Home » Gallery » Other » Milan: FM Nirmala Sitharaman meets ADB President Masatsugu Asakawa #Gallery Masatsugu Asakawa is the President of the Asian Development Bank (ADB) and the Chair of ADB’s Board of Directors He played a key role in rolling out a series of new and innovative financing initiatives—including an Energy Transition Mechanism — to spur the region’s low-carbon development and elevated ADB’s 2030 cumulative climate financing ambition to $100 billion as ADB continues to focus on the battle against climate change he served as Special Advisor to Japan’s Prime Minister and Minister of Finance and has a close-to-four decades’ career at the Ministry of Finance with diverse professional experience that cuts across both domestic and international fronts Asakawa obtained his BA from University of Tokyo (Economics Faculty) in 1981 Kan-ichi Asakawa tried to forge connections and promote peace over a half century in the United States Mark Alden Branch ’86 is executive editor of the Yale Alumni Magazine ten middle school students from Nihonmatsu file into New Haven’s Grove Street Cemetery with their chaperones and a dignitary or two from their town—sometimes the mayor They find the grave marker they’re looking for except for an interruption during the COVID-19 pandemic chosen for the trip by a competitive process are there to pay tribute to Kan-ichi Asakawa 1902PhD (1873–1948) a native of Nihonmatsu who spent his last 42 years in New Haven Asakawa was on the history faculty at Yale—the first Japanese person to receive a faculty appointment at a major American university the students look at selections from his papers at the Beinecke Library visit the East Asia collection in Sterling Memorial Library and stop at a memorial garden dedicated to Asakawa in Saybrook College where he lived as a resident fellow.Asakawa’s interest in feudalism was more than theoretical: he was himself the son of a samurai heir of a family who had fought on the losing side in the war that led to the Meiji Restoration Asakawa became a Christian and met the Reverend Tokio Yokoi who in turn connected the young scholar to the Reverend William Jewett Tucker who would become a kind of second father to Asakawa arranged for him to come to Dartmouth as a scholarship student “If you were in the network of Christians and missionaries in Japan you had access to knowledge about the Western world,” says Daniel Botsman the Sumitomo Professor of History at Yale and a scholar of nineteenth-century Japan “and in an era where the whole country is focused on westernization that was a good way to get a leg up.” It was at Dartmouth that Asakawa began to consider making an academic career for himself in the United States instead of returning to Japan “If my training in this country be such that it may be used for greater benefit abroad than at home I must follow the former line,” he wrote to a friend in 1899 he was admitted to graduate school at Yale he became the tenth person to receive a PhD in history from the university Asakawa returned to Dartmouth as a lecturer in “the history and civilization of the Far East,” but world events soon opened other avenues for him and Asakawa was uniquely suited to explain the conflict to a curious American audience he had delivered more than 20 lectures about the war and the issues behind it He wrote articles on the subject for Collier’s and the Yale Review and in November 1904 he published a book about the war Yale appointed Asakawa as an instructor in the history of Japanese civilization and as curator of Japanese and Chinese collections in the library Botsman suggests Asakawa’s emergence as a kind of public intellectual may have piqued Yale’s interest “I think the fact that he had become a figure who could talk with authority about affairs in the Far East was what led people to think ‘Oh we should have this person here instead of letting him go back to Dartmouth,’” he says.Before Asakawa began his work in New Haven he returned to Japan for a year to work on another project Asakawa had a vision to establish a library of important Japanese texts in the United States he arranged to collect books for Yale and for the Library of Congress forming the nucleus of collections that are still significant today.At Yale Asakawa taught both Japanese and European history extending his interest in Japanese feudalism to that of Europe and juxtaposing the two at a time when even comparative history didn’t usually include East Asia Asakawa never did attract a following among undergraduates though; it has been suggested that his lectures were dry and his personality rather formal and forbidding His diaries make clear his disdain for proms and student tomfoolery; he was consistently bookish and for fun would write essays on Hamlet or other intellectual topics beyond his specialty.He also kept his eye on international affairs Having spoken up for the Japanese cause during and after the Russo-Japanese War he was dismayed to see his home country renege on promises in the Treaty of Portsmouth regarding Manchuria and Korea he wrote a book called Japan’s Crisis warning presciently that Japan’s growing militarism would eventually lead to war with the United States a dressmaker from New Haven he had met while in graduate school She died in 1913 while recovering from surgery “I discover now that I had been too reserved to her in my expressions of sentiment,” he wrote shortly after her death “She often appeared to note with concealed disappointment that I put my work before her.” He never married again And in 1929 he published his most important piece of scholarship he had traveled to the Japanese island of Kyushu to review and copy documents from the collection of a family of local gentry spanning more than 600 years Asakawa translated the documents into English and published them with extensive commentary as The Documents of Iriki providing an extraordinary look at the evolution of social structures across the entire feudal period “The tragedy of that book is that in the introduction he says that he intended it as just a preliminary study to be followed by a broad interpretive history of feudalism in Southern Japan,” says Botsman “But he never managed to write that book in large part because he was such a painstakingly careful scholar.” Asakawa’s approach using local records to explore social and institutional change over long periods of time was consonant with the budding social history that scholars like Marc Bloch were pioneering in France (Asakawa and Bloch in fact exchanged letters in the 1930s.) It would be decades before social history came into its own in the United States Asakawa had a number of outside initiatives He was a go-to source for Japan-related questions consulting with the Remington company on a Japanese typewriter and with the Brooklyn Museum on Japanese inscriptions for their building’s façade he was intimately involved in the International Auxiliary Language Association which sought to create a common world language called Interlingua “It was in keeping with his diplomatic interests—that idealistic idea that we can connect the world,” says Haruko Nakamura who has researched Asakawa’s role in the organization.Meanwhile Asakawa struggled to be taken seriously at Yale he was an untenured assistant or associate professor combining his teaching duties with curatorial duties at the library he was appointed a research associate in history he wrote to President James Rowland Angell to suggest that however innocent the university’s intentions the title was giving colleagues in Japan “the impression that I had been side-tracked or shelved” and hinted that they might see a kind of racism in the gesture he was appointed a full professor with tenure at age 64 In a letter to Dartmouth president Ernest Hopkins Angell admitted that Asakawa “has been very shabbily treated here In recent years we have dealt more decently by him but in earlier years the record was really quite wretched.”Asakawa’s final years on the faculty were darkened by Japan’s growing aggression in the Pacific imperiling the friendship he had always championed between Japan and the United States and vindicating his warning from 30 years before As war between the two countries seemed inevitable the Harvard historian of East Asian art Langdon Warner Drawing on his understanding of Japanese culture Asakawa drafted a letter for President Roosevelt to send to Emperor Hirohito a last-ditch diplomatic effort to avoid war Warner had connections in the federal government and he told Asakawa he would get the letter to the president “I realize that the chances are one in a million,” Asakawa wrote to a friend “But I pray that a miracle be granted.”The letter Asakawa wrote for FDR urged the emperor to a complete change of course away from war appealing to his sense of honor and history in a way Asakawa believed would be most effective “Your loyal people would be relieved of the crushing burden weighing upon their mind and body for which they have hardly been responsible”; it read “and all the nations near and far would find themselves freed from the fears of continued and fresh calamities caused by what they cannot regard but as an unfortunate error Everyone would immediately comprehend and applaud so noble an act of complete self-conquest.”The letter did find its way to the White House Roosevelt sent a different message to the emperor on December 6 that Asakawa later said would have had no chance of working; in any case the emperor wasn’t shown the letter until moments before the attack on Pearl Harbor began the university offered its support to Asakawa Yale president Charles Seymour ’08 wrote to Asakawa his assurance that “all that lies within the power of the university will be done to keep your internal life normal.” One tangible thing they offered was a place to live Asakawa had been living in Saybrook College as a resident fellow but he was slated to retire in the spring of 1942 he would have been required to leave his fellow’s apartment worried that he might face discrimination in looking for a place to live offered to let him stay as a kind of  “sanctuary,” as Asakawa described it but he accepted an apartment in the Hall of Graduate Studies where he apparently stayed for the rest of his life.Asakawa was always reassuring in his letters to friends that he was treated well during the war He wrote in February 1942 of going to the local FBI office as an “enemy alien,” but added that “the FBI man—Mr Fisher—who looks after the aliens in the university is extremely friendly and says I should let him know if I had any difficulty.” In the same letter he allowed that “it is getting a little hysterical in California.”In 1943 there was a reception for Asakawa in the courtyard of Sterling Memorial Library perhaps in honor of his retirement from his curatorial duties there He had written remarks in case he was called on to speak “I always marvel how through these long years my colleagues in the library and in the university could have been so tolerant of me as they have been,” he wrote because I know that I am still not acclimatized to American life not any more than I was to my native country I am neither a complete Occidental nor a complete Oriental; I am neither here or there.” The university community was the closest thing Asakawa had to a family in his later life as became apparent when he died in 1948 at age 75 while vacationing in New Hampshire It fell to the dean and staff at the Graduate School to deal with his books and to answer inquiries and condolences from friends here and abroad.  Asakawa’s legacy as a symbol of peace grew in Japan in the years following his death a time when the country was rebuilding and dealing with the consequences of its imperialism “The thing that made him appealing in the context of postwar Japan was that he was vehemently anti-Communist and he was also someone who had said Japan shouldn’t go to war against the US,” says Botsman “Most of the people who had been critical of militarism in Japan had been Communist or left-leaning So here was this guy who was not a leftist who was critical of the military and obviously very sympathetic to the US.” The memorial garden in Saybrook College was dedicated in 2007 to commemorate the centennial of his joining the Yale faculty Designed by the landscape architecture firm Zen Associates and bamboo in a small walled space in the corner of Killingworth Court—an appropriate monument to a man of understatement and quiet introspection The other monument to Asakawa at Yale is the library collection he built and curated for 37 years he continued to add to the works he collected in 1906 Botsman says that Yale’s collection of pre-modern Japanese manuscript materials is “widely considered the best at any university outside Japan.” Botsman “It’s been one of the joys of being here having access to all that.” Surely nothing would please Asakawa more.    Thank you for such a beautifully written story about this man's life I agree with your perspective on the memorial I appreciate this very complete account of the life of an extraordinary man As a librarian at Yale and occasional docent for the Grove Street Cemetery I have long admired Kanichi Asakawa for his contributions to scholarship and diplomacy I was interested to read here that the Brooklyn Museum consulted him on the "Japanese inscriptions for their building’s façade." It reminded me that he was likewise consulted on the Chinese inscription carved into the front façade of Sterling Memorial Library According the 1931 Yale Library Gazette [1]: "This inscription selected and translated by Professor Asakawa illustrious in Chinese history for the high literary attainments and the patriotic acts of several of its members" 84 in https://elischolar.library.yale.edu/cgi/viewcontent.cgi?article=1000&context=yale_history_pubs including a reporter and a documentary film crew from the Japanese American National Museum in Los Angeles’ Little Tokyo through the history-filled land of Koda Farms the iconic farm that was started 97 years ago by her grandfather Just about every Japanese American is familiar with Koda Farms — especially its best-known brands Kokuho Rose rice and Blue Star Mochiko mochi rice flour In Asian markets and even mainstream supermarket chains across the country you’re likely to see stacks of Koda Farms’ rice (there’s also Sho Chiku Bai Sweet Rice) in bags from five to 50 pounds which was developed and first sold in the early 1960s is credited in a story by the Los Angeles Times as being the rice that made the introduction of sushi in America possible with its taste and texture the perfect complement to raw fish and nori seaweed The rice helped convince restaurants in Los Angeles’ Little Tokyo to import the glass-refrigerated counter displays from Japan for the first American sushi bars (Read related story here.) JAs know the rush to buy Kokuho Rose — especially the company’s “Heirloom” product — when the “New Crop” designation appears on the stack of sacks at the store each fall Robin Koda with Mochiko (Photo: Gil Asakawa) there was a panicked rush to stock up on Koda Farms products when news media ran stories about Koda Farms that gave the impression that the operation was shutting down the granddaughter and grandson of Keisaburo who now run the farm have licensed five of the family’s products — including its seeds products such as Kokuho Rose and Blue Star Mochiko — to a Northern California company which broke the news to most of the country “California’s Rice Royalty Is Stepping Down: Koda Farms a family run rice business revered by chefs the San Francisco Chronicle’s even more dire headline read “This California Farm Supplied Rice to Chefs and Homecooks for 97 years Both articles and others that followed mentioned the licensing deal and noted the products would continue who might scan a headline but not fall for the click-baity sensationalism to actually read the details just caught the gist of the story and assumed the worst Culinary fans thought that Kokuho Rose would not be available anymore or that there would be no more Blue Star Mochiko sold to make butter mochi cake and though it’s true the Kodas are giving up the tough life of farming in an age of economic strife and climate change and rice will still be grown there under the supervision of Western Foods as well as at the company’s farms near Sacramento There will actually be more rice from more land who lives on the family farm in South Dos Palos in California’s Central Valley with her 99-year-old mother and she was swamped with social media messages phone calls and texts from fans far and wide The Sacrarmento Bee had it right in its headline which stated the Koda legacy is moving to Yolo County where Western Foods is located north of Sacramento The Los Angeles Times set the record straight with a headline and article that included this direct statement from Robin Koda: “Stop freaking out The new chapter will be written by Western Foods The company is licensing the right to use the Koda Farms name as well as the names and logos for its famous products in addition to Koda Farms’ special heirloom rice seeds and production processes The deal was made possible because Keisaburo Koda was visionary enough to trademark his products and brand names decades ago so that they could someday