclonal hypergammaglobulinemia (a) The median serum IP-10 level was significantly higher in the TAFRO-iMCD group than in the other 2 groups (b) The median serum PDGF-AA level was significantly lower in the TAFRO-iMCD group than in controls and tended to be lower in the TAFRO-iMCD groups than in the iMCD-NOS group and VEGF-A (e) levels were significantly higher in the TAFRO-iMCD and iMCD-NOS groups than in the control group IP-10: chemokine interferon γ-induced protein 10 kDa PDGF-AA: platelet-derived growth factor -AA VEGF-A; vascular endothelial growth factor-A The serum IL-13 levels tended to be higher in the iMCD-NOS group than in the controls (P = 0.05) and tended to be lower in the TAFRO-iMCD group than in the controls (P = 0.06) (data not shown). The serum IL-1β, IL-5, IL-27, and IL-12p70 tended to be higher in the iMCD-NOS group than in the other 2 groups (Table 2) The serum IFN-γ, IL-17A, IL-2, IL-9, IL-22, IL-6, IL-4, and TNF-α levels were not significantly different between the 3 groups (Table 2) Although human and animal studies have demonstrated that IL-6 plays a major role in the symptomatology and pathogenesis of MCD there are few reports concerning other cytokine profiles in MCD we report the serum cytokine profiles in patients with non-HHV-8-associated MCD including TAFRO-iMCD and iMCD-NOS This is the first report to evaluate the cytokine profile in patients with TAFRO-iMCD ITP is a clinical syndrome characterized by a decrease in circulating platelets due to peripheral thrombocyte consumption caused by autoantibodies against platelet antigens It also is characterized by an increase in the number The patients with TAFRO-iMCD in our study also showed marked thrombocytopenia and hypermegakaryocytes patients with TAFRO-iMCD had much lower serum PDGF-AA levels than those noted in ITP These findings suggest that thrombocytopenia in TAFRO-iMCD is not caused by increased peripheral thrombocyte consumption alone both TAFRO-iMCD and iMCD-NOS patients had high serum IL-10 levels the correlation between cytokine levels and clinical outcomes could not be evaluated because of the small sample size TAFRO-iMCD and iMCD-NOS shared some common cytokine profiles some of which were similar to those observed in HHV-8-associated MCD TAFRO-iMCD had a distinct cytokine spectrum characterized by high levels of IP-10 These findings might be key for understanding the pathogenesis of this hypercytokine lymphoproliferative disorder The present study investigated 17 patients including 11 patients with TAFRO-iMCD and 6 patients with iMCD-NOS who were evaluated at the Department of Pathology We assessed 21 healthy subjects as controls Clinicopathological data were reviewed retrospectively by pathologists and physicians Informed consent for the use of their samples in research was obtained from patients All patients’ samples and medical records (clinical history and treatment) were obtained with the approval of the Institutional Review Board (IRB) at Okayama University The samples were limited to excess human material; therefore the IRB waived the need for written consent from the patients The controls were 21 healthy subjects (11 males and 10 females aged 27–70 years with a mean age of 47 years of Japanese descent They had no history of vaccinations or acute or chronic infections within the previous 6 months Serum samples from all participants were collected and stored at −80 °C until use TAFRO-iMCD must meet the histopathological criteria (3 major criteria and ≥ 1 minor criterion) Exclusion criteria were based on possible differential diagnoses including rheumatic diseases such as systemic lupus erythematosus Histopathological inclusion criteria were negative latency-associated nuclear antigen-1 and the presence of atrophic germinal centers with enlarged nuclei in endothelial cells the proliferation of endothelial venules with enlarged nuclei in the interfollicular zone and small numbers of mature plasma cells in lymph nodes The major inclusion criteria for TAFRO were the presence of 3 of the following 5 characteristics: thrombocytopenia the presence of pleural fluids and ascites on computed tomography; fever a body temperature of >38.0 °C (100.4 °F); reticulin fibrosis evaluated via bone marrow biopsy; organomegaly or splenomegaly on computed tomography; the absence of hypergammaglobulinemia Minor inclusion criteria included hyper- or normoplasia of megakaryocytes in the bone marrow and high levels of serum alkaline phosphatase (ALP) without marked elevations of serum transaminases There is also no consensus definition of a clinical flare-up of MCD we defined a flare-up as requiring treatment due to the presence of at least 1 clinical symptom (e.g. or anasarca) and 1 laboratory abnormality (e.g. vascular endothelial growth factor (VEGF)-A and chemokine interferon γ-induced protein 10 kDa (IP-10) were analyzed using a FlowCytomix™ kit (Bender MedSystems Austria) and MACSQuant® Analyzer (Miltenyi Biotec Germany) in accordance with the manufacturers’ instructions The thresholds of detection were as follows: 1.2 pg/mL for IL-6; 1.5 pg/mL for IL-9 and IL-12p70; 1.6 pg/mL for IFN-γ and IL-5; 1.9 pg/mL for IL-10; 2.5 pg/mL for IL-17A and PDGF-AA; 3.2 pg/mL for TNF-α; 4.2 pg/mL for IL-1β; 4.5 pg/mL for IL-13; 6.0 pg/mL for IP-10; 7.2 pg/mL for VEGF-A; 10 pg/mL for IL-27; 16.4 pg/mL for IL-2; 20.8 pg/mL for IL-4; 21.9 pg/mL for IL-23; and 43.3 pg/mL for IL-22 We categorized cases into 3 groups as TAFRO-iMCD The Kruskal-Wallis test was to compare the cytokine and chemokine levels between the 3 groups When a between-group difference was detected A statistically significant difference between the 2 groups was determined using the nonparametric Mann-Whitney U test and ALP which were measured in fresh blood samples from TAFRO-iMCD and iMCD-NOS patients were performed using the Fisher’s exact test for categorical variables and the Mann–Whitney U test for continuous variables and a P-value ≤ 0.05 was considered statistically significant Elevated serum interferon γ-induced protein 10 kDa is associated with TAFRO syndrome Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Localized mediastinal lymph-node hyperplasia resembling thymoma A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease: clinical findings and clinicopathologic correlations in 15 patients Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease Kaposi’s sarcoma-associated herpesvirus sequences in benign lymphoid proliferations not associated with human immunodeficiency virus [Human herpesvirus 8 and associated diseases: Kaposi’s sarcoma body cavity based lymphoma and multicentric Castleman disease: clinical and molecular epidemiology] HHV-8 infection status of AIDS-unrelated and AIDS-associated multicentric Castleman’s disease idiopathic multicentric Castleman disease: novel insights into biology Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease Castleman-Kojima disease (TAFRO syndrome): a novel systemic inflammatory disease characterized by a constellation of symptoms and organomegaly: a status report and summary of Fukushima (6 June disease severity classification and treatment strategy for TAFRO syndrome Interleukin-6 is a potent thrombopoietic factor in vivo in mice Human interleukin 6 is a direct promoter of maturation of megakaryocytes in vitro Interleukin-6/STAT3 signaling regulates the ability of naive T cells to acquire B-cell help capacities IL-6 triggers IL-21 production by human CD4+ T cells to drive STAT3-dependent plasma cell differentiation in B cells European consensus on grading bone marrow fibrosis and assessment of cellularity CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications Chemokine (C-X-C motif) ligand (CXCL) 10 in autoimmune diseases High serum procalcitonin concentrations in patients with sepsis and infection In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue The biology of platelet-derived growth factor The pathogenesis of atherosclerosis: a perspective for the 1990s Platelet alpha granules contain a growth factor for fibroblasts Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications Progression activity for platelet-derived growth factor in plasma of patients with idiopathic thrombocytopenic purpura and aplastic anemia High levels of human herpesvirus 8 viral load and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease Atypical hyaline vascular-type Castleman’s disease with thrombocytopenia Complete resolution of TAFRO syndrome (thrombocytopenia reticulin fibrosis and organomegaly) after immunosuppressive therapies using corticosteroids and cyclosporin a: a case report Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics Download references This work was partially supported by a Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI Grant Number JP16K08666) from the Japan Society for the Promotion of Science Okayama University Graduate School of Medicine Hematology/Respiratory Medicine Kanazawa University Faculty of Medicine Division of Clinical Infection Control and Prevention Niigata University Graduate School of Medical and Dental Sciences Fukushima Medical University School of Medicine Okayama University Graduate School of Health Sciences Department of Hematology and Medical Oncology Fujita Health University School of Medicine All authors read and approved the final manuscript Download citation Sorry, a shareable link is not currently available for this article. