Your browser does not support JavaScript, or it is disabled．Please check the site policy for more information Editorial The judiciary is facing a significant question about its integrity If it is revealed that the presiding judge in a trial secretly met with a party interested in the case and shared details about the trial’s progress and his desired outcome It is imperative for the judiciary to address this question earnestly and uphold its commitment to fairness and integrity The Tokyo High Court dismissed a lawsuit on Jan 31 brought by former defendants in the so-called Sunagawa incident in 1957 whose fines were finalized about 60 years ago claimed their right to a fair trial had been violated and sought compensation from the government including then-Meiji University student Gentaro Tsuchiya were indicted under a special criminal law based on the Japan-U.S Security Treaty for entering the grounds of the former U.S The Tokyo District Court declared them not guilty and the special criminal law is invalid,” but the Supreme Court overturned the decision The verdict with a fine of 2,000 yen was finalized later official documents in this century that Kotaro Tanaka the chief justice of the Supreme Court at the time the high court recognized that during three meetings with the ambassador and other officials Tanaka discussed the possible timing of the top court decision and expressed his hope that the top court ruling would be a unanimous decision by the 15 justices The court acknowledged that Tanaka’s actions were “inappropriate” because they risked raising doubts about the trial’s fairness the court also stated that “there is no convincing argument that the circumstances made it difficult to expect a fair and objective trial.” While the high court’s decision is more receptive to the plaintiffs’ complaint than the ruling by the district court which avoided directly evaluating Tanaka’s actions Acknowledging the impropriety of the chief justice’s behavior while simultaneously concluding it didn’t affect the trial’s fairness creates a logical inconsistency government was closely watching how the Supreme Court would address the district court’s decision that the presence of U.S The fact that the chief justice himself communicated information about the proceedings to the U.S side raised serious doubts about the fairness of the trial and the independence of the judiciary not only for those judged but also for the general public The Supreme Court’s decision on the Sunagawa incident is known as a precedent that avoided a clear judicial review of the constitutionality of the security treaty Only by properly evaluating the historical facts behind it can the judiciary regain trust which protects the Supreme Court and Tanaka demonstrates how unfair the judiciary is,” mentioning his plan to appeal The Supreme Court has established standards that judges should not only be fair but also appear impartial and neutral by exercising proper self-restraint and autonomy How it decides this case from that standpoint will be closely monitored for clues to its commitment to this principle The top court must directly address issues causing doubts about judicial integrity without dismissing them for formal reasons EDITORIAL: Top court chief’s behavior during Sunagawa case crossed the line EDITORIAL: Yashio’s sinkhole shows the urgent need to fix aging infrastructure EDITORIAL: Trump’s tariff bluster threatens trade war and economic chaos world still must seek to stem global warming EDITORIAL: Dentsu held accountable for Tokyo Olympic bid-rigging gender report runs afoul of its principles Information on the latest cherry blossom conditions Please right click to use your browser’s translation function.) A series based on diplomatic documents declassified by Japan’s Foreign Ministry Here is a collection of first-hand accounts by “hibakusha” atomic bomb survivors chefs and others involved in the field of food introduce their special recipes intertwined with their paths in life A series about Japanese-Americans and their memories of World War II In-house News and Messages No reproduction or republication without written permission Asan Woori Bank Woori Won's Kim Dan-bi poses with Natsuki Sunagawa during an interview with the JoongAng Ilbo at the team’s clubhouse in central Seoul on Oct prepares to shoot during a 2023-24 WKBL Championship game against Cheongju KB Stars at Asan Yi Sun-sin Gymnasium in Asan Spots We are pleased to introduce "Everybody's Factory," a new initiative of the cosmetic brand SHIRO This is SHIRO's new manufacturing base as well as a complex facility based on the themes of manufacturing and we will introduce details of each area where SHIRO's deep commitment can be felt The company is known throughout Japan for its lifestyle products that utilize natural materials from Japan and abroad and draw out the inherent power of the materials "Everybody's Factory" was created on the former site of Eyo Elementary School in Sunagawa City It houses a factory where SHIRO products are manufactured as well as a children's playground and a small library The space is decorated with white as its precious color and the gentle warmth of wood creating an open and free space where people can spend their time freely and thoughtfully we will introduce you to the "factory area" where SHIRO products are manufactured The "factory area" includes the R&D room where visitors can observe a series of manufacturing processes through glass windows visitors can experience creating their own unique fragrance You can choose a special bottle or a bottle left over from past production processes blend your favorite fragrance from several fragrances and create your one and only "My Fragrance" in the world In addition to the standard fragrances of "Savon," "White Lily," "White Tea," "Earl Grey," and "Kinmokusei," you can freely choose a fragrance that matches the season from the limited edition fragrances of the past The "SHIRO Sunagawa Main Store," originally located in Sunagawa City has relocated and opened as the new "SHIRO Shop This fragrance is characterized by its soft scent which contains the aroma of various fruits encountered in Sorachi SHIRO CAFE" is a place where one can spend time while enjoying coffee and food The first menu features a number of dishes that can only be enjoyed here such as pancakes made with yellow cedar seed and spaghetti with sake lees from the Kobayashi Sake Brewery in Kuriyama-cho and yuzu citrus from Kochi The restaurant also boasts freshly baked pizzas that allow you to simply savor the natural ingredients and are hand-cooked by artisans in a wood-fired pizza oven Spaghetti with Sake Dregs from Kobayashi Sake Brewery and Yuzu from Kochi The "Kids' Space," with a jungle net stretched across the ceiling is designed for both adults and children to spend time together To prevent children's voices from echoing too loudly the ceiling is covered with sound-absorbing material made from upcycled old store staff uniforms The large tables in the "lounge area" are available for both single and multiple guests to spend time resting Counter seating with a large window opening to the west allows visitors to relax and enjoy the view of the Pine Silli Mountains there is a stairway bench and a bookshelf with 2,400 books and magazines visitors can view archived products from the days of LAUREL Minna no Factory" also takes the outdoor environment into consideration Through the "Seed Workshop," which aims to protect and nurture the local Sunagawa native species seedlings grown together with local people are planted and native grasses are left to grow wild in the plaza the soil is prepared using compost made from food scraps from the cosmetics material processing and the café A "purification pond" has also been installed where wastewater from the facility is discharged into the Ishikari River after being cleaned by natural purification As a recycling-oriented facility that takes into consideration local communities and the global environment "Minnano Factory" is based on initiatives that consider people and the environment such as "reducing the burden on the global environment as much as possible and protecting limited resources" and "business operations based on perspectives and ideas that take into consideration the global environment and society is a new type of facility where visitors can dine and experience while observing the cosmetics manufacturing process Please visit to spend your time to your heart's content Address: 54-1 Toyonuma-cho, Sunagawa City Business hours：10:00 - 19:00 Closed: Unscheduled holidays *Factory is closed on Sundays and national holidays See details of "Everybody's Factory" on Domingo [7 minutes walk from Sapporo Station] Enjoy hot springs A comfortable stay at the 605-room "Sapporo Hotel by Granbell" [Updated for 2025] A complete guide to accessing Daiwa House Premist Dome (Sapporo Dome) and nearby hotels "So cute it's unfair" - Feel the healing power of a sleeping miniature horse [Information on the early opening on April 25th] Sapporo Odori's newest attraction Floor details and highlights of "4PLA" opening in summer 2025 A hotel in the center of Sapporo with a superb sauna and large public bath Experience the warmth that is unique to Hokkaido at "Danyuki Sapporo" [2025 Edition] 7 recommended cherry blossom spots in the Kitami and eastern Hokkaido areas Enjoy cherry blossom viewing in the great outdoors Seasonal “news” of Hokkaido can be checked by category You can check the information of your “town” in one place Events” held throughout the province are easy to find and can be saved This page has been automatically translated by Google Translate service Metrics details A planetary-scale understanding of the ocean ecosystem multidisciplinary project to assess the complexity of ocean life across comprehensive taxonomic and spatial scales the team sampled plankton at 210 globally distributed sites at depths down to 1,000 m We describe publicly available resources of molecular and discuss how an ecosystems biology approach has expanded our understanding of plankton diversity and ecology in the ocean as a planetary These efforts illustrate how global-scale concepts and data can help to integrate biological complexity into models and serve as a baseline for assessing ecosystem changes and the future habitability of our planet in the Anthropocene epoch Prices may be subject to local taxes which are calculated during checkout Primary production of the biosphere: integrating terrestrial and oceanic components A new look at ocean carbon remineralization for estimating deepwater sequestration Global patterns in efficiency of particulate organic carbon export and transfer to the deep ocean The impact of remineralization depth on the air-sea carbon balance The ecological role of water-column microbes in the sea Molecular eco-systems biology: towards an understanding of community function A holistic approach to marine eco-systems biology The Sorcerer II global ocean sampling expedition: northwest Atlantic through eastern tropical Pacific Environmental genome shotgun sequencing of the Sargasso Sea This study applies high-throughput DNA sequencing to produce a large data set of microbial community genome fragments from surface seawaters of the Sargasso Sea and identifies more than 1.2 million previously unknown genes illustrating the diversity of ocean microbial life The Sorcerer II global ocean sampling expedition: expanding the universe of protein families Open science resources for the discovery and analysis of Tara Oceans data Marine microbial metagenomes sampled across space and time Seafaring in the 21st century: the Malaspina 2010 Circumnavigation Expedition Microbial oceanography and the Hawaii ocean time-series programme Seasonal cycles of pelagic production and consumption Computational eco-systems biology in Tara Oceans: translating data into knowledge Marine viruses and their biogeochemical and ecological effects Marine viruses-major players in the global ecosystem Virioplankton: viruses in aquatic ecosystems Rising to the challenge: accelerated pace of discovery transforms marine virology Patterns and ecological drivers of ocean viral communities This article describes the first of the Tara Oceans efforts to investigate the diversity and structure of double-stranded DNA viral communities in the oceans supporting a model of passive global transport by ocean currents and selection by local environmental conditions Marine DNA viral macro- and microdiversity from pole to pole Ecogenomics and potential biogeochemical impacts of globally abundant ocean viruses Comparative omics and trait analyses of marine pseudoalteromonas phages advance the phage OTU concept Single-virus genomics reveals hidden cosmopolitan and abundant viruses Long-read viral metagenomics captures abundant and microdiverse viral populations and their niche-defining genomic islands Environmental viral genomes shed new light on virus-host interactions in the ocean Taxonomic assignment of uncultivated prokaryotic virus genomes is enabled by gene-sharing networks vConTACT: an iVirus tool to classify double-stranded DNA viruses that infect Archaea and bacteria Minimum information about an uncultivated virus genome (MIUViG) Consensus statement: virus taxonomy in the age of metagenomics Geobiologie of Inleiding tot de Milieukunde (Van Stockum & Zoon Global trends in marine plankton diversity across kingdoms of life Light-dependent adsorption of photosynthetic cyanophages to Synechococcus sp Light-driven synchrony of Prochlorococcus growth and mortality in the subtropical Pacific gyre Locality and diel cycling of viral production revealed by a 24 h time course cross-omics analysis in a coastal region of Japan A myovirus encoding both photosystem I and II proteins enhances cyclic electron flow in infected Prochlorococcus cells Marine ecosystems: bacterial photosynthesis genes in a virus Prevalence and evolution of core photosystem II genes in marine cyanobacterial viruses and their hosts Metabolic reprogramming by viruses in the sunlit and dark ocean Regulation of infection efficiency in a globally abundant marine Bacteriodetes virus Plankton networks driving carbon export in the oligotrophic ocean This study integrates Tara Oceans data across organismal size classes from epipelagic depths revealing that unexpected taxa can predict the downward export of carbon by biological processes in subtropical Phage-specific metabolic reprogramming of virocells Viruses and nutrient cycles in the sea - viruses play critical roles in the structure and function of aquatic food webs Depth-stratified functional and taxonomic niche specialization in the ‘core’ and ‘flexible’ Pacific Ocean virome Exploring nucleo-cytoplasmic large DNA viruses in Tara Oceans microbial metagenomes Reverse transcriptase genes are highly abundant and transcriptionally active in marine plankton assemblages Environmental characteristics of Agulhas rings affect interocean plankton transport The earth is small for “Leviathans”: long distance dispersal of giant viruses across aquatic environments Taxon richness of “Megaviridae” exceeds those of bacteria and archaea in the ocean Life-cycle modification in open oceans accounts for genome variability in a cosmopolitan phytoplankton Deep sequencing of amplified Prasinovirus and host green algal genes from an Indian Ocean transect reveals interacting trophic dependencies and new genotypes Unveiling of the diversity of prasinoviruses (Phycodnaviridae) in marine samples by using high-throughput sequencing analyses of PCR-amplified DNA polymerase and major capsid protein genes Prasinovirus distribution in the northwest Mediterranean Sea is affected by the environment and particularly by phosphate availability Degenerate PCR primers to reveal the diversity of giant viruses in coastal waters Blanc-Mathieu, R. et al. Viruses of the eukaryotic plankton are predicted to increase carbon export efficiency in the global sunlit ocean. Preprint at bioRxiv https://doi.org/10.1101/710228 (2019) iVirus: facilitating new insights in viral ecology with software and community data sets imbedded in a cyberinfrastructure Are we missing half of the viruses in the ocean Gene expression changes and community turnover differentially shape the global ocean metatranscriptome Structure and function of the global ocean microbiome This study catalogues 40 million ocean microbial genes and shows temperature to be a main driver of open-ocean microbial community composition in the epipelagic zone at a global scale MOCAT: a metagenomics assembly and gene prediction toolkit An integrated catalog of reference genes in the human gut microbiome A human gut microbial gene catalogue established by metagenomic sequencing Community genomics among stratified microbial assemblages in the ocean’s interior Molecular diversity and ecology of microbial plankton Annually reoccurring bacterial communities are predictable from ocean conditions activity and population genomic profiling with mOTUs2 Delineating ecologically significant taxonomic units from global patterns of marine picocyanobacteria Light color acclimation is a key process in the global ocean distribution of Synechococcus cyanobacteria Global genetic capacity for mixotrophy in marine picocyanobacteria Exploring microdiversity in novel Kordia sp (Bacteroidetes) with proteorhodopsin from the tropical Indian Ocean via single amplified genomes Ecological and functional capabilities of an uncultured Kordia sp Global distribution and vertical patterns of a prymnesiophyte-cyanobacteria obligate symbiosis Cyanobacterial symbionts diverged in the late Cretaceous towards lineage-specific nitrogen fixation factories in single-celled phytoplankton a newly characterized open ocean sublineage of the symbiotic N2 -fixing cyanobacterium Candidatus Atelocyanobacterium thalassa Nitrogen-fixing populations of Planctomycetes and Proteobacteria are abundant in surface ocean metagenomes Deep mitochondrial origin outside the sampled alphaproteobacteria This study exemplifies the use of Tara Oceans data to formulate new hypotheses by reconstructing genomes that support a mitochondrial origin before the divergence of all Alphaproteobacteria sampled to date Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life The reconstruction of 2,631 draft metagenome-assembled genomes from the global oceans A distinct abundant group of microbial rhodopsins discovered using functional metagenomics MerMAIDs: a family of metagenomically discovered marine anion-conducting and intensely desensitizing channelrhodopsins Decoupling function and taxonomy in the global ocean microbiome Quantitative 3D-imaging for cell biology and ecology of environmental microbial eukaryotes PhytoREF: a reference database of the plastidial 16S rRNA gene of photosynthetic eukaryotes with curated taxonomy The protist ribosomal reference database (PR2): a catalog of unicellular eukaryote small sub-unit rRNA sequences with curated taxonomy Single-cell genomics of multiple uncultured stramenopiles reveals underestimated functional diversity across oceans Single cell genomics yields a wide diversity of small planktonic protists across major ocean ecosystems Eukaryotic plankton diversity in the sunlit ocean This study surveys the eukaryotic diversity of ocean plankton from the smallest protists to millimetre-sized animals by 18S ribosomal RNA gene amplicon sequencing revealing 150,000 taxonomic groups dominated by protistan parasites and symbiotic hosts Extreme diversity of diplonemid eukaryotes in the ocean Worldwide occurrence and activity of the reef-building coral symbiont Symbiodinium in the open ocean Determinants of community structure in the global plankton interactome This study evaluates the effect of abiotic and biotic factors on organismal interactions among bacteria pathogenicity and parasitism as predictors of plankton community structure The epibiotic life of the cosmopolitan diatom Fragilariopsis doliolus on heterotrophic ciliates in the open ocean Insights into global diatom distribution and diversity in the world’s ocean Global patterns of pelagic dinoflagellate diversity across protist size classes unveiled by metabarcoding Diversity and oceanic distribution of prasinophytes clade VII the dominant group of green algae in oceanic waters The Tara Oceans voyage reveals global diversity and distribution patterns of marine planktonic ciliates Marine biodiversity and the chessboard of life Biogeography and diversity of Collodaria (Radiolaria) in the global ocean Assessing the diversity and distribution of apicomplexans in host and free-living environments using high-throughput amplicon data and a phylogenetically informed reference framework Exact sequence variants should replace operational taxonomic units in marker-gene data analysis Metacoder: an R package for visualization and manipulation of community taxonomic diversity data Nanoplanktonic diatoms are globally overlooked but play a role in spring blooms and carbon export Influence of diatom diversity on the ocean biological carbon pump Diversity dynamics of marine planktonic diatoms across the Cenozoic Universal power laws govern intermittent rarity in communities of interacting species Morphological identification and single-cell genomics of marine diplonemids The symbiotic life of Symbiodinium in the open ocean within a new species of calcifying ciliate (Tiarina sp.) In situ imaging reveals the biomass of giant protists in the global ocean Survey of the green picoalga Bathycoccus genomes in the global ocean Particle size distribution and estimated carbon flux across the Arabian Sea oxygen minimum zone Phylogenetic analysis of Thecosomata Blainville 1824 (holoplanktonic opisthobranchia) using morphological and molecular data Evolutionary history of Chaetognatha inferred from molecular and morphological data: a case study for body plan simplification population structure and natural selection from the genome of the epipelagic copepod Oithona Discovering millions of plankton genomic markers from the Atlantic Ocean and the Mediterranean Sea Community-level responses to iron availability in open ocean plankton ecosystems Meta-omics reveals genetic flexibility of diatom nitrogen transporters in response to environmental changes Modelling the complexity of plankton communities exploiting omics potential: From present challenges to an integrative pipeline Evolution and measurement of species diversity A latitudinal diversity gradient in planktonic marine bacteria Oceanographic boundaries constrain microbial diversity gradients in the South Pacific Ocean Observational needs supporting marine ecosystems modeling and forecasting: from the global ocean to regional and coastal systems Globally consistent quantitative observations of planktonic ecosystems bioinformatics and biotechnology (M2B3) data reporting and service standards Expanding Tara Oceans protocols for underway ecosystemic sampling of the ocean-atmosphere interface during Tara Pacific expedition (2016–2018) The Tara Pacific expedition — a pan-ecosystemic approach of the “-omics” complexity of coral reef holobionts across the Pacific Ocean Atlantic Ocean Research Alliance — marine microbiome roadmap (AORA Seasonal and interannual variability of the marine bacterioplankton community throughout the water column over ten years Seasonal patterns in plankton communities in a pluriannual time series at a coastal Mediterranean site (Gulf of Naples): an attempt to discern recurrences and trends The taxonomic and functional diversity of microbes at a temperate coastal site: a ‘multi-omic’ study of seasonal and diel temporal variation Comprehensive model of annual plankton succession based on the whole-plankton time series approach ICES phytoplankton and microbial plankton status report 2009/2010 (eds O’Brien High resolution time series reveals cohesive but short-lived communities in coastal plankton Coccolithovirus facilitation of carbon export in the North Atlantic When microbiologists plunge into the ocean Marine microbes in 4D-using time series observation to assess the dynamics of the ocean microbiome and its links to ocean health Four stages of a scientific discipline; four types of scientist A sea of change: biogeochemical variability in the North Pacific Subtropical Gyre Scientists’ warning to humanity: microorganisms and climate change This review article provides a consensus statement the ‘microbiologists’ warning to humanity’ documenting how microorganisms will affect and will be affected by climate change Tara Oceans studies plankton at planetary scale Metagenomic 16S rDNA Illumina tags are a powerful alternative to amplicon sequencing to explore diversity and structure of microbial communities Single-cell genomics unveiled a cryptic cyanobacterial lineage with a worldwide distribution hidden by a dinoflagellate host a dinoflagellate commonly found in symbiosis with polycystine radiolarians in Marine Protists: Diversity and Dynamics (eds Ohtsuka Download references Sunagawa thanks the European Molecular Biology Laboratory and ETH Zürich’s high-performance computing facilities for computational support acknowledges funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement 835067) as well as the Radcliffe Institute of Advanced Study at Harvard University for a scholar’s fellowship during the 2016–2017 academic year thanks the Gordon and Betty Moore Foundation (award 3790) and the US National Science Foundation (awards OCE#1536989 and OCE#1829831) as well as the Ohio Supercomputer for computational support thanks the Spanish Ministry of Economy and Competitiveness (CTM2017-87736-R) thanks the Institut Universitaire de France as well as the EMBRC platform PIQv for image analysis Sunagawa is supported by ETH Zürich and the Helmut Horten Foundation and by funding from the Swiss National Foundation (205321_184955) The authors declare that all data reported herein are fully and freely available from the date of publication publications and ownership of data are free from legal entanglement or restriction by the various nations in whose waters the Tara Oceans expeditions conducted sampling This article is contribution number 100 of Tara Oceans Institute of Microbiology and Swiss Institute of Bioinformatics Department of Marine Biology and Oceanography Max Delbrück Center for Molecular Medicine Research Federation for the Study of Global Ocean Systems Ecology and Evolution Laboratoire d’Océanographie de Villefranche Québec Océan and Takuvik Joint International Laboratory (UMI 3376) Biologie Intégrative des Organismes Marins are the lead authors of the article and all other authors contributed to discussion of the content The authors declare no competing interests Nature Reviews Microbiology thanks David Hutchins reviewer(s) for their contribution to the peer review of this work Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Referring to uppermost layer of the ocean that receives sunlight enabling the organisms inhabiting it to perform photosynthesis Referring to the ocean layer that receives very little to no sunlight ranging from about 200 to 1,000 m in depth Capable of incorporating organic carbon into biomass Derived from the breakdown of organic matter into its simplest inorganic form Capacity to incorporate carbon into biomass from either inorganic or organic sources Capacity to derive energy from light and carbon from organic matter Group of single-celled photosynthetic planktonic organisms Consensus genome sequences that are reconstructed using sequencing reads of DNA extracted from whole microbial communities Second geological epoch of the Palaeogene period (66 million to 23 million years ago) that began 56 million years ago and ended 34 million years ago Pathways of the oceanic circulation that are influenced by the displacement of continents (for example South African gateway and the Tasman gateway between Antarctica and South America Organisms that obtain carbon and energy primarily from the consumption of bacteria First geological epoch of the Neogene period (2.6 million to 23 million years ago) that extends from about 23 million to 5 million years ago Oceanic system south of Africa where warm and salty Indian Ocean waters leak into the South Atlantic Ocean impacting the global oceanic circulation Download citation DOI: https://doi.org/10.1038/s41579-020-0364-5 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Syuya Sunagawa (Horobi) and Daisuke Nakagawa (Jin) talk about their characters and their time on Kamen Rider Zero-One The movie is referred to as the “True Finale” of the series Were there any moments you experienced where you realize that this is the end Nakagawa: Jin this time around has taken up a much more brighter role He’s also different from the TV series and I had a lot of fun portraying the character Sunagawa: Maybe it was when the five of us (Fuwa Isamu I was told “This is Jin’s final transformation so do your best!” And I really did put in a lot of effort Then it dawned on me that this is in fact the end Nakagawa: Sunagawa cried when we wrapped up (laughs) I cried because I thought that this was the last time Seiji Takaiwa and I would be playing Horobi I thought this would be the last time we’d be working together with the Staff and Director Teruaki Sugihara I had a lot of happy scenes so I wrapped up happily Jin has become more trustworthy as a character since the TV series is there anything you realized about the character on top of portraying his growth Nakagawa: What I noticed after the TV series when Jin was revived… I was told to portray Jin as the leader of a revolution army but because I acted in the scenes I was able to work hard on the character Then the Assistant Producer told me “Jin doesn’t seem like he has much confidence.” That’s when I realized “I see I’ll never be able to fulfill the role of his character.” It was in episode 32… or 33 when I understood the role that the show desired that’s when I realized his trustworthiness and portrayed that in my acting Horobi confronts the issue of the “heart” and begins to oversee the evil of the world what’s something you became aware of when you played his character Sunagawa: There’s a scene in the TV series finale where Horobi seemingly smiled I didn’t want to destroy Horobi’s image in the film it just ended up being a smile of my own and not his (laughs) It was hard to find the right soft expression (laughs) when the wrinkles between his brows closed in his facial expression looked like it didn’t change but I did my best to capture a soft expression for Horobi I especially had to be careful when I was conversating with the other characters I fight alongside with Did you feel that contrast of Horobi when you were on set Nakagawa: I feel that Horobi really has become kinder I was amazed when I saw his expression and the kind of presence he (Sunagawa) expresses He didn’t seem closed off at all like he did in the TV series The composed Horobi seen in the movie has the power of cogency The Jin we see after he comes back to life is very mature but the one we see in the film is very cutesy Sunagawa: It felt like you were back to who you were at the beginning of the TV series I thought “oh he sure is having fun” (laughs) One of the highlights of the movie is seeing a five-person transformation scene Sunagawa: It would have been nice if Aruto was there too but I was happy That must’ve been an awesome feeling (laughs) Sunagawa: As far as simultaneous transformations goes Transforming alongside the two AIMS members and Thouser was a fresh idea I remember seeing Nachi (who portrays Gai) transforming and I was like We’re all on the same side now.” Especially since he was such an antagonist to the other characters Nakagawa: Jin on the other hand has transformed with the other characters as well Seeing Horobi in the mix-up seemed out of place Especially since he was front and center (laughs) Tell us some highlights about Jin and Horobi in this film Nakagawa: So Jin has a lot more cheerful scenes this time around Even during fight scenes he has fun fighting and that’s just very Jin-like to me Sunagawa: How Horobi becomes a helping hand to Aruto and everyone So it’s because there’s a mutual bond between the two that Jin and Horobi are able to separate and be on their own Can you tell us your impression of each other when you first met Nakagawa: You’re always saying that (laughs) Sunagawa: Don’t forget the earrings (laughs) Nakagawa: I’m not the confrontational type so I was worried that we wouldn’t see eye-to-eye on things (laughs) Sunagawa: I thought he was one of those cool types He was the friendliest… and the loudest (laughs) Sunagawa: I had a feeling you’d break something on set but you didn’t Nakagawa: I broke the belt a lot… (laughs) But it’s not like you were having so much fun that you broke it right Sunagawa: So my impression of him didn’t change He’s more open than he was at the beginning Nakagawa: My impression of Sunagawa changed He’s actually super super nice (laughs) Sunagawa: Did you really think that highly of me (laughs) You usually only commend me at these kinds of places Nakagawa: You’re someone with a really kind heart Your lifestyle on the other hand is very careless though (laughs) and he’s the most human as the days go by And I realize that he’s someone that everyone loves but it turns out he was super nice (laughs) Sunagawa: (laughs) You don’t have to say it twice what do you feel is the strongest bond between Jin and Horobi Sunagawa: That’s actually something that can be felt in this movie but their relationship with each other is strong which is why they’re able to do things on their own Nakagawa: There was a scene in episode 43 where Jin was destroyed and Horobi began shedding tears We weren’t sure if our performance would go well but we were able to express ourselves better than we had expected Sunagawa: Nakagawa understands Jin the most so I trusted him Sunagawa’s face is pretty straight forward so I can feel the amount of information coming out of him Sunagawa: (laughs) “information” Even if we didn’t talk about anything ahead of time he was able to naturally bring out expressions when we met face to face Sunagawa: We did plan some things out once or twice Director Tasaki told us to chat things out when Horobi walked away trembling after having destroyed Izu Nakagawa: I was told that whatever I did to try and restrain you I was told that I have to act like I was really trying to stop him And Sunagawa and I talked about how it would play out and he would turn around with a look on his face like he was going somewhere far away Nakagawa: It was a scene that required a lot of emotion on top of pushing ourselves to our limits Were there any moments where you two felt the other was suffering Nakagawa: The final scene that Director Tasaki directed Sunagawa: It was when Horobi finally began to develop feelings Nakagawa: Director Tasaki helped him get into it Have you two ever felt that it’s because you were your characters that you could understand each other Nakagawa: Sunagawa’s endurance is strong I can’t fathom having a role where I don’t express anything until episode 43 Nakagawa: It’s because I played Jin that my character had more expression I don’t think he got any degree of range until the final episodes I believe that Nakagawa has a lot of range so he and Jin are very alike Jin has a lot of emotions and Nakagawa himself is very cute Because Nakagawa has such a wide range that he was able to expand Jin’s character You made such a cute character… wait how old are you again Sunagawa: It must be cringey for a 22 year old man playing a cute character (laughs) Sunagawa: Usually that’s not cute (laughs) and then quiet… I can’t do that The casting directors are amazing (laughs) Sunagawa: I’m able to wake up early in the morning now (laughs) Sunagawa: I’m more dependable now (laughs) Sunagawa: I was never a morning person but I’ve become better at getting up there’s a lot more people who support Kamen Rider Zero-One you see I’m actually a pessimistic person and seeing that we gained more supporters helped me I couldn’t feel out a fictional character But when I saw that we had so many support from fans who love Jin that’s when I really felt that he had come alive Now let’s play the “Which character of Zero-One is most likely to be a ~~” game Let’s start with the “crybaby” Sunagawa: When it comes to who cries the most He cried within the story as well as when we wrapped up filming I cry about things in real life but when I watch a touching film I cry too Sunagawa: Yeah that’s Nakagawa again (laughs) Nakagawa: Not Ryutaro Okada (portrays Fuwa) Sunagawa: He’s a different kind of free (laughs) Nakagawa: He’s the type to be himself the most (laughs) Sunagawa: He has a lot of conviction so he seems the most free Nakagawa: So the most free would be… She’s always the type to make her own schedule and she’s always so bubbly Sunagawa: Hmm that would be Igeta Hiroe (portrays Yua) Sunagawa: You just want to smile when she laughs a bit Even when we played the metsuboujinrai game at the Final Event I felt so happy just watching her have fun Nakagawa: Even on people’s birthdays she prepares everything for everyone ahead of time Those who are people person tend to end up feeling lonely when they’re not with them Sunagawa: But I only like the Zero-One members Sunagawa: When we were nearing the end of filming or when I’m by myself on set Even on episode 8 I was like “I don’t want it to be over just yet!” “I don’t want everyone to leave just yet…” We’ve met up plenty of times after the final episode so I haven’t felt that lonely yet but I feel like I’ll feel lonely in a few months after the movie ends be in different shows… oh man I feel lonely now (laughs) Nakagawa: You really are the one who tends to feel lonely (laughs) Source: Yahoo! 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Enter your email address to subscribe to the Tokusatsu Network and receive notifications of new posts by email National Report Hokkaido--A gunshot rang out on a recent morning in a meadow in northern Japan watched by a handful of city officials and hunters The bear had been roaming around a nearby house and eating its way through adjacent cornfields so officials and hunters in Sunagawa city had set a trap with a deer carcass to lure the voracious creature it’s always a bit deflating when a bear gets caught,” Haruo Ikegami Japan is grappling with a growing bear problem A dwindling band of aging hunters is on the front line A record 219 people were victims of bear attacks while more than 9,000 black and brown bears were trapped and culled over that period Both species’ habitats have been expanding; the ministry estimates that the number of brown bears in Hokkaido more than doubled to about 11,700 in the three decades through 2020 most of which live on the main island of Honshu though a widely cited 2023 analysis estimated their numbers at roughly 44,000 Restrictions on hunting practices and greater emphasis on conservation contributed to a surge in bear sightings over recent decades according to Japan’s Forest Research and Management Organization With Japan’s rural areas experiencing rapid demographic decline bears are venturing closer to towns and villages and into abandoned farmland an environment ministry expert panel said in February But bear expertise among local governments is spotty and Japan’s reliance on recreational hunters to protect settlements looks unsustainable as its population ages according to Reuters interviews with almost two dozen people Many called for changes to the way Japan manages human-bear conflict to address safety concerns while ensuring a future for the bears In Hokkaido cities and towns like Sunagawa some residents wonder what will happen when hunters can no longer do the job said he was “terrified” by a bear that would wander into his farm a few years ago As local authorities weighed how to respond they ultimately relied on the hunters’ association Sunagawa’s city government told Reuters that efforts to capture the bear were complicated by its proximity to homes and deliberations about what to do once the animal was trapped Although some hunters stalk bears as a hobby Ikegami reckons not many are thrilled about culling trapped bears for local governments “I don’t want people to think of hunting as something fashionable It’s a big burden to take a life,” he said The hunter that shot the bear in Sunagawa would get about 8,000 yen (about $50) perhaps enough to cover fuel and expenses but little else Hunters also risk clashing with authorities Ikegami’s guns were seized by Hokkaido authorities in 2019 after they deemed his attempt to shoot a bear near a house was ill-judged He is battling in court to have the weapons returned The Hokkaido safety officials involved in the matter declined to address Reuters questions about the case Japanese government officials this year proposed relaxing rules around gun use to make it easier for hunters to shoot bears in urban areas Takikawa and Iwamizawa told Reuters that regional and national authorities could go further to address the problem This could include promoting the recruitment of hunters and improving their conditions Japan’s environment ministry said it subsidises efforts to train local officials and conduct bear drills in towns but added that regional differences in human-bear conflicts called for tailor-made approaches The Hokkaido government’s wildlife bureau said it ran various initiatives to incentivize and recruit hunters including promotional events and training people in how to handle brown bears Environmental group WWF said in an email that to preserve Japan’s bear population authorities should take actions including developing human-wildlife buffer zones and formulating a national protection and management plan It declined to comment specifically on the culling of bears in Japan While its numbers have been growing in Japan the Asiatic black bear is listed as vulnerable on the IUCN’s red list of threatened species globally Bear hunting was lucrative until the 1980s and hide and bile were traded for high prices But with growing environmental awareness and changes to regulations and consumer tastes Japan issued some 218,500 hunting licenses in the 2020 fiscal year less than half of the 517,800 it issued in 1975 While about 98% of those issued in 1975 were for shooting About 60% of license holders were aged over 60 Traps need to be checked daily while bears lurk nearby Rifle owners must abide by Japan’s strict firearms laws and invest in ammunition and gun storage Those difficulties came to a head earlier this year in Naie accused the local government of taking hunters for granted without investing in a longer-term solution “Once we grow old and have no choice but to quit this reliance on the hunters’ association is not going to work,” Yamagishi said Naie’s local government declined to comment on the dispute with Yamagishi but said officials were taking steps to address the bear problem including working with licensed hunters from outside the area a professor at Tokyo University of Agriculture who studies bears said depopulation and a decline in the amount of managed farmland in recent decades may have led bears to become bolder about approaching towns Clearer demarcation between habitats would help humans and bears coexist professor of agriculture at Rakuno Gakuen University said bears appeared to be raising cubs closer to human settlements causing young bears not to fear people as much as before Climate change-driven shifts in the ripening and flowering of fruits nuts and leaves may drive bears to raid crops when their usual food sources are low consistent effort to make sure that bears don’t enter human areas,” Sato said Japan should create a system where hunters are paid enough to support a family we can’t nurture the next generation of hunters,” he said Harada carries the scars of a bear attack more than 20 years ago when the animal sank its teeth into his skull “It sounded like it was munching on some raw radish,” he said Harada is now part of a non-profit organization that helps communities keep problematic wildlife at bay Japan’s environment ministry in September warned about the possibility of a surge in bear attacks towards year-end when the animals typically scavenge for food to store up fat for hibernation bear sightings and attacks peaked in October With Japan’s population aging and shrinking some companies are turning to technology to manage bears the “Monster Wolf” robot sold by Sapporo-based Wolf Kamuy emits growls Priced at about 400,000 yen (roughly $2,550) and powered by solar energy the gleaming-eyed beast has demonstrated some success in warding off bears though its sensor can be triggered by other animals said it takes years of analyzing pawprints and dung and learning to read bears’ signs to understand how to trap them adding that human expertise will remain integral to managing the problem Yamagishi thinks it would take three to five years to train a new generation of hunters Hunters demand higher pay to risk lives against Hokkaido’s bears Hunter passes down lessons from horrific bear attack conservationists join forces to protect Formosan black bear Hokkaido confirms cattle-attacking brown bear culled Wildlife experts: ‘Protect bears by better protecting people’ The dates displayed for an article provide information on when various publication milestones were reached at the journal that has published the article activities on preceding journals at which the article was previously under consideration are not shown (for instance submission All content on this site: Copyright © 2025 Elsevier B.V. Researchers led by Hidetoshi Masumoto and Genshiro Sunagawa at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have developed a new method of protecting organs during heart and aortic surgery when blood circulation has to be blocked Rather than relying on cold temperatures to induce hypometabolism and reduce the need for oxygen the