be handed on as valuable assets Koda Farms was the largest rice grower in the U.S Koda was called the “Rice King” by consumers and media He invented an efficient way to sow rice seeds using airplanes to drop seeds that had been soaked overnight onto wet fields so they could withstand the Central Valley’s dry climate and soil he worked with a scientist to develop the special seed for medium-grain rice that would be sticky and chewy and have flavor and floral notes his wife and two sons — was incarcerated at Amache in Colorado where outside the family’s barrack was a concrete usu mortar to pound mochi the Rice King returned to California and found that almost all of his land and equipment had been sold He simply moved down the road a couple of miles and started the farm where the Koda family has built a new rice kingdom over the decades Koda didn’t just farm the land (his sons took over) he began social justice and community efforts that included being a leader in the JACL and Japanese governments to bring young Japanese farmers to Koda’s land to learn American agricultural techniques and even filing for and eventually winning (after his death unfortunately) reparations for his wartime losses Keisaburo Koda made sure he wasn’t just growing rice to hand off to other companies to truck Koda made his operation vertically integrated milled and packaged the products under his family brands “I’m extremely grateful and consider myself extremely lucky that he had the foresight to get his IP (intellectual property) all in order,” Robin Koda said as she gave a tour of the farm and all the industrial equipment and various buildings that take the rice from farm to end products Her grandfather built a unique vertically integrated agribusiness that they could control every step of the way from growing to harvesting to processing and then selling products that’s the only reason why we have these trademarks to continue to license out,” Robin Koda added is also glad for the founding Koda’s visionary acumen Reyna knew about Koda Farms before he founded Western Foods in 2004 when he worked for a company that milled Koda’s rice He says he was contacted by Ross Koda a year ago when Robin and Ross began to consider making the change including a host of gluten-free rice and ancient grain products and he’s excited to become the company behind Kokuho Rose Blue Star Mochiko and Sho Chiku Bai Sweet Rice and other products Reyna and Robin Koda say that consumers can expect new though hopefully not the hockey-pucklike rice snacks that have been a staple of supermarkets for years Reyna also runs a separate line of healthy snacks Western Foods will continue to manufacture such beloved Koda Farms products as Kokuho Rose Reyna agrees that some of the media coverage has been challenging the stories were all overboard a little bit I think the messaging sometimes didn’t come across very clear,” he said He also acknowledges that consumers can be skeptical of change like this especially when a family owned company’s products will be made by a different company He says he respectes the Koda family’s achievement and hopes to maintain the Koda legacy with his own family and Western Foods can become a multigenerational family legacy Some of the farming will continue at the current site and Ross and Robin are not going anywhere.” to be the familiar face of Koda Farms’ rice (though she won’t be driving to farmers markets up and down California on the weeknds anymore) Ross will continue to work with Western Foods to run the seed program though he’s also involved in a new business selling sake Uka Sake is made from Koda Farms’ rice that is fermemted and shipped to brewers in Japan’s Tohoku region where Keisaburo Koda emigrated from in the early 1900s played on the farm equipment and climbed the towers that rise up to give a view of the acres around the family compound all the way to the Coast Range mountains to the west She’s convinced her grandfather would approve because he was a restless soul who left Japan for a life in the U.S and tried his hand at several businesses before landing on rice farming and the family will be forever connected to Kokuho Rose and the other rice brands but it will continue under a new leadership Yen' Kanda likely successorJapanese Finance Ministry veteran says it is time for new leadership Japan's former vice finance minister for international affairs is being nominated to take over the presidency of the Asian Development Bank early next year MANILA/TOKYO -- The Asian Development Bank announced on Monday that its president the former top financial diplomat under Fumio Kishida's government Today's print edition Home Delivery still remembers the continuing smiles of his younger sister despite her long battle against the aftereffects of the Aum Shinrikyo doomsday cult's sarin nerve gas attack on Tokyo's subway system 30 years ago died in 2020 at the age of 56 after suffering severe aftereffects from the sarin attack on March 20 which left 14 people dead and more than 6,000 others injured.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); she would have been delighted," Kazuo Asakawa said about the birth of his granddaughter in January this year 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 Kanda has held various senior roles at Japan’s finance ministry over the past four decades including deputy director-general of the budget bureau The United Nations has declared 2025 to be the International Year of Glaciers’ Preservation making it a fitting moment to confront the stark reality that the world’s ice sheets are melting particularly in the Hindu Kush Himalayas – a region known as the Earth’s Third Pole because it contains the largest volume of ice outside of the Arctic and Antarctica which stretches across 3,500 kilometres and spans eight countries is warming roughly three times faster than the global average If temperatures rise by 3° Celsius above pre-industrial levels by the end of this century up to 75 per cent of the region’s glaciers will melt Glacial melt thus threatens irreversible damage to nearby communities and local economies But it would also fuel instability around the globe by increasing migration The 2021 flood disaster in Nepal’s Melamchi River offers a glimpse of what is to come triggered a debris flow that wiped out thousands of hectares of agricultural land and destroyed critical infrastructure leaving hundreds of thousands of people without access to water there will be too little water – a problem that is projected to afflict the Hindu Kush Himalayas by 2050 Dwindling river flows would make it more difficult to irrigate crops in an area that produces around one-third of the world’s rice and one-quarter of its wheat Water supply and sanitation systems will become difficult to maintain adding to the one billion people who already lack access to basic sanitation in the region Food insecurity will almost surely worsen as well while communities and even entire industries will likely need to migrate in search of fresh water Asia’s poorest and most vulnerable populations will be hit the hardest The world must take urgent action to avert the disastrous effects of accelerating glacial melt in this region That means deepening our knowledge by investing in multi-hazard risk assessment because the extent of the damage will largely depend on whether global temperatures rise by 1.5°C We must also strengthen integrated river-basin management by enhancing data collection and coordinating among people and communities living upstream and downstream Ensuring that new and existing infrastructure is climate-resilient is essential for maintaining access to safe drinking water and energy security It is equally important to protect ecosystems and promote nature-based solutions such as afforestation Every component of this strategy requires more financing Development institutions must continue to scale up investment in the Hindu Kush Himalayas and to work together to recast this glacial region and its river basins as a global public good especially given their importance for agricultural and industrial activities the international community must advance the equitable use of shared glacial resources through cooperation and diplomacy This would help defuse potential tensions and promote sustainable development ensuring that the region’s glaciers serve as a force for peace rather than conflict The Asian Development Bank has taken steps to meet some of these goals Together with the Green Climate Fund and country partners ADB recently launched the Glaciers to Farms program which will mobilise US$3.5 billion to strengthen climate resilience in agriculture in Central and West Asia its Building Adaptation and Resilience in the Hindu Kush Himalayas-Bhutan and Nepal initiative is helping plan and design climate-resilient infrastructure and services And ADB is also piloting new financing instruments When UNESCO and the World Meteorological Organization launched the International Year of Glaciers’ Preservation last month WMO Secretary-General Celeste Saulo said that it should serve as “a wake-up call to the world” The global community must do everything in its power – from building climate resilience to accelerating the green transition and promoting regional cooperation – to ensure a sustainable future for the billions of people who depend on glaciers and their related ecosystems Failure to act now would have catastrophic consequences for us all Masatsugu Asakawa is President of the Asian Development Bank.© Project Syndicate 2025www.project-syndicate.org View the discussion thread. This season marked something of a step-up for the brand, and it showed in Paris for the first time, to a modest standing audience at the Palais de Tokyo. The recipient of this year’s Fashion Prize of Tokyo—which exists to help Japanese designers expand their international reach—Asakawa will show his collections for Ssstein in Paris both this season and next. As well as the clout this will bring, it also means a great opportunity for Asakawa to flex his creative muscles in a new setting. This was, as usual, a collection of beautiful clothes—his trademark trench coats were there, as were plenty of other brilliantly wearable pieces (from super-clean shirts to intentionally dirtied denim and cargo pants)—but the reliance on the usual suspects made it hard to shake the feeling that Ssstein had played it safe. Those small nitpicks aside, Asakawa’s knack for making quality, sellable product is undeniable. “I wanted to make clothes you can casually wear on your doorstep but that somehow feel very elegant,” he explained. Doorstep elegance—it has a nice ring to it. Vivienne Westwood Fall 2025 Ready-to-Wear Maison Rabih Kayrouz Fall 2025 Ready-to-Wear By Caroline Carr When Lifelong announced it was getting out of the thrift business in January they were naturally met with disappointment from the community they couldn’t yet reveal what would come next for the Broadway thrift shop that had been a quintessential Capitol Hill spot for more than twenty years The Lifelong nonprofit will be moving away from retail to focus its efforts on an expanded kitchen and meal services mission doubling its size in Georgetown making way for a new effort in reuse and recycling: Magpie Thrift The new beginning on Broadway starts next week Magpie will be a thrift store that encourages patrons to reuse “Although we are sad and have been grieving the loss of that identity life is about moving forward and creating new things,” said owner Tamara Asakawa who previously served as the longtime director of Lifelong Thrift The new store will be a space for shopping along with upcycling workshops Magpie will begin as a for-profit venture that will fund the launch of Everly she hopes to raise the money to merge the two entities and return the thrift back to its roots as a nonprofit Asakawa was intent on transparency with the store’s new for-profit status and is confident that this is both necessary and temporary CHS first reported on the changes here earlier this year as Asakawa made plans to keep the long-running 12,500-square-foot two-level thrift shop space on Broadway dedicated to reuse and vintage retail Lifelong Thrift opened in the space in early 2015 the store was part of the Red Light Vintage family The interior will be fairly indistinguishable from Lifelong with many of the same queer mementos from the store’s past hanging on the wall it has been an unofficial meeting space for people who belong to marginalized groups Magpie will continue to hold up its predecessor’s values of helping those affected by HIV/AIDS and the larger LGBTQ+ community by providing assistance for the unique struggles faced by each group this will look like help with paring down possessions in preparation for moving or aging in place “We just want to give back and also take that opportunity to make sure that whatever they’re getting rid of is recycled properly,” said Asakawa Asakawa imagines using the store to host sewing and mending workshops “All of us that work here are really passionate about thrifting but also reusing,” said Asakawa “There’s just so much waste in the world.” The store will also develop its existing volunteer program in an effort to place a bigger emphasis on providing students and young people with practical job skills volunteers will learn about repairing and refinishing items for reuse through three courses of their choosing Magpie hopes to eventually double as a queer community center The store’s grand opening on April 5th will be the first taste of this new era with giveaways and a blessing by the Sisters of Perpetual Indulgence The store will still be accepting donations March 25th-31st with a soft opening on April 1st there is a drop-off area behind the store off E Thomas Magpie Thrift is opening at 312 Broadway E. Learn more at magpiethriftseattle.com Excited about this evolution of my family’s fave neighborhood thrift store did Lifelong reveal why they were getting out of the Thrift business I hope Magpie doesn’t have to deal with the constant flow of fentanyl and meth addicted shop-lifters that have been plaguing the other thrift stores on the Hill Reply + SUBSCRIBE TO CHS: Support journalism dedicated to your neighborhood. SUBSCRIBE HERE TODAY Got a tip? E-mail CHS — [email protected] — Call or text (206) 399-5959 — About CHS Join the Capitol Hill Seattle Facebook Group 🗣️ Let’s talk about the neighborhood TRAFFIC CAMS Volume 9 - 2021 | https://doi.org/10.3389/fcell.2021.640414 This article is part of the Research TopicZebrafish Models for Human Disease StudiesView all 36 articles Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord Spinal motor neurons align along the spinal cord length within the vertebral column and extend long axons to connect with skeletal muscles covering the body surface spinal motor neurons are among the most difficult cells to observe in vivo Larval zebrafish have transparent bodies that allow non-invasive visualization of whole cells of single spinal motor neurons combined with its amenability to genome editing enables functional analyses of ALS-associated proteins in the spinal motor neurons in vivo with subcellular resolution we review the zebrafish skeletal neuromuscular system and the optical methods used to study it We then introduce a recently developed optogenetic zebrafish ALS model that uses light illumination to control oligomerization phase transition and aggregation of the ALS-associated DNA/RNA-binding protein called TDP-43 we will discuss how this disease-in-a-fish ALS model can help solve key questions about ALS pathogenesis and lead to new ALS therapeutics Better understanding of the causes and consequences of TDP-43 aggregation will increase our understanding of ALS pathogenesis and aid in the development of therapeutics dissecting oligomerization- or phase transition-dependent toxicity from overexpression-dependent toxicity has remained a challenging but important task in understanding the mechanism of TDP-43 neurotoxicity we describe the skeletal neuromuscular system of larval zebrafish and optogenetic approaches for controlling in vivo phase transition of TDP-43 in motor neurons pertinent to the study of ALS pathogenesis This ability is worth further study for its potential contribution to regenerative therapy of motor neurons in humans (C) Schematic illustration of a wild-type CaP innervating the ventral myotome CaPs (arrows) are selectively labeled in Tg[SAIG213A] Tg[UAS:EGFP] fish Knowledge of the mechanisms underlying this neuron-specific cytoplasmic opTDP-43 relocation could aid in our understanding of cytoplasmic relocation of TDP-43 in the context of ALS motor neurons whose mechanism is almost entirely unknown at present potential intercellular propagation of opTDP-43-driven TDP-43 aggregation could be directly tested within an intact CNS we suggest that future studies take full advantage of zebrafish in a whole organism compound screening advancing the opTDP-43-based zebrafish ALS model into a system for screening small molecules that mitigate toxic TDP-43 phase transition for developing effective ALS therapeutics KA wrote the manuscript and generated the figures All authors approved the submitted version This work was supported by the SERIKA FUND (KA) and KAKENHI (JP19K06933 and