Graduate School of Life Sciences, Tohoku University Latest news. https://www.lifesci.tohoku.ac.jp/ Graduate School of Life Sciences, Tohoku University Open Assistant Professor Position Watershed Ecology Lab Tohoku University, Graduate School of Life Sciences 2024-03-13T16:00:00+09:00 A full-time assistant professor position with a maximum of 8 years is available in the