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Our Standards: The Thomson Reuters Trust Principles., opens new tab , opens new tab Browse an unrivalled portfolio of real-time and historical market data and insights from worldwide sources and experts. , opens new tabScreen for heightened risk individual and entities globally to help uncover hidden risks in business relationships and human networks. © 2025 Reuters. All rights reserved John P. Miersma of Whitinsville has been appointed president of Iwaki America Inc., a subsidiary of Iwaki Co. Ltd. of Tokyo. Iwaki America includes Iwaki's pump operations in the Americas and the global operations of Iwaki's Walchem controls business. Mr. Miersma has previously served as executive vice president of Iwaki America, and is a past chairman of the Hydraulic Institute, the largest North American pump industry trade organization. He is also a treasurer of the Whitinsville Christian School and a corporator of Whitinsville-based UniBank. 25 Apr 2025 10:00:00 GMT?.css-1txiau5-AnswerContainer{color:var(--GlobalColorScheme-Text-secondaryText2);}Iwaki FC won 4–3 over V-Varen Nagasaki on Fri The current head to head record for the teams are V-Varen Nagasaki 3 win(s) Haven't kept a clean sheet in 7 matches Have scored 6 goals in their last 5 matches Haven't kept a clean sheet in 9 matches Who won between V-Varen Nagasaki and Iwaki FC on Fri 25 Apr 2025 10:00:00 GMT?Iwaki FC won 4–3 over V-Varen Nagasaki on Fri 25 Apr 2025 10:00:00 GMT.InsightsHave scored 5 goals in their last 5 matches V-Varen Nagasaki is playing home against Iwaki FC on Fri Volume 14 - 2020 | https://doi.org/10.3389/fnbeh.2020.554147 The prefrontal cortex plays a key role in emotional state Electroencephalography (EEG) studies have reported relationships between frontal asymmetry in the alpha band The current study investigated whether the positive or negative valence of emotional stimulation or the behavioral intention to either facilitate or suppress one’s facial expression in response to these stimuli is reflected in relevant changes in frontal EEG asymmetry EEG was recorded while participants either produced a facial expression that was in accord with positive or negative feelings corresponding to image stimuli The laterality index of frontal alpha power indicated greater relative right frontal activity while participants suppressed facial expression compared with facilitating facial expression during emotional stimulation there was no difference in frontal asymmetry between the presentation of image stimuli showing facial expressions corresponding to positive vs These results suggested that frontal asymmetry was related to the control of facial emotional expressions rather than the perception of positive vs microstate analysis revealed that the appearance rate of microstate class B with polarity in the left frontal area increased during the suppression of facial expressions The present results suggested that frontal asymmetry reflects the control of facial emotional expressions which supports the motivational direction model with technological progress in machine learning and measurement instruments new techniques for estimating emotion have been developed Psychophysiological studies estimating emotion are employed in various fields such as neuromarketing and the development of communication tools for people with physical disabilities To examine the neural mechanisms of emotion brain function imaging devices such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have been widely used to measure whole brain activity electroencephalography (EEG) has also been used in psychophysiological studies because EEG measurement involves a relatively small burden for participants with the development of analytical technology is now capable of examining cortical neuronal networks the relationship between frontal EEG asymmetry and emotional state has been investigated for a relatively long time Frontal EEG asymmetry is assumed to be present when there are differences between the left and right frontal regions in alpha band (8–13 Hz) power. Higher alpha band power is used as an index to indicate cortical activity suppression (Pfurtscheller et al., 1996; Klimesch, 1999; Coan and Allen, 2004) Activation of the frontal region is considered to be caused by decreased alpha band power values Several studies have focused on alpha band power and examining the relationship between frontal asymmetry and emotional state The affective valence model and the motivational direction model are subject to ongoing debate regarding whether frontal EEG asymmetry reflects emotional state or motivations related to approach–withdrawal behavior The results revealed that positive stimuli elicited greater relative left frontal activity elicited greater relative right frontal activity These findings support the affective valence model Conversely, the motivational direction model predicts that relative frontal asymmetry reflects motivational direction. Motivational direction distinguishes approach motivation to move toward a stimulus from withdrawal motivation to move away from a stimulus (Harmon-Jones et al., 2013) the affective valence model and the motivational direction model predict the same result because positive emotions are associated with approach and negative emotions are associated with withdrawal the experimental results described above can be explained not only by the affective valence model but also by the motivational direction model participants with higher levels of detachment showed EEG responses indicating more relative activation related to withdrawal and less relative activation related to approach relative frontal asymmetry reflected personality traits as motivational direction rather than just reflecting anger or sadness This finding indicated that the two models can be compared by focusing on motivational direction for emotions other than anger Papousek et al. (2018) interpreted their results in a social–emotional context we paid attention to emotional control in communicative situations people sometimes exhibit facial expressions that are contrary to their actual feelings These facial expressions are important for positive communication and in clinical applications we focused on the control of facial emotional expressions as motivational direction These findings indicated that high approach positive emotion caused greater relative left frontal activity compared with low approach positive emotion in accord with the motivational direction model the suppression of facial emotional expression may be related to withdrawal motivation we directly compared affective valence using affective images (positive vs negative) and motivational direction using the control of facial emotional expressions (facilitation vs we sought to test the following two hypotheses: (1) if PFC asymmetry reflects the perception of positive and negative emotional states relatively greater activity of the left compared with right PFC would be expected following stimulation with positive compared with negative images; and (2) if PFC asymmetry reflects the control of facial emotional expressions of facilitation and suppression relatively greater activity of right than left PFC would be expected following emotional stimulation with instructions to suppress emotional expressions regardless of the valence of the emotional stimuli Characteristic EEG activity related to emotional state or the control of facial emotional expressions was investigated by comparing the appearance rate of microstate maps and the sequences of microstate maps between conditions 25 undergraduate or graduate students (10 females age range 19–26 