JP20H05345) (KA) The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations A calibrated optogenetic toolbox of stable zebrafish opsin lines TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis Homology Directed Knockin of Point Mutations in the Zebrafish tardbp and fus Genes in ALS Using the CRISPR/Cas9 System ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43 Cellular dissection of the spinal cord motor column by BAC transgenesis and gene trapping in zebrafish Optogenetic modulation of TDP-43 oligomerization accelerates ALS-related pathologies in the spinal motor neurons An mnr2b/hlxb9lb enhancer trap line that labels spinal and abducens motor neurons in zebrafish A transgenic zebrafish for monitoring in vivo microtubule structures Protocadherin-Mediated Cell Repulsion Controls the Central Topography and Efferent Projections of the Abducens Nucleus Genetic dissection of neural circuits by Tol2 transposon-mediated Gal4 gene and enhancer trapping in zebrafish Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis Central and peripheral innervation patterns of defined axial motor units in larval zebrafish Dynactin1 depletion leads to neuromuscular synapse instability and functional abnormalities Zebrafish Tg(hb9:MTS-Kaede): a new in vivo tool for studying the axonal movement of mitochondria Potassium channel-based optogenetic silencing Neuromuscular junction abnormalities in a zebrafish loss-of-function model of TDP-43 Functional characterization of a FUS mutant zebrafish line as a novel genetic model for ALS Locomotor repertoire of the larval zebrafish: swimming Google Scholar Optogenetic protein clustering and signaling activation in mammalian cells A new zebrafish model produced by TILLING of SOD1-related amyotrophic lateral sclerosis replicates key features of the disease and represents a tool for in vivo therapeutic screening Coaggregation of RNA-binding proteins in a model of TDP-43 proteinopathy with selective RGG motif methylation and a role for RRM1 ubiquitination Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis Next-generation optical technologies for illuminating genetically targeted brain circuits TDP-43 is directed to stress granules by sorbitol a novel physiological osmotic and oxidative stressor Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations Real-time visualization of oxidative stress-mediated neurodegeneration of individual spinal motor neurons in vivo Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons Mechanisms of photoswitch conjugation and light activation of an ionotropic glutamate receptor Long-Range Optogenetic Control of Axon Guidance Overcomes Developmental Boundaries and Defects Tardbpl splicing rescues motor neuron and axonal development in a mutant tardbp zebrafish Myelin degeneration induced by mutant superoxide dismutase 1 accumulation promotes amyotrophic lateral sclerosis Characterization of genetic loss-of-function of Fus in zebrafish Differential requirement for MuSK and dystroglycan in generating patterns of neuromuscular innervation A Drosophila model for TDP-43 proteinopathy Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins Transcriptomic Analysis of Zebrafish TDP-43 Transgenic Lines Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations RNA Binding Antagonizes Neurotoxic Phase Transitions of TDP-43 Beyond aggregation: Pathological phase transitions in neurodegenerative disease Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization A topographic map of recruitment in spinal cord A gradient in endogenous rhythmicity and oscillatory drive matches recruitment order in an axial motor pool Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function Development and axonal outgrowth of identified motoneurons in the 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cytotoxic and reveals the evolution of ALS-FTD pathology Handa H and Kawakami K (2021) Illuminating ALS Motor Neurons With Optogenetics in Zebrafish Copyright © 2021 Asakawa, Handa and Kawakami. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Kazuhide Asakawa, a2FzYWthd2FAbmlnLmFjLmpw 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 A demonstration of an artificial intelligence-powered suitcase designed to assist visually impaired individuals as a robotic alternative to guide dogs The latest model incorporates generative AI technology enabling it to describe the surrounding environment through voice feedback Equipped with a built-in camera and sensors the suitcase can analyze its surroundings and provide real-time guidance to users.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); an AI suitcase was demonstrated at the National Museum of Emerging Science and Innovation the museum's chief executive director and a key member of the development team was guided by the suitcase as it moved quietly Sponsored contents planned and edited by JT Media Enterprise Division. Volume 7 - 2013 | https://doi.org/10.3389/fncir.2013.00100 This article is part of the Research TopicThe world according to zebrafish: How neural circuits generate behaviourView all 34 articles Bacterial artificial chromosome (BAC) transgenesis and gene/enhancer trapping are effective approaches for identification of genetically defined neuronal populations in the central nervous system (CNS) we applied these techniques to zebrafish (Danio rerio) in order to obtain insights into the cellular architecture of the axial motor column in vertebrates by using the BAC for the Mnx class homeodomain protein gene mnr2b/mnx2b we established the mnGFF7 transgenic line expressing the Gal4FF transcriptional activator in a large part of the motor column Single cell labeling of Gal4FF-expressing cells in the mnGFF7 line enabled a detailed investigation of the morphological characteristics of individual spinal motoneurons as well as the overall organization of the motor column in a spinal segment we identified transgenic lines that marked discrete subpopulations of spinal motoneurons with Gal4FF Molecular characterization of these lines led to the identification of the ADAMTS3 gene which encodes an evolutionarily conserved ADAMTS family of peptidases and is dynamically expressed in the ventral spinal cord should facilitate an understanding of the cellular and molecular architecture of the spinal cord motor column and its connection to muscles in vertebrates we applied BAC transgenesis and gene/enhancer trapping to the dissection of the spinal cord motor column we modified a BAC containing the Mnx-class homeodomain protein gene mnr2b/mnx2b to establish a transgenic line expressing Gal4FF in a large number of spinal motoneurons Single cell labeling allowed us to identify diverse types of the spinal motoneurons and to describe both their morphological characteristics and distribution in a spinal segment we dissected the motor column by means of gene trapping and identified transgenic lines in which specific subpopulations of spinal motoneurons were labeled with Gal4FF Molecular characterization of one of these lines led to the identification of the ADAMTS3 gene provides insights into the cellular and molecular architecture of the motor column and its connection to muscles in vertebrates Construction and characterization of the BAC transgenic line (A) The mnr2b genomic locus in the mnr2b-GFP enhancer trap line The hsp70p-EGFP enhancer trap construct was integrated 1.9 kb upstream of the mnr2b gene (B) Expression of mnr2b at 48 hpf detected by fluorescent in situ hybridization A confocal section of the spinal cord above the yolk extension in a wild type embryo is shown The PCR-amplified Gal4FF-polyA-Kmr cassette is inserted downstream of the 5′UTR of the mnr2b (open blue box) by homologous recombination The coding sequence of exon1 of mnr2b (filled blue box) is left intact after the recombination (D–F) The lateral view of the spinal cord of the mnGFF7;UAS:RFP; mnr2b-GFP triple transgenic embryo at 48 hpf and merged (right) images of a single confocal slice The RFP-positive cells whose somata are identifiable are indicated by the arrowheads in (F) The dotted lines demarcate the dorsal and ventral limit of the spinal cord (G) GFP expression in mnr2b-GFP (top) and mnGFF7;UAS:GFP (bottom) embryos at 48 hpf The arrows indicate the GFP expression in the gut The open arrowheads indicate the abducens motoneurons (H) The dorsal view of the mnGFF7;UAS:GFP larvae at 72 hpf GFP is expressed in the abducens and pectoral fin motoneurons The open and double arrowheads indicate the soma positions and the axon terminals of the abducens motoneurons The brackets indicate the axon terminals of the pectoral fin motoneurons The dotted lines demarcate the dorsal (top) and ventral limit of the spinal cord in (B,D–F) The bars indicate 500 base-pair (bp) in (A) and (C) Single cell labeling of Gal4FF expressing cells in mnGFF7 (A) The plot of the single GFP-labeled motoneurons (open gray circles) with respect to the soma size on the horizontal axis and to the position of the soma along with the DV axis on the vertical axis The DV soma position is normalized to the dorsal (y = 1) and the ventral (y = 0) edge of the spinal cord (B) Distribution of the GFP-labeled cells plotted with respect to the soma position along the RC axis on the horizontal axis and to the DV soma position on the vertical axis The exit point of the ventral root from the spinal cord is indicated on the RC axis by the gray vertical line marked as vr (x = 0) laterally and ventrally projecting cells are shown as red The cells with bifurcating main axon and the vmS motoneurons are shown as gray squares and open triangles (C) Cell counts of the neurons innervating the axial muscles based on the axon trajectory and muscle innervation pattern P and S indicate primary and secondary motoneurons Diagonally-striped bars indicate iS-type neurons “Bifurc” indicates the motoneurons with a bifurcating main axon (D) Primary motoneurons innervating ventrally (a) (E) Muscle innervation territory of the primary motoneurons The position of the horizontal myoseptum (y = 0.5) is indicated as a gray horizontal bar (F) Secondary motoneurons innervating ventrally (a The arrowhead in (c) indicates the bifurcation in the main axon The asterisk in (b) is the axon of another motoneuron in the opposite hemi-segment (G) The secondary motoneuron innervating the ventral (a) The arrows indicate the axon terminals and roughly indicate their direction of extension The percentiles show the ratio among the laterally projecting cells (H) A cell innervating the dorsal myotseptum This cell is identical to the one shown in (Ge) and the image was taken 6 h after the image (Ge) was taken Note that the morphology of the soma changed dramatically in 6 h (I) The superficial myoseptal region of (H) merged with the DIC image The inset shows a stack of a few confocal sections indicated in the dotted square in (I) The axon collaterals cross the myoseptal boundary marked by the black dotted line The arrow and arrowheads indicate the axon terminal and the collaterals extending along the blood vessels All images in (D–I) were taken during 72–100 hpf and the rostral is to the left the oblique and horizontal dotted lines demarcate the myoseptal boundaries and the ventral edge of the spinal cord The brackets roughly indicate the innervation territory along the dorsoventral axis in (D,F) These observations prompted us to examine in more detail the GFP-labeled cells in the spinal cord of the mnGFF7;UAS:GFP larvae suggesting that a small population of descending interneurons is also labeled in mnGFF7 fish Summary of the cell types identified in the spinal cord of mnGFF7 larvae We tentatively named this cell-type “vmS,” for “ventromedial secondary,” because the target tissue(s) of vmS remained to be determined These observations imply a topographic connection between the GFP-labeled dorsally projecting cells and the dorsal musculature (see Discussion) A plasmid DNA containing a Gal4FF construct and the transposase mRNA were co-injected into fertilized eggs The injected fish were raised and mated with the reporter fish homozygous for the UAS:GFP insertion The resulting F1 embryos were analyzed with a fluorescence stereomicroscope F1 embryos expressing GFP were collected and raised for further studies (B) Examples of GFP expression in the spinal cord and the motor nerve in F1 embryos at 48 hpf the primary motoneurons are exclusively labeled a large number of GFP labeled cells are observed in the ventral spinal cord The dotted line demarcates the ventral limit of the spinal cord suggesting that M602A visualizes a subpopulation of the spinal motoneurons (H) Distribution of the GFP-labeled cells plotted with respect to the soma position along the RC axis on the horizontal axis and to the DV soma position on the vertical axis and ventrally projecting cells are shown as red (I) Cell counts of the neurons innervating the axial muscles based on the axon trajectory and muscle innervation pattern Diagonally-striped bars indicate iS type neurons In order to identify the types of the spinal motoneuron labeled by the M602 insertion we performed a single cell labeling experiment by injecting the UAS:GFP plasmid and observed individual GFP-labeled cells at 72–96 hpf we observed 40 single GFP-labeled cells that possessed an axon that exited the spinal cord (N = 31 larvae) The rate of identifying the single GFP-labeled cells was substantially lower in M602A than mnGFF7 most likely due to the early Gal4FF expression in the progenitor cells in M602A we identified other cell types as a single GFP-labeled cell as well including spinal interneurons and floorplate cells these observations suggest that the M602A insertion predominantly labels the motoneurons that are located dorsally in the motor column and have a highly extensive axonal arborization these results suggest that the M602A insertion traps the ADAMTS3 gene Figure 5. The M602A insertion traps ADAMTS3. (A) Structure of the ADAMTS3 locus and the integration site of M602A. M602A is inserted in the 3rd intron of ADAMTS3. The long horizontal bar and vertical bars denote the genomic DNA and the exons of ADAMTS3, respectively. ADAMTS3 consists of multiple functional domains: pro, pro domain; PD, metalloprotease domain; TSP1, thrombospondin type 1 motif; spacer, spacer region [according to Porter et al. (2005)] (B,C) Expression of ADAMTS3 at 24 hpf (B) and 48 hpf (C) (D–F) Expression of ADAMTS3 and EGFP detected by double fluorescent in situ hybridization A confocal section of the spinal cord of the M602A;UAS:GFP embryo at 24 hpf was shown The scale bars indicate 20 kbp (top) and 50 amino acids (bottom) in (A) Such cross-myoseptal innervation would help achieve a near synchronous and unilateral activation of body wall muscles so as to generate coordinated axial movements during the larval which have been only poorly characterized thus far The observation that axon terminals and collaterals of this cell type were often observable in the vicinity of blood vessels and pronephric ducts raises the possibility that the vmS neurons serve as a part of the autonomic nervous system by directly innervating these tissues or indirectly innervating them via ganglia These ideas need to be validated in the future by identifying the synaptic targets of vmS neurons This is most likely because the transient expression of GFP from the UAS:GFP plasmid tends to label cells with stronger Gal4FF activity which results in a biased staining compared to the rather uniform labeling achieved with the stable UAS:GFP reporter transgene the number of the spinal motoneurons expressing Gal4FF in mnGFF7 fish will be estimated more accurately by retrograde labeling using the photoconversion of the Kaede protein at the ventral root in mnGFF7;UAS:Kaede double transgenic larvae (Kazuhide Asakawa The 102 motoneurons that were analyzed in the single cell labeling experiment displayed a variety of dendritic morphologies: some displayed elaborate branches while others displayed only very tiny ones The relationship between the dendritic morphologies and the cellular properties we have reported remains a subject for future investigation Whether ADAMTS3 function in the spinal cord is evolutionarily conserved also remains elusive at present the change in fluorescent intensity of the GCaMP associated with body movements was detectable in the cell bodies as well as the axons of spinal motoneurons in larvae the change in fluorescent intensity of the GCaMP was also detectable in pectoral and abducens motoneurons (Kazuhide Asakawa the mnGFF7 and M602A lines should be applied not only to a functional analysis of axial motoneurons but also to that of the abducens and limb motoneurons in the near future This study was carried out in accordance with the Guide for the Care and Use of Laboratory Animals of the Institutional Animal Care and Use Committee (IACUC approval identification number 24-2) of the National Institute of Genetics (NIG which has an Animal Welfare Assurance on file (assurance number A5561-01) at the Office of Laboratory Animal Welfare of the National Institutes of Health (NIH For BAC manipulation, the purified mnr2b-BAC DNA (CH211-172N16, BACPAC Resources Center) was introduced into SW102 E coli cells (Warming et al., 2005). Transformation through electroporation was performed as described in (Suster et al., 2009b). For Tol2 transposon-mediated BAC