technique works by stimulating Q neurons in the brain which slow metabolism down to a hibernation-like state the procedure protected mouse kidneys from damage due to lack of oxygen and avoided harmful side effects related to extended hypothermia The findings could lead to new ways of performing similar surgeries in people For some kinds of heart and aortic surgery doctors must cut off blood circulation as they work to repair the aorta this type of surgery has been performed after using cold temperatures to induce deep hypothermia which slows down the body’s metabolism so that organs can survive with very little oxygen While this is effective in protecting organs like the kidneys causing excessive bleeding and the need for blood transfusions Masumoto and his team at RIKEN BDR have been looking for ways to slow down metabolism without inducing hypothermia We know that many animals—such as bears and squirrels—can hibernate and that despite the extremely slow metabolism during hibernation This was the end of the story until a few years ago when Sunagawa’s group discovered a way to induce a hibernation-like state in mice—animals that do not normally hibernate there are many possibilities for using hibernation-like states in cardiovascular medicine or other cases in which organ protection via hypothermia is insufficient or inappropriate,” says Sunagawa the technique’s effectiveness needs to be verified in animal models The new study is the first clinical implementation of the technique and tested its effectiveness using a mouse model of aortic surgery that requires circulatory arrest The team’s previous studies showed that hibernation-level hypometabolism could be achieved by activating special neurons in the brain’s hypothalamus called Q neurons Chemogenetic biotechnology allowed the researchers to trigger activation of these specific neurons with an injection They compared four groups of model mice that varied in whether or not cold temperatures were used to induce hypometabolism and whether or not Q neurons were activated Kidney damage and renal function were evaluated by looking at levels of biomarkers in the blood Analysis showed hypometabolism induced by Q-neurons at normal temperatures protected the kidneys as well as that induced using hypothermia we now know that Q neurons ­induced hibernation-like states can be used to protect organs,” says Masumoto The ultimate goal of Masumoto and Sunagawa’s research is to slow down people’s metabolism during heart surgery But because Q neurons in people cannot be selectively activated the way they can in experimentally engineered mice the team is now looking at ways to protect organs downstream from the brain “Activating Q neurons triggers some sequence of biological events that allows organs to exist in a hypometabolic state for days,” explains Sunagawa “Once we know precisely what these events are we are confident we can induce them pharmacologically in the body without needing to first activate the Q neurons.” The study was published in JTCVS Open on November 7 10.1016/j.xjon.2022.11.001 are not responsible for the accuracy of news releases posted to EurekAlert by contributing institutions or for the use of any information through the EurekAlert system Copyright © 2025 by the American Association for the Advancement of Science (AAAS) Researchers led by Genshiro Sunagawa at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have shown that an animal’s stem cells possess the same level of cold resistance as the animal itself the study focuses on mice with different hibernation-like characteristics showing that those with the best resistance to cold temperatures have stems cells that generate energy differently than others the study establishes mouse stem cells as a practical model system for further research into organ preservation and even human hibernation Whether it’s to move organs for transplant or put the brain in temporary stasis after a stroke cold temperatures eventually cause irreparable damage hibernating animals can survive for months with low body temperature because their metabolism becomes extremely slow Sunagawa and his team at the RIKEN BDR Laboratory for Hibernation Biology are trying to understand how an animal they are using laboratory mice because genetic variables can be controlled The goal of the new experiments was to determine if mouse stem cells can be used to study organ preservation and hibernation This would open up the field to experimental systems already developed for studying stem cells as well as reduce the need for using live animals in the research they can enter a short one-hour hibernation period called torpor The researchers tested strains of inbred laboratory mice and characterized torpor by the lowest body temperature and the lowest oxygen use the mice achieved They then established embryonic stem cell lines from each mouse strain and examined cell metabolism at around mouse body temperature (37°C / 98.6°F) and a cold temperature (31°C / 88.6°F) and we can feel its byproduct in our muscles when we exercise and use up our available oxygen called oxidative phosphorylation or OXPHOS takes place in the mitochondria and does require oxygen The researchers found that stem cells from the shallow- and medium-torpor mice switched to glycolysis at the colder temperature while the stem cells from the deep-torpor mice did not Those stem cells maintained a high rate of oxygen consumption at all temperatures oxygen remained available despite the cold Further tests revealed that the way energy is generated using oxygen in the mitochondria of the deep-torpor stem cells differed from the others with the oxygen coming from an outside source the researchers asked whether what they learned from the stem cells was actually relevant in adult mice They examined liver tissue from each of the mouse lines and found that as in the stem cells the tissue from the deep-torpor mice did not rely on glycolysis in the cold and maintained a high degree of oxygen use tissue from these mice remained better preserved at lower temperatures “We've proven that the distinct responses to lower temperatures are preserved even at the cellular level,” says Sunagawa “This provides a huge opportunity to conduct in vitro studies of cold tolerance in tissues from torpor-capable animals.” Eventually they hope to be able to induce similar cold-resistance in tissue from any animal insights from this system will help us develop ways to implement human hibernation or human organ cryopreservation.” Adam Phillips RIKEN International Affairs Division Tel: +81-(0)48-462-1225 Email: adam.phillips [at] riken.jp (Left) Body temperature during torpor was examined in three types of laboratory mice (Middle) Metabolism was examined in embryonic stem cell lines generated from the three types of mice and was compared between normal (37°C/98.6°F) and cold (31°C/87.8°F) conditions (Right) Liver tissue was sampled from each type of adult mouse and metabolism was compared Mice that underwent deep torpor differed from the other two types: Body temperature was much lower during torpor and at low temperatures energy generation was dominated by OXPHOS (ATP by oxygen consumption) rather than glycolysis (ATP from glucose no oxygen needed) in the stem cells and in the liver samples from adult mice Top Metrics details Some mammals enter a hypometabolic state either daily torpor (minutes to hours in length) or hibernation (days to weeks) when reducing metabolism would benefit survival Hibernators demonstrate deep torpor by reducing both the sensitivity (H) and the theoretical set-point temperature (TR) of the thermogenesis system resulting in extreme hypothermia close to ambient temperature these properties during daily torpor remain poorly understood due to the very short steady state of the hypometabolism and the large variation among species and individuals To overcome these difficulties in observing and evaluating daily torpor we developed a novel torpor-detection algorithm based on Bayesian estimation of the basal metabolism of individual mice we evaluated fasting induced torpor in various ambient temperatures (TAs) and found that H decreased 91.5% during daily torpor while TR only decreased 3.79 °C in mice These results indicate that thermogenesis during daily torpor shares a common property of sensitivity reduction with hibernation while it is distinct from hibernation by not lowering TR our findings support that mice are suitable model animals to investigate the regulation of the heat production during active hypometabolism thus suggesting further study of mice may provide clues to regulating hypometabolism in mammals This is striking in two points: 1) warming begins with the animal in a hypometabolic state in which it cannot produce heat as usual and 2) live cells cannot usually survive such a rapid thermal change System for recording the metabolism of free-moving mice under controlled ambient temperature (a) A block diagram of the thermoregulatory system in mammals when the animal is not moving therefore assumed to exert no external work The upper loop and the lower loop represent the heat loss and heat production loop The time derivative of body temperature (TB) is derived from the difference of heat production (Qin) and heat loss (Qout) divided by the thermal capacity (C) Qout is derived from the difference of ambient temperature (TA) and TB multiplied by heat conductance (G) Qin is derived from the difference of theoretically defined set-point temperature (TR) and TBmultiplied by H which is the open-loop gain of the thermoregulatory feedback system (b) A system for evaluating the metabolism of free-moving mice The temperature-controlled animal chamber (left panel) and the inside of the chamber (middle panel) in which four mice can be recorded at once Each animal had an intraperitoneally implanted body-temperature transmitter (right panel Each animal was housed in a metabolic chamber and the VO2 were recorded by gas mass spectrometry (c) A representative recording of mouse metabolism for three consecutive days Once the mouse was placed in the metabolic chamber there was no physical contact with researchers during the recording period Note the clear circadian rhythm seen in the TB (d) A representative recording of metabolism during fasting-induced daily torpor The mouse was placed in the chamber for three days; food was removed on the second day (filled triangle) Daily torpor started during the latter half of the second day The mouse returned to a euthermic state immediately after the food was returned to the chamber (unfilled triangle) Because past studies have used various definitions of daily torpor we sought to define daily torpor based on statistical prediction of the individual metabolism of the animal Modelling and predicting metabolism from a single day recording (g) CI coverage rate of the metabolism on the second and third days when applying different CI ratios 99.9% of the CIs covered more than 99% of the sampling points of the latter two days the first day’s recording was sufficient to predict the dynamics of TB and VO2 for the following two days a 99.9% CI was applied for estimating the baseline distribution for TB and VO2 Development of this simple but individualized metabolism modelling allowed us to define daily torpor as an outlier from the individually predicted baseline dynamics of metabolism Defining daily torpor as an outlying low metabolism (c) Boxplots for various torpor statistics according to the different torpor definitions listed in Fig and the top of the box represent the median The end of the upper whisker is the highest value that is within 1.5 times the inter-quartile range (IQR) The end of the lower whisker is the lowest value that is within 1.5 times the IQR Body-temperature homeostasis is actively controlled during daily torpor (a) Protocol of the fasting-induced daily torpor experiment Animals were placed in the TA-constant chamber on Day 0; data were recorded for 72 hours from the beginning of Day 1 Food was removed and returned at the beginning of Day 2 and Day 3 Water was freely accessible throughout the experiment red and blue denote normal and torpid status the minimum TB of the dark phase of Day 1 was used for analysis the minimum TB during torpor was used for analysis the dots with the vertical error bars denote the observed mean and SEM of the minimum variables (TB in b and the line and the shaded area denote the mean and the 89% HPDI intervals of the estimated minimum variables (c) The posterior distribution of the slope (a1) of TA−TB relationship Including the following distribution panels in this figure the bold and thin lines denote the mean and the 89% HPDI intervals of the estimated values Minimum VO2 was defined as the VO2 recorded when the TB was minimum (e) The posterior distribution of the slope (a2) of TA-VO2 relationship (f) The rate of successful daily torpor induction at various TAs (g) The averaged torpor duration for each episode One torpor episode is tended to be shorter when the TA gets higher i) The posterior distribution of the estimated mean (n = 6) of TB (h) and VO2 (i) at a TA of 8 °C Because the observed mean (dashed lines) is larger than the 89% HPDI in both TB and VO2 the animal exhibited higher metabolism than expected The bin size is 0.1 °C and 0.01 ml/g/hr for TB and VO2 To model the temperature dependent metabolism we linearly regressed minimal VO2 and TB with TA during the second-half of Day 1 as follows: an additional thermoregulatory mechanism has been kicked in This was not apparent when TA was at the range of 12 to 24 °C to evaluate the extent of active reduction of metabolism during daily torpor we calculated the Q10 temperature coefficient of VO2 with TB during torpor decreased along with the lowered TA and reached to 3.12 at TA = 12 °C the reduction of VO2 cannot be explained solely by the effect of hypothermia implicating that the metabolism was actively decreased resulting in hypothermia these results demonstrate that the metabolic regulation for homeostatic control of the TB is weakened during daily torpor The thermoregulatory system is further altered when the TA drops to 8 °C implying the existence of a secondary mechanism that remains active to keep the metabolism at a certain level even during daily torpor To estimate the target components of thermoregulation during daily torpor we next fitted the data to a mathematical model to estimate the parameters of the thermoregulatory system This analysis revealed a difference between daily torpor and hibernation thermoregulation This model describes the thermoregulatory feedback system of the animal when the animal is not moving The energy lost from the animal (Qout) is thermodynamically determined by the difference of TB from TA and the heat conductance (G) of the animal The metabolic rate (Qin) is the energy used for heat production per unit time and it is designed to be a function of the difference of TR from TB we expressed both Qin and Qout as oxygen consumption rates (O2 ml/g/hr) and assumed the measured VO2 is equals Qin This is possible when the energy production is proportional to VO2 divided by heat capacity C yields the time derivative of TB as: In the heat loss loop (the upper loop in Fig. 1a) because no energy is used for external work by exercise the Qout from the animal is mainly governed by the difference of TB and TA as: Substituting Qout in equation (4) with VO2 yields: This means all of the oxygen consumption is utilized for heat production to fill the gap between the body and ambient temperature On the other hand, in the heat production loop (the lower loop in Fig. 1a) Qin is proportional to the difference between the set-point temperature TR and TB as: Eliminating VO2 by joining equations (5) and (7) In this model, three parameters are modifiable by the body. One is the heat conductance (G), which is the main parameter quantifying the heat loss of the animal, and the other two are the body temperature set-point (TR) and the gain of the negative feedback loop of heat production (H). Because not all animals enter torpor when TA = 8 °C (Fig. 4f) we employed TB and VO2 recorded under TA = 12 The sensitivity of the heat production system is largely reduced during daily torpor while the reduction of set-point temperature was small (d) The posterior distribution of the estimated TR (e) The posterior distribution of the estimated H H became dramatically smaller than normal states which the mean difference reached to 4.70 ml/g/hr/°C This is clearly showing that the open-loop gain of the heat production system reduced to 8.5% during daily torpor from the normal state Because we have estimated the relationship of TB and VO2 with TA from equations (1) and (2) in the previous section we used those results to further estimate TR and H Eliminating TA from equations (1) and (2) results in: The averaged estimated H of torpid status showed 91.5% reduction from the normal status we conclude that the striking reduction in the open-loop negative feedback gain of the heat production system plays the central role in regulating the hypometabolism during daily torpor The contributions of a small reduction of TR and G are secondary Since the baseline is defined from the animals in ad libitum access to food (day 1) the abnormal low metabolism detected in our study may include the metabolic drop caused by fasting itself This may be a problem to discriminate the fasting response and the torpid response to evaluate what extent the torpor time is influenced by fasting our main aim to apply the baseline metabolism is to absorb the individual variance in metabolism we defined daily torpor of an animal by including the fasting response as a part of the hypometabolisc response tracking the minimum TB phenotype among genetically modified or genetically distinct mice such as genetically knockout animals or other inbred strains may contribute to our understanding of the resistance to hypothermia which is one of the four major requirements for active hypometabolism capability This suggests that a common mechanism underlies both daily torpor and hibernation and that studying torpor in mice may help to reveal a universal mechanism of active hypometabolism If the sex difference in torpor phenotype is globally observed through Mus musculus it may be a good lead to investigate the dynamic change of the thermoregulatory parameters during daily torpor In this study, estimating G, TR and H from observations of TB and VO2 among various TAs, we concluded that the reduction in H is the main effector of hypometabolism during daily torpor (Fig. 1a and 5c) equation (8) shows the ratio of G and H determines the contribution of TR and TA to TB G/H increased from 0.044 to 0.330 when the animal entered torpor This is clearly showing that during daily torpor the thermoregulatory system shifted to accept the effect of TA and as a result the effect of TR had been relatively weakened the degree of reduction of H during daily torpor was similar to that of hibernators This is indicating that the sensitivity reduction in thermogeneration in daily torpor may share a common mechanism with hibernation H is reduced from 0.781–1.20 to 0.032–0.073 ml/g/hr/°C which is more than a 90% reduction There are, at least, three possible explanations for dominantly lowering H but not TR during daily torpor. One is based on structure of the thermoregulatory system (Fig. 1a) It is possible to control TB by changing both TR and H regulating multiple actuators is much complicated than controlling a single actuators usually it is easier to obtain stability when the number of actuator is less since daily torpor is only induced for hours where hibernators stay in hypometabolic states for days it is reasonable to keep the regulatory system during torpor simpler and much controllable than in hibernation The drawback of keeping the TR high is the higher TB when having G and H at the level as low as hibernators with a fixed TA which have to survive for several months without eating lowering the TR along with H is reasonable The slower dynamics of TR regulation imply a certain underlying mechanism to prevent the TR to decrease as quick as H it is natural to assume the TR is controlled through the dynamic change in the neural network such as synpatic plasticity which may require considerable energy and time in either increasing or decreasing TR changing the TR would be nothing but a hurdle which can be a possible reason why it is not lowered as in hibernators suppressing any of the sites can reduce the feedback gain they can be grouped into central or peripheral mechanisms according to the suppressed site it is possible that the preoptic area in the brain there should be less neural activity at the thermoregulatory centre or at upstream of that it is possible that even though the brain is sending signals to produce heat brown adipose tissue or skeletal muscle) may not be producing heat because it does not receive the signal properly or is unable to respond to the signal Either scenario can reduce H without altering the set-point temperature While alternation in thermoregulatory system is another requirement for the capability to undergo active hypometabolism further investigation is necessary to narrow down the mechanism of reduced H in daily torpor Determining whether specific parts of the brain are active or inactive during daily torpor will provide important clues to how the regulatory network of hypometabolism functions The other approach is to examine the peripheral tissue during torpor the overall reduction of the animal’s metabolism can be evaluated by analysing the VO2 from respiration the variations in hypometabolism among organs and tissues can only be evaluated by testing the metabolism in each component Because the basic metabolic rate varies among organs and tissues during euthermia the reduction in metabolic rate may also differ among organs and tissues during hypometabolism Investigating the localization of hypometabolism during daily torpor will offer new insights into the regulatory mechanism of active hypometabolism and may also offer clues to the mechanism by which the animal rewarms from a very hypometabolic state which is another requirement for an animal to safely enter a hypometabolic state If we could reduce the demand for oxygen by inducing active hypometabolism the patient could buy time by slowing the progress of brain damage and thus may survive periods of hypooxygenation Tissue and organ preservation can also benefit from induced hypometabolism Regenerative therapies have been approved for selected organs (Mandai et al. and clinical studies are underway for others One of the inherent problems in this field is how to preserve tissues or organs once produced Cooling is currently a mainstay for preserving organs reducing the metabolism by active hypometabolism may solve this problem Torpid animals do not have low metabolism because they are cold; they are cold because they have low metabolism Although it is