years) participated Participants reported their handedness based on the Edinburgh Handedness Inventory All participants had normal or corrected-to-normal vision and no participants reported any neurological or psychiatric problems Written informed consent was obtained from all participants prior to participation in the experiment All experimental procedures were approved by the ethics committee of Hiroshima International University (No These 90 images were used as image stimuli in this study The content of the positive images included smiling children and similar subjects and was intended to elicit positive emotions The content of negative images included the scene of a robbery and an accident scene and was intended to elicit negative emotions Neutral images were objects and landscapes A facial expression task was used to manipulate the control of participants’ facial emotional expressions while the image stimuli were presented The facial expression task had two conditions: facilitation and suppression the participant was instructed to produce a facial expression that was in accord with each image stimulus (positive or negative) the participant was instructed to not change their facial expression regardless of the image stimulus being presented Both conditions were performed for all participants the participant performed facial control according to the experimental condition After a blank screen was presented for 1 s subjective rating of the image stimuli was performed (see “Measurements” section) This trial was repeated for all 90 image stimuli The image stimuli were presented in a random order at a visual angle of 11.64° on a 20-inch LCD monitor (2007FPb USA) approximately 1.5 m in front of the participants Protocol for stimulus presentation and facial expression responses The three labeled images show examples of the image stimuli from international affective picture system (IAPS) and open affective standardized image set (OASIS) that were presented in the experiment (positive: IAPS The two images of the woman show the facial expression task that was performed by participants during presentation of the image stimuli Participants evaluated the image stimuli by rating them on a nine-point scale for the following three items: positive–negative (valence) and elicited facial expression—did not elicit facial expression (facial expression strength) the emotions elicited by the stimuli were selected from six categories: sadness EEG and electromyography (EMG) were continuously recorded throughout the experiment using a Neurofax device (EEG-1100 EEG was sampled at a rate of 500 Hz and amplification of 0.05–120 Hz according to the International 10-20 system EEG was recorded from 25 scalp sites using an EEG cap with Ag–AgCl electrodes and was re-referenced from the average of earlobe measurements Electrode impedances were below 10 kΩ EMG was sampled at a rate of 500 Hz and amplification of 5–250 Hz The electrodes were attached to the right sides of the face over each corrugator supercilii (CS) and zygomatic major (ZM) muscle region EMG of the CS and ZM was recorded using the same filter as the EEG and was used as an index during the facial expression task EEG data analysis was performed with independent component analysis (ICA) using EEGLAB 15 (Delorme and Makeig, 2004) in the MATLAB platform (2017b; MathWorks Independent components that were considered to arise from eye blinks epochs were discarded if they included extreme amplitude values (exceeding −100 or +100 μV) the average numbers of trials for each condition after removing invalid components and epochs were as follows The facilitating facial expression condition had an average of 29.64 trials for the positive condition The suppressing facial expression condition had an average of 29.48 trials for the positive condition The following preprocessed EEG data were analyzed following EEG data collection Spectral analysis: The power spectrum of each site was computed for every 6 s (one trial) of EEG data using a fast Fourier transform (FFT) for 25 scalp sites The Hamming window was used for smoothing; the window size was 2 s For the computed power spectrum of the alpha band (alpha power) the standard deviation (SD) was calculated for each participant and any epochs that included extreme alpha power (exceeding three SD) were removed from further analysis For the corresponding right and left regions the laterality index was calculated using the following formula: (left side alpha power − right side alpha power)/(left side alpha power + right side alpha power) × 100 Greater alpha band power was used as an index of the suppression of cortical activity; positive values on the laterality index indicate greater relative right regional activity while negative values on the laterality index indicate greater relative left regional activity EEG microstate analysis: EEG microstate analysis was performed using Cartool (Brunet et al., 2011) an alpha band filter was applied to all EEG waveforms and the global field power (GFP) at the local maxima was detected EEG topographies were obtained from detected GFP peaks Cluster analysis was performed using the k-means clustering algorithm the appearance rate of microstate classes and the sequence of microstate classes were computed The EMG data were analyzed to confirm whether the participant made a facial expression consistent with the experimental condition EMG amplitude was averaged with 6 s epochs while presenting image stimuli for each condition mean EMG amplitude values of 3,000 points data for 6 s were calculated for each trial These amplitudes were averaged for each image stimulus and facial expression condition in the CS and ZM regions Two-way repeated-measures analysis of variance (ANOVA) was used to compare the subjective evaluation of image stimuli and post hoc testing was then performed using the Bonferroni correction The Greenhouse–Geisser correction was used to adjust the degrees of freedom The appearance rates of microstate classes computed by microstate analysis were compared using the Wilcoxon signed-rank test and nonparametric statistics A paired t-test was also performed to compare the doublet sequence of map patterns in the microstate analysis Statistical significance was defined as p < 0.05 for all analyses Analyses were performed using SPSS 24.0 (IBM Data for the subjective rating scores were analyzed using two-way repeated ANOVA with 2 levels of control (facilitation vs. suppression) × 3 levels of emotion (positive vs. neutral vs. negative). Figure 2 shows the results of the subjective rating scores for the image stimuli there was a significant interaction (F(1.17,28.30) = 5.45 there was a significant difference between positive and negative images in the two facial expression conditions (p < 0.001) there was a main effect of the emotion condition (F(1.22,29.45) = 9.25 Post hoc testing revealed that the scores for negative images were significantly higher than those for positive (p < 0.05) or neutral (p < 0.001) images The interaction was significant for facial expression strength (F(1.60,38.51) = 28.57 there was a significant difference for positive (p < 0.01) and negative (p < 0.001) images between the two facial expression conditions in the facilitating facial expression condition scores of facial expressions for positive (p < 0.001) and negative (p < 0.001) images were significantly higher than that those for neutral images in the suppressing facial expression condition the scores of facial expressions for positive (p < 0.05) and negative (p < 0.01) images were significantly higher than those for neutral images Mean subjective rating scores for valence (A) **p < 0.01 and ***p < 0.001 In addition to the subjective ratings, the EMG responses of the CS and ZM were analyzed using two-way repeated ANOVA. Figure 3 shows the mean amplitude of EMG responses for each region The interaction was significant for the EMG amplitude of the CS (F(1.21,29.11) = 6.94 there was a significant difference between the two facial expression conditions for positive (p < 0.001) the CS EMG amplitude for negative images was significantly greater than those for positive (p < 0.01) and neutral (p < 0.05) images in the facilitating facial expression condition The interaction was significant in the EMG amplitude of the ZM (F(1.07,25.69) = 21.14 the ZM EMG amplitude for positive images was significantly greater than that for neutral (p < 0.001) and negative (p < 0.001) images Mean electromyography (EMG) amplitude for CS (A) and ZM activity (B) in each condition