transgenesis, the iTol2-amp cassette (Suster et al., 2009b) was introduced into the backbone (pBeloBAC11 The iTol2-amp cassette was amplified by PCR with the primer pair iTol2A-f (5′-gcg cgc caa tag tca tgc ccc gcg ccc acc gga agg agc tga ctg ggt tgC CCT GCT CGA GCC GGG CCC-3′) and iTol2A-r (5′-agc aat ata gtc cta caa tgt caa gct cga ccg atg ccc ttg aga gcc ttA TTA TGA TCC TCT AGA TCA GAT CT-3′) where the lower and upper cases indicate the pBeloBAC11 sequences for homologous recombination and the iTol2-amp annealing sequences Two hundred ng of the PCR product (1~2 μl) were used against 25 μl of cell pellet for transformation by electroporation using a Gene Pulser cuvette (0.1 cm For introducing the Gal4FF gene into the mnr2b locus in the resulting mnr2b-iTol2-amp-BAC the Gal4FF-polyA-Kmr cassette was amplified by PCR using the pKZGFFKm plasmid as the template with the primer pair mnr2b-Gal4FF-f (5′-tat cag cgc aat tac ctg caa ctc taa aca caa caa aag tgt tgc aAT GAA GCT ACT GTC TTC TAT CGA A-3′) and Km-r (5′-ggt tct tca gct aaa agg gcg tcg atc ctg aag ttc ttt gac ttt tcc atC AAT TCA GAA GAA CTC GTC AAG AA-3′) where the lower and upper cases indicate the mnr2b sequences for homologous recombination and the pKZGFFKm-annealing sequences BAC DNAs were purified with Nucleobond® BAC100 (MACHEREY-NAGEL) A wild-type embryo at the one-cell stage was injected with 45 pg of the purified BAC DNA and 45 pg of Tol2 transposase mRNA Germline transmission was confirmed by crossing the injected fish with the homozygous UAS:GFP fish By crossing sixteen injected fish with the UAS:GFP reporter fish we identified three founder fish that gave rise to the GFP-positive F1 offspring (germline transmission rate 19%) because it displayed the strongest GFP signal when combined with UAS:GFP at 24 hpf while the overall GFP reporter expression patterns were indistinguishable among these F1s For single cell labeling of Gal4FF-expressing cells in mnGFF7 and M602A larvae, 18pg of pT2KUASGFP plasmid (Asakawa et al., 2008) were injected into a blastomere at the 4- or 8-cell stage The injected embryos were raised in embryonic buffer containing 0.003% (w/v) N-Phenylthiourea (SIGMA The cells uniquely labeled with GFP or clearly identifiable as isolated single cells in a hemi-segment were analyzed by confocal microscopy The GFP-labeled motoneurons at the segment levels 4–20 were analyzed which was defined by measuring the largest cross sectional area of the soma and location (center of mass) were determined by ImageJ software Dorsal and ventral limits of the spinal cord were determined based on a DIC image taken with a GFP image Statistical analyses were performed using Mann–Whitney U tests Wild type fish were injected with the pT2GgSAIzGFFM plasmid, containing a Tol2-based gene trap construct with a splice acceptor from the zebrafish gata6 gene and the codon-optimized Gal4FF gene, and the synthesized mRNA encoding codon-optimized Tol2 transposase (Abe et al., 2011) at one-cell stage raised and crossed with the UAS:GFP reporter line Details of pT2GgSAIzGFFM will be described elsewhere (Abe et al Adaptor ligation-mediated PCR was carried out as described previously (Asakawa and Kawakami, 2009) the total RNA was prepared from 147 wild-type embryos at 48 hpf by homogenizing the embryos in 1 ml of Trizol Reagent (Life Technologies) Five μg of the total RNA were used for cDNA synthesis along with a primer in the ADAMTS3 coding sequence adamts3-ex4r (5′- GAT TGG CTG GTA ATC CAA AGA G-3′) and the 5′RACE System for Rapid Amplification of cDNA Ends version 2.0 (Invitrogen) The 5′RACE products were cloned with a TA cloning kit (Invitrogen) and sequenced the primer pair adamts3-f1 (5′-AGG CCT ACC ATG GTT GTC CTG TCA CTT AGG TTA-3′) and adamts3-r1 (5′-CTC GAG TCA TCT CTC CAC CTC AGA AGA TGT-3′) were used based on the nucleotide sequence for the putative ADAMTS3 (XM_692142) The cDNA obtained from wild type embryos at 48 hpf was used as the PCR template The cDNA of ADAMTS3 were cloned with a TA cloning kit (Invitrogen) and sequenced (KC894955) Antisense probes for ADAMTS3 and EGFP were synthesized with DIG RNA labeling kit (Roche) and Fluorescenin RNA labeling kit (Roche) The DIG-labeled ADAMTS3 and Fluorescein-labeled EGFP were detected with a TSA Kit#16 AlexaFluor647 tyramide and TSA Plus Fluorescein system (NEL74100KT Leica) equipped with a CCD camera (DFC300FX Leica) was used to observe and take images of GFP-expressing embryos A live embryo or larva was embedded in 1% low-melting agarose (NuSieve® GTG® Agarose 3010-035) and subjected to confocal microscopy using an Olympus FV-1000D laser confocal microscope Images of live embryos and larvae were acquired as serial sections along the z-axis and processed with an Olympus Fluoview Ver2.1b Viewer and Adobe Photoshop CS6 This work was supported by JSPS KAKENHI Grant numbers 23241063 (Koichi Kawakami) MEXT KAKENHI Grant number 23115720 (Kazuhide Asakawa) The Uehara Memorial Foundation (Kazuhide Asakawa) The Kao Foundation for Arts and Sciences (Kazuhide Asakawa) Daiichi-Sankyo Foundation of Life Science (Kazuhide Asakawa) and the National BioResource Project from the Ministry of education Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Motor neurons with axial muscle projections specified by Wnt4/5 signaling Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Motoneuron fate specification revealed by patterned LIM homeobox gene expression in embryonic zebrafish Pubmed Abstract | Pubmed Full Text Visualizing neurons one-by-one in vivo: optical dissection and reconstruction of neural networks with reversible fluorescent proteins Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Optical control of zebrafish behavior with halorhodopsin Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Targeted gene expression by the Gal4-UAS system in zebrafish Pubmed Abstract | Pubmed 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reveals spatiotemporal activation of the spinal motor neurons in zebrafish Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Spinal motoneurons of the larval zebrafish Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Pubmed Abstract | Pubmed Full Text Insertional mutagenesis by the Tol2 transposon-mediated enhancer trap approach generated mutations in two developmental genes: tcf7 and synembryn-like Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Adaptation of GAL4 activators for GAL4 enhancer trapping in zebrafish Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Spatial and temporal regulation of ventral spinal cord precursor specification by Hedgehog signaling Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Repulsive interactions shape the morphologies and functional arrangement of zebrafish peripheral sensory arbors Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Time course of the development of motor behaviors in the zebrafish embryo Pubmed Abstract | Pubmed Full Text | CrossRef Full Text ADAMTS proteases: key roles in atherosclerosis Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Genetic single-cell mosaic analysis implicates ephrinB2 reverse signaling in projections from the posterior tectum to the hindbrain in zebrafish Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Targeting neural circuitry in zebrafish using GAL4 enhancer trapping Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Functional repression of Islet-2 by disruption of complex with Ldb impairs peripheral axonal outgrowth in embryonic zebrafish Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics Pubmed Abstract | Pubmed Full 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efficient transgenesis in fish Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Molecular heterogeneity among primary motoneurons and within myotomes revealed by the differential mRNA expression of novel islet-1 homologs in embryonic zebrafish Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Pubmed Abstract | Pubmed Full Text Simple and highly efficient BAC recombineering using galK selection Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Emergence of patterned activity in the developing zebrafish spinal cord Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Identified motoneurons and their innervation of axial muscles in the zebrafish Pubmed Abstract | Pubmed Full Text Pubmed Abstract | Pubmed Full Text | CrossRef Full Text The dorsal raphe modulates sensory responsiveness during arousal in zebrafish Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Pubmed Abstract | Pubmed Full Text | CrossRef Full Text A descending interneuron identified in the single cell labelling experiment (A,B) The dorsal view of a larvae at 76 hpf The soma of the GFP-labelled cell located at the level of the anterior boundary of somite 1 The axon descended ipsilaterally to the level of somite 18 The dotted lines indicate the position of the midline (C and D) The lateral view of the same larva The oblique lines indicate the anterior boundary of somite 1 and 18 the DIC image was superimposed onto the GFP image The scale bars indicate 100 μm in (B) and (D) Distribution of the laterally projecting cells in mnGFF7 (A) and M602A (B) plotted with respect to the soma position along the RC axis on the horizontal axis and to the DV soma position on the vertical axis laterally and dorsolaterally projecting cells are shown as circles Abe G and Kawakami K (2013) Cellular dissection of the spinal cord motor column by BAC transgenesis and gene trapping in zebrafish Copyright © 2013 Asakawa, Abe and Kawakami. This is an open-access article distributed under the terms of the Creative Commons Attribution License distribution and reproduction in other forums provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc *Correspondence: Kazuhide Asakawa and Koichi Kawakami, Division of Molecular and Developmental Biology, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka, 411-8540, Japan. e-mail:a2FzYWthd2FAbmlnLmFjLmpw;a29rYWthd2FAbmlnLmFjLmpw The Asian Development Bank said on Monday that its president has announced his intention to step down from his position The Yomiuri Shimbun reported earlier on Monday that Japan is set to back former top financial diplomat Masato Kanda as a candidate for the next president of the ADB.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); Finance Minister Shunichi Suzuki said in a statement that Japan hoped to promptly nominate someone most appropriate as a candidate The Finance Ministry declined to comment on the reported nomination of Kanda Asakawa became ADB president in January 2020 and oversaw the Manila-based lender's launch of measures to help the region's economies deal with the COVID-19 pandemic The election of the ADB's new president will follow "an open and merit-based process" in accordance with the lender's charter the development lender said in a statement ssstein" won the "FASHION PRIZE OF TOKYO 2025" and held a show in Paris. The collection had a quiet and delicate strength that logically and carefully gave shape to invisible nuances. What did the designer, Mr. Asakawa, want to convey? The day after the show, we visited the showroom to talk about it. With experience as a fashion buyer, Asakawa consistently combines his sharp eye for product with a near-pathological obsession with fabrication, and this was another collection that expertly chimed the chic and commercial. No surprise that business is booming—though it was only founded in 2016, the Tokyo-based brand now has 32 global stockists, from Scandinavia to the U.S. Still, Stein’s laser-focus on making impressive product can mean its larger sense of brand identity sometimes feels undercooked. Asakawa knows how to create formidable clothing; now he needs to finish building the world around it. The Asia and Pacific region stands at a critical juncture positioned both as a significant contributor to global greenhouse gas emissions and a potential leader in transformative climate action is steering the region towards a sustainable future through support for a just transition Our vision aims to reorient economic and social frameworks to foster low-carbon climate-resilient growth that enhances prosperity and inclusion one that puts people at the center of the shift to net zero Asia and the Pacific account for over half of the world’s annual greenhouse gas emissions more than 200 million people in the region are impoverished with many lacking access to basic electricity and relying on traditional biomass for cooking and heating ADB prioritizes an inclusive approach to ensure that the costs and benefits of the transition to net zero are fairly distributed Achieving net zero requires us to restructure our economies and change the way we live and work the burdens of change are not imposed on the most vulnerable and that the benefits of a low-carbon economy are both maximized and shared equitably share in these benefits is critical to the success of our just transition efforts To create opportunities for inclusive and sustainable growth ADB works with partners to implement robust policy frameworks enhance institutional capacities and engage stakeholders through participatory processes These just transition efforts align with global commitments such as the Paris Agreement and at the country level we support our developing members in crafting policies and programs that respond to their unique climate challenges and development needs ADB launched a Just Transition Support Platform to help drive a just transition within our developing member countries This platform focuses on supporting countries to incorporate just transition into their institutional and policy frameworks and identify innovative financing approaches that attract public and private capital for a just transition The platform also supports the mainstreaming of just transition in ADB’s operations ADB launched an inclusive process to design a Just Transition Finance Facility that will provide targeted finance to address the socio-economic challenges of the transition to net zero It will help countries realize the economic and social benefits of the transition and ensure these benefits are inclusive and widespread ultimately supporting a robust and equitable shift to low-carbon and resilient economies Just transition is also a core part of ADB’s Energy Transition Mechanism (ETM) Developed in partnership with ADB member countries ETM is a scalable initiative that has the potential to be one of the largest carbon-reduction programs in the world public and private investments – from governments philanthropies and other long-term investors – finance country-specific ETM funds These funds are designed to retire or repurpose coal power assets on an earlier schedule compared with a business-as-usual timeline Just transition principles are a cornerstone of ETM’s implementation helping us to ensure that potential negative socio-economic impacts are minimized through policies and programs retraining and reskilling programs provide new opportunities in emerging industries for women and vulnerable workers The importance of managing the social impacts associated with the transition to net zero can be seen through ADB’s work on the Cirebon 1 coal-fired power station in Indonesia for which ADB completed a preliminary just transition assessment earlier this year – the first of its kind for ADB and for the region The assessment utilized a comprehensive methodology to identify impacts along the coal value chain and within the community and surrounding areas It also established a process to further assess and develop a plan to manage impacts at the appropriate project stages Just transition offers a compelling vision for green and inclusive development across Asia and the Pacific Its promise lies not only in avoiding the worst impacts of climate change but in creating a more equitable social order that values well-being and gender equality We must encourage optimism and concerted effort from all sectors of society to embrace the principles of justice and inclusivity that will be needed for a low-carbon This journey faces challenges but is also filled with opportunities for transformative change that can forge a healthier The path we chart now will determine the climate legacy we leave for future generations Masatsugu Asakawa is President of the Asian Development Bank. This article was first published in the OECD Development Co-operation Report 2024: Tackling Poverty and Inequalities through the Green Transition [https://doi.org/10.1787/357b63f7-en] Why Silknet's eSIM could be your top choice in Georgia  Since its introduction An event will be held at the museum on the 22nd to donate moon jar works to Takumi Asakawa Museum of Art in Hokuto City who is said to have reproduced Joseon white porcelain Hokutoshi is the hometown of Takumi Asakawa a Japanese white porcelain researcher who widely introduced Joseon's moon jars to Japan Brothers Takumi Asakawa and Noritaka delivered the beauty of Joseon white porcelain to the Japanese culture and art world and critic Muneyoshi Yanagi praised the beauty Takumi Asakawa was buried at Manguri Cemetery in Korea while studying white porcelain The donation was made through years of consultations between the Joseon White Porcelain Research Institute and the city of Hokuto ※ This service is provided by machine translation tool pictured at one of his favorite places to be — a Japanese restaurant — was selected by the Japanese government on April 29 to receive Order of the Rising Sun When he’s not doing that, Asakawa shoots and shares pics of his latest gastronomic conquests — “food porn,” as he calls it — via social media. And, just recently, the Los Angeles Times featured him in a video with reporter Daniel Miller to explore the origin of sushi in L.A. (see tinyurl.com/2s4ytacp) Although a labor of love (and nominal income) be a “physical bridge between Japan and the U.S.” Why “Because I was born there and because I moved here when I was 8 I became very Americanized very young — and yet I have these kind of deep roots … and I feel very connected,” Asakawa told the Pacific Citizen Those circumstances also extend to his involvement with JACL at the national level as a past member of the Pacific Citizen board (including serving as P.C Editorial Board chair) and the local level with the Mile High JACL chapter as well as with the Denver-Takayama Sister City Committee the U.S.