tempting to investigate hypometabolism in an animal that is close to humans monkeys are difficult to use due to their limited availability Non-primate hibernators are alternative candidates for understanding the mechanism of hypometabolism but the seasonal effect of the hypometabolism is a burden for aggressive research we think mouse is an ideal animal to investigate hypometabolism for future clinical application this study has great importance as a pioneering and fundamental work to clarify the mechanism of active hypometabolism in mouse for the development of the next generation hypometabolic medicine All animal experiments were performed according to the guidelines for animal experiments of RIKEN Center for Developmental Biology and approved by the Animal Experiment Committee of the RIKEN Kobe Institute (Approval ID: AH27-05-4) C57BL/6NJcl mice were purchased from CLEA Japan and C57BL/6J mice were from Oriental Yeast Co. Until the mice were used in torpor experiments they were given food and water ad libitum and maintained in an ambient temperature of 21 °C Two C57BL/6NJcl male mice were used for the experiments shown in Fig. 1c,d; 57 C57BL/6J male mice were used for the rest of the experiments The age at the time of the experiment was 8.01 ± 0.15 weeks (mean ± SD each animal was housed in a temperature-controlled chamber (HC-100 and the temperature inside the chamber was monitored continuously by a temperature logger (Thermochron iButton a telemetry temperature sensor (TA11TA-F10 DSI) was implanted in the animal’s abdominal cavity under general inhalation anaesthesia at least 7 days before recording The metabolism of the animal was continuously analyzed by respiratory gas analysis (ARCO-2000 mass spectrometer the animal was monitored through a network video camera (TS-WPTCAM This video camera’s ability to record infrared movies made it possible to monitor the animal’s health during the dark phase without opening the chamber When the unobservable baseline of TB or VO2 is defined as a time-variable αk and the total number of days in the time series D the observed state Yt can be described as: αt is defined in a circulatory secondary trend model as Each daily torpor induction experiment was designed to record the animal’s metabolism for three days (Fig. 4a) The animals were introduced to the chamber the day before recording started (Day 0) The thermosensor implanted in the mouse was turned on before placing the mouse in the chamber We began recording metabolic data at the beginning of the light phase We assumed 5.3 cal of energy is equivalent to consumption of 1 ml of oxygen and 1 cal = 4.184 J was applied for unit conversion The Q10 temperature coefficient of oxygen consumption rate among normal and torpid condition was calculated in the following equation: Because most biological reactions proceed with a Q10 of ~2 or 339 if the Q10 during torpor is larger than this the decrease of oxygen consumption rate cannot be explained by simple temperature effect; rather it can be assumed that the metabolism was suppressed actively Hypometabolism during Daily Torpor in Mice is Dominated by Reduction in the Sensitivity of the Thermoregulatory System Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Natural hypometabolism during hibernation and daily torpor in mammals Advances in molecular biology of hibernation in mammals Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature Mechanisms of cell survival in hypoxia and hypothermia Effects of Mild Cold Shock (25 °C) Followed by Warming Up at 37 °C on the Cellular Stress Response Phase-specific central regulatory systems of hibernation in Syrian hamsters CNS regulation of body temperature during hibernation CNS regulation of body temperature in euthermic and hibernating marmots (Marmota flaviventris) An energy-based body temperature threshold between torpor and normothermia for small mammals Q10 and energy metabolism during daily torpor and hibernation in rodents Regulation of body temperature and energy requirements of hibernating alpine marmots (Marmota marmota) Concepts to utilize in describing thermoregulation and neurophysiological evidence for how the system works Thermoregulation: some concepts have changed Functional architecture of the thermoregulatory system CNS regulation of body temperature in euthermic hibernators Induced torpor in different strains of laboratory mice Torpor and nest-sharing in free-living Sminthopsis crassicaudata (Marsupialia) and Mus musculus (Rodentia) Torpor in mice is induced by both leptin-dependent and -independent mechanisms Food restriction increases torpor and improves brown adipose tissue thermogenesis in ob/ob mice Central adenosine receptor signaling is necessary for daily torpor in mice A role for the melatonin-related receptor GPR50 in leptin signaling SIRT1 activation ameliorates hyperglycaemia by inducing a torpor-like state in an obese mouse model of type 2 diabetes The pharmacology and molecular mechanisms underlying temperature regulation and torpor Cardiovascular changes during daily torpor in the laboratory mouse Sex differences in paradoxical sleep: influences of estrus cycle and ovariectomy Effects of estrogen and progesterone on sleep patterns of female rats Central circuitries for body temperature regulation and fever Integrative and Comparative Physiology 301 Cellular Level Brain Imaging in Behaving Mammals: An Engineering Approach Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis Streamlining of prehospital stroke management: The golden hour Physiology: Hibernation in a tropical primate - Even in the wound-down hibernating state Hibernation in the pygmy slow loris (Nycticebus pygmaeus): multiday torpor in primates is not restricted to Madagascar Stan Development Team. Stan: A C++ Library for Probability and Sampling. at http://mc-stan.org/ (2016) Stan Development Team. RStan: the R interface to Stan. at http://mc-stan.org/ (2016) R Core Team. R: A language and environment for statistical computing. at https://www.r-project.org/ (2016) Statistical Rethinking: A Bayesian Course with Examples in R and Stan Mammalian peripheral circadian oscillators are temperature compensated Download references Michiko Mandai and Take Matsuyama for insightful comments This work was supported by a Grant-in-Aid for Young Scientists (B) (Grant No designed the study and performed the experiments and analyses The authors declare no competing financial interests Download citation Sorry, a shareable link is not currently available for this article. The Journal of Physiological Sciences (2024) Journal of Comparative Physiology B (2023) Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. The Antimicrobial Stewardship Program (ASP) at Nebraska Medicine collaborated with a board-certified allergist to develop a penicillin allergy guidance document for treating inpatients with self-reported allergy. This guidance contains an algorithm for evaluating and safely challenging penicillin-allergic patients with beta-lactams without inpatient allergy consults being available. Both intravenous and oral beta-lactam graded challenges were implemented successfully in a hospital without a regular inpatient allergy consult service. They were well-tolerated, administered primarily in non-ICU settings, and were often ordered by non-specialist services. In patients with a self-reported penicillin allergy, these results demonstrate the utility and safety of a broadly adopted beta-lactam GC process. Volume 4 - 2023 | https://doi.org/10.3389/falgy.2023.1161683 This article is part of the Research TopicAntibiotic Allergy De-Labelling and ManagementView all 8 articles Background: The Antimicrobial Stewardship Program (ASP) at Nebraska Medicine collaborated with a board-certified allergist to develop a penicillin allergy guidance document for treating inpatients with self-reported allergy This guidance contains an algorithm for evaluating and safely challenging penicillin-allergic patients with beta-lactams without inpatient allergy consults being available Methods: Following multi-disciplinary review an order set for beta-lactam graded challenges (GC) was implemented in 2018 This contains recommended monitoring and detailed medication orders to challenge patients with various beta-lactam agents Inpatient orders for GC from 3/2018–6/2022 were retrospectively reviewed to evaluate ordering characteristics and whether documentation of the allergy history was updated All beta-lactam challenges administered to inpatients were included 157 GC were administered; 13 with oral amoxicillin and 144 with intravenous (IV) beta-lactams Ceftriaxone accounted for the most challenges (43%) All oral challenges were recommended by an Infectious Diseases consult service as were a majority of IV challenges (60%) Less than one in five were administered in an ICU (19%) 96%) were tolerated without any adverse event There was one reaction (1%) of hives and six (4%) involving a rash Allergy information was updated in the electronic health record after 92% of the challenges Conclusion: Both intravenous and oral beta-lactam graded challenges were implemented successfully in a hospital without a regular inpatient allergy consult service administered primarily in non-ICU settings and were often ordered by non-specialist services In patients with a self-reported penicillin allergy these results demonstrate the utility and safety of a broadly adopted beta-lactam GC process the parameter update focused on single to multi-step graded challenges and a proactive approach to de-labeling patients with penicillin allergies The following report describes an updated analysis (7) on our use of a graded challenge process and the associated changes to the Penicillin Allergy Guidance Document as a result of the Practice Parameter update The focus of this review was to assess characteristics of patients undergoing graded challenges and subsequent allergy documentation of beta-lactam graded challenges in patients with a self-reported penicillin allergy Patients with orders for a graded challenge with oral amoxicillin (January 2019–June 2022) or intravenous beta-lactam (March 2018–June 2022) were retrospectively reviewed Patients were included if they were admitted to Nebraska Medicine and received an intravenous or oral graded challenge and had a reported beta-lactam allergy documented If patients received single doses of amoxicillin for indications other than an oral challenge Patients were selected by providers to receive a graded challenge based on the need to receive a beta-lactam antibiotic and ASP's Penicillin Allergy Guidance document for treating inpatients with self-reported allergy The EHR-abstracted data included characteristics of the graded challenge (i.e. and infectious diseases consultation) and patient characteristics (i.e. Historical penicillin reactions were recorded and categorized based on the Penicillin Allergy Guidance Document The primary outcome was safety of the graded challenge as defined by characterization of reaction to the graded challenge Other outcomes included appropriateness of graded challenge need for intensive care unit (ICU) care due to allergic reaction days of therapy for challenged antibiotic class Data was abstracted from the EHR by manual review Descriptive statistics were used including counts and percentages for categorical variables and means and medians for continuous data This project was assessed by the Institutional Review Board at the University of Nebraska Medical Center as a quality improvement project and the need for full IRB review was waived Of the 161 intravenous graded challenges ordered, 147 were administered and 144 were IV beta-lactams. The others were discontinued prior to administration for reasons such as new culture susceptibility results. Additionally, of the 216 one-time amoxicillin orders, 203 were excluded due to indications other than an oral challenge. Thirteen oral amoxicillin challenges were administered. See Table 1 for a detailed description of patient characteristics Patient and graded challenge characteristics For the intravenous graded challenges (Table 1) the most common antibiotics challenged were ceftriaxone (43%) and cefepime (29%) The majority of the intravenous graded challenges were administered in a non-ICU setting (80%) and were recommended by an Infectious Diseases (ID) service (60%) All oral amoxicillin challenges were administered in a non-ICU setting and all were recommended by an ID service The most common oral amoxicillin challenge dose was a one-time 250 mg dose (85%) Of the 144 intravenous beta-lactam graded challenges, 137 (96%) were tolerated without any documented adverse event (Table 2). Of the seven with documented adverse events (Table 3) one developed hives that resolved after one dose of oral diphenhydramine The other six adverse events were either rash or itching One of these six patients did not require any rescue medications while the other five patients experienced resolution of rash or itching after one dose of oral diphenhydramine four of these patients received an intravenous graded challenge with ceftriaxone (7.5% of 53 challenges with this agent) The one patient that developed hives was administered a ceftriaxone graded challenge and had previously reported a penicillin allergic reaction of hives Two patients were transferred to the ICU prior to administration of the intravenous graded challenge due to staff request for enhanced monitoring; neither had a reaction All 144 intravenous beta-lactam graded challenges were deemed to be appropriate based on the updated AAAAI/ACAAI practice parameter and institutional guidance 132 (92%) of the patients had their allergy profile updated in the EHR The median subsequent duration of the challenged antibiotic class was six days with a majority (92/144) of patients receiving a course of ceftriaxone (37%) or cefepime (27%) Subpopulation of patients with reaction to intravenous graded challenge Of the 13 oral amoxicillin challenges, all were tolerated without any documented adverse event. No patients required ICU level of care or rescue medications (Table 2) Twelve (92%) of the oral amoxicillin challenges were deemed to be appropriate based on preset criteria (i.e. One patient was not classified as low-risk due to their documented penicillin allergic reaction as anaphylaxis with no charted date of the reaction; however the infectious diseases service was consulted and had documented explanation of the oral amoxicillin challenge and patient consent Twelve (92%) patients had their allergy profile updated in the EHR and the median subsequent duration of the challenged antibiotic class was 14 days The most common indications for subsequent antibiotic use after administering oral amoxicillin challenges were intra-abdominal abscess (31%) and neurosyphilis (23%) After the evaluation of graded challenge outcomes, the order set was updated to include oral amoxicillin. Previous institutional guidance did not include recommendations for de-labeling penicillin allergies in the inpatient setting. Therefore our Penicillin Allergy Guidance Document was also revised (Figure 1) to incorporate many of the updates included in the AAAAI/ACAAI Practice Parameter (e.g. Preset orders for cefazolin and ceftazidime/avibactam were added to facilitate future ordering Future guidance updates will incorporate additional recommendations for patients with allergies to cephalosporins and carbapenems Updated ASP recommendations for challenging penicillin allergic patients this review is unique in its aim to assess the safety and tolerability of both intravenous beta-lactam and oral amoxicillin challenges in a hospital setting through the successful use of graded challenges beta-lactams could often be utilized instead of vancomycin or clindamycin which are associated with less nephrotoxicity and Clostridioides difficile infection This review demonstrated that intravenous and oral graded challenges can be administered in a non-ICU level of care and without infectious diseases or allergy consultation. Previous literature supports the safety of both inpatient and outpatient intravenous and/or oral graded challenges (9, 12, 15, 25) This process was implemented at our institution through provider education and buy-in from nursing staff to understand the safety of graded challenges in patients with self-reported beta-lactam allergies education to providers improved their understanding and utilization of our ASP Penicillin Allergy Guidance Document more non-ID clinicians ordered a graded challenge for a patient with a self-reported beta-lactam allergy The ability to streamline and implement ASP guidance regarding graded challenges was due This order set has clearly defined monitoring parameters and rescue medications to ensure patient safety when administering the graded challenge Patient allergy profile updates and documentation of successful graded challenge completion occurred for over 90% of patients. Drug allergy documentation and updated drug allergy profiles are important not only for patient safety but also quality of care (27) Inpatient beta-lactam allergy documentation and interventions require an interdisciplinary approach where all healthcare providers interacting with the patient should be assessing their allergy history and recording it in the EHR One of the challenges with allergy documentation is that it can be re-added even after a patient has undergone a successful graded challenge the ASP team in conjunction with the University of Nebraska Medical Center's Division of Allergy and Immunology identified the opportunity to create a pharmacy consult Nurses initiate the consult after communication of monitoring parameters to the graded challenge and pharmacists document a permanent note in the EHR outlining the outcome of the intravenous or oral graded challenge and it may also prevent unnecessary repeated graded challenges This review shows the applicability and real-world experience of successfully implementing penicillin allergy guidance algorithms and a graded challenge order set in an inpatient setting without direct allergy/immunology consultation but we recognize that there are also several limitations the majority of the graded challenges were intravenous we saw this as an opportunity to provide updated penicillin allergy guidance that incorporates an oral amoxicillin challenge and additional education to our clinicians on the safety and utility of oral amoxicillin challenges to help de-label penicillin allergies inpatient we recognize that this warrants further study to determine if a two-step oral amoxicillin challenge is required instead of the one-step challenge we utilized we did not compare our graded challenges with penicillin skin testing for patients with self-reported penicillin allergies; however this is in line with the more recent drug allergy practice parameter and since no patients had documented follow-up with allergy after hospital discharge we did not prospectively follow the patients administered a graded challenge to determine how this impacted selection of any future antimicrobial courses after the first during this review period there were no repeated graded challenges in the same patient which we attribute to the high percentage of updated allergy profiles our review demonstrated that based on previous and current drug allergy practice parameter updates in combination with ASP allergy guidance both intravenous and oral graded challenges are safe and well-tolerated in an inpatient population The original contributions presented in the study are included in the article/Supplementary Material further inquiries can be directed to the corresponding author/s Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements and SM: contributed to conception and design of the project and wrote the first draft of the manuscript All authors contributed to the article and approved the submitted version 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 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 The diagnosis and management of anaphylaxis practice parameter: 2010 update Drug allergy: an updated practice parameter Healthcare utilization and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study The use of cephalosporins in penicillin-allergic patients: a literature review CrossRef Full Text | Google Scholar 5. Wolfe M, Bergman SC, Van Schooneveld TC, May SM. Penicillin allergy guidance document. Omaha (NE): Nebraska Medicine (2017). Available at: https://www.unmc.edu/intmed/_documents/id/asp/penicillin_allergy_guidance_document_v7.pdf Drug allergy: a 2022 practice parameter update Use of a beta-lactam graded challenge process at an academic medical center Google Scholar Predictive factors of amoxicillin immediate hypersensitivity and validation of PEN-FAST clinical decision rule Oral amoxicillin challenge for low-risk penicillin allergic patients Establishing amoxicillin allergy in children through direct graded oral challenge (GOC): evaluating risk facotrs for positive challenges and risk of cross-reactivity to cephalosporines Amoxicillin oral provocation challenge in a primary care clinic: a descriptive analysis De-labeling penicillin allergy in acutely hospitalized patients: a pilot study Direct challenges to penicillin-based antibiotics in the inpatient setting Comparing direct challenge to penicillin skin testing for the outpatient evaluation of penicillin allergy: a randomized controlled trial Safety and outcomes of oral graded challenges to amoxicillin without prior skin testing Efficacy and safety of 5-day challenge for the evaluation of nonsevere amoxicillin allergy in children Direct oral amoxicillin challenge without antecedent penicillin skin testing in low-risk patients CrossRef Full Text | Google Scholar Amoxicillin challenge without penicillin skin testing in evaluation of penicillin allergy in a cohort of marine recruits De-labeling self-reported penicillin allergy within the emergency department through the use of skin tests and oral drug provocation testing Identifying allergic drug reactions through placebo-controlled graded challenges Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and nonimmediate reactions to amoxicillin in children Outcomes from an inpatient beta-lactam allergy guidance across a large US health system A proactive approach to penicillin allergy testing in hospitalized patients Tackling inpatient penicillin allergies: assessing tools for antimicrobial stewardship Addressing inpatient beta-lactam allergies: a multihospital implementation Consequences of avoiding beta-lacatms in patients with beta-lactam allergies CrossRef Full Text | Google Scholar Redesigning the allergy module of the electronic health record Appropriateness of aztreonam use after education and implementation of a Beta-lactam graded challenge process Vizient consortium pharmacy user group meeting NV: Vizient Consortium Pharmacy User Group Meeting (2019) Van Schooneveld TC and May SM (2023) Use of a beta-lactam graded challenge process for inpatients with self-reported penicillin allergies at an academic medical center Received: 8 February 2023; Accepted: 29 June 2023;Published: 31 July 2023 © 2023 Sunagawa, Bergman, Kreikemeier, Watkins, Alexander, Miller, Schroeder, Stohs, Van Schooneveld and May. 