The laterality index of F3/4 and FC1/2 did not show any significant differences and FC5/6 all exhibited significant differences in the laterality index The main effect of the facial expression condition was significant at Fp1/2 (F(1.00,24.00) = 4.31 Laterality indices of the pairs of electrode sites at the frontal region (A) and for each image stimulus (B) The main effect of emotion was significant at F7/8 (F(1.72,41.48) = 5.39 ɛ = 0.86) and FC5/6 (F(1.81,43.47) = 6.72 Post hoc testing revealed that the laterality index in the neutral condition had a larger negative value than that for negative images (p < 0.01) These results indicate that the facilitating facial expression condition was associated with greater relative left frontal activity whereas the suppressing facial expression condition was associated with greater relative right frontal activity We observed that the appearance rate of the microstate classes did not differ between the emotion conditions but differed between facial expression conditions To analyze the difference in appearance rate between facial expression conditions the Wilcoxon signed-rank test was performed The appearance rate of microstate class B (from right occipital to left frontal areas) was significantly higher in positive (Z(24) = −2.65 r = −0.47) images in the suppressing facial expression condition compared with the facilitating facial expression condition Microstate class maps (A) and the appearance rates of microstate classes for positive (B) to examine the relationship between the order of the appearance pattern of microstate classes and emotional state the numbers of doublet sequences of each microstate class were compared between the facilitating and suppressing facial expression conditions for each emotion using a paired t-test The doublet sequences of the microstate classes were calculated as follows: the number of transitions from each microstate class to another microstate class normalized by the fraction of the total number of microstate class transitions of participants the AA sequence means that microstate class A appears after microstate class A and the AB sequence means that microstate class B appears after microstate class A The BB sequence was significantly higher for positive (t(24) = −3.43 r = 0.54) images in the suppressing facial expression condition compared with the facilitating facial expression condition the EB sequence was significantly higher for positive (t(24) = −2.25 r = 0.41) and negative (t(24) = −2.09 r = 0.39) images in the suppressing facial expression condition compared with the facilitating facial expression condition the BE sequence was significantly higher for only positive (t(24) = −2.07 r = 0.38) images in the suppressing facial expression condition compared with the facilitating facial expression condition The present study directly compared affective valence and motivational direction in PFC asymmetry by manipulating the presentation of affective images (positive and negative) and facial expression tasks (facilitating and suppressing facial emotional expressions) We hypothesized that PFC asymmetry would support: (1) the affective valence model if PFC asymmetry reflected the perception of emotional state and relatively greater activity of the left than right PFC would be expected following stimulation with positive compared with negative images; or (2) the motivational direction model if PFC asymmetry reflected the control of facial emotional expressions and relatively greater activity of the right than left PFC would be expected following emotional stimulation with an instruction to suppress emotional expressions It is noteworthy that the level of arousal was higher in the negative condition than in the other conditions the arousal rating scores were still relatively low and there was no difference between the two facial expression conditions these results suggest the validity of the manipulation of emotion induction and facial control in the present study the current results suggest the involvement of an asymmetrical model We first examined the laterality index of the alpha power alpha power was greater in the left frontal area during suppression of facial expression compared with when facial emotional expression was facilitated during emotional stimulation Because greater alpha power is used as an index to indicate suppression of cortical activity these results indicate that greater relative left PFC activity was exhibited in the facilitating facial expression condition and greater relative right PFC activity was exhibited in the suppressing facial expression condition negative images elicited greater relative right PFC activity compared with neutral images Applying these results to the affective valence model right PFC activity was consistent with negative emotional stimulation but inconsistent with positive emotional stimulation PFC asymmetry appeared to be caused by facial control rather than emotional state This result supports the hypothesis that PFC asymmetry reflects the control of facial emotional expressions of facilitation and suppression This result is inconsistent with our findings of right frontal activity while suppressing facial expression the experimental conditions included suppressing facial expression for positive images as well as negative images It is possible that suppressing facial expression for positive images is more strongly related to withdrawal behavior the positive suppression condition might have effectively induced right frontal activity while suppressing facial expression participants performed facilitating facial expressions producing facial expressions according to their own emotional state and suppressing facial expressions that conflicted with their own emotional state asymmetry in the frontal pole area appeared to reflect participants’ choice of facial control for emotional stimulation and/or responses when suppressing emotional facial expressions Although both of these studies used facial expression images the greater relative right frontal area activity in negative images was caused by the perception of emotion elicited by controlling facial expressions because positive images are associated with approach motivation relative left frontal activity would be expected in response to positive images The right frontal activity mentioned above for facial control may have canceled out left frontal activity related to approach motivation the laterality index for positive images may not have differed between neutral and negative images microstate classes similar to these were also found although the experimental conditions were different to those reported in previous studies Focusing on the appearance rate of each microstate class revealed differences between the facial expression conditions there were no differences between the emotion conditions microstate class B showed a difference in the appearance ratio and this was significantly higher in the suppressing facial expression condition than the facilitating facial expression condition microstate analysis showed an increase in the appearance rate of microstate class B (from the right occipital to left frontal areas) This finding is consistent with the laterality index results our model supported the notion that (2) PFC asymmetry reflects the control of facial emotional expression of facilitation and suppression based on the results of the microstate analysis These findings may be related to the increase in the appearance rate of microstate class B in the suppressing facial expression condition in the current study in terms of the doublet sequence of the microstates the BB sequence was increased for all image stimuli in the suppressing facial expression condition This result was interpreted as indicating that the appearance rate of microstate class B was higher in the suppressing facial expression condition than in the facilitating facial expression condition the BE sequence in the positive and negative images and the EB sequence in the positive images only were greater in the suppressing facial expression condition than in the facilitating facial expression condition Although there was no evidence of a relationship between emotion or facial control and the specific sequences of microstate maps the results suggested that a sequence from microstate classes B to E may be related to the suppression of emotion This conclusion was supported by the greater appearance rate of microstate class B in the suppressing facial expression condition and the finding that these