-Japan Council and the Japan America Society Colo.-based Asakawa was flattered and surprised to learn that his activities had been noticed — by the government of Japan he was informed that he was among a group of people who were named as recipients of the Spring 2023 Conferment of Decorations on Foreign Nationals Asakawa will receive the Order of the Rising Sun for having “contributed to improving the social status of Japanese Americans in the United States and promoting understanding of Japan.” at the Consul General’s residence here in Denver,” Asakawa said.  he says: “My dad probably would have gotten a kick out it.” As for his mother he said he isn’t sure she’d understand if he told her — but remains curious about what she might say when he shows her the Japanese language announcement on the consulate’s webpage As for being recognized by Japan’s government after all the years of writing reporting and blogging on Japanese American and Japanese topics I’m glad that they saw that everything I’ve done has been about explaining JA history explaining the immigration background of Japanese Americans and the World War II experience and everything since then.” while Asakawa knows that “it’s definitely a big honor,” he added that he knows “there are a lot of people across the country who deserve these awards.” For now it’s Asakawa’s turn to take a bow as his family’s rising son IBMIBM Master Inventor Chieko Asakawa's innovations include an app that helps blind people navigate public spaces by using their smartphones I had no idea a person like me could become an inventor,” Asakawa says she got a job with IBM Tokyo’s research group to help create a computer that would translate text from English to Braille She moved to Tokyo to live on her own for the first time creating a word processor that translated digitized text into Braille so that it could be printed and edits or corrections were practically impossible This breakthrough led to the creation of a digital library for Braille documents Her idea was developed into an IBM product called IBM Home Page Reader “That’s the beauty of IBM,” says Asakawa “I just wanted to develop a home page reader But  IBM helped me start contributing to a better world Home Page Reader was a real turning point for me Receiving her PhD in 2004 was another turning point for Asakawa It gave her the confidence to set her sights on becoming a technical leader During this process she acquired new mentors, including Nick Donofrio, now retired, who eventually became executive vice president of innovation and technology, and John E. Kelly III, currently the IBM executive vice president who oversees intellectual property. They encouraged her to take on the increased management responsibilities that would help her achieve her goal. She became an IBM Fellow in 2009 National Inventors Hall of Fame for the invention of Home Page Reader she is currently working in Pittsburgh as the IBM Distinguished Service Professor at Carnegie Mellon University Her more recent work includes collaboration with IBM partners through Carnegie Mellon an app that helps blind people navigate public spaces by using their smartphones to connect to sensors placed around an indoor environment The system was deployed at Carnegie Mellon the Pittsburgh airport and a shopping mall in Japan She is working with a group to take this technology one step further with AI Suitcase which could eliminate the need for Bluetooth beacons to enable visually impaired navigation of an environment “IBM has a culture that respects each person’s own perspective discussion and thinking about ideas together,” Asakawa says See more Master Inventor profiles → Chieko Asakawa, the IBM Distinguished Service Professor in the Robotics Institute and an IBM Fellow at IBM Research, is among 19 innovators who will be inducted this year into the National Inventors Hall of Fame is being honored for her invention of the Home Page Reader (HPR) the first practical voice browser providing internet access for blind and visually impaired computer users enabling users to surf the internet and navigate webpages through a computer's numeric keypad instead of a mouse The HPR soon was widely used around the world and its interface technology has been adopted by many other voice browsers Asakawa and the rest of the 2019 class will be honored and inducted May 1-2 at a celebration in Washington hosted by the Inventors Hall of Fame and the U.S Patent and Trademark Office headquarters in Alexandria "The National Inventors Hall of Fame honors the innovation game-changers who have transformed our world," said Michael Oister CEO of the National Inventors Hall of Fame "Through inventions as diverse as life-saving medicines and web browsers for the visually impaired these superhero innovators have made significant advances in our daily lives and well-being." The new inductees include David Walt of Harvard University which revolutionized genetic analysis by making it possible to analyze thousands of genes simultaneously; Turing Award winners Ken Thompson and the late Dennis Ritchie who created the UNIX operating system and the C programming language; and Jeff Kodosky and James Truchard of National Instruments who introduced the graphical programming language LabView™ Posthumous inductees include Joseph Muhler and William Nebergall who developed stannous fluoride toothpaste for reducing cavities who invented the landing craft known as Higgins Boats used to land U.S troops on the beaches of Normandy on D-Day in 1944 who has been blind since a swimming accident at age 14 has been instrumental in developing a number of technologies to aid people with visual impairments or other disabilities These include technologies to help the blind community in Japan access digital Braille books a disability simulator to help web designers make sites user-friendly to all and standardized design and programming interfaces that help developers create accessibility tools and applications At Carnegie Mellon, Asakawa has worked with Kris Kitani, assistant research professor of robotics, and her students, as well as IBM Research, to create NavCog a smartphone app that analyzes signals from Bluetooth beacons to help people with visual disabilities navigate their surroundings The system has been deployed on the CMU campus Asakawa now is working on an "AI suitcase," a lightweight motorized device that could guide people with visual impairments through airports or other public spaces Thanks for visiting The use of software that blocks ads hinders our ability to serve you the content you came here to enjoy We ask that you consider turning off your ad blocker so we can deliver you the best experience possible while you are here Let’s Eat!”When Gil Asakawa moved to the United States from his native Japan in 1966 most Americans scrunched their faces at the idea of eating raw fish “So the fact that sushi is now available at your neighborhood supermarket is a major cultural accomplishment,” he writes in a new book.  Let’s Eat” mixes the larger story of Japanese-American cuisine with Asakawa’s own taste adventures – from a Japanese salsa made with Pueblo chile to the comfort of ladling gravy over rice The longtime Denver journalist and self-described foodie sat down with Colorado Matters Senior Host Ryan Warner Here are highlights from their conversation LISTEN: From sushi to salsa, yes salsa, a history of Japanese-American cuisine Ryan Warner: Your mother was a major influence on your palate and she cooked both Japanese and American food but I figure we should start with her teriyaki sauce which you invoke in the opening pages She would just pour some sake into a bowl and then pour some shoyu and so I used beer for the longest time in my homemade teriyaki sauce I think that's one thing about probably all foods You can be like my mom and go with your gut Warner: Your wife Erin has also helped shape your palate Will you tell us about a dish her family makes Asakawa: It's actually like a teriyaki chip ‘Being Japanese American.’ It's a chip that's sweet and salty but its main ingredient is Tostitos corn chips Warner: This idea of fusing ingredients– true Japanese-American food – is also exemplified in a type of salsa. Would you describe Karami for us Asakawa: Karami is something that I was introduced to about a decade ago A friend of mine who lives in Boulder had started a company to mass produce Karami which is a Japanese-American variation from Pueblo The family of a former mayor of Pueblo was making this It's a side dish in Japan to have pickled vegetables and various things and you serve it with rice or next to your protein Japanese Americans who were farmers or railroad workers in Pueblo found but they found something that had a very similar mouthfeel in terms of sliminess and texture It has the flavor of a Japanese condiment with soy sauce and sugar but it has a little kick because of the green chiles Warner: I was surprised to read in the book that it's not good form to pour soy sauce over your plain rice I used to put all sorts of things on all sorts of food Warner: You also posted to social media recently that you put gravy on rice and then I just got a craving for gravy on rice Asakawa: There's actually a couple of ways that's come into the culinary vocabulary which is rice covered with one or two hamburger patties and then topped with brown gravy and then a fried egg I've also had it with the white gravy that comes with chicken-fried steak and you use your little spoon to make that little volcano crater in your mashed potatoes Then we'd put gravy on both rice and the mashed potatoes I was shocked at how much interaction it got that's what I love best about Thanksgiving." It's true I'm not a huge fan of turkey or dressing but Warner: I think the rise of seaweed as food in the United States must follow a similar trajectory to sushi sushi is often wrapped in seaweed.) I remember when it became more en vogue to have dried seaweed– a little strip of dried seaweed their parents would pop those into their lunches Seaweed was part of the movement for health food that started in the late 1960s My mom is from the northern island of Hokkaido and she always swore that the seaweed from her hometown of Minato is the best in Japan.  Warner: I'd like to talk about how the imprisonment of Japanese Americans during World War II shaped foodways we can focus on soy sauce that was made in the camps Asakawa: Some of the camps had the wherewithal and the materials where they could make soy sauce So it helped take the edge off camp food and make it more authentic Camp food was something that was important It helped change the things that Japanese Americans ate– and got sick of eating– certain things they were fed all the time Author Gil Asakawa On Being Japanese American: ‘I Was A Banana’ You want to know what is really going on these days We can help you keep up.  The Lookout is a free daily email newsletter with news and happenings from all over Colorado Sign up here and we will see you in the morning Colorado Postcards are snapshots of our colorful state in sound. They give brief insights into our people and places, our flora and fauna, and our past and present, from every corner of Colorado. Listen now. © 2025 Colorado Public Radio. All Rights Reserved. Privacy Policy Chieko Asakawa, Ph.D., SWE’s 2010 Achievement Award recipient, was inducted into the National Inventors Hall of Fame (NIHF) At a ceremony held in May at the National Building Museum in Washington Asakawa was among the new inductees recognized for their patented inventions which “revolutionized their industries and changed people’s lives.” honors and celebrates the world’s foremost inventors and their contributions to society the 2019 inductees are visionary innovators each of whom patented inventions that revolutionized their industries and changed people’s lives this year’s inductees included one other woman who was honored for patenting medical devices for low-resource settings She and her team developed HPR at IBM Research – Tokyo combining existing synthetic-speech technology with an understanding of HTML programming HPR enabled users to independently navigate the web and text links; describe graphical elements such as clickable maps; allow users to understand complex tables such as television listings; and differentiate content through devices like reading hyperlinks in a female voice and plain text in a male voice Asakawa’s contributions to accessibility technology have helped change how visually disabled individuals communicate and interact which includes a digital system to input and edit Braille; a network allowing Braille libraries to upload documents and books; aDesigner a disability simulator enabling sighted web developers to mimic the experience of blind users; and a collaboration between IBM Research and Carnegie Mellon University to use artificial intelligence and computer-aided vision to supply real-world accessibility through smartphone apps Asakawa earned her doctorate in engineering from the University of Tokyo She joined IBM in 1985 and was named an IBM fellow in 2009 She holds 20 patents and counts the SWE Achievement Award among her many honors She joins eight others — SWE members and SWE Achievement Award recipients — who have been inducted into the National Inventors Hall of Fame They are: Beatrice Hicks; Mildred Dresselhaus SWE Members Honored at National Inventors Hall of Fame Museum Member Spotlight: Maria Telkes, Biophysicist & Inventor Women Making News All Together is the blog of the Society of Women Engineers It’s up-to-date information and news about the Society and how our members are making a difference everyday “Being Japanese American: A JA Sourcebook for Nikkei & their Friends.” He says the expression meant he was "yellow on the outside white on the inside" -- someone born in Japan but not knowing its history and culture Now he thinks of himself as a "banana split," someone comfortable in both worlds His book is an instruction manual of sorts for folks like him looking to connect with both sides of their culture Reprinted from Being Japanese American: A JA Sourcebook for Nikkei Hapa...