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Sunagawa c3N1bmFnYXdhQG5lYnJhc2thbWVkLmNvbQ== 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 For the umpteenth time I certainly don’t know enough about the insider workings of the yakuza to know how realistic The Fable is in that respect and the whole mythical hitman organization angle plays like a dramatic MacGuffin (and a good one) But the “mundane” elements of mob existence are another matter One can easily imagine this is how is works and that the average low-ranking hood isn’t far off how they’re depicted here What helps in that respect is how nonchalantly The Fable plays most of this stuff The minimalist production is obviously mostly a cost-saving measure But there are times when a lack of style can actually be a style (whether intentionally or not) And this episode is a case where that happens in very effective terms tricksy cinematography – makes the horror of what we’re watching play out that much more affecting It’s just life on the other side of the curtain Rules are rules It seems pretty clear that Ebihara took out Kojima as a means of making peace with Sunagawa – a tacit admission that Kojima had taken out Sunagawa’s business partner Ebihara stone-faces his way through this ugliness but he’s not a robot – this had to cut him pretty deep Ebihara is demonstrating his loyalty here – the family over his family He probably knew all along that it would come to this eventually – that his brother was an irredeemable troublemaker and that most of the trouble would land on him The most impactful part of this for me was his asking Akira “What do you think?” – and Akira’s lack of response Ebihara is expressing grief in the only manner he feels he can and trying to understand just what sort of man Akira is And Akira has no answer for this – he simply doesn’t operate on that level detached reply – and that answers Ebihara’s questions about him But Akira did what he promised to do – a promise Ebihara knows was not his to extract a violation of the terms his group had agreed to with Fable which Akira simply lacks the emotional literacy to realize were not ones he should have made With Kojima out of the picture, the focus now turns to Sunagawa – both in terms of his second target and his unhealthy interest in Fable. And then there’s Kuro who despite orders from Ebihara immediately starts grilling Takahashi and Kickboxer (does he have a name?) about the mysterious hooded hitman Kuro’s interest is purely personal – he has a man-crush – but it still has the potential to create enormous problems both for himself and for Maguro Those final moments between Ebihara and Kojima would not have felt out of place in The Sopranos to me honestly and I don’t consider there be a greater “crime show” than that one Definitely the highlight of the episode for me The animation quality was quite hard to stomach at first but I’ve similarly found the story to be compelling enough to look past it It’s become one of my favorite parts of each Saturday afternoon That absolute SLAPPER of an ending theme doesn’t hurt in that regard There’s a moment where Fable walks through the garage after the cleanup and glances at the chair where Kojima had laid and it seems like he experiences some emotion and it’s interesting that it’s brought about by Kojima of all people There’s an interesting philosophical issue here – can Fable be okay with essentially taking Kojima to be murdered because he would have been murdered slightly earlier had he not I hope this issue will be explored further in the next cour Was Kojima actually Shrimp Man’s little brother With all the aniki thrown around I assumed it was just the Yakuza senpai-kohai thing which as far as I know (and I don’t know that much) isn’t yakuza-jargon It was always my impression that they were literally brothers – I mean I did note Akira looking over as he left the room I’m not so sure if it’s something so simple as him feeling emotion I got the sense that he was trying to understand Ebihara’s feelings in that moment this was one of my favourite of the season I almost dropped it in the beginning but glad i stuck with it the lowFi style which was a distraction in the start begins to remind me of those b-grade cult films that tarantino references to I am glad it’s continuing with the second cour Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" Please consider becoming an LiA patron through one of the methods below and the episodes leading up to the finale of Kamen Rider Zero-One Oricon: How do you feel about your role in Kamen Rider Zero-One my character Horobi and I look completely different so I’ve only ever been recognized one time in public (laughs) But my family and friends who like the franchise are watching it without being weird about it there are actually a lot of people who like him Sunagawa: Izu is a beloved character in Zero-One I’m glad that the audience understood Horobi’s inner feelings I portrayed Horobi in a way where a tiny bit of him would regret doing what he did to Izu I’m glad that the audience caught that – if Aruto represented the justice of humans then Horobi represented the justice of Humagears Horobi will continue to fight without deterring from his beliefs Maybe it’s strange to say that since I’m the one who’s portraying him but he never strays from his beliefs Human extinction has been his goal since episode 1 Horobi killed Izu with more emotion than just evil intention We actually did a lot of takes to get the filming right For the longest time he didn’t have any emotions and just until episode 40 he spoke in a normal tone Oricon: What did you and Tsurushima (who portrays Izu) discuss before filming that scene I didn’t think I had to have any speaking lines with her When I’m with Daisuke Nakagawa (portrays Jin) we talk about how we should act on the bus But that scene we had was heavy so we didn’t talk at all I learned a lot about expressing emotions on episode 42 thanks to Director Ryuta Tasaki How do you feel about this past year when you look back at it in the time I was a regular I feel like I’ve made one step forward in my career And I feel like I’ve deepened my relations with my costars Nakagawa (who portrays Jin) was really easy to talk to on set – he was a warm person to be around We talked about going to my hometown Okinawa And in the episodes leading up to the finale Fumiya (portrays Aruto) and I had a lot more scenes together He’s definitely the lead and has developed the sense of responsibility Oricon: Can you talk about a time when you were noticed when I was walking with Fumiya or Nakagawa but he tapped me on the shoulder from behind and told me: “Sunagawa-san I’m always watching you.” I was so happy (laughs) it’s like they were saying “You’re the only one for me” Oricon: So Horobi is a Father-Type Humagear Did you have any fatherly expressions that you tried to keep in mind I have more photos of Nakagawa than I have of myself I don’t have any kids so I’m not sure what it means to be a dad Oricon: What kind of roles do you want to do moving forward Sunagawa: I want to try a more relaxed role I’ve had the villain role for a year now I’d be willing to give an unexpected role a chance too I wanna try wearing a school uniform and confess under the cherry blossom tree (laughs) I didn’t get to experience that kind of life so it’s on my mind Source: Oricon Metrics details human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution By combining previously published empirical clinical data analysis and multi-level mathematical modeling we find that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher peak in viral load dynamics but a shorter duration of infection Selection for increased transmissibility shapes the viral load dynamics and the isolation measure is likely to be a driver of these evolutionary transitions we show that a decreased incubation period and an increased proportion of asymptomatic infection are also positively selected for as SARS-CoV-2 mutated to adapt to human behavior (i.e. The quantitative information and predictions we present here can guide future responses in the potential arms race between pandemic interventions and viral evolution but how viral load dynamics are altered in vivo has not yet been explored We were thus interested in the role of isolation as a strong NPI and explored the possible impact of such human behavioral changes on SARS-CoV-2 evolution individual-level virus infection model) considering both individual and variant-specific variations in kinetics to explain and predict the evolutionary patterns of SARS-CoV-2 variants in terms of the time-series pattern of viral load we developed a multi-level population dynamics model by coupling a population-level virus transmission model with the individual-level virus infection model Under different clinical phenotypes for COVID-19 patients defined here as the incubation period and the proportion of symptomatic infections we evaluated how the time-series patterns of viral load and evolve under isolation of infected individuals We interestingly demonstrate that NPIs may select for earlier and higher peak viral load but shorter duration of infection in SARS-CoV-2 Although there are multiple ways to cause the recent evolutionary trajectory the concepts and variables that affect the current transition can be anticipated We discuss the potential evolution of SARS-CoV-2 as it adapts to maximize transmissibility in the presence of a human behavior change The distributions illustrated alongside the top and right parts are for the cumulative viral load and the duration of viral shedding f The time-dependent transmission probability of each variant is calculated mainly characterized by an advanced peak time and a shorter duration of viral shedding compared with the pre-Alpha variants suggesting tFhe evolutionary process promotes effective and rapid transmission within human populations (see below for details) These findings demonstrate that the Alpha-like and the Delta-like variants showed a high peak viral load but a relatively short duration of viral shedding as the virus evolved among human populations Symptomatic patients primarily generate secondary infections prior to symptom onset asymptomatic patients can be infectious during the whole duration of viral shedding defined as the isolation of symptomatic infected individuals after symptom onset could be a driving force for SARS-CoV-2 evolution Note that although we can easily incorporate variant-specific virological characteristics such as infectivity per virus by changing the probability of transmission (see METHODS) we ignore these differences here for simplicity The sum of newly infected individuals (i.e. [\(c\left(t\right)\): number of contacted individuals per day (everybody is susceptible)] × [\(\rho \left(t\right)\): transmission probability per contacted individual]) during the infectious period is calculated as \({R}_{{TP}}\) Note that the focal infectious individuals are assigned one of two properties: symptomatic or asymptomatic Whether being symptomatic or asymptomatic is randomly assigned by a constant probability f or 1-f It is assumed that the transmission chains from the focal symptomatic infectious individuals are perfectly inhibited by isolation after symptom onset \({R}_{{TP}}\) is calculated using the whole duration of viral shedding of the focal asymptomatic infectious individual \({R}_{{TP}}\) for the symptomatic and asymptomatic individuals are different here from the assumption that the virus evolves to increase its “transmission potential” the total number of secondary cases generated throughout the infectious period) we calculate \({R}_{{TP}}\) under various patterns of infection rate the transmissibility fitness landscape of \({R}_{{TP}}\) is constructed as a function of \(\left(\beta,p\right)\) and the proportion of symptomatic patients Note that the transmissibility fitness landscape of \({R}_{{TP}}\) is constructed as a function of only β and p because the other parameters or initial values are estimated or determined (see METHODS) we considered the (additional) effect of isolation which is only applicable to symptomatic individuals and which assumes that isolation always perfectly prevents the transmission chain (i.e. which is applicable to all individuals regardless of symptomatic or asymptomatic infection (e.g. is assumed to be involved in the parameters in our multi-level model without loss of generality because of smaller transmission potential (i.e. secondary [focal] infectious individuals may not be effectively generated and sometime less than one) isolation-driven evolution might be unlikely to occur under this situation The black line is the mean trajectory of the GA through 300 generations b The mean transmissibility fitness landscapes aggregated solely from the asymptomatic (top row) and symptomatic (bottom row) individuals are described The white dot represents the maximum value of the mean transmissibility fitness Note the asymptomatic individuals have larger transmissibility fitness than symptomatic cases on average c The trajectories of \({R}_{{TP}}\) along the course of GA with different \({T}^{*}\) are calculated The gray dotted lines are the mean trajectory over 100 trials of colored lines d The time-series patterns of viral load with the optimal parameters of (β,p) with different \({T}^{*}\) e The contour-plot for the timing of peak viral load (i.e. The gray region is the parameter range satisfying \({R}_{{TP}} \ the higher proportion of symptomatic infection enhances the selection pressure for virus evolution via isolation these results suggest that while isolation inhibits the chain of transmission from symptomatic focal infectious individuals after symptom onset SARS-CoV-2 evolves toward the acute phenotypes we conducted further analysis to investigate the impact of prior immunity caused by vaccinations or prior infections on our findings These confirmed that the statistical trend for SARS-CoV-2 evolution is remained regardless of the prior infections The selective pressure for increased transmissibility shapes the viral load dynamics and isolation measures are likely to be a critical driver of these evolutionary transitions even considering the prior immunity and the error bands represented as shadow regions indicate the 95% interquantile range of the inferred viral load interval for all individuals at each time point c The distributions of the peak viral load and duration of viral shedding for each patient are shown with their mean values (vertical solid bars) A statistically significant difference between two groups was found only for peak viral load (p-values by the two-sided Mann-Whitney-Wilcoxon test are \(1.3\times {10}^{-6}\) for peak viral load We discuss a mechanism behind those convergent phenotypic changes in detail later (see Discussion) Our quantitative empirical clinical data analysis based on our hypothesis could support that SARS-CoV-2 variants have evolved their acute phenotypes via a human-mediated selection pressure such as isolation using quantitative empirical data analysis and the multi-level population dynamics model we suggested that isolation potentially plays the role of a human-mediated selection pressure for SARS-CoV-2 evolution the current framework of our multi-level model cannot explain the evolution of a “stealth” phenotype showing a decreased peak viral load with a high proportion of asymptomatic infection A further detailed analysis is required once numerous datasets of different Omicron subvariants While strictly demonstrating the influence of population-level immune status on viral evolution through empirical data analysis may pose challenges we maintain that our research offers significant insights into the potential interplay between human behavior changes and viral evolution mutation-selection balance is not negligible when discussing the evolutionary and epidemic outcomes in the future We assumed that isolation truncated transmissibility time-series so that an earlier peak was selected for in a plausible way there may be another selection pressure to increase the number of secondary infections by increasing the initial slope of viral load dynamics and how favorable they are compared with other strains should all be combined to predict the future trajectory of COVID-19 Although several types of COVID-19 vaccine are now available many breakthrough infections are still being observed NPIs still play an important role in controlling the COVID-19 pandemic It is also expected that new variants of concern after Omicron will become dominant assuming that new variants and other pathogens will emerge in the future it is important to consider the evolution of pandemic viruses when shaping public health strategies We searched for longitudinal viral load data from COVID-19 patients categorized with pre-Alpha and Omicron variants in PubMed and Google Scholar Data meeting the following criteria were used to estimate parameters of the viral dynamics model: (1) viral loads were assessed at two time points or more and (2) samples were collected from the upper respiratory tract Because all the data were extracted from published papers ethics approval was not required in this study To describe SARS-CoV-2 dynamics among susceptible target cells we used a simple mathematical model for virus infection dynamics to define viral load for each patient: and \({V}\left({t}\right)\) are the number of uninfected target cells and the amount of virus at time t since infection and c represent the rate constant for virus infection which we employed to analyze the viral load data in this study: where \(\gamma=p\beta T\left(0\right)/c\) corresponds to the maximum viral replication rate under the assumption that target cells are continuously depleted during the course of infection \(f\left(t\right)\) is equal to or less than 1 and continuously declines The dynamics of viral load calculated by this individual-level virus infection model will be translated into a probability of transmission and used in the following population-level model where k and θ are the shape parameter and the scale parameter, respectively (see Table S3) and θ influences the variance of the distribution The mean contact number through the history is the product of k and θ we simply employed the step function as the range of viral load; thus the transmission probability \(\rho \left(t\right)\) at time t is described by For example, \(\rho \left(t\right)\) for SARS-CoV-2 variants are calculated based on Eq. (3) in Fig. 1f In addition, since there is a positive correlation between the duration of viral shedding (D) and the cumulative log-transformed viral load (\({V}_{{{{{{\rm{total}}}}}}}\)) for COVID-19 patients observed in Fig. 1e and thus the transmissibility fitness landscape of \({{R}}_{{{TP}}}\) is constructed as a function of β and p We here simply assumed the transmission chains from the focal infectious individuals are perfectly inhibited by isolation after symptom onset if the focal infectious individual is symptomatic we stopped calculating the cumulative number of secondary cases at symptom onset Symptom onset starts after \({{T}}^{{*}}\) days of infection GA starts with an arbitrary set of parameters (β,p) and initial values (Initialize) and calculates \({{R}}_{{{TP}}}\) as transmissibility fitness (Evaluate) the values of (β,p) with higher \({{R}}_{{{TP}}}\) are selected to produce the next solutions (selectSolutions) the two highest-performing solutions are always chosen for the next iteration (Elitism) and each parameter is slightly altered by adding a random variable drown from a Uniform distribution with a pre-determined range (Mutate) which corresponds to the rate of evolutionary change of the virus we explore a better set of values (β,p) that maximizes \({{R}}_{{{TP}}}\) Note that the set of values at the end of the GA run is not necessarily a global optimum These iterations can be considered as the virus “evolving” its properties of β and p toward an optimal solution so that the virus can increase its own fitness in the evolutionary history Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article Humans as the world’s greatest evolutionary force COVID-19 lockdown allows researchers to quantify the effects of human activity on wildlife The influence of vector-borne disease on human history: socio-ecological mechanisms After the pandemic: perspectives on the future trajectory of COVID-19 Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England Development of a model-inference system for estimating epidemiological characteristics of SARS-CoV-2 variants of concern Generation time of the alpha and delta SARS-CoV-2 variants: an epidemiological analysis Rapid increase in Omicron infections in England during December 2021: REACT-1 study Qu, P. et al. Distinct neutralizing antibody escape of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2. bioRxiv 2022.10.19.512891, https://doi.org/10.1101/2022.10.19.512891 (2022) Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans genomic diversity and global spread of SARS-CoV-2 Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies Designing isolation guidelines for COVID-19 patients with rapid antigen tests Revisiting the guidelines for ending isolation for COVID-19 patients A quantitative model used to compare within-host SARS-CoV-2 and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2 Detection of significant antiviral drug effects on COVID-19 with reasonable sample sizes in randomized controlled trials: A modeling study Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies An investigation of transmission control measures during the first 50 days of the COVID-19 epidemic in China Effect of non-pharmaceutical interventions to contain COVID-19 in China The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak The effect of large-scale anti-contagion policies on the COVID-19 pandemic Respiratory virus shedding in exhaled breath and efficacy of face masks Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study The impact of COVID-19 nonpharmaceutical interventions on the future dynamics of endemic infections Serial interval of SARS-CoV-2 was shortened over time by nonpharmaceutical interventions Modeling the evolution of SARS-CoV-2 under non-pharmaceutical interventions and testing Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: A retrospective cohort study Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective Viral dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated persons Timing of antiviral treatment initiation is critical to reduce SARS-CoV-2 viral load Contact-number-driven virus evolution: A multi-level modeling framework for the evolution of acute or persistent RNA virus infection Garrett, N. et al. High rate of asymptomatic carriage associated with variant strain Omicron. medRxiv 2021.12.20.21268130, https://doi.org/10.1101/2021.12.20.21268130 (2022) Incubation period of COVID-19 caused by unique SARS-CoV-2 strains: a systematic review and meta-analysis Vaccination and non-pharmaceutical interventions for COVID-19: a mathematical modelling study and the SARS-CoV-2 delta variant in England: a mathematical modelling study Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 vaccine Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic Hay, J. A. et al. Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant. medRxiv 2022.2001.2013.22269257, https://doi.org/10.1101/2022.01.13.22269257 (2022) Marc, A. et al. Impact of variants of concern on SARS-CoV-2 viral dynamics in non-human primates. bioRxiv 2022.2011.2009.515748, https://doi.org/10.1101/2022.11.09.515748 (2022) Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe The proportion of SARS-CoV-2 infections that are asymptomatic: a systematic review Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis Estimation of the incubation period of COVID-19 using viral load data Impact of SARS-CoV-2 Delta variant on incubation transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France Evolution of human respiratory virus epidemics tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults Virulence-driven trade-offs in disease transmission: A meta-analysis Increased household transmission and immune escape of the SARS-CoV-2 Omicron compared to Delta variants Antigenic escape selects for the evolution of higher pathogen transmission and virulence Substantial impact of post-vaccination contacts on cumulative infections during viral epidemics Epistasis at the SARS-CoV-2 receptor-binding domain interface and the propitiously boring implications for vaccine escape Epidemic spreading under mutually independent intra- and inter-host pathogen evolution Physical distancing versus testing with self-isolation for controlling an emerging epidemic Number of infection events per cell during HIV-1 cell-free infection Transmission of COVID-19 in 282 clusters in Catalonia Viral load difference between symptomatic and asymptomatic Covid-19 patients: systematic review and meta-analysis Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea Adaptation in natural and artificial systems: an introductory analysis with applications to biology Sunagawa, J. & Park, H. Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution (https://zenodo.org/records/10031081) Download references This study was supported in part by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2022R1C1C2003637) (to K.S.K.); Grant-in-Aid for Transformative Research Areas A 22H05215 (to S.I.) JSPS Scientific Research (KAKENHI) B 18H01139 (to S.I.) Scientific Research in Innovative Areas 20H05042 (to S.I.); JSPS Overseas Research Fellowships (to R.Y.); ACT-X JPMJAX22AK (to R.Y.); AMED CREST 19gm1310002 (to S.I.); AMED Development of Vaccines for the Novel Coronavirus Disease 21nf0101638s0201 (to S.I.); AMED Japan Program for Infectious Diseases Research and Infrastructure 20wm0325015s0301 (to S.I.); AMED Research Program on HIV/AIDS 22fk0410052s0401 (to S.I.); AMED Research Program on Emerging and Re-emerging Infectious Diseases 20fk0108140s0801 (to S.I.) 21fk0108428s0301 (to S.I.); AMED Program for Basic and Clinical Research on Hepatitis 21fk0210094 (to S.I.); AMED Program on the Innovative Development and the Application of New Drugs for Hepatitis B 22fk0310504h0501 (to S.I.); AMED Strategic Research Program for Brain Sciences 22wm0425011s0302; AMED JP22dm0307009 (to K.A.); JST MIRAI JPMJMI22G1 (to S.I.); Moonshot R&D JPMJMS2021 (to K.A and S.I.) and JPMJMS2025 (to S.I.); Institute of AI and Beyond at the University of Tokyo (to K.A.); Shin-Nihon of Advanced Medical Research (to S.I.); SECOM Science and Technology Foundation (to S.I.) We would like to thank Sarah Otto for her helpful feedback on earlier versions of the manuscript These authors contributed equally: Junya Sunagawa These authors jointly supervised this work: Shingo Iwami Department of Advanced Transdisciplinary Sciences interdisciplinary Biology Laboratory (iBLab) Institute for Life and Medical Sciences (LiMe) Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research International Research Center for Neurointelligence The University of Tokyo Institutes for Advanced Study Institute for the Advanced Study of Human Biology (ASHBi) Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS) Japanese Foundation for Cancer Research (JFCR) Department of Zoology & Biodiversity Research Centre All authors contributed to writing the manuscript 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/s41467-023-43043-2 Shuya Sunagawa held an event on April 24 to commemorate the release of his first photobook the actor for Horobi in Kamen Rider Zero-One held an event in Tokyo to commemorate the release of his first photobook Sunagawa interacted with fans through an acrylic sheet Sunagawa stated that he has “always wanted to say thank you” to his fans He said he was grateful for the opportunity to thank his fans with a smile despite the circumstances The book also contains an interview about the actor’s life and career The book has 112 pages and is available for 3080 yen Source: MANTANWEB The photobook will show two different sides of the Kamen Rider Zero-One actor Shuya Sunagawa’s first photo book will be named BASE and will include photos taken in Okinawa and Tokyo both of which Sunagawa considers his hometowns The Okinawa photos of Sunagawa will show the “true expressions” unique to the locale while the Tokyo photos will have a completely different look An interview with Sunagawa about his work as an actor and his private life will also be recorded for the book Sunagawa portrayed Kamen Rider Horobi in Kamen Rider Zero-One which just finished airing this past August “I’m very happy to publish my first photo book This photo book is my starting point and will be a collection of photos taken in my two ‘bases’ as I grow: Okinawa and Tokyo you can express the inner you that is surrounded by your favorite things I would be happy if you could take away some feelings about the environments and locations that raised me.” will be holding bookstore commemoration events for its release Sources: Mantan Web, Shuya Sunagawa Official Site Ashton is a medical professional that makes tokusatsu videos in his spare time The chief justice of the Supreme Court met with an interested party in a high-profile military base in Japan that the top court was actively hearing and provided the party with information concerning the trial The shocking revelations about this unprecedented scandal where the nation’s highest jurist engaged in unethical and potentially unlawful conduct have seriously eroded public trust in the judicial system A recent court ruling that said the chief justice did not violate any law cannot convince the public 15 dismissed a lawsuit filed by people convicted 67 years ago in the so-called Sunagawa Incident in which some protesters against the expansion of a U.S Air Force base in the Tokyo suburbs entered the air base and were consequently indicted The three plaintiffs of the latest suit claimed that they did not receive a fair trial were arrested and indicted for violating a special criminal law based on the Japan-U.S The Tokyo District Court acquitted the defendants military presence violated Article 9 of the Constitution and the special criminal law was “invalid.” the Grand Bench of the Supreme Court overturned the ruling stating the case involved an issue of a “highly political nature” and was “unsuitable for judicial judgment,” rendering a guilty verdict against the defendants it was revealed from 2008 that Kotaro Tanaka the then chief justice of the Supreme Court who presided over this case ambassador to Japan and other officials before the verdict and discussed the proceedings Tanaka expressed his view that the district court ruling was “inappropriate” and his expectations that the lower court decision would be overturned in “a unanimous decision by the 15 judges.” These revelations naturally raise doubts about what transpired leading up to the verdict 15 district court ruling did not recognize the illegality of the former chief justice's actions Even if the former chief justice had made remarks referring to the trial in conversations with the ambassador and other U.S it cannot be recognized that there was any special relationship that brought bias or prejudice to the case there was no evidence that the chief justice made judgments outside of the court procedures dismissing the plaintiffs’ claim that it was not a “fair court” as demanded by the Constitution The judgment is far removed from the fairness that citizens expect from trials and courts The chief justice should have avoided any unofficial meetings with an interested party and could have invited suspicions of leaking confidential information if he had discussed the proceedings with such a party The court also stated that the ambassador and other U.S government was closely watching to see if the lower court decision would be overturned in light of the upcoming revision of the bilateral security treaty Multiple contacts between the chief justice and U.S officials could have undermined the foundation of “judicial independence” that Tanaka himself championed since his appointment who was a student at Meiji University at the time of the incident “I felt proud when I heard the not-guilty ruling but I doubted the legitimacy of the judiciary when I later was convicted.” documents that referred to Tanaka’s actions and they filed the lawsuit seeking compensation from the state The Supreme Court has always preached that judges should not only be fair but also appear to be impartial How does this apply to the former chief justice The judiciary should sincerely address the doubts raised over the important top court precedent that represents one landmark in the nation’s post-war history Court blocks bid by 7 for Minamata disease recognition EDITORIAL: Swift retrial only way to ensure Hakamada receives justice Activating a certain brain circuit causes mice and rats—non-hibernating animals—to enter a hibernation-like state This finding could have implications for other non-hibernating mammals and it might eventually find application in space travel and the transportation of seriously injured patients survive the harsh temperatures and food scarcity of winters by hibernating Hibernation is essentially an energy-saving mode since it lowers the metabolic rate allowing an animal to expend much less energy than normal “Some squirrels when they enter hibernation their oxygen consumption rate drops to 1% its normal level,” says Genshiro Sunagawa of the RIKEN Center for Biosystems Dynamics Research “That’s just amazing—I don’t know why they don’t die.” Takeshi Sakurai’s group at the University of Tsukuba made the remarkable discovery that injecting genetically engineered mice with a certain compound lowered their body temperature by about 10 degrees Celsius for more than 12 hours (Fig This was surprising because it indicated that mice have the ability to either turn off the heater of their body or to lower their body temperature set point—something that was considered to be unique to hibernating animals Sakurai and co-workers have shown that mice and rats lower their temperature set point And they have pinpointed the brain circuit that is responsible for causing rodents to enter this hibernation-like state they identified a set of neurons in the hypothalamus—a small region in the brain that regulates body temperature among other things—that induces the hibernation-like state when activated by either injection with the compound or stimulation by light If a similar neural circuit exists in humans it would open up the possibility of inducing low-metabolic states in people This would have many exciting applications “It takes one and a half years to travel to Mars,” notes Sunagawa “If we can reduce an astronaut’s metabolism to 10% its normal level food and water they need during the flight by the same amount.” An application that is closer to home is the transportation of sick patients to and between hospitals This possibility first got Sunagawa interested in hibernation “I used to be a pediatrician and sometimes there were kids who were too sick to be transferred to a hospital with the facilities they needed,” he recalls we had to give up treating them—it was heartbreaking.” If patients could be induced into a lower metabolic state Metrics details Full-field electroretinograms (ERGs) are used to objectively assess the mass function of the retina whereas focal ERGs are used to evaluate the focal retinal function The purpose of this study was to determine the usefulness of a multiple electrode array (MEA) system for recording ex vivo micro ERGs (mERGs) together with multiunit spike responses of the retinal ganglion cells (RGCs) to assess focal retinal function in isolated mouse retinas The a- and b-waves of the full-field ERGs were present in the mERG an inhibitor of the mGluR6 receptor and the OFF-component was blocked by exposure to PDA an antagonist of ionotropic glutamate receptors mERGs were also recorded from mice with progressive retinal degeneration from which conventional full-field ERGs are non-recordable A blockade of the glutamate receptors indicated that the negative wave of rd1 mice do not originate from the photoreceptors but from the second or third order neurons This technique of recording mERGs will be useful in assessing the focal properties of the retinas obtained from eyes with pathology and also to follow the recovery of the physiology of the retina in regenerative studies ERGs can be used to determine which neural elements of the retina are the cause of a specific pathologic condition and the findings can contribute to making a diagnosis This has been done in eyes with photoreceptor degenerative diseases and bipolar cell dysfunction because of the difficulty in focusing the stimuli on focal areas in small eyes in situ and in eliminating the effects of stray light recording mfERGs from mice and rats are still challenging We studied mERGs during the degenerating process in these mice and studied the different components of the mERGs with the use of two glutamate receptor inhibitors We were able to record light-evoked mERGs together with consistent RGC spike responses the negative wave did not originate from the photoreceptors as normally observed in wild type retina but from the OFF bipolar cells and/or third order neurons Representative micro ERGs (mERGs) and retinal ganglion cell (RGC) multiunit spike responses recorded with a multi electrode array (MEA) system from isolated C57BL/6 mouse retinas (a) Averaged micro electroretinograms (mERGs) with 2 different anchor weights Eight x 8 panels of waves indicate the recordings from 64 electrodes (b) The number of channels in which the b-waves were detected with the 1 g and 2 g anchor weights and the averaged b/a amplitude ratios “n” indicates the number of retinas tested (c) Representative mERG from Channel 24 of Fig 1a (averaged from the responses to 3 serial stimuli) (d) Multiunit RGCs responses in the retina in Fig 1a with 1.0 g anchor (averaged from the responses to 3 serial stimuli) The red bar indicates the light stimulus onset and offset (e) Representative RGC layer nuclei over one electrode after DAPI nuclear staining The white dotted square indicated MEA electrode The counted RGCs were of single layered structures in the XZ and YZ planes We evaluated the effect of the stimulus intensity on the amplitudes of the a- and b-waves of the mERGs in the dark-adapted retina. The results showed that the amplitudes of both the a- and the b-waves increased as the intensity increased and the amplitudes of both waves decreased after 20 min of light-adaption by 1.67 log cd/m2 (Fig. 2 mean ± SD, 192 electrodes of 3 retinas). Light intensity dependency of mERGs of C57BL/6 mouse retinas (a) Representative mERG responses elicited by different light intensities (averaged from the responses to 3 serial stimuli) (b) Averaged amplitude of a-waves from 64-channels of 3 retinas (mean ± SD) (c) Averages of amplitude of b-waves from 64-channels of 3 retinas (mean ± SD) Pharmacological evaluations of mERG components and RGC spike responses in C57BL/6 mouse retinas (a) Representative mERG patterns with and without exposure to 20 μM L-AP4 (average of 3 responses) (b) Effects of L-AP4 on the a-wave amplitudes (mean ± SD of 192 channels of 3 retinas) (c) Effects of L-AP4 on the implicit time of the a-wave (mean ± SD of 192 channels of 3 retinas) (d) Representative mERGs with or without exposure to L-AP4 and 6 mM PDA (averaged from the responses to 3 serial 0.45 log cd/m2 stimuli) Note that time calibration is modified in this figure for a better visualization of the changes in the a-wave (e) Effects of L-AP4 only and L-AP4 with PDA on the a-wave amplitudes (mean ± SD of 192 channels in 3 retinas) (f) Representative RGC responses with and without L-AP4 (g) Corresponding peristimulus time histograms (PSTHs) of addition of spike numbers from all the 64 channels All of the recorded responses were analyzed using spike sorting and the summation of the firings of all of the RGCs are shown as PSTHs (h) Representative RGC responses with L-AP4 and L-AP4 with PDA The origin of these reduced components were supposed to be from the second- and third-order retina neurons of the OFF-pathway mERGs and RGC responses in rd1-2J mice (a,b) Averaged mERGs and RGCs responses recorded by 64 channels from a 4-week-old rd1-2J isolated retina elicited by 3 serial stimuli of 0.45 log cd/m2 (c) Representative mERGs from the retina shown in Fig 4a with L-AP4 and with additional PDA (recorded from the channel indicated by the asterisk in Fig (d) Representative RGCs responses in the same channel as Figure 4c with L-AP4 and addition of PDA (recorded from the channel indicated by the asterisk in Fig we could still detect reduced mERGs with the a- and the b-waves from the peripheral retinal area until postnatal 5-weeks-of-age The L-AP4 treatment eliminated the ON responses and enhanced the OFF responses Addition of PDA eliminated the RGCs spike responses Expression of opsins and peripherin2 in C57BL/6 and 3 week old rd1-2J mice Three week old rd1-2J mouse had few rhodopsin positive cells (arrow heads) (e i) and cones had short outer segments indicated by the colocalization of cone opsin (arrows) and peripherin 2 (f Even with a minimal presence of photoreceptor contribution to the mERGs, there were light-responsive components in the mERGs of rd1-2J retinas for up to 5 postnatal weeks and overall detection rate of RGC responses to light seemed higher than that of mERG during degeneration (Table 1) we reviewed the changes in RGC responses from progressively degenerating retinas of rd1-2J by classification of the spike patterns of the ON responses Classification of RGC responses in degenerating rd1-2J mice retinas all detected firing patterns were clustered into transient ON delayed ON and not-classified groups (see Methods for detail) (a) Distribution of firing patterns of individual cells in wild type (C57BL/6) and rd1-2J retinas of 3 age groups Sustained and delayed ON are presented as “others” (b) All of the spikes of the individual cells that were classified as transient ON (red) or Low signals (blue) are plotted along the horizontal time axis in raster plots The colored numbers denote the number of cells clustered as transient ON (red) and low signal (blue) The pink shaded area in the middle of each panel indicates the light stimuli Note that low signal group has overall lower signals than transient ON group (c) Histograms presented as the summation of all firings of all the cells in each clustered firing pattern in wild type and rd1-2J of each age group The numbers denote the cell number clustered in each group (d) Implicit time to the transient ON peaks calculated on each channel with transient ON spikes are presented as the means ± SDs in the wild type retina and rd1-2J retinas of different age groups Numbers indicate the number of channels with transient ON spikes Seven-week old sample was excluded from the statistic analysis because of the small number of positive channels (e) Implicit time to the transient OFF peaks calculated on each channel with transient OFF spikes are presented as the means ± SDs in the wild type retina and rd1-2J retinas of different age groups Low signal category included the cells with no definite ON responses and some with OFF responses instead and others had spontaneous spiking activity We have refined our protocol to study focal retinal function in a more detailed manner by identifying the neural elements contributing to the a- and the b- waves by using two of glutamate receptor inhibitors We also found a light intensity dependency of the a- and b- waves and we were able to apply this system to mice with progressive photoreceptor degeneration it was necessary to maintain an adequate electrical contact between the retina and the electrodes a heavier anchor was considered to damage the retinal tissue appropriate conditions including the anchor weight must be determined to record reliable responses 1 g weight anchor was better than a 2 g anchor to record the a- and b- waves The use of a perforated MEA may also help to minimize these problems the use of the optimized conditions for recording the mERG responses also worked well for RGC spike recordings an exposure to PDA in addition to AP-4 almost reversed the increased a-wave amplitude by AP-4 possibly due to the elimination of the negative components contributed by the OFF bipolar cells and third-order retinal neurons The remaining negative component after AP-4 and PDA application was considered to be of photoreceptor origin These results indicate that the mERGs consisted relatively similar components as regular corneally recorded full-field ERGs The results of the RGC responses and mERGs were quite consistent and support each other in the interpretation of the intraretinal events Even with the absence of photoreceptor-driven components the transient ON responses were recorded in 10% and 6% of all the RGCs with detected spikes including all the spontaneous and background spikes in rd1-2J retinas of 3–4-weeks and 5–6-weeks-of-age Implicit time to transient ON responses also became prolonged with degeneration All of these results suggest that the retinal visual circuit may have developed to some extent in some parts of the retina in rd1 mice but may be rapidly lost with increasing age This may justify the use of this model for studies whose aim is to ‘restore’ and further rebuild visual function after some kind of repair process They reported the increase in b-waves by adding BaCl2 that inhibited glial slow PIII component and by adding NiCl2 or ZnCl2 that inhibited GABA release from horizontal or amacrine cells