sequences were different for positive and negative images in the suppressing facial expression condition the aim of the present study was to examine traditional PFC asymmetry models as the affective valence model and the motivational direction model by directly comparing the combination between affective images and the control of facial emotional expressions The results suggest that PFC asymmetry reflects the control of facial emotional expressions These findings supported the motivational direction model it is possible that the sadness elicited by the affective images may have included anger and this may have influenced the results of PFC asymmetry PFC asymmetry was observed both in the laterality index and in the EEG microstate no neutral condition for facial expressions was included in the current experimental design If PFC asymmetry during facial expression was contrasted with an appropriate neutral condition the activation of frontal asymmetry could be confirmed more clearly facial control was manipulated by instructing participants to change their facial expressions the observation of asymmetry in the frontal region (F7/8 and FC5/6) might be related not only to the motivational direction but also to the function of producing facial expressions Emotional regulation should therefore be investigated using a form of manipulation other than facial expression in future studies EEG microstate analysis suggested the existence of map sequence patterns that are related to positive and negative emotions during suppressing facial expression including studies examining cognitive processing in the emotional state and emotional regulation as well as studies focusing on temporal dynamics are needed to construct a more robust frontal asymmetry model The raw data supporting the conclusions of this manuscript will be made available by the authors The studies involving human participants were reviewed and approved by the ethics committee of Hiroshima International University The patients/participants provided their written informed consent to participate in this study and TI contributed to the conception and design of the study HT performed the EEG and statistical analysis and wrote the first draft of the manuscript TI contributed to the interpretation of data and assisted in preparing the manuscript All authors contributed to the article and approved the submitted version This work was supported by a KAKENHI Grant-in-Aid for Scientific Research (C) (18K12022) The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a 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social emotional behavior Prototypes are attractive because they are easy on the mind Ishihara S and Iwaki T (2020) Comparison Between Facilitating and Suppressing Facial Emotional Expressions Using Frontal EEG Asymmetry Received: 21 April 2020; Accepted: 03 September 2020; Published: 09 October 2020 Copyright © 2020 Takehara, Ishihara and Iwaki. 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Volume 13 - 2019 | https://doi.org/10.3389/fnbeh.2019.00124 Successful behavioral inhibition involves both proactive and reactive inhibition allowing people to prepare for restraining actions and cancel their actions if the response becomes inappropriate we utilized the stop-signal paradigm to examine whole-brain contrasts and functional connectivity for proactive and reactive inhibition The results of our functional magnetic resonance imaging (fMRI) data analysis show that the inferior frontal gyrus (IFG) and the primary motor cortex (M1) were activated by both proactive and reactive inhibition We then created 70 dynamic causal models (DCMs) representing the alternative hypotheses of modulatory effects from proactive and reactive inhibition in the IFG-SMA-STN-M1 network Bayesian model selection (BMS) showed that causal connectivity from the IFG to the SMA was modulated by both proactive and reactive inhibition To further investigate the possible brain circuits involved in behavioral control we compared 13 DCMs representing the alternative hypotheses of proactive modulation in the dorsolateral prefrontal cortex (DLPFC)-caudate-IFG-SMA neural circuits BMS revealed that the effective connectivity from the caudate to the IFG is modulated only in the proactive inhibition condition but not in the reactive inhibition our results demonstrate how fronto-basal ganglia pathways are commonly involved in proactive and reactive inhibitory control with a “longer” pathway (DLPFC-caudate-IFG-SMA-STN-M1) playing a modulatory role in proactive inhibitory control and a “shorter” pathway (IFG-SMA-STN-M1) involved in reactive inhibition These results provide causal evidence for the roles of indirect and hyperdirect pathways in mediating proactive and reactive inhibitory control These areas combine with the basal ganglia to form a network that inhibits the activation of the M1 during reactive inhibition We hypothesized that there are overlapping regions in the neural systems involved in proactive and reactive inhibitory processes and that the effective connectivities between the relevant brain regions are modulated differently in those processes we used a special neuroimaging contrast to isolate fMRI activity associated with proactive inhibition via the stop-signal paradigm in order to identify the cortical and subcortical areas involved in proactive and reactive inhibition We then incorporated the identified regions of interest (ROIs) into dynamic causal models (DCMs) of proactive and reactive inhibition Bayesian model selection (BMS) was applied to investigate the effective connections associated with each type of inhibition 21.75 ± 2.57; range: 19–31 years; 11 males) excluding 10 participants with excessive head movement in the MRI scanner defined as translational or rotational displacement greater than 2.5 mm in any direction performed a stop-signal task during fMRI scanning All participants were recruited from the University of Tsukuba as paid volunteers had normal or corrected-to-normal vision and provided written informed consent prior to the experiment No participant was taking medicine during the experiment The present study was approved by the Institutional Review Board (IRB) of the National Institute of Advanced Industrial Science and Technology (approval number: 2014-481) and all participants gave informed consent prior to participation In the present study, we divided the “go,” “stop,” and “switch” trials into several substages to isolate proactive and reactive inhibition (Figure 1) Unlike previous studies regarding proactive inhibition we did not use additional cues to indicate “certain go” trials All trials of the present study remained “uncertain” at the initial stage a fixation cross appeared on a black background for 500 ms then the point of fixation cross was replaced by the initial character (“X” or “O”) for 1,500 ms Participants were required to press “1” on the button-box if the stimulus was “X” and “2” if “O” appeared unless the background color change participants need to switch their response to press “3.” If the background color change to red participants were instructed to withhold their response regardless of the current initial character The duration between the appearance of initial character and the change of background color is 500 ms participants were required to withhold their planned response and wait for any possible upcoming cue to avoid an incorrect response when the initial character (“X” or “O”) appeared Participants had to totally abort the responses that were already in progress if the background changed to red or switch their response to press “3” if the background changed to blue The proactive component was thus present in all trials (“go,” “stop,” and “switch” trials) and the reactive component was present in successful “stop” and “switch” trials Participants were required to press “1” or “2” as quickly as possible following the appearance of the stimulus unless the color of the background changed to red or blue They were required to withhold response when the background turned red and to press “3” when the background turned blue Each run consisted of 40 “go” trials An equal distribution of the characters “X” and “O” was ensured across trials Each participant needs to complete three runs We applied paired t-test on mean RTs for “go” and “switch” trials to test if there were significant difference between them. Because the fixed stop-signal delay (SSD) was used in the current procedure, we estimated SSRT with integration method (Logan and Cowan, 1984) by