& Their Friends"  by Gil Asakawa with permission of Stone Bridge Press That’s what I’ve been told by people who know—Japanese Americans who’ve been involved in community activism all their lives I haven’t studied my roots in Japanese culture or even the history of Japanese Americans all my life I was told I was a banana: Yellow on the outside white on the inside.It’s true that I grew up among Caucasian friends—especially after my family moved to the States—and I wasn’t involved politically or socially with Asians or Asian causes But I like to think of myself as more than just a fruit with both my “yellow” and “white” sides sharing equal attention I know more about Japan than some other Japanese Americans I have vivid memories of Japan (albeit the Japan of thirty-five years ago before the first McDonald’s or KFC stormed the Yamato shores) I’ve also immersed myself in Japanese history and pop culture in recent years and I feel I’m as much a Japanese as I am an American My Japanese-language skills are still pretty wretched But that’s not uncommon for Japanese Americans My mother tried to teach my brother and me to read and write Japanese after our family moved to the States I learned every American obscenity I could and went around the summer of 1966 proudly enunciating some of the foulest language on Earth even though my eight-year-old mind had no idea what any of those words meant My idea of a cool four-letter word wasn’t “kana,” and my vocabulary didn’t include any Japanese alphabets my accent on the few words I know is pretty authentic but I can surprise an employee in a Japanese restaurant by sounding first-generation It’s my appearance that’s more American: rumpled jeans the loping way I walk (as if I’m moving to the beat of rock music in my head) with my head up and making eye contact with others Since I didn’t have Asian friends in grade school and high school and I hung around with my white friends and acted like any American kid I was only reminded of my different face and skin color (why do they call it “yellow” anyway I’m not yellow...) when racism periodically raised its ugly head and confronted me.Even while I was attending art school it didn’t occur to me that I might be a banana—or any ethnic flavor My work followed the paths of centuries of white Eurocentric artists from Leonardo da Vinci to Andy Warhol including the ukiyo‑e woodcut prints that influenced the French Impressionists I loved so well yet I never felt the urge to make “Japanese-inspired” art I was Japanese in all sorts of very visible ways—not the least of which was my skin I usually took off my shoes even in my friends’ homes as I got older and began to feel the need to get involved in the community around me I began to realize that the part of me that was the banana peel wanted to reach below the surface I wanted to be around others who looked like me (whether or not they were also bananas didn’t matter) I became involved in the local Japanese and Asian Pacific Islander communities joining non-profit organizations and participating in Asian Pacific American events These outlets helped me connect my internal and external selves and make sense of my self-image the interaction with others has helped me accept my split personality and feel comfortable in my own skin there are millions of people who are more Japanese than me I’ve also met JAs who are even more banana-like than me: people who can’t speak any Japanese without fumbling over the syllables who’ve never dined on Nihon meshi (Japanese food) and prefer hamburgers and fries and people who just have no clue that they have a wonderfully rich culture that’s deeply rooted in their DNA but I feel more aware of political issues and the pervasive racism that surrounds all people of color in our culture and why the No-No Boys deserve some respect I am a Nikkei—someone of Japanese descent living outside Japan.To be specific or “second-and-a-half generation,” because I was born in Japan to a Nisei father from Hawaii and an Issei mother from Hokkaido.I was eight years old when my family moved to the States and I became aware of being Japanese American I was just a Japanese kid who went to American schools I grew up in a bicultural world where I spoke English and attended American schools on U.S but my family always lived off-base so I played after school with Japanese pals The language at home was a mish-mash of Japanese and English I embraced the American side of my culture wholeheartedly I ate my fist McDonald’s hamburger (I had lived in pre-fast food Japan) and I became enchanted with The Man from U.N.C.L.E. I never learned to read or write despite my mom’s valiant efforts to get my older brother and me to study the grade school hiragana and katakana primers she’d brought across the Pacific I was too busy learning those English cuss words But—and here’s the part I think is consistent with many JAs—even though I stopped thinking in Japanese It was in the rice that we ate with our meals virtually every day of our lives and other all-American foods that mom served with it It was in the smelly things my mother sometimes cooked so stinky that I was embarrassed to bring my friends over It was in the ritual of taking our shoes off at the front door It was the fact that my mother would speak to my brothers and me mostly in Japanese and we would reply mostly in English Our brains had settled into a groove that allowed Japanese and American stuff to live side by side.In college I had a tiny rice cooker my mom had given me and I learned some of my mom’s recipes for authentic Japanese cooking But I also cherished learning to cook authentic Italian food from my roommate and dined on every kind of ethnic food available in New York City It never occurred to me that I was performing an internal balancing act where I had a weekly show playing country-rock music for the mostly East Coast students I gave myself a nickname that unwittingly reflected this duality: I would go on the air in my best “laidback FM disc jockey” impersonation the ‘Teriyaki Cosmic Cowboy.’ ” I wince when I think back on those days When my grandmother in Hokkaido called me in the middle of the night to wish me a happy birthday although I understood enough to know that she was berating me for not speaking Nihongo back to her I went back to bed feeling like a complete loser and a bit irritated that I had to be reminded that I had become “too American” and was losing touch with my own past It took the death of my father in the early 1990s to jolt me into being curious about my heritage When he was diagnosed with cancer (he had smoked all his life) it finally occurred to me to ask what life was like for him and his family to live in Honolulu when Pearl Harbor was bombed He was born and raised in Hawaii with his seven brothers and sisters It turns out my grandfather had decided in 1940 to take his family back to Japan where they lived in his hometown of Fukui on the west coast for the duration of the war This revelation sparked a fascination with wartime and postwar Japan for me as well as with the Japan of my early childhood And it also initiated my interest in how I’ve evolved but as a Japanese American.My Japanese isn’t much better today but at least now I appreciate my duality more than when I was a punk kid I’m involved in both Japanese and Japanese American organizations and events there is more of a Japanese presence infusing all aspects of my life Nowadays I cherish my Japanese heritage and value my American spirit I really wish I’d paid attention to those damn Nihongo primers–the “Dick and Jane” versions of Japanese language books I would love to have a job that sends me to Japan once or twice a year but there’s no chance without the ability to communicate in Japanese That’s one of the basic facts I’ve learned to accept as a Japanese American—I’m simply not Japanese I figured it would be a piece of cake—mochi cake Since I spend an awful lot of my time thinking about my heritage and have written a column about pop culture and politics from my JA perspective since 1998 I thought all the words for the book were already swimming around in my head But when it came time to actually write it I found that defining Japanese American culture is a lot more complicated than just looking Japanese and living in North America or living in the West and celebrating the traditions of the East The problem is Japanese Americans don’t necessarily have a lot in common with each other I’ve come to realize that there is a huge range in the amount of Japanese culture we incorporate into our lives The variety inherent in the JA community means that anything and everything counts whether we speak lots of Japanese or can’t even pronounce our family name “correctly.” We may share roots across the Pacific but our family experiences can be wildly divergent The one common theme that is in many accounts woven throughout the JA experience—the internment of 120,000 people of Japanese ancestry in the United States during World War II (along with the internment of Japanese Canadians and the expulsion and imprisonment in this country of Japanese Latin Americans)—can’t even be applied universally my mom was growing up in fear of American bombers over her hometown; my dad’s family who had just moved back to Japan from Hawaii were being heckled as “American spies” by Japanese kids Only the JA population along the western United States suffered the imprisonment that Congress in 1988 declared had been unconstitutional and based on nothing more than racial prejudice and war hysteria The fact of internment is a dividing line between JAs whose families date back to the prewar decades and those who’ve arrived in the States since World War II The JAs—especially the younger ones—with internment in their family past often want to explore that time But any Japanese who came to America after the war is loathe to relive the era because Japan’s loss and brutal conduct brought such shame to the entire society (although the Japanese government is still coming to terms with its wartime military atrocities).Still the scars of internment have affected the JA community at large I was spared because on both sides my parents’ families were in Japan during the war I’ve met lots of people who have internment in their family history Because of the enormous injustice of internment a significant number of JapaneseAmericans are often overlooked who arrived long after World War II who have immigrated recently to the United States for work or school Some have become naturalized citizens and many have had children here who are American citizens by birth These new Jas live with the same duality as those who have been in this country for generations—the duality of being Japanese to whatever extent in America This book needs to include these newer JAs and even sixth generations descended from mothers and great-grandparents who came to America to start a new life the fist who could truly be called Japanese Americans because they were American citizens by birth and because they were raised with very traditional values and Japanese culture at home while absorbing the American culture around them One of the ironies of immigrant communities maintaining their heritage is that the culture that’s kept alive and handed down through the generations becomes preserved as if it were in a time capsule the Japanese traditions they keep may be outdated and harken back to the Japan of the late 1800s or the early 1900s Even the language has changed in a century; some of the words commonly used by JAs are hopelessly old-fashioned like benjo for bathroom (Japanese today say otearai or toire) but the amount of each side that enriches our lives is as varied and dynamic as the American landscape Some of us look very Japanese and act very American thanks to increasing numbers of JAs who marry non-Japanese We can’t be pigeonholed as a group that shares the same cultural values and interest in our heritage Some Japanese Americans can speak perfect Japanese while others speak only enough to get by at family gatherings The purpose of this book is to explore those things that make us Japanese Americans: to celebrate the traditions that keep us connected as Japanese and also to note how we’re not Japanese This isn’t a comprehensive manual by any means Consider it a starting point for exploration of our (sometimes distant) collective Japanese roots and how we’ve adapted them to our Western upbringing The history of our community is rich and can’t be squeezed into a few chapters So let the resources at the back of the book guide you to further discoveries Many of them have inspired me in recent years I’ll take a loving look at our roots in Japan and at how Japanese culture still colors our day-today lives—from the pearls of wisdom of our grandmothers (obaachan) the words we grew up hearing (urusai for “noisy” and gambatte for “work hard”) and the constant presence of rice in our lives.For many of us these cultural echoes of Japan have started to fade and it’s important to keep them vivid if we are to appreciate our heritage For others who may have lost touch with our common culture or have grown up without Japanese accents in your lives I hope this book will be a worthy introduction to your roots and a starting point for your own journey Like the Nisei who first faced the dilemma of living within two cultures in America we aren’t always accepted as Americans One of the great things about being JA is that we can be proud of both our American and Japanese sides So we champion George Takei’s role as Sulu in Star Trek but we’re also proud as hell of the accomplishments of Ichiro Suzuki There’s still time to hold onto the best of what it means to be Japanese even as we strive to find our place as Americans Metrics details Cytoplasmic aggregation of TDP-43 characterizes degenerating neurons in most cases of amyotrophic lateral sclerosis (ALS) we develop an optogenetic TDP-43 variant (opTDP-43) whose multimerization status can be modulated in vivo through external light illumination Using the translucent zebrafish neuromuscular system we demonstrate that short-term light stimulation reversibly induces cytoplasmic opTDP-43 mislocalization leading to an axon outgrowth defect associated with myofiber denervation opTDP-43 forms pathological aggregates in the cytoplasm after longer-term illumination and seeds non-optogenetic TDP-43 aggregation we find that an ALS-linked mutation in the intrinsically disordered region (IDR) exacerbates the light-dependent opTDP-43 toxicity on locomotor behavior our results propose that IDR-mediated TDP-43 oligomerization triggers both acute and long-term pathologies of motor neurons which may be relevant to the pathogenesis and progression of ALS Despite its correlation with and causation of ALS the role of TDP-43 in ALS pathogenesis has been largely unknown at the mechanistic level interconversion of normal and toxic TDP-43 forms with spatiotemporal precision has not been achieved in animal models yet which is central for the understanding of TDP-43 toxicity in vivo we develop an optogenetic TDP-43 variant (opTDP-43) carrying a light-dependent oligomerization module of cryptochrome-2 attached to the IDR and analyze the mechanisms of TDP-43 toxicity in spinal motor neurons in vivo Transgenic expression and light stimulation of opTDP-43 in transparent zebrafish larvae show that oligomerization and aggregation of opTDP-43 is inducible and tunable in vivo by external light illumination short-term light illumination reversibly increases the cytoplasmic opTDP-43 pool and elevates myofiber denervation frequency in the absence of distinct aggregate formation longer chronic light stimulation eventually leads to accumulation of cytoplasmic opTDP-43 aggregates that further seed aggregation of non-optogenetic TDP-43 The sequential pathological alterations of spinal motor neurons triggered by opTDP-43 oligomerization may provide clues about how motor neuron degeneration progresses at both molecular and cellular levels in a prodromal phase of ALS a The structures of Tg[UAS:mRFP1-CRY2olig] and Tg[UAS:opTDP-43z] c Skeletal muscle of Tg[SAGFF73A] Tg[UAS:mRFP1-CRY2olig] and Tg[SAGFF73A] Tg[UAS:opTDP-43] fish from 28 hpf (0 min) to 31.5 hpf (210 hpf) The blue light was illuminated from 0 to 210 min Montages of single skeletal muscle cells expressing mRFP1-CRY2olig and opTDP-43z (dashed boxes) are shown on the right e The averaged change of opTDP-43z intensity in the cytoplasm (d) and nucleus (e) of skeletal muscle cells in Tg[SAGFF73A] Tg[UAS:opTDP-43z] fish during the illumination (N = 8 cells from the same animal) and the center of the error bars is the mean The asterisks indicate the statistically significant change in opTDP-43z fluorescence intensity at each time point in comparison to the opTDP-43z level at t = 0 and adjustments were not made for multiple comparisons f Immunofluorescence of the skeletal muscle of fish illuminated for 3.5 h using anti-RFP (for opTDP-43z) and anti-ubiquitin antibodies Arrows indicate the representative of opTDP-43z foci that are partially ubiquitinated showing that CRY2olig clustering is rapidly and reversibly controllable by light in the spinal motor neurons in vivo a The dorsal view of the spinal cord at the segment 14–17 levels of a Tg[SAIG213A] Tg[mnr2b-hs:Gal4] Tg[UAS:opTDP-43z] Tg[UAS:EGFP] quadruple transgenic fish A spinal motor neurons (SMN) and a Rohon-Beard sensory neuron (RB cell S) were highlighted with dashed boxes and analyzed in detail in (b c Montages of the spinal motor neurons and the RB cell during the light illumination The graphs show the fluorescent intensities of opTDP-43z along the dotted line drawn from the lateral (L) to medial edges (M) of the EGFP signal The blue arrows indicate the cytoplasmic increase of opTDP-43z The unit for y-axes are the same between 0 and 270 min d Montage of the spinal motor neuron expressing mRFP1-CRY2olig in the same illumination condition as in (a) e Cytoplasmic mislocalization of opTDP-43z in Tg[SAIG213A] Tg[UAS:opTDP-43z] fish injected with a plasmid harboring UAS regulated EGFP-tagged histone H2A variant H2afva The graphs show the fluorescent intensities of opTDP-43z and EGFP-H2afva along blue dotted line drawn across the cell axes Tg[SAIG213A] Tg[UAS:opTDP-43z] Tg[UAS:EGFP] fish with (BL and Tg[SAIG213A] Tg[UAS:mRFP1-CRY2olig] Tg[UAS:EGFP] fish with the stimulation (7 cells g CaPs (arrowhead) and other mnr2b-positive motor neurons in the segment 14 (f) and 13–17 (g) of Tg[SAIG213A] Tg[UAS:opTDP-43z] Tg[mnr2b-hs:EGFP-TDP43z] fish that was illuminated with a blue light during 28–32 hpf i Cytoplasmic shift of opTDP-43z and EGFP-TDP-43z in the CaP in (f) The fluorescence intensities of opTDP-43z (magenta) and EGFP-TDP-43z (green) were plotted along the blue dashed arrows (h) Images shown are enhanced to identify soma outline i The relative intensity of cytoplasmic signal (F(min)/F(max)) for opTDP-43z (magenta) and EGFP-TDP-43z (green) in each spinal segment demonstrating that light-induced opTDP-43z mislocalization occurs independently of the non-optogenetic TDP-43 pool These observations suggest that the perturbation of axon outgrowth by light-stimulated opTDP-43z is unlikely to be caused by loss of TDP-43 function due to nuclear TDP-43 reduction or depletion a A CaP motor axon of Tg[SAIG213A] Tg[UAS:EGFP] fish DCCT (green box) was magnified on the right secondary and tertial branchings were indicated in red growth rate (d) and fluctuation of axon terminal number (e) of DCCTs Results were obtained from 5 independent animals in opTDP-43z/Dark condition and otherwise from 3 animals The numbers in the histograms are total numbers of the cells examined f The lateral view of the trunk of Tg[SAIG213A] Tg[UAS:V2V] Tg[actc1b:tdT-chrnd] fish (left) and neuromuscular synapses of the DCCT (right) at 56 hpf The dashed yellow lines indicate the CaP axon shaft g Neuromuscular synapses of a DCCT in Tg[SAIG213A] Tg[UAS:opTDP-43z] Tg[UAS:V2V] Tg[actc1b:tdT-chrnd] fish at 56 hpf i Occurrence of Vamp2-Venus/ tdT-chrnd juxtaposition prior to illumination at 56 hpf (h) and fluctuation of terminal number with Vamp2-Venus/tdT-chrnd juxtaposition at 72 hpf (i) The numbers in the histograms show the total numbers of axon terminals (h) and DCCTs (i) that were examined Results were obtained from 4 independent animals in D/L condition and otherwise from 3 animals j Live imaging of DCCT neuromuscular synapses Yellow arrowheads indicate the neuromuscular synapses that were not present at 72 hpf and contact sites with the myotomal boundaries of CaPs Z-stacks are produced from 3D-rotated images made by Imaris to make the denervation events (arrowhead) clearly visible (j these observations show that the DCCT shrinkage is associated with myofiber denervation and that optogenetic TDP-43 oligomerization raises the denervation frequency a Chronic field illumination of unrestrained Tg[mnr2b-hs:EGFP-TDP43z] Tg[mnr2b-hs:opTDP-43h] fish by blue LED light b Live imaging of the spinal motor column from 48 to 120 hpf Horizontal dashed lines demarcate approximate positions of dorsal and ventral limits of the spinal cord c Cytoplasmic opTDP-43h foci colocalize with EGFP-TDP-43z d FRAP analyses of nuclear opTDP43h that had not been exposed to blue light (left Dark Pre) and cytoplasmic opTDP43h foci that had been induced by a 72-h blue light illumination (right Yellow dashed circles (Pre) include photobleached area and arrows indicate the bleached position The results were obtained from 6 cells in independent 6 animals for each condition and the center of the error bars is the average value c Chronically light-stimulated opTDP-43h (top) and opTDP-43hA315T (bottom) aggregate in the cytoplasm and seed EGFP-TDP-43z aggregation Arrowheads indicate opTDP-43 and opTDP-43hA315T aggregates that contain EGFP-TDP-43z d RT-PCR analysis for opTDP-43h and opTDP-43hA315T transcripts at 72 hpf e Failure rate of swimming bladder (SB) inflation of Tg[mnr2b-hs:EGFP-TDP43z] (none) Tg[mnr2b-hs:EGFP-TDP43z] Tg[mnr2b-hs:opTDP-43h] and Tg[mnr2b-hs:EGFP-TDP43z] Tg[mnr2b-hs:opTDP-43hA315T] (A315T) larvae at 120–144 hpf The average failure rates were defined from at least three independent assays where six or more fish were illuminated (Source data are provided as a Source Data file) SB inflation failure was not observed when fish were raised under normal dark light cycles (N > 100 for each) f–i Immunofluorescence analyses of phospo-TDP-43 (f) TIAL1 (h) against cytoplasmic opTDP-43h and opTDP-43hA315T aggregates at 120 hpf twenty cells with distinct opTDP-43h or opTDP-43hA315T aggregates were examined for each of three independent fish j Stability of opTDP-43h or opTDP-43hA315T Fluorescence intensities of opTDP-43h or opTDP-43hA315T (RFP) relative to EGFP-TDP-43z (GFP) were examined at 48 hpf and 72 hpf in the same set of 64 cells from three independent animals and imply that the A315T mutation causes toxicity by generating stable TDP-43 oligomers through modulating IDR-mediated oligomerization TDP-43 forms oligomers via its N-terminus and is primarily localized in the nucleus Spinal motor neurons keep the cytoplasmic concentration of TDP-43 oligomers at a low level to prevent them from turning into toxic irreversible oligomers mediated by the C-terminus IDRs (toxic “knots”) which possess competence for developing into pathological TDP-43 aggregates CRY2olig-driven opTDP-43 oligomerization promotes pathological change of the motor neurons such as axon retraction associated with myofiber denervation prior to accumulation of distinct cytoplasmic aggregates Whether CRY2olig-diriven opTDP-43 aggregates are toxic to motor neurons and whether CRY2olig-diriven aggregates eventually deplete endogenous nuclear TDP-43 pools are unknown thereby contributing to the acute toxicity that involves neuromuscular synapse destabilization could identify such potentially multiple pathogenic origins in the future which is likely a remnant of such compensatory collateral reinnervation events we found by live imaging of axon collateral that an innervation territory of healthy spinal motor neurons is determined by a balance between assembly and disassembly of neuromuscular synapses in zebrafish We further discovered that optogenetic opTDP-43 oligomerization could tip the balance toward disassembly and decrease the total collateral length once a cellular concentration of IDR-mediated TDP-43 oligomers reaches a critical level a spinal motor neuron would begin to reduce its motor unit size through repetition of incomplete denervation/reinnervation cycles Such neurons would also be defective in complementing damaged neighboring motor units through collateral reinnervation which would accelerate the manifestation of motor decline We envision that opTDP-43 allows for approaching the mechanisms underlying such dynamic innervation/reinnervation balancing of spinal motor axons in health and TDP-43-associated pathology as well as for interrogating how not only motor neurons but also diverse types of surrounding cells combined with the feasibility of high-throughput whole organism chemical screening in zebrafish opTDP-43-mediated motor neuron pathogenesis should be extended for exploring small molecules that restore a normal denervation/reinnervation balance for spinal motor neurons which might serve as drugs for ALS and other TDP-43 proteinopathy Fish were raised under 12:12 light-dark (L/D) cycles during the first 5 days after birth Tg[mnr2b-hs:opTDP-43h] and Tg[mnr2b-hs:opTDP-43hA315T] lines were generated by the same procedure except that opTDP-43h and opTDP-43h A315T were used The opTDP-43h consists of the zebrafish-codon-optimized human TDP-43 that is fused directly to the zebrafish-codon-optimized mRFP1 at the N-terminus and indirectly to CRY2olig via the linker peptide TRDISIE opTDP-43hA315T is identical to opTDP-43h except the A315T mutation (GCT>ACT) All transgenic lines were created via Tol2-mediated transgenesis Twenty-five pg of these plasmids were injected into the embryos at the one-cell stage For the generation of tardbp and tardbpl knockout fish, target sequences for Cas9-mediated cleavage were searched by CRISPRscan63 The target sequences CAAGACTTAAAAGACTACTTcgg and CAAGACTTAAAAGACTACTTcgg where the protospacer adjacent motifs (PAMs) are indicated by lower cases were chosen for the generation of tardbp-n115 and tardbpl-n94 alleles hSpCas9 was in vitro-transcribed with mMESSAGE mMACHINE Kit (Thermo Fisher Scientific AM1340) by using pCS2 + hSpCas9 plasmid as a template (a gift from Masato Kinoshita Wild type embryos were injected with 25 pg of sgRNA and 300 pg of hSpCas9 mRNA at the one-cell stage For the expression of human and zebrafish TDP-43 and its derivatives via mRNA injection the open reading frames of zebrafish tardbp (TDP-43z) zebrafish-codon optimized human TDP-43 (TDP-43h) mRFP1-tagged zebrafish tardbp (mRFP1-TDP-43z) and opTDP-43z was cloned into pCS2+ vector in vitro-transcribed with mMESSAGE mMACHINE Kit we injected varied amount of TDP-43z mRNA into the offspring obtained from incrosses of parental zebrafish carrying homozygous tardbp-n115 and heterozygous tardbpl-n94 mutation or heterozygous tardbp-n115 and homozygous tardbpl-n94 mutation at the one cell stage After investigating the presence or absence of blood flow at 36–48 hpf all fish were subjected individually to genotyping for tardbp-n115 and tardbpl-n94 alleles The uninjected tardbp-n115 tardbpl-n94 double homozygotes displayed a swollen heart that was beating but the blood cells were completely stacked on the yolk surface and cannot reach the heart An injection of 300 ng of TDP-43z mRNA was the most effect effective in restoring blood flow (up to 40% of the double homozygotes) of the double homozygotes with a minimum developmental abnormality due to overexpression we scored that the blood flow was “rescued” when any blood cell flowing through the beating heart was observed The function of TDP-43h and TDP-43 derivatives were tested by the microinjection of 300 ng mRNA each The tardbpl-n115 allele was identified by performing Heteroduplex Mobility Assay (HMA) against PCR product obtained with a primer pair: tardbp-6F3 (5′-gcc aga taa taa gag gaa gat gga-3′) and tardbpl-6R3 (5′-tga cag tac aaa gac aaa cac cac-3′) The tardbpl-n94 allele was similarity identified by using a primer pair: tardbpl-4F2 (5′-caa tca ctg aat gaa tgc act ttt-3′) and tardbpl-4R2 (5′-gtt tgc tta tac taa cct gca cca-3′) Short-term (<4 h) light stimulations of mRFP1-CRY2olig and opTDP-43z were carried out by embedding fish in the 0.8–1% low-melting agarose (NuSieve® GTG® Agarose Lonza) and conducting confocal scanning with the laser with 473 nm wave length using an Olympus FV1200 microscope The average optical power of the confocal laser was ~44.66 µW per cm2 and the dish was placed on a blue LED panel The intensity of blue LED light that reached the E3 buffer was ~0.69 mW per cm2 and its wavelength peaked at 456 nm Zebrafish larvae were fixed for overnight in PBT (Phosphate Buffered Saline with 0.25% Triton X-100) containing 4% paraformaldehyde (#15710 fish were incubated at 70 °C in 150 mM Tris-HCl permeabilized in PBT with 0.025% trypsin and 0.01% EDTA for an hour on ice and treated with antibodies after an hour of blocking with PBT with 1% bovine serum albumin 2% normal goat serum and 1% dimethyl sulfoxide For the mono- and poly-ubiquitinated protein staining Tg[SAGFF73A] Tg[UAS:opTDP-43z] fish at 31.5 hpf that had illuminated with a blue light were taken out from the agarose and immediately subjected to immunofluorescence The mouse monoclonal antibody for mono- and polyubiquitinate conjugates (FK2 1:100) and goat anti-mouse IgG Alexa Fluor 488 (Molecular Probes 1:1000) were used as primary and secondary antibodies For the detection of opTDP-43z and opTDP-43h the rabbit anti-RFP polyclonal antibody (pAb 1:100) and goat anti-rabbit IgG Alexa Fluor 633 (Molecular Probes Mouse anti-phospho TDP-43 (pS409/410) (TIP-PTD-MO1 1:100) and mouse anti-human G3BP antibody (611127 1:100) were detcted by goat anti-mouse IgG Alexa Fluor 488 (Molecular Probes 1:100) was detected by goat anti-rabbit IgG Alexa Fluor 488 (Molecular Probes All other images were acquired from live fish embedded in 0.8–1% low-melting agarose (NuSieve® GTG® Agarose 3010-035) with Olympus FV1200 laser confocal microscope with ×20 water immersion objective (NA1.0) fish were raised in embryonic buffer containing 0.003% (w/v) N-Phenylthiourea (SIGMA Confocal images were acquired as serial sections along the z-axis and analyzed with Olympus Fluoview Ver2.1b Viewer and Image J and processed for presentation with Adobe Photoshop CS6 The axon length and branching frequency were measured by Imaris Filament Tracer Morphological analyses of CaPs were restricted to the spinal segment 14–17 before 50 hpf and to 13–17 during 56–72 hpf A neurite with more than 5 µm of length was counted as branch FRAP experiments were performed on Olympus FV1200 laser confocal microscope with ×20 water immersion objective (NA1.0) Photobleaching of opTDP-43h was conducted by scanning of a region of interest (ROI) set in the nucleus or cytoplasm which was determined using EGFP-TDP-43z signal as a reference with 599-nm laser at 100% intensity for 5 s Fluorescence recovery was monitored at 10 min intervals for 30 min the shape of the nucleus was determined based on EGFP-TDP-43z signal and the opTDP-43h signal included in the nuclear ROI was used to estimate the photobleaching due to the post-bleach imaging for fluorescence recovery for cytoplasmic opTDP-43h foci bleaching (BL) cells with at least two distant cytoplasmic foci were chosen and the one that was not beached was used to estimate the photobleaching during the post-bleach imaging for fluorescence recovery The recovery of opTDP-43h signal was determined by subtracting the signal reduction caused by the post-bleaching imaging The total RNA was prepared from Tg[mnr2b-hs:EGFP-TDP43z] (none) Tg[mnr2b-hs:EGFP-TDP43z] Tg[mnr2b-hs:opTDP-43h] (opTDP-43) and Tg[mnr2b-hs:EGFP-TDP43z] Tg[mnr2b-hs:opTDP-43hA315T] (A315T) larvae at 72 hpf (17 larvae each) by homogenizing in 1 ml of Trizol Reagent (Life Technologies) Three µg of the total RNA is used for cDNA synthesis using oligo dT (SuperScriptn®III First-Strand opTDP-43h and opTDP-43hA315T were detected by a primer pair against the zebrafish codon-optimized mRFP1: zmRFP1-123f (5′-TCA GAC AGC TAA ACT GAA GGT CAC-3′) and zmRFP1-633r (5′-GAC GAT GGT ATA GTC TTC GTT GTG-3′) EGFP-TDP-43z was detected by a primer: EGFP-f2s (5′-CAC ATG AAG CAG CAC GAC TTC T-3′) and EGFP-r5s (5′-ACG TTG TGG CTG TTG TAG TTG T-3′) zfand5b expression was detected by a primer pair: zfand5b–133f (5′-ATA GTA CAC ACC GAA ACG GAC AC-3′) and zfand5b-772r (5′-TTA TAT TCT CTG GAT TTT ATC GGC-3′) The z-stack images of the spinal motor column were first created by Sum Slices function of Image J the ROIs covering the somas of individual spinal motor neurons were determined based on the contour of weak cytosolic fluorescence of EGFP-TDP-43z that became clearly visible by signal enhancement and EGFP-TDP-43z in the individual ROI were measured by Image J software Sample sizes are reported in figure legends Further information on research design is available in the Nature Research Reporting Summary linked to this article TDP-43 immunoreactivity in neuronal inclusions in familial amyotrophic lateral sclerosis with or without SOD1 gene mutation TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration Functional and dynamic polymerization of the ALS-linked protein TDP-43 antagonizes its pathologic aggregation TDP-43 dimerizes in human cells in culture The dual functions of the extreme N-terminus of TDP-43 in regulating its biological activity and inclusion formation ALS Mutations disrupt phase separation mediated by alpha-helical structure in the TDP-43 low-complexity C-terminal domain and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity Accelerated disease onset with stabilized familial amyotrophic lateral sclerosis (ALS)-linked mutant TDP-43 proteins Role of selected mutations in the Q/N rich region of TDP-43 in EGFP-12xQ/N-induced aggregate formation Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity A single N-terminal phosphomimic disrupts TDP-43 polymerization The N-terminal dimerization is required for TDP-43 splicing activity Mutant TDP-43 causes early-stage dose-dependent motor neuron degeneration in a TARDBP knockin mouse model of ALS Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice Progressive motor weakness in transgenic mice expressing human TDP-43 TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration Wild-type human TDP-43 expression causes TDP-43 phosphorylation Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice Pathological TDP-43 changes in Betz cells differ from those in bulbar and spinal alpha-motoneurons in sporadic amyotrophic lateral sclerosis Spatiotemporal control of intracellular phase transitions using light-activated optoDroplets RNA Binding antagonizes neurotoxic phase transitions of TDP-43 Active nuclear import and passive nuclear export are the primary determinants of TDP-43 localization Disturbance of nuclear and cytoplasmic TAR DNA-binding protein (TDP-43) induces disease-like redistribution Protocadherin-mediated cell repulsion controls the central topography and efferent projections of the abducens nucleus Intrinsic disorder in proteins involved in amyotrophic lateral sclerosis YB-1 recruitment to stress granules in zebrafish cells reveals a differential adaptive response to stress Zebrafish P54 RNA helicases are cytoplasmic granule residents that are required for development and stress resilience Disease causing mutants of TDP-43 nucleic acid binding domains are resistant to aggregation and have increased stability and half-life ALS-implicated protein TDP-43 sustains levels of STMN2 a mediator of motor neuron growth and repair Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43 Identification of neuronal RNA targets of TDP-43-containing ribonucleoprotein complexes Characterizing the RNA targets and position-dependent splicing regulation by TDP-43 RNA targets of TDP-43 identified by UV-CLIP are deregulated in ALS Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response TDP-43 extracted from frontotemporal lobar degeneration subject brains displays distinct aggregate assemblies and neurotoxic effects reflecting disease progression rates Lumbar motoneurons of man: I) number and diameter histogram of alpha and gamma axons of ventral root Age-related reduction in 8th cervical ventral nerve root myelinated fiber diameters and numbers in man The numbers of limb motor neurons in the human lumbosacral cord throughout life Age-dependent motor unit remodelling in human limb muscles Motor innervation and fiber