It would also be useful to add these ions to reduce b-wave variability in mERG recordings using MEA The second was that we were able to analyze only a small area of 1.05 mm × 1.05 mm with the present system detailed analyses of the specific area of interest would help evaluate the status of small areas such as a grafted area in regenerative studies by characterizing the focal retinal function as being not just an “all or none” type analysis this 2-way approach using mERG combined with RGC spike recordings may also be helpful in interpreting the intraretinal connection such as host-graft interaction in evaluating if the graft light response is transmitted to host RGCs we showed that mERGs and RGC multiunit spike responses can be recorded with the MEA system from isolated mouse retinas The responses were reliable and had similar components of the in vivo full-field ERG responses Our results showed that this system can be used to analyze the retinas during the degenerating process and hopefully during the regenerating process All animal experiments were conducted in accordance with local guidelines and the ARVO statement on the use of animals in ophthalmic and vision research All of the experimental protocols were approved by the committee of the RIKEN Center for Developmental Biology (CDB) Adult C57BL/6N mice were obtained from the RIKEN CDB animal experiment committee The C57BL/6J-Pde6brd1-2J/J (rd1-2J; same as nmf137) mice were obtained from the Jackson Laboratory (Bar Harbor C3H/HeJ and C3H/HeN mice were obtained from Nihon SLC (Shizuoka Japan) and used for building templates for RGC spike pattern clustering (see “Generating templates of light responses of RGCs” in METHODS) The animals were maintained under a 12-hour light-dark cycle and they were dark-adapted overnight before the eyes were used for the MEA experiments Neural retinas were prepared for recordings as described in detail with minor modifications17 rodents were anesthetized with sevoflurane (Abbott Japan The eyes were enucleated and the neural retinas were isolated from the RPE and sclera and vitreous under dim red light After trimming 2 to 3 mm off of the margins of the retina the retina was mounted over a MED64 probe with the ganglion cell against the electrodes The MED64 probe consisted of 64 electrodes (50 μm × 50 μm square The MED probes were treated with 0.1% polyethyleneimine (Sigma-Aldrich USA) in 25 mM borate buffer (pH 8.4) over night at room temperature Custom-made anchors were made of stainless steel washers (weighing 1.0 or 2.0 g) with nylon and polyurethane mesh attached with glue for every experiment the mounted retina was placed in a chamber and continuously perfused with bicarbonate-based Ames’ medium (Sigma-Aldrich USA) gassed with 95% O2 and 5% CO2 maintained at 34–37 °C with a temperature controller (TC324B mERGs and multiunit responses from the RGCs were recorded with the MED64 system (Alphamed Scientific Inc. The signal were amplified and filtered between 1 Hz and 10 kHz for the mERGs and 100 Hz and 10 kHz for the RGC multiunit spike responses The RGC multiunit signals were also filtered before the spike sorting The light stimuli were obtained from white LEDs (NSPW500C duration and frequency were controlled by an electronic pulse generator (DSP-420 A stimulus duration of 10 ms was used to elicit the mERGs and 1 s stimuli were used to elicit the RGC spike responses a three-time serial stimuli were repeated with an interval of 1 min and a single recording time was 10 s for the mERGs and 21 s for the RGC multiunit recordings The light intensities were measured with an optometer (ModelS471 and 268R The regularly used light intensity was 0.45 log cd/m2 which is equivalent to 0.0285 (−1.545 log) cd.s/m2 for the 10 ms mERG stimulus L-2-amino-4-phosphonobutyric acid (L-AP4; Wako Japan) was used at a concentration of 20 μM and cis-2,3-piperidine-dicarboxylic acid (PDA) was used at 6 mM USA) was added to the Ames’ medium to block the activity of the intrinsic melanopsin ganglion cells For nuclear staining of wholemount retinas neural retinas were fixed after the MEA recordings with 4% paraformaldehyde in phosphate buffered saline (PBS) at room temperature for 30 min on the MED64 probe Then the specimens were washed 3 times with PBS and stained with 4′,6-diamidino-2-phenylindole (DAPI Kyoto)/PBS at room temperature for 20 min and wash with PBS 3 times Then the tissue was cleared with 60% 2,2′-thiodiethanol (TDE) in PBS and z-stack images were obtained with a confocal microscope (SP8 Germany) from randomly selected 10 electrodes from 3 retinas and the number of nuclei in the RGC layer were counted and averaged the retinas from 3-week-old rd1-2J mice were fixed with 4% paraformaldehyde in PBS at room temperature for 30 min and with 30% sucrose in PBS at 4 °C overnight Then the eyes were embedded in OCT compound (Tissue Tec O.C.T frozen at −30 °C and sectioned at 10 μm with a cryostat (HM560 the sections were stained with primary antibodies: mouse anti-rhodopsin at 1:1000 (clone Ret P1 USA); goat anti-OPN1SW at 1:200 (Santa Cruz Biotechnology USA); and rabbit anti-peripherin2 at 1:500 (Proteintech The secondary antibodies were anti-mouse/goat/rabbit IgG conjugated with AlexaFluor546/647/488 at 1:1000 (Thermo Fischer Scientific USA) and DAPI at 1:1000 in 1% donkey serum The stained sections were mounted in FluoSave reagent (Merch Millipore Germany) and were examined with a confocal microscope (SP8 The RGC multiunit responses recorded by the MED64 system were imported into the Spike2 software (version 7.11c; Cambridge Electronic Design UK) by the implemented converting function Each recording had 64 channels of RGC multiunit responses that was recorded from the isolated retina and each channel was filtered by a second order Butterworth band pass filter (200 to 2800 Hz) followed by spike sorting The signals from each channel were separated into individual units representing the spike responses from individual RGCs The time series of individual spikes were exported into text files for further analysis The implicit times of the transient ON and transient OFF responses were manually calculated after spike sorting using the peristimulus time histograms (PSTHs) for each channel (bin size 0.1 sec) the spiking data were converted to firing frequency data with a bin size of 100 ms A three second window beginning two seconds before the light stimuli and ending at the end of the light stimuli was used to characterize the responses Three thousand out of 13609 light responses were randomly selected but 1008 out of 3000 light responses were not analyzed because there were no spikes during the time of the window of interest The remaining 1992 light responses were annotated as any of ‘transient ON’ ‘sustained ON’ or ‘low signal’ by visual inspection These patterns were used as a training dataset for classification of the light responses recorded in this study Two source codes are included in this document “train.R” is the source code for machine learning which build the decision model “predict.R” is the source code for prediction applying the trained model Evaluation of micro Electroretinograms Recorded with Multiple Electrode Array to Assess Focal Retinal Function ISCEV Standard for full-field clinical electroretinography (2015 update) Electrial phenomena in the retina in Adler’s physiology of the eye 8th edn Origin of the Electroretinogram in Principles and Practice of Clinical Electrophysiology of Vision 2nd edn 185–196 (Massachusetts Institute of Technology Multifocal ERG recordings under visual control of the stimulated fundus in mice The Retinasensor: An in vitro Tool to Study Drug Effects on Retinal Signaling in Advances in Network Electrophysiology - Using Multi-Electrode Arrays Improvement of acquisition and analysis methods in multi-electrode array experiments with iPS cell-derived cardiomyocytes JNK and p38 MAPK in pain-related spatial and temporal enhancement of synaptic responses in the hippocampal formation of rats: Multi-electrode array recordings N-type voltage gated calcium channels mediate excitatory synaptic transmission in the anterior cingulate cortex of adult mice Pharmacological analysis of intrinsic neuronal oscillations in rd10 retina Developmental time course distinguishes changes in spontaneous and light-evoked retinal ganglion cell activity in rd1 and rd10 mice Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse Missing optomotor head-turning reflex in the DBA/2J mouse Subtype-Dependent Postnatal Development of Direction- and Orientation-Selective Retinal Ganglion Cells in Mice Spontaneous oscillatory rhythm in retinal activities of two retinal degeneration (rd1 and rd10) mice Recording of neural activity of mouse retinal ganglion cells by means of an integrated high-density microelectrode array doi: 10.1109/TRANSDUCERS.2011.5969341 (2011) Biological application of microelectrode arrays in drug discovery and basic research Detection of localized retinal malfunction in retinal degeneration model using a multielectrode array system Protective effects of hydrogen-rich saline against N-methyl-N-nitrosourea-induced photoreceptor degeneration Two mouse retinal degenerations caused by missense mutations in the b-subunit of rod cGMP phosphodiesterase gene Ganglion cells distribution in the retina of the mouse The Major Cell Populations of the Mouse Retina Rod and cone contributions to the a-wave of the electroretinogram of the macaque Push-pull model of the primate photopic electroretinogram: A role for hyperpolarizing neurons in shaping the b-wave Photoreceptor and bipolar cell contributions to the cat electroretinogram: a kinetic model for the early part of the flash response Photoreceptor and post-photoreceptoral contributions to photopic ERG a-wave in rhodopsin P347L transgenic rabbits Scotopic threshold response of proximal retina in cat Aspartate separation of the scotopic threshold response (STR) from the photoreceptor a-wave of the cat and monkey ERG The scotopic threshold response of the cat erg is suppressed selectively by GABA and glycine The photopic negative response of the macaque electroretinogram: Reduction by experimental glaucoma The uniform field and pattern ERG in macaques with experimental glaucoma: Removal of spiking activity An excitatory amino acid antagonist blocks cone input to sign-conserving second-order retinal neurons A proximal retinal component in the primate photopic ERG a-wave Characterization of the rod photoresponse isolated from the dark-adapted primate ERG Dissecting the dark-adapted electroretinogram The rod-driven a-wave of the dark-adapted mammalian electroretinogram Preservation of inner retinal responses in the aged royal college of surgeons rat: Evidence against glutamate excitotoxicity in photoreceptor degeneration Differential effect of the rd mutation on rods and cones in the mouse retina Spontaneous oscillatory activity in rd1 mouse retina is transferred from ON pathway to OFF pathway via glycinergic synapse Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179 Electroretinography as a Screening Method for Mutations Causing Retinal Dysfunction in Mice Third-order neuronal responses contribute to shaping the negative electroretinogram in sodium iodate-treated rats Ex vivo ERG analysis of photoreceptors using an in vivo ERG system Effect of ZnCl2 and chelation of zinc ions by N,N-diethyldithiocarbamate (DEDTC) on the ERG b-wave amplitude from the isolated superfused vertebrate retina Two separate Ni(2+) -sensitive voltage-gated Ca(2+) channels modulate transretinal signalling in the isolated murine retina R. Core Team R: A Language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URLhttp://www.R-project.org/ (2015) The H2O.ai team. H2O Machine Learning Platform. version 3.6.0.8. URL http://h2o.ai/ (2016) Download references Jun Kaneko and Kohei Homma for technical advice and Chikako Yamada and Junki Sho for animal care assistance and all members of the laboratory for retinal regeneration for helpful discussions and comments This study was supported by a grant from the Research Center Network for Realization of Regenerative Medicine Japan Agency for Medical Research and Development Mie University Graduate School of Medicine Download citation Vox Populi Vox Dei is a daily column that runs on Page 1 of The Asahi Shimbun A single article in a science journal transformed the life of Genshiro Sunagawa Sunagawa casually picked up the publication in an empty doctor’s office after finishing his night shift at the National Center for Child Health and Development in Tokyo He was a medical practitioner in his fifth year The journal carried an article about the discovery of a hibernating lemur species in Madagascar but primates going into such a state was unheard of could also be induced into a state of hibernation he had treated children whose lives could have been saved with a little more effort Hibernation puts animals in a dormant state that substantially lowers the burden on the body than when they are asleep If hibernation could be induced artificially Sunagawa reasoned that precious time could be gained while a patient is being taken to a hospital or being treated Eager to develop this theory further and save lives Sunagawa quit his job and switched careers to a sleep researcher Sunagawa is now working on a human hibernation project on the Kobe campus of the Riken national research institute he and his coworkers successfully induced mice into a state that resembled hibernation He is convinced that artificial hibernation will become reality someday it all sounds like a wild tale from a science-fiction movie that aging and illnesses could be conquered Would it allow people to be whisked to the world 100 years from now or to travel to the furthest reaches of outer space people may begin to harbor different views about climate change and peace issues than they do now It feels exciting to envisage such a scenario but at the same time it is also somewhat disquieting “People should start giving serious thought to the matter now,” Sunagawa said Vox Dei is a popular daily column that takes up a wide range of topics the column provides useful perspectives on and insights into contemporary Japan and its culture Scientists induce state of artificial hibernation in mice Scientists record behemoth in waters 2 km deep off Shizuoka Scientists locate cedar gene that could end pollen season for good Scientists try to unravel mystery of eerie ‘mermaid mummy’ Scientists created ‘smell of fear’ in a lab Metrics details Unconventional Cooper pairing originating from spin or orbital fluctuations has been proposed for iron-based superconductors Such pairing may be enhanced by quasi-nesting of two-dimensional electron and hole-like Fermi surfaces (FS) which is considered an important ingredient for superconductivity at high critical temperatures (high-Tc) the dimensionality of the FS varies for hole and electron-doped systems so the precise importance of this feature for high-Tc materials remains unclear Here we demonstrate a phase of electron-doped CaFe2As2 (La and P co-doped CaFe2As2) with Tc = 45 K which is the highest Tc found for the AEFe2As2 bulk superconductors (122-type; AE = Alkaline Earth) possesses only cylindrical hole- and electron-like FSs This result indicates that FS topology consisting only of two-dimensional sheets is characteristic of both hole- and electron-doped 122-type high-Tc superconductors illustrating the hole-like FSs around the zone center in the kz–k‖ plane for Ba1-xKxFe2As2 and Ba(Fe1-xCox)2As2 (d) Sketch of the present ARPES results for Ca0.82La0.18Fe2(As0.94P0.06)2 ARPES measurements are more feasible for this system due to the availability of larger single crystals and the lack of surface effects associated with REO layers ARPES experiments in the 122 system are thus believed to more closely reflect bulk electronic structure ARPES studies in the 122 system reveal the presence of hole-like and electron-like Fermi surfaces at the center of the Brillouin zone and the corner respectively and the cylindrical shape of the electron-like Fermi surfaces at the zone corner are common features of the electronic structure in high-Tc 122-type superconductors are considered to be linked to the emergence of high-Tc in iron-based superconductors since the FS dimensionality varies for these two iron-based superconductors with high-Tc the importance of a two-dimensional Fermi surface topology is unclear An electron-doped CaFe2As2 superconductor derived by co-doping La and P was recently discovered with Tc = 45 K29 The Tc of this new iron-based superconductor is the highest among the 122-type bulk superconductors that have ever been studied with ARPES it is important to study the electronic structure using ARPES to clarify the FS topology of the iron-based superconductors at such a high Tc we revealed the Fermi surface of the electron-doped CaFe2As2 ARPES measurements were conducted with three photon polarizations to resolve multiple bands and tunable excitation photon energy to observe the three-dimensional shape of the Fermi surfaces (kz dispersion of Fermi surfaces) All Fermi surfaces of this new superconductor had a weak kz dispersion Since this characteristic is common to Ba1-xKxFe2As2 which has the maximum Tc among hole-doped 122-type superconductors the two-dimensional topology of the Fermi surface is relevant to the presence of high Tc in the iron-based superconductors and does not rely on the character of doped carriers Polarization and photon energy dependent ARPES data for Ca0.82La0.18Fe2(As0.94P0.06)2 near the zone center We now find that the α2 and β bands form a nearly cylindrical small and large hole-like FS Photon energy-dependent ARPES data for Ca0.82La0.18Fe2(As0.94P0.06)2 around the zone corner (a),(b) ARPES intensity plots at EF as functions of two-dimensional wave vectors taken at hν = 69 eV and hν = 86 eV (c),(d) ARPES intensity plots along cuts C and D Cuts C and D are shown by blue arrows in (a) and (b) Filled and open circles indicate the peak position of the MDCs and EDCs (e) ARPES intensity plot at EF as a function of photon energy together with kFs (green dots) determined from the MDC analysis The direction of k‖ is the same as (c) and (d) ([100] direction) The intensities are symmetrized about the k‖ = 0 Fermi surface shape for Ca0.82La0.18Fe2(As0.94P0.06)2 determined by ARPES The shapes of Fermi surfaces (FSs) in the (a) kx-ky and (b) kz–k‖ planes are drawn with lines Dotted blue and sky blue lines in (a) are two hole-like FSs around the zone center shifted by the antiferromagnetic vector (black arrows) black open circles represent experimentally determined kFs from photon energy-dependent ARPES The positions of kF have been symmetrized with respect to the symmetry lines the pnictogen height is not available thus far that of Ca0.82La0.18Fe2(As0.94P0.06)2 is the shortest among the three compounds this does not necessarily mean a shorter pnictogen height in Ca0.82La0.18Fe2(As0.94P0.06)2 detailed structural studies of Ca0.82La0.18Fe2(As0.94P0.06)2 are indispensable we have investigated the three-dimensional electronic structure near EF in electron-doped Ca0.82La0.18Fe2(As0.94P0.06)2 (Tc = 45 K) The observed FS topology is nearly two-dimensional and similar to that of Ba1-xKxFe2As2 indicating the existence of universality in the FS topology for realizing high-Tc in 122-type superconductors High quality Ca0.82La0.18Fe2(As0.94P0.06)2 single crystals were grown as described elsewhere25 Polarization dependent ARPES measurements (hν = 19–31 eV) were carried out at BL-9A of Hiroshima Synchrotron Radiation Center (HSRC) ARPES measurements using circularly polarized light (hν = 40–86 eV) were carried out at BL-28A of the Photon Factory The total energy resolution was set to 10–30 meV Clean surfaces were obtained by in situ cleaving of the crystal in a working vacuum better than 3 × 10−8 Pa and measured at 60 K (above Tc) The inner potential was determined to be 14 eV from photon energy-dependent ARPES studies as described above Calibration of EF of the sample was achieved using a gold reference To What Extent Iron-Pnictide New Superconductors Have Been Clarified: A Progress Report Pairing symmetry and pairing state in ferropnictides: Theorical overview The Electron-Pairing Mechanism of Iron-Based Superconductors Unconventional Superconductivity with a Sign Reversal in the Order Parameter of LaFeAsO1-xFx Unconventional Pairing Originating from the Disconnected Fermi Surfaces of Superconducting LaFeAsO1-xFx Orbital-Fluctuation-Mediated Superconductivity in Iron Pnictides: Analysis of the Five-Orbital Hubbard-Holstein Model Two types of s-wave pairing due to magnetic and orbital fluctuations in the two-dimensional 16-band d-p model for iron-based superconductors Electronic structure of the iron-based superconductor LaOFeP Momentum Dependence of the Superconducting Gap in NdFeAsO0.9F0.1 Single Crystals Measured by Angle Resolved Photoemission Spectroscopy Angle-resolved photoemission spectroscopy study of PrFeAsO0.7: Comparison with LaFePO Three-dimensional electronic structure and interband nesting in the stoichiometric superconductor LiFeAs Angle-Resolved Photoemission Spectroscopy of the Iron-Chalcogenide Superconductor Fe1.03Te0.7Se0.3: Strong Coupling Behavior and the Universality of Interband Scattering Quasinested Fe orbitals versus Mott-insulating V obitals in superconducting Sr2VFeAsO3 as seen from angle-resolved photoemission Nodeless superconducting gap in AxFe2Se2 (A = K,Cs) revealed by angle-resolved photoemission spectroscopy Absence of a Holelike Fermi Surface for Iron-Based K0.8Fe1.7Se2 Superconductor Revealed by Angle-Resolved Photoemission Spectroscopy Distinct Fermi surface topology and nodeless superconducting gap in a Tl0.58Rb0.42Fe1.72Se2 superconductor Observation of Fermi-surface-dependent nodeless superconducting gaps in Ba0.6K0.4Fe2As2 Fermi surface nesting induced strong pairing in iron-based superconductors Orbital characters of bands in the iron-based superconductor BaFe1.85Co0.15As2 Electronic structure studies of BaFe2As2 by angle-resolved photoemission apectroscopy Two-Dimensional and Three-Dimensional Fermi Surfaces of superconducting BaFe2(As1-xPx)2 and Their Nesting Properties Revealed by Angle-Resolved Photoemission Spectroscopy Hole doping in BaFe2As2: The case of Ba1-xNaxFe2As2 single crystals Electronic band structure and momentum dependence of the superconducting gap in Ca1-xNaxFe2As2 from angle-resolved photoemission spectroscopy Out-of-Plane Momentum and Symmetry-Dependent Energy Gap of the Pnictide Ba0.6K0.4Fe2As2 Superconductor Revealed by Angle-Resolved Photoemission Spectroscopy Observation of a ubiquitous three-dimensional superconducting gap function in optimally doped Ba0.6K0.4Fe2As2 Importance of the Fermi-surface topology to the superconducting state of the electron-doped pnictide Ba(Fe1−xCox)2As2 Three-Dimensional Electronic Structure of Superconducting Iron Pnictides Observed by Angle-Resolved Photoemission Spectroscopy Superconductivity at 54 K in F-Free NdFeAsO1-y Emergence of superconductivity at 45 K by lanthanum and phosphorus co-doping of CaFe2As2 Magnetic and structural transitions in layered iron arsenide systems: AFe2As2 versus RFeAsO magnetic and superconducting phase transitions in CaFe2As2 under ambient and applied pressure Unexpected Fermi-surface nesting in the pnictide parent compounds BaFe2As2 and CaFe2As2 revealed by angle-resolved photoemission spectroscopy Experimental investigation of the electronic structure of Ca0.83La0.17Fe2As2 Least momentum space frustration as a condition for a ‘high Tc sweet spot’ in iron-based superconductors Suzuki, K. et al. Key role of prioritized diagonal motion of electrons in the iron-based superconductors. http://arxiv.org/abs/1311.2413v1 (2013) Enhanced Fermi-Surface Nesting in Superconducting BaFe2(As1-xPx)2 Revealed by the de Haas-van Alphen effect Pressure versus Concentration Tuning of the Superconductivity in Ba(Fe1-xCox)2As2 Superconductivity at 38 K in the Iron Arsenide (Ba1-xKx)Fe2As2 Download references Inada for Laue x-ray diffraction experiments Yoshida for their ARPES data analysis program Polarization dependent ARPES experiments at HSRC were performed with the approval of HSRC (Proposal No ARPES experiments at the Photon Factory were approved by the Photon Factory Program Advisory Committee (Proposal No Part of this work was performed at the Advanced Science Research Center at Okayama University This work was partially supported by MEXT KAKENHI Grant Number 20102003 and JSPS Grant Number 25400372 This work was also partially supported by the Funding Program for World-Leading Innovative R&D in Science and Technology (FIRST program) from JSPS and the program for promoting the enhancement of research universities from MEXT The Graduate School of Natural Science and Technology High Energy Accelerator Research Organization Japan Synchrotron Radiation Research Institute (JASRI)/SPring-8 Supplementary information for Characteristic two-dimensional Fermi surface topology of high-Tc iron-based superconductors This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ Download citation Ryuichi Sunagawa calls himself the "half-Japanese pastor" in Tsukishiro Christ Church the Okinawa gubernatorial election was held along with 24 municipal assembly elections which attracted a wide variety of candidates One of them was Ryuichi Sunagawa, the 52-year-old pastor from Nanjo City Ryuichi was born Johnny Sunagawa Escovedo to a former American soldier and a Japanese woman who worked in a restaurant frequented by American soldiers. According to Ryuichi, this is a common story and there are many "hafu" in Okinawa.  