subtracting SSD from the finishing time that is determined by the distribution of no-signal go RTs All fMRI scans were obtained using a 3-Tesla scanner (Ingenia 3T Netherlands) at the Department of Information Technology and Human Factors Each participant’s head was fixed using foam padding to reduce head movement Single-shot echo-planar imaging (EPI) sequences were used to acquire functional images EPI parameters were as follows: repetition time (TR) = 2,000 ms; echo time (TE) = 35 ms; flip angle = 90° The SPM12 software toolbox1 and Matlab 2015b were used for the analysis of fMRI data and for the creation of the DCMs. All coordinates are reported in standard Montreal Neurological Institute (MNI) space and were labeled using the Anatomical Automatic Labeling (AAL) toolbox in SPM12 (Brett et al., 2002; Tzourio-Mazoyer et al., 2002) Successful “go” trials were regarded as those in which the participant selected the appropriate button following the waiting period Successful “stop” and “switch” trials were regarded as those in which the participant withheld appropriate responses until the subsequent signals appeared We divided the trials into several components (Figure 2) When the initial character (“X” or “O”) appeared participants were required to withhold their planned responses and wait for any possible upcoming cue to avoid an incorrect response the proactive inhibitory component appeared at the beginning of all trials The action component was involved when participants figured out the “go” trial and pressed the corresponding button For both “stop” and “switch” trials participants needed to cancel the planned action that resulted in reactive inhibitory component The difference is in “switch” trial participants needed to press the alternative button the components in the “go” trials included proactive inhibitory component and an action component The “stop” trials were subdivided into a proactive and a reactive component and the “switch” trials consisted of a proactive the fixation cross was replaced by the initial character (“X” or “O”) for 1,500 ms reactive inhibition was analyzed by comparing the successful “switch” trials to successful “go” trials We did not apply the classical comparison that used for race model between successful “stop” trials (proactive inhibitory component + reactive inhibitory component) and successful “go” trials (proactive inhibitory component + action component) because the result cannot be explained by isolated reactive inhibitory component Proactive inhibition was isolated by the conjunction of all successful trials (“go,” “stop,” “switch”) We used a general linear model for first-level event-related analysis in each participant Events (successful “go,” successful “stop,” successful “switch”) were modeled after a duration of 0.5 s from trial onset A second-level SPM analysis used contrasts from the first level with one-sample tests to investigate the group-level activation A peak-level false discovery rate (FDR) at p < 0.05 was applied to correct for multiple comparisons We used DCM12 (Friston et al., 2003) for the analysis of effective connectivity between the prior selected set of brain regions fMRI-based DCM is a deterministic model of neural dynamics that describes how neural activity and interactions generate the hemodynamic BOLD response The effective connectivity between brain regions or nodes was estimated by three matrices: the endogenous connectivity between nodes (A matrix) the modulation effects on the connection during the special experimental conditions (B matrix) and the driving inputs that influence the connectivity to other nodes (C matrix) If there were connections modulated by other regions (nonlinear connectivity effects) the parameters were modeled as an additional matrix (D matrix) We defined MNI coordinates of the ROIs for DCM analysis that met all of the following criteria: (1) the coordinate of the spherical ROIs should show significant activations in both proactive and reactive contrasts with a cluster-based FDR at p < 0.05 in the second-level SPM analysis; and (2) the regions have been reported to be involved in behavioral control in previous research We constructed 70 DCM models on four regions: the right IFG (x = 48 The set of 70 DCM models was divided into two groups: a linear and a nonlinear group. Each group was divided into several sub-groups based on the location of the proactive modulatory input (IFG to SMA, SMA to IFG, IFG to STN, SMA to STN) and the connectivity between the IFG and the SMA (bidirectional, unidirectional, no connection; Figure 3) Average self-connections were applied to all nodes The STN was connected with the IFG and the SMA directly or indirectly Structure of the DCM families tested for proactive and reactive inhibition Red arrows represent the location associated with the proactive modulatory input Dotted arrows represent the nonlinear modulation The different numbers represent the different locations related to the reactive modulatory input The nodes, which receive driving input, are the regions in the model that first experience the neural changes caused by the manipulations of the experimental conditions. The modulatory inputs, which represent the specific experimental factor, realize the modulation by influencing the intrinsic connections in the network (Penny et al., 2004) the experimental conditions we chose as modulatory inputs should include the specific experimental factor and avoid the other factors that may drive the network activity in different modulatory effects “stop” and “switch” trials we selected all “go” trials (correct “go,” incorrect “go”) as proactive modulators to separate proactive from reactive modulation We considered the frontal regions (IFG and SMA) as nodes receiving driving inputs across all models The modulatory inputs include proactive modulatory inputs and reactive modulatory inputs We applied the modulatory inputs in the fronto-STN connections (IFG to SMA All trials (“go,” “stop,” “switch”) were chosen as driving inputs which represent the extrinsic influences on the IFG-SMA-STN-M1 network To separate proactive from reactive modulation we selected all “go” trials (correct “go,” incorrect “go”) as proactive modulator The reactive modulator was acquired by selecting “stop” and “switch” trials in which participants provided appropriate responses following the appearance of the signal We defined group peak coordinates from the second-level group analysis of proactive and reactive contrasts combined with the AAL atlas implemented in the SPM toolbox All trials were used for extracting the first eigenvariate of the BOLD time series for STN and M1 and the conjunction contrast of proactive and reactive modulators for IFG and SMA All first eigenvariates were adjusted for the F-test of effects of interest To extract the time series from the ROIs for each participant we combined the local maximum close to the group peak and extracted the eigenvariate from a 5-mm sphere There were significant differences in mean RTs between “go” trials (mean ± SD range: 836–1092 ms) and “switch” trials (mean ± SD range: 948–1,350 ms; p < 0.0001) ” and “switch” trials mean accuracy was 0.890 (SD: 0.117) and 0.853 (SD: 0.165) The mean SSRT was 454 ms (range: 304–737 ms Activated brain regions associated with (A) proactive inhibition and (B) reactive inhibition during the stop-signal functional magnetic resonance imaging (fMRI) experiment Group-level statistical maps were calculated (A) as conjunction of all successful “go,” “stop” and “switch” trials for proactive inhibition and (B) as a contrast between successful “switch” trials and successful “go” trials for reactive inhibition The results were thresholded at peak-level false discovery rate (FDR)-corrected significance of p < 0.05 We investigated 70 DCMs representing the alternative hypotheses of modulatory effects from proactive and reactive inhibition. BMS with fixed-effect analysis (FFX) provided strong evidence for one model being optimal, above all other models (Figure 5) (A) Log evidence and (B) model posterior probability to compare DCM model families and (C) the most possible model selected based on Bayesian model selection (BMS) denoting connectivity coefficients for the comparison between proactive and reactive modulatory inputs The connections in red represent increased excitatory connectivity while blue connections represent decreased inhibitory connectivity The dotted lines represent the driving inputs Two parameters were measured in the BMS to compare the optimal