type pattern in amyotrophic lateral sclerosis and in Charcot-Marie-Tooth disease CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo Download references The authors would like to thank Drs Keiko Imamura Shin Kwak for valuable discussions and Kawakami lab members for generous support This work was supported by SERIKA FUND (K.A.) The Nakabayashi Trust For ALS Research (K.A.) THE KATO MEMORIAL TRUST FOR NAMBYO RESEARCH (K.A.) Daiichi-Sankyo Foundation of Life Science (K.A.) National BioResource Project from Japan Agency for Medical Research and Development (AMED) (K.K.) and KAKENHI Grant Numbers JP15H02370 (K.K.) Division of Molecular and Developmental Biology Graduate University for Advanced Studies (SOKENDAI) analyzed the data and wrote the manuscript with inputs from H.H A patent application covering this work (application no PCT/JP2019/037829) has been filed in which Inter-University Research Institute Corporation Research Organization of Information and Systems Peer review information Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work 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/s41467-020-14815-x Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Cellular and Molecular Neurobiology (2024) Cellular and Molecular Neurobiology (2023) Sign up for the Nature Briefing newsletter — what matters in science Author Gil Asakawa’s books are a celebration of Japanese American history and heritage Of the three books Denver-based journalist Gil Asakawa has written — 1991’s “The Toy Book” (with his pal Leland Rucker) and 2015’s “Being Japanese American: A Sourcebook for Nikkei Hapa … and Their Friends” — it’s likely safe to say that his new one is closest to his heart Enjoying that last bit of a fine Japanese meal That’s because the foodophile’s stomach is heart-adjacent Let’s Eat!: A Tasty History of Japanese Food in America” (p-ISBN 978-1-61172-068-6; SRP $18.95) is Asakawa’s informative and chatty exploration-cum memoir of the sundry Japanese foods he grew up with mixed with his memories of first encounters with those victuals and his historical research on how many of those foods originated with some actually reaching these shores to become as American as pizza pie “I really had a lot of fun writing it,” Asakawa told the Pacific Citizen for which he has in the past served on its Editorial Board “I think it’s fascinating and important to cover not just kind of the tradition in the history of Japanese food in Japan but how it adapted to suit the tastes of Americans and follow how it became popular and why it became popular,” Asakawa continued he gives credit to the restaurant chain Benihana “is what made Japanese food safe for Middle America.” Although it might simply appear to be a case of “write what you know,” since Asakawa is one of those gourmands who regularly posts photos of his latest feasts of all kinds of cuisines on his social media feeds turning his particular passion for Japanese — and Japanese American — foods into a book was despite having a Hokkaido-born Japanese mother and Hawaii-born Japanese American father and I learned a lot of stuff to write ‘Tabemasho!’” Asakawa said “I was surprised at how much I didn’t know about the food that I love.” In other words there is still something about Asakawa’s deep dive into learning about Japanese food that you probably did not know Part of Asakawa’s journey into Nihonshoku includes “foreign” foods like ramen and curry — arguably even tonkatsu —that have become part of the modern menu of foods Japanese people eat nowadays Writing and blogging about Japanese and Japanese American cuisine is nothing new for Asakawa as evidenced by this Pacific Citizen column from 2014 “One of the things that I’ve learned about Japanese food in general is that a lot of the things that we think of as Japanese food didn’t originate in Japan and are not necessarily traditional in the historical sense,” Asakawa pointed out curry is so popular in Japan that many people there eat it at least once a week But Japanese curry is not like curry from India The Japanee “took it from the British and then adapted it for the Japanese palette.” one of the items Asakawa used in his research for “Tabemasho!” was a 1952 menu from Los Angeles restaurant Imperial Gardens that provides a snapshot of what Japanese food used to mean to people in America The restaurant’s menu “only featured three kinds of food,” said Asakawa not too far removed from the end of World War II when what most non-Japanese Americans knew of Japanese food was what American GIs coming back from the occupation of Japan remembered eating “It’s hard to find a Japanese restaurant that will serve sukiyaki anymore — but that used to be the standard.” In “Tabemasho!” Asakawa once a former music critic for Denver’s alt-weekly Westword relays that the erstwhile popularity of sukiyaki the dish is why the 1963 No “Sukiyaki,” aka “Ue o Muite Arukō,” got its name In “Tabemasho!” Asakawa also gives ink to hugely popular Japanese American dishes — spam musubi the California roll (with avocado as an ingredient) and mochi ice cream for example — that might be difficult to find on any menu in Japan those are examples of what were in actuality fusion cuisine (before that became a label) borne of the necessity of using local ingredients whatever was available or plain old Yankee ingenuity Part of Asakawa’s fascination with Japanese food also comes from being old enough to remember when Japanese food was a punchline Gil Asakawa captures a photo of his meal before digging in when supermarkets selling prepackaged sushi are ubiquitous some young people might find that hard to believe But Asakawa remembers how in the 1985 movie “The Breakfast Club,” the character played by Molly Ringwald was mocked by Judd Nelson’s character for bringing sushi for lunch since the movie’s writer-director was John Hughes who was also repugnantly responsible for Long Duk Dong in 1984’s “Sixteen Candles.”) Fox was featured on the cover of Esquire magazine in the late 1980s with a plate of sushi sparking conversation about its growing popularity in America Fox was on the cover of Esquire magazine eating a plate of sushi.” The image of Japanese food — for the majority of white Americans But Fox and Esquire can only claim partial credit for the changing perception of Japanese food in America Originally developed in the 1950s by Momofuku Ando “Because it was so damn cheap,” both versions especially the square noodle brick version with hungry and impoverished college students — no doubt still true — “even though it wasn’t the world’s greatest ramen.” It may have been the unintentional gateway to seeking out better ramen have been getting rated and reviewed by “ramen connoisseurs” on social media sites Combined with the continued soft power appeal of Hello Kitty the popularity of Japanese baseball players like Shohei Ohtani and progression of acceptance through the decades of Japanese foods from sukiyaki to sushi to ramen Asakawa’s timing for “Tabemasho!” is a recipe for success As for what Japanese food item might be next to find American fans Asakawa knows it would be foolhardy to hazard a guess though he thinks yakisoba might have a chance to cross over it’s far easier to predict the foods that will probably never stand a chance of crossing over Natto — mucilaginous and funky fermented soybeans — remains another unlikely candidate the beverage had to be rebranded as Calpico which he says has a striking resemblance to what you’d find in your cat’s litterbox karintō’s coloring and sweetness come from a brown sugar coating Asakawa just hopes that anyone who reads “Tabemasho!” finishes with a couple of outcomes “And I hope it makes them want to try different kinds of Japanese food.” The Asakawa family at Benihana restaurant in Virginia where they enjoyed a meal with a family friend ready to pounce with my hashi.” (Photo: Gil Asakawa) President of the Asian Development Bank (ADB) Masatsugu Asakawa has written an article on finance for net-zero transition The following is the full text of the article Hanoi (VNA) - President of the Asian Development Bank (ADB) Masatsugu Asakawa has written an article on finance for net-zero transition The path we chart now will determine the climate legacy we leave for future generations./ Deputy Prime Minister Tran Luu Quang on July 31 called for acceleration of Asian Development Bank (ADB) financed projects while hosting ADB Country Director for Vietnam Shantanu Chakraborty in Hanoi Country Director of the Asian Development Bank (ADB) for Vietnam Shantanu Chakraborty has expressed his impression of the Southeast Asian nation’s economic growth of 6.4% in the first half of this year The Asian Development Bank (ADB) has revised its economic growth forecast for developing Asia slightly up thanks to stronger domestic demand and export growth is currently being cared for before being released back into its natural habitat With a processing capacity of 2,250 tonnes of waste per day and night and 37MW of power generated Seraphin is designed to process all waste collected at the Xuan Son landfill where an average of 1,500 tonnes of waste from 12 districts and Son Tay township is received daily Promoting nature-based tourism linked to wildlife conservation is believed to be essential for sustainable development in the near future Conservation and Creature Development under Phong Nha – Ke Bang National Park in the central province of Quang Binh has reported the voluntary handover of endangered the MAG has carried out mine clearance on an area of 135,000 sq.m safely removing 325 dangerous explosive items Vietnam’s energy sector must strike a balance of ensuring robust economic growth and national energy security while simultaneously advancing the transition to green clean energy and reducing greenhouse gas emissions in line with global trends the Central Highlands province of Gia Lai have reported the presence of a flock of Asian open-bill storks (Anastomus oscitans) a rare and endangered species listed in Vietnam’s Red Data Book are around seven months old and were bred in captivity at Nakhon Ratchasima Zoo following a mandatory quarantine period at the Saigon Zoo and Botanical Gardens and now are eligible for relocation to Tram Chim for conservation and growth The fourth Partnering for Green Growth and the Global Goals 2030 (P4G) Summit in Hanoi reached five major areas of consensus including pooling finance for green transition through public-private partnerships and innovative financial policies advancing research in green technological solutions; transforming agricultural and food systems for sustainability developing a skilled workforce in sci-tech and innovation; and pursuing an efficient Vietnam is pioneering a new model of cooperation a country’s value lies not in its GDP but in its concrete climate actions and collaborative spirit Vietnam’s vision of fair and inclusive multilateralism could chart a new path - much-needed and hopeful - for the global climate order a large-scale waste-to-energy facility using Japanese technology has been established in the northern province of Bac Ninh a Johkasou system has been installed in Ha Long Bay the northern coastal province of Quang Ninh through Japanese non-refundable aid and support from the Japan International Cooperation Agency (JICA) Vietnam is accelerating strategic breakthroughs and making the best preparations for a development path that is rapid From the night of April 12 to the morning of April 13 two forest fires occurred in Ha Long city's Dai Yen ward widely known as the country’s “capital of conservation,” is currently home to thousands of endangered and rare wild animals Its conservation programmes are recognised at both regional and global levels including those to protect endangered primates Vietnam's hosting the fourth Partnership for Green Growth and the Global Goals 2030 (P4G) Summit reflects its push to meet climate commitments and shift its growth model with global support Among the 30 countries analysed in the survey 11 were identified as more exposed to climate risks from the macroeconomic perspective: Afghanistan Vietnam’s agriculture sector has great potential to shift towards low-carbon emission production The Government has instructed the People's Committees of Hanoi and HCM City to urgently implement measures aimed at achieving safe Air Quality Index (AQI) levels within five years These are the first two companies in Vietnam to successfully achieved carbon neutrality in accordance with PAS 2060:2014 standards the Can Gio Island mangrove forest became Vietnam's first Biosphere Reserve recognised by UNESCO in 2000 Assessments have revealed a high level of biodiversity and home to the largest and most beautiful concentrated mangrove forest in Southeast Asia 2008 by the Ministry of Information and Communications Email: vietnamplus@vnanet.vn Reproduction in any form is prohibited without written consent the content you were looking for was not found Sorry, we couldn’t find that content. 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Read our privacy policy for more information.Accept and Close bluesy lament Nemuru No Ga Kowai (Scared to Go to Sleep) there’s brass-backed R&B and a sad but swinging re-working of Oscar Brown Jr’s Rags and Old Iron Lauren Warden-Rodgers an academic adviser who has worked with more than 220 students in the Department of Mechanical Engineering is joining the Office of the Vice Provost for Education as assistant director of the newly organized Student Academic Success group assistant vice provost for Student Academic Success and Equity processes and partnerships designed to support students in achieving their full academic potential She will work on academic adviser professional development efforts the ReCharge program in partnership with Enrollment Services and the Division of Student Affairs and with students experiencing challenges making progress toward their degree Warden-Rodgers will start her new position Jan Masatsugu Asakawa, a special advisor to Prime Minister Shinzo Abe and the Ministry of Finance, has been unanimously elected as the next president of the Manila-based Asian Development Bank (ADB) by the board of governors to serve the unexpired term of Takehiko Nakao Asakawa’s extensive and diverse experience in international finance and development will serve ADB well in pursuing its vision of a prosperous and sustainable Asia and the Pacific,” said Hong Nam-Ki the Republic of Korea’s deputy prime minister and minister of economy and finance who also chairs the bank’s board of governors “The ADB Board of Governors looks forward to working with Mr ADB said it “is committed to achieving a prosperous while sustaining its efforts to eradicate extreme poverty it made commitments of new loans and grants amounting to $21.6 billion it is owned by 68 members—49 from the region.”  In an interview with Sankei Shimbun before the announcement Asakawa expressed his vision for ADB to introduce a common Asian currency to encourage trade in the region “The main currency used in trade is often not the local currency To achieve the global integration of trade and financial markets we need to start using local currency,” he explained He explained that the currency doesn’t have to another Asian currency like the Japanese yen but instead a common currency — “the Asian Common Unit Asakawa specified that this change “can’t happen overnight,” however He was clear about the potential benefits to the stability in the market “The Asian currencies now are very dependent on the exchange rate with the dollar and perhaps also move the interest [to Asia].” Asakawa was clear that his first order of business as ADB president would be tackling poverty and the income inequality is widening,” therefore he advocated for sustaining economic growth “It’s important that we invest in the enrichment of soft society infrastructure such as education and the welfare system,” he explained Asakawa has also set the concrete long-term aims of promoting gender equality and a policy against climate change The former Japanese statesman vowed to listen to the opinions of all ADB members “I play to have an attentive ear to the opinions of all 68 countries and territories take into account the singular circumstances He likened his management style to that of a medical doctor: “In Asia it’s an issue which the world has never experienced before… I [therefore] would like to contribute by being like the ‘Family Doctor’ of Asia should other countries in the world be affected by a similar problem.” Asakawa has held senior positions in his four-decade career at the Ministry of Finance of Japan He was vice minister of finance for international affairs he was finance deputy for the G20 Osaka Summit and the G20 Finance Ministers and Central Bank Governors meeting in Fukuoka As executive assistant to the then-Prime Minister Taro Aso he took part in the first G20 Leaders’ Summit Meeting  in the immediate aftermath of the Global Financial Crisis Asakawa chaired the committee on fiscal affairs of Organisation for Economic Co-operation and Development You must be logged in to post a comment ' + scriptOptions._localizedStrings.webview_notification_text + ' " + scriptOptions._localizedStrings.redirect_overlay_title + " " + scriptOptions._localizedStrings.redirect_overlay_text + "