His parents divorced when he was little. Afterward, he and his older sister were raised by their mother alone Their lives were marked by poverty. At that time, having a Japanese father was a prerequisite for obtaining Japanese citizenship Ryuichi couldn't receive adequate public assistance He still remembers being overjoyed when he finally received Japanese citizenship at the age of 13 He chose the name "Ryuichi" because it was the name of a character from his favorite manga.  the real Ryuichi was viciously bullied in junior high school He became the target of a group of delinquents who punched and kicked him every day Although he managed to escape the bullying by studying hard and entering a technical high school he dropped out because teachers insulted his mother by calling her a "nightlife worker." Having lost sight of his future and on the verge of giving up on himself his mother urged him to go to the United States to see his father.  traveling abroad was a pipe dream for most But Ryuichi's mother took out a huge loan to purchase a plane ticket for him She hoped that her son would regain his confidence once he knew his father Although Ryuichi was welcomed by his father the language barrier prevented them from making any meaningful connection Ryuichi's arrival also created a rift in his father's family He felt he had hit rock bottom: nobody needed him his heart — everything about himself he loathed spoken by the Japanese pastor who interpreted for him and his father Ryuichi studied at a seminary and started a church in Okinawa He wanted to reach the hopeless and tell them Helping children from disadvantaged families became a core focus of his efforts Ryuichi married at the age of 24 but chose not to have any biological children he fostered orphans and children who had been abused including those to whom he provided short-term care Ryuichi also became active in political campaigns — a passion triggered by the North Korean abductions issue He couldn't accept that families had been torn apart and sympathized with conservatives who were committed to solving the issue He also ran for the city assembly and called for increased taxation on gambling establishments as he believed that the biggest cause of children's unhappiness was their parents' gambling addiction Despite coming last in the election and failing to win a seat There must be a meaning to this result as well." The gubernatorial election held on the same day resulted in the reelection of Denny Tamaki was born to an American father who was a soldier and raised by a Japanese single mother.  Although their political beliefs differ considerably Ryuichi sends these words of support to the Governor But our suffering was less about racial descent and more about not being able to receive the love of a father and mother equally I want Okinawa to be a place where children from such a background can also smile." (Read the story in Japanese at this link.) You must be logged in to post a comment ' + scriptOptions._localizedStrings.webview_notification_text + ' " + scriptOptions._localizedStrings.redirect_overlay_title + " " + scriptOptions._localizedStrings.redirect_overlay_text + " In addition to its distinctive and satisfyingly tough texture dried bamboo shoots also have a rich umami flavor which is not something that can be tasted when the fresh one is boiled TOKYO — Takenoko bamboo shoots are generally a boiled delicacy enjoyed in the spring there are a wide variety of processed bamboo shoot products available year-round One such product comes from a city in Kumamoto Prefecture whose residents traditionally dry the shoots giving them a distinctive flavor and texture is known as a major production area of bamboo shoots At the Michi-no-Eki Kahoku Ogurigo rest area there are packages of locally sourced dried bamboo shoots lining the shelves dried bamboo shoots taste really good,” said Kazuki Sunagawa The Kyushu region’s mild climate provides a suitable environment for growing bamboo shoots and dried takenoko is rarely found in other parts of Japan “The drying process helps enhance the flavor of the bamboo shoots,” Sunagawa said which is not something that can be tasted when fresh takenoko is boiled An 80-gram package of dried takenoko costs about ¥500 they need to be soaked in cold or lukewarm water for five to six hours They will swell to about five times their original size After the shoots are completely rehydrated fill a pot with water and bring it to a boil add the shoots and bring it to a low heat to cook them for one to two hours until soft Turn off the heat when the takenoko becomes soft enough simmered with other ingredients or sauteed as kinpira all using dried bamboo shoots and prepared by Kazuki SunagawaThe Yomiuri Shimbun “Fresh bamboo shoots are delicious when they’re in season but the dried ones have a different flavor,” said a homemaker in her 70s from Kahoku they basically disappear as soon as they’re served.” Dried bamboo shoots are increasing in popularity outside of Kyushu as a result of their rich flavors they are being incorporated into more recipes who used to work as a chef at a French restaurant moved to Kahoku because he found the local food and nature of Kumamoto Prefecture fascinating While developing new dishes for the restaurant at the rest area Sunagawa would sometimes use dried bamboo shoots He has now been thinking of ways to use dried takenoko in some Western-style foods and sauces “As they can go well with various ingredients Takeman’s menma uses takenoko harvested from unmanaged bamboo forests in Itoshima has been producing menma using takenoko from unmanaged forests in the city since 2015 as it is seasoned with soy sauce and sugar which is mixed with chili oil and tastes like tonkotsu pork broth Itoshima Menma costs ¥594 per 100-gram pack the texture of locally made menma is slightly crispier than the imported ones which is working to revitalize the city and surrounding areas has been selling Menma no Tora (the tiger of menma) since September 2019 is also made from locally sourced bamboo shoots and is sold for ¥500 per 100 grams “We hope we can help solve local issues through the production of menma,” said Takeman President Yuko Yoshino Pickled takenoko that was jointly developed by a Michi-no-Eki rest area and an agricultural high school in Yame has developed a pickled product using locally sourced takenoko in collaboration with an agricultural high school in the city is light pink as a result of being soaked with red shiso leaves The product won an award in a competition for processed food organized by the prefectural government in fiscal 2019 “We hope people will enjoy takenoko all year round with the refreshing flavor of pickled takenoko,” said an official at the rest area By Star-Advertiser Staff Four Hawaii students are taking home awards from the Intel International Science and Engineering Fair in Los Angeles won fourth place yesterday in their respective research categories They competed against more than 1,500 high school students from around the world was on “triangle centers,” used widely in engineering and facial recognition technology “Determining ‘Hot Spots’ Through Correlations of CMEs and Solar Flares,” won in the physics and astronomy category Priory seniors Shawnalyn Sunagawa and Sara Middendorf each won $1,000 Thursday from the United Technologies Corporation for their project on a bladeless wind turbine Twenty-six Hawaii students presented their science research at the fair Sleep research typically involves recording electroencephalography (EEG) and electromyography (EMG) signals of brain activity over long periods of time then painstakingly analyzing these records in a process called sleep staging to determine how much time the subject spent in each stage of sleep Genshiro Sunagawa from the Laboratory for Systems Biology at the RIKEN Center for Developmental Biology and colleagues have now developed a fully automated analysis process that promises to improve the speed and reliability of sleep staging analysis1 Sleep consists of several different stages and each has a characteristic pattern of brain activity Sleep staging is commonly performed by visual inspection of EEG and EMG recordings to identify these characteristic patterns—a process that is both slow and susceptible to variations among even well-trained observers Both of these problems could be solved by the introduction of an automated process this is not as straightforward as it seems “Even though there are some rules that define sleep stages the definitions are not clear enough to allow sleep staging to be performed by computers if there is a lot of noise in the recordings then we have to extract the real data—using a computer to do this is not easy,” he says but either require human input to define sleep stages with some subjectivity or use ‘hard’ rules that are not always appropriate and can fail Sunagawa and his colleagues combined a set of recently developed algorithms to develop an unsupervised automated sleep staging program called FASTER that eliminates these problems the researchers used brain recordings from healthy mice to optimize the hard rules used by the program They then tested it with mice with drug-induced disrupted sleep patterns and with mice that displayed sleep defects due to genetic modification FASTER proved to be accurate more than 90% of the time “FASTER stages sleep using animal EEG and EMG and requires no human judgment,” says Sunagawa “While it takes a few hours to analyze mouse data from one day manually FASTER can do the same analysis in ten minutes.” the benefits of the system’s speed and accuracy are clear “By dramatically improving the sleep staging process in both quality and throughput FASTER will help with processes such as screening for drugs and searching for sleep mutants It will open the door to quantitative and comprehensive animal sleep research.” Today's print edition Home Delivery when the Hokkaido Prefectural Government asked municipalities for their views on compiling a plan to manage brown bears many local governments called for the need to clarify the role of police in cases when brown bears are spotted in urban areas Such feedback reflects a sense of crisis among municipalities that if the current situation is left as is without any effective measures being taken it could lead to people getting harmed.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); Along with the rise in the brown bear population the animal is increasingly being spotted in urban areas Many municipalities have urged the Hokkaido government to resume so-called spring brown bear hunting — shooting bears in remote mountains while there is still snow remaining regardless of whether or not damage has been reported around human dwellings 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 Please view the main text area of the page by skipping the main menu. The page may not be displayed properly if the JavaScript is deactivated on your browser 2024 years 11 month 22 Date 09 when 00 minutes Please note that this article contains advertisements The second installment of the short drama series "Work Can Be More Enjoyable," starring Nakamura Shido will be released on a special website and YouTube from today This drama series is a short drama series produced by ASICS Japan with the theme "Work can be more enjoyable." It is a human drama that supports all working people with the main characters being "people who work on-site" in the construction This second installment tells the story of the protagonist who works in the construction industry and is on the verge of giving up on his job and begins to change his feelings as he watches them grow who gained popularity in the TV drama series "Omusubi," and Sunagawa Shuya an actor active mainly in 2.5-dimensional stage productions The drama is directed by Chenko Tsukagoshi who has worked on music videos and commercials including the film "MAN WITH A MISSION THE MOVIE -TRACE the HISTORY-" The theme song will be sung by Tomonari Sora who has been gaining attention for his viral hit "Oni no Utage" on social media "Mirai Denwa," is a positive song that will gently encourage those who are struggling to take a step into the future when asked about the person whose working method she thought was cool I've always wanted to work with a great director like Kitano Takeshi He was a great director who really influenced the way things progressed on set and the way he directed." Kodama who was a member I worked with (when I was an idol) and is now active in Korea She's been active at the forefront as an idol for a long time without taking a break so I think her stoicism and the strength to keep going are really amazing." They talked about the people they respect Regarding an incident that helped him break down a wall at work "I used to feel that I was really bad at dancing but I had the opportunity to dance for the first time in a recent production I realized that dancing is fun and I'm glad I took on the challenge." Regarding the secret to enjoying work "Kabuki was a fun but also difficult world The secret is to stop thinking about unnecessary things and think about fun things with labor shortages and an aging population in the construction industry and other sectors making securing future human resources a major issue for the industry this film was produced with the aim of getting people interested in working on site by focusing on the people who actually work there One Home," in which working people of different ages and personalities along with "ASICS Working Shoes," worry about people and are saved by others Please pay attention to the well-coordinated acting of the three actors who are acting together for the first time URL:https://www.asics.com/jp/ja-jp/mk/working/brand-movie2 One Home" ・Staff/Performers Director: Chenko Tsukagoshi Screenplay: Patterned Shirt Man Cast: Shido Nakamura Bunsiri Theme song: “Mirai Denwa” Tomonari Sora but at the last construction site he meets two new recruits Naito (Kodama Haruka) and Jinnai (Sunagawa Shuya) so what are your impressions of each other It was so much fun." Sunagawa: "When I first met Shido I want to be just like him." Nakamura: That's a lie and I feel like he has a similar vibe to me What was it like wearing ASICS working shoes during the shoot They have a toe cap in the toe but they're not heavy at all I think safety shoes used to be quite heavy I think they make them as light as possible." Sunagawa: "I tried them on yesterday I could walk on a slope covered with oil without any problems I really feel that this is a great effort by the company." Kodama: "The designs are really fashionable and stylish I shoot for long periods of time starting early in the morning but wearing ASICS shoes reduces the strain on my feet." "To break down the walls between you and the other craftsmen you must first break down your own walls." Is there an incident in your work where you broke down a wall of your own and changed yourself Nakamura: "Many people think that I've been appearing on TV and in movies since I was in my twenties but I never actually appeared in movies in my twenties I was only given roles like those of a crowd There was a part of me that wanted to give up but at the same time I felt the inner conflict of thinking I'll keep trying," and it was a repetition of that I guess when I broke out of my shell and tore down the walls That was the audition for the movie "Ping Pong." I think that feeling of taking on challenges is something that you never want to forget and I think it was connected to my acting in that production." Sunagawa: "I used to feel that I was not very good at dancing but in my recent work I was able to dance quite hard for the first time It made me feel glad that I had broken down my barriers and glad that I had taken on the challenge." Kodama: "I used to be an idol too but when I made the transition from idol to actor I worked hard to break down that wall that was an idol for me Looking back at the changes from my past self to now Please tell us about someone you met at work who you thought had a cool way of working I had hoped that I would one day be able to work with such a great director on a Kitano Takeshi film He doesn't give you very detailed instructions and he really influenced how things progressed on set and how I directed." Kodama: "I actually used to work with Miyawaki Sakura She's been active at the forefront as an idol without taking a break (To Nakamura Shido) Do you have any stories about Director Kitano such as what he said to you or something that has stayed in your mind so at first we didn't really make eye contact he gave me a small envelope - isn't that a famous anecdote about Takeshi I was really impressed that Takeshi would really do that I do a live event called ACTOR'S NIGHT with fellow actors (Asano Tadanobu Asano and Omori appeared in the movie "The Neck" (directed by Kitano Takeshi) so we formed a joint band and held an event at a small bar in Aoyama In keeping with the drama's theme of "Enjoying work more," please tell us your secret to enjoying your job you are given a role that has been played by many generations of actors That's why it's easy to be compared to others "People in the past didn't do it like that." To be honest The secret is to not think about unnecessary things You will get irritated or depressed over small things But try not to think about such unnecessary things and think about fun things Like there are still fun things waiting for you in the next 10 or 20 years He made his debut at the Kabukiza Theatre at the age of eight He has been active in a wide range of genres beyond Kabuki He won five Newcomer Awards at the Japan Academy Prize Japan Movie Critics Award and Mainichi Film Awards for his role in "Ping Pong" (directed by Fumihiko Sori) and won the Japan Academy Prize for Best Supporting Actor for his role in "Like Ashura" (directed by Yoshimitsu Morita) His major film appearances include "Yamato" (directed by Jun'ya Sato) the "Death Note" series (directed by Shusuke Kaneko "Letters from Iwo Jima" (directed by Clint Eastwood) "Red Cliff Part I & Part II" (directed by John Woo) "The World's Evilest Guys" (directed by Kazuya Shiraishi) "The Blood of Wolves" series (directed by Kazuya Shiraishi) "The Cookbook" (directed by Haruki Kadokawa) "The Village" (directed by Michihito Fujii) "The Head" (directed by Takeshi Kitano) and "The Monster Lumberjack" (directed by Takashi Miike) the film "Legend of the Eight Dogs" (directed by Fumihiko Sori) and the Amazon Original film "Broken Rage" (directed by Takeshi Kitano) are scheduled for release she passed the audition for the first generation of HKT48 members and began her activities as a member of the group She graduated from HKT2019 in June 6 and began working full-time as an actress His major appearances include the TV drama "Something's Wrong 2" and the film "From a World Without Sky." In October 2024 she appeared in the TV drama "Omusubi" and became a hot topic he is active in various fields including drama and stage He began his entertainment career in his hometown of Okinawa from a young age and gained attention in 2019 with his role in the drama "Kamen Rider Zero-One" (as Metsu/Kamen Rider Metsu/EX) His subsequent appearances include the stage production of the "ROAD59 -New Era Ninkyo Tokku-" series (as Himuro Shou) the musical "Hakuoki Shinkai" series (as Miki Saburo) the stage production of the "Yowamushi Pedal" series (as Imaizumi Shunsuke) and the stage production of "Touken Ranbu" Shinden Tsuketari Kitan no Karumato (as Magoroku Kanemoto) Fans commented on Instagram posts by Hitomi "It's so nostalgic!" and "She hasn't changed at all!" She also opened an official YouTube channel and released the full-length music video for her debut song "Let's Play Winter" for the first time The title of the major debut song of the popular girl group At Seventeen 2025 years 5 month 4 Date 22 when 23 minutes {excerpt}<\/p><\/li>"},"theme":{"name":""}}What's New Food terrorism!? Shio Reira's "Miso Soup and Butter" playing video will be released on May 5th! 2025 years 5 month 5 Date 20 when 43 minutes 2025 years 5 month 5 Date 20 when 00 minutes 2025 years 5 month 5 Date 19 when 27 minutes 2025 years 5 month 5 Date 19 when 14 minutes 2025 years 5 month 5 Date 19 when 00 minutes 2025 years 5 month 5 Date 18 when 55 minutes