architecture of the models: relative log-evidence and posterior probability The former corresponds to the balance between accuracy and complexity of the model while the latter represents the probability that the specific model provides the best explanation for all participants DCM estimates the observed BOLD responses and models the effects of neuro-vascular processes and spectral noise at different levels The parameters represent the rate of change in activity in one region that influences the activity in another region and the effective connectivity was thus expressed in Hz The average connectivity between two regions represents how rapidly activity (per second) in one region influences the activity in another region (Friston et al., 2003; Penny et al., 2004; Almgren et al., 2018) A positive value represents an excitatory influence from the source region on another region while a negative value represents an inhibitory influence modulatory effects on a region or connection indicate an increase or decrease in average activity or connectivity the right IFG modulates the connection between the left SMA and the left STN and the connection from the IFG to the SMA is modulated by both proactive (modulation effect = 0.8622 HZ) and reactive modulatory inputs (modulation effect = 0.8404 HZ) The results indicate that when people “prepare to cancel” and then “cancel” a planned response successfully both proactive and reactive modulation influence on the effective connection from the IFG to the SMA and the decreased activity in the SMA influences the subsequent areas via a causal relationship and then increases the excitatory influence of the STN on the M1 To further investigate the possible brain circuits involved in the implementation of behavioral control including proactive and reactive inhibitory processes we added extra regions to the DCM models for proactive inhibition The regions of interests were selected based on the same criteria as the previous DCM models (1) these regions should show significant activation in proactive contrasts with a cluster-based FDR at p < 0.05 in the second-level SPM analysis; and (2) the regions have been reported to be involved in behavioral control in previous research We constructed 13 DCM models including four ROIs: the right IFG As previous results showed that the modulatory effects were related to the connection from the IFG to the SMA this modulatory effect should be a direct or indirect effect from other effective connections that end in the IFG we think our model with four regions DLPFC-caudate-IFG-SMA is sufficient to investigate the proactive modulation Since converging evidence indicates that the prefrontal areas project to the STN in the DCM analysis of proactive inhibition the DLPFC-IFG-SMA-caudate is the minimum and effective set required to test hypotheses We have found reactive modulatory effects on effective connection from IFG to SMA in the previous step so there are two possibilities for the “real” neural underpinning of reactive modulation: (1) the IFG-SMA is the real effective connectivity that is modulated by reactive inhibition; and (2) the real effective connectivity is the other connectivity in prefrontal-STN network The modulatory effect was transferred to the effective connectivity IFG to SMA and observed in the IFG-SMA-STN-M1 DCM model Based on the result from whole brain contrast related to reactive inhibition there are no other activations in frontal areas involved in inhibitory control and prefrontal-STN connections which means no other effective connectivity responds to reactive inhibition so the IFG-SMA is the real effective connectivity that modulated by reactive inhibition We considered the frontal regions (DLPFC and SMA DLPFC/IFG/SMA) as nodes receiving driving inputs across all models The modulatory inputs are only proactive inputs We applied modulatory inputs to the effective connections in the DLPFC-caudate-IFG-SMA network (IFG-DLPFC Structure of the DCM families tested for proactive inhibition The yellow arrows show the direction of loops that represent indirect modulation from other effective connections that end in the IFG The different numbers represent the different locations related to the proactive modulatory input We extracted the first eigenvariate of the BOLD time series from two regions of interests All time series were adjusted for the F-test of effects of interest The results of BMS (FFX) indicated that there was one model that was superior to all other models (Figure 7) the connection from the caudate to the IFG was associated with the proactive modulation (modulation effect = 0.7851) The results indicate that when people prepare for a possible upcoming stop-signal the caudate increases its excitatory influence on the IFG which leads to an inhibitory influence of the IFG on the SMA and (C) the most possible model selected based on BMS denoting connectivity coefficients for the DCMs with proactive modulatory inputs and blue connections represent decreased inhibitory connectivity Red dotted lines represent the driving inputs we used fMRI data acquired during a stop-signal paradigm task to identify the cortical and subcortical areas involved in proactive and reactive inhibitory processes To evaluate the modulatory effects of proactive and reactive inhibition on the effective connections between these areas we first conducted a DCM analysis where 70 DCM models were compared The results indicate that the increasing activity in effective connectivity from the left SMA to the left STN was modulated by the right IFG and the decreasing activity in effective connectivity from the right IFG to the left SMA was modulated by both proactive and reactive modulatory effects We further investigated an alternative hypothesis with 13 additional DCM models in which the causal connection from/to the right DLPFC and the left caudate were considered for proactive inhibition The results of the additional DCM model comparison show that the increased activity of the effective connection from the left caudate to the right IFG was modulated by proactive modulatory control which resulted in the inhibitory effects in the connections from the right IFG to the left SMA in the comparison between proactive and reactive inhibitory control previous studies were unable to determine the interactions that exist between these regions or to describe how the brain can “identify” the different kinds of inhibitory control We used DCMs to demonstrate which connections in the common network contribute to proactive and reactive inhibitory control The DCMs also provided us with information regarding the directions and excitatory or inhibitory modulatory effects of these connections Our results reveal that the effective connection from the IFG to the SMA is associated with both proactive and reactive modulatory effects which is in line with previous neurophysiology and neuroimaging evidence showing that the IFG is connected with the SMA Our results further show that in the most likely model both proactive and reactive inhibition decreased the excitatory influence from the IFG to the SMA and inhibited the activity of M1 The results of our further investigation of proactive inhibition show that the neural underpinning of proactive modulation is the effective connection from the right DLPFC via the left caudate to the right IFG while the subsequent effect of transmission is reflected in the effective connection from the IFG to the SMA in a common network The brain thus uses the DLPFC-caudate-IFG-SMA-STN-M1 pathway to implement proactive modulation These results support the prior hypothesis that basal ganglia circuits are involved in proactive and reactive inhibition which suggested that a hyperdirect pathway that allows for faster behavioral control than the direct and indirect pathways The indirect pathway is functionally similar to the hyperdirect pathway but transfers the modulatory effects through the striatum These findings are consistent with our result that the DLPFC acts as a driving input during proactive inhibition Our results indicate that the left caudate is related to modulatory input consistent with the findings of previous studies reporting that the caudate nucleus contributes to behavior through the selection of appropriate sub-goals we used fMRI to investigate inhibitory behavior The limited temporal resolution of fMRI may result in limited scope in the DCM analysis multiple methods such as electroencephalography (EEG) or ECoG we had to exclude participants with excessive head movement and the reduced number of effective participants might have caused us to miss some regions with significant activations We show that the effective connection from the IFG to the SMA is associated with reactive inhibition while the effective connection from the caudate to the IFG is associated with proactive inhibition The indirect DLPFC-caudate-IFG-SMA-STN-M1 pathway is involved in the implementation of proactive modulation while the hyperdirect pathway that bypasses the striatum contributes to reactive inhibition The function of the IFG is more related to attention control and the caudate more likely acts as a “gate” between proactive and reactive inhibition FZ and SI conceived and designed the experiments and wrote the 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Sunao Iwaki, cy5pd2FraUBhaXN0LmdvLmpw 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 is not renowned as a destination for leisure or tourism it does have some excellent and historic hot springs but the modern city has developed out of mining Iwaki enjoys a close-to-ideal location.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); there are fertile agricultural flatlands and forested mountains this is where the warm Kuroshio current from the south meets the Arctic waters of the Oyashio current forming some of the richest fishing grounds in the country Sponsored contents planned and edited by JT Media Enterprise Division. , opens new tabFishing communities and others suffering reputational harm from the release will be compensated, Tokyo Electric Power (9501.T), opens new tab said.Catches from waters near the plant are tested for radiation as the meltdown spread huge amounts of radioactive material over air land and sea.Most restrictions on fishing have been lifted as he stepped into the cockpit of his boat at Onahama."We have just started to return to full-scale operations I'm afraid that we will go back to where we were," he said.Others seemed just as resigned."The government has said releasing the water is scientifically safe," said Motonobu Kimura a 38-year-old trader sorting fish at the port."The only thing we can do is to trust them and do business with those who will do business with us."Reporting by Akira Tomoshige in Iwaki Japan; Writing by Rikako Maruyama and Aaron Sheldrick in Tokyo; Editing by Tom Hogue Dome Corporation president Shuichi Yasuda has the vision Satoshi Okura the know-how and former Dutch international and Rangers player Pieter Huistra the experience The goal now is to combine their respective talents as they embark on the task of building a professional soccer club from scratch Yasuda announced the creation of the new team earlier this week at the Dome Kickoff party at Ariake Coliseum He wants the club to become a pillar in Iwaki Fukushima Prefecture (among the areas devastated by the Great East Japan Earthquake in 2011) help change Japan's sporting landscape.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); "We would like to energize Japan through sports," Yasuda said Wednesday When you look at America and European countries such as Germany and Britain We've looked closely at what they do and we've always wanted our society to do the same We've talked about this project over the past year and it has materialized." Switzerland – The World Baseball Softball Confederation today announced the official competition schedule for the WBSC U-15 Baseball World Cup 2016 which will be staged from 29 July to 7 August in Iwaki LAUSANNE, Switzerland – The World Baseball Softball Confederation today announced the official competition schedule for the WBSC U-15 Baseball World Cup 2016 a total of 50 National Team games will be contested across Iwaki Green with a 30-game Opening Round launching the 2016 international youth baseball flagship event All 12 nations of the III WBSC U-15 Baseball World Cup will begin on the path “For Title of World Champion” on Friday and will have to compete in a challenging five-games-in-five-days group stage to start the tournament (29 July to 2 August) National Team rosters will be able to carry the countries’ top 20 players (born between 2001-2003) to Iwaki. The length of each game will be the regulation nine-innings. The official tournament microsite of the WBSC U-15 Baseball World Cup has been launched in five languages (English It is the first time the South American nation has qualified into the U-15 Baseball World Cup 1 Samurai Japan will open against world No Japan finished seventh at the 18-nation WBSC U-15 Baseball World Cup 2014 in Mazatlán while the Oceania representative finished 10th 16 Czech Republic will be the official Game 1 opener It will be the first time the South Korean National Team will be on the U-15 pinnacle stage European representative Czech Republic finished 13th in 2014 3 Chinese Taipei will be among the most anticipated games of day one 7 Mexico will be each other’s first opponent Venezuela captured the bronze medal in 2014 Panama advanced to the Super Round in 2014 and finished sixth overall while New Zealand finished 15th in the nation’s debut on the U-15 world stage the top three nations from Group A will face the top three nations from Group B in a nine-game Super Round A nine-game Consolation Round will be staged alongside the Super Round to determine 7th to 12th place in the final standings of the III WBSC U-15 Baseball World Cup 2016 The top two nations at the conclusion of the Super Round will play in the world title game (Game 50) on Sunday while the bronze medal match (Game 49) will take place ahead of the finale The winning nation of the WBSC U-15 Baseball World Cup will be awarded 440 world ranking points The full allocation of world ranking points is as follows: Sitemap Media Data Protection Contacts Avenue Général-Guisan, 45 CH-1009 Pully | Switzerland The WBSC is recognised as the sole competent authority in Baseball and Softball by the International Olympic Committee Switzerland – The World Baseball Softball Confederation today announced the groups and Official Look of the WBSC U-15 Baseball World Cup 2016 Switzerland – The World Baseball Softball Confederation today announced the groups and Official Look of the WBSC U-15 Baseball World Cup 2016 The 12 nations that have qualified into the III U-15 Baseball World Cup have been drawn into two Opening Round groups of six: Group A features defending U-15 Baseball World Cup 2014 champions Cuba and also No 13 Australia – Oceania’s top-ranked nation 16 Czech Republic – Europe’s third-highest ranked nation Group B features four nations from the Americas in No 2 6 Venezuela – the U-15 Baseball World Cup 2014 silver and bronze medallists 3 Chinese Taipei (the U-15 Baseball World Cup 2012 bronze medallist) out of Asia and No 30 New Zealand out of Oceania complete the group Venezuela’s U-15 National Team won the inaugural U-15 Baseball World Cup 2012 in Chihuahua Only the top three nations from each group will advance and battle each other in the phase two Super Round for a spot in the finals (Third/Fourth Place match and U-15 World Championship Final) The competition schedule will be confirmed in the coming weeks With the most recent release of the WBSC Baseball World Rankings the U-15 Baseball World Cup in Iwaki is set to be the most elite U-15 competition on record and will feature the top ranked nations in baseball The winner of the U-15 Baseball World Cup 2016 will be awarded 440 world ranking points Official Look of the U-15 Baseball World Cup Unveiled The Official Look and core visual elements of the WBSC U-15 Baseball World Cup were revealed, complementing the recently designed Official Emblem The visual identity aims to reflect a modern and powerful youth world championship brand which also serves to reinforce and fit within an overall branding system of all WBSC Baseball World Cups and the flagship Premier12™ The logo and core assets were designed by the British firm WBSC has rolled out the first-ever Official Slogan of the Baseball World Cup™ platforms: “For the Title of World Champion” The tagline will form a central and unified theme across the branding strategy and the merchandising/licensing of all Baseball World Cups (U-12 The WBSC is recognised as the sole competent authority in Baseball and Softball by the International Olympic Committee. The main space measures 600m², has full orchestral lighting and pneumatic orchestral percussion riser. The space is named after Maestro Hiroyuki Iwaki, whose long association with the Melbourne Symphony Orchestra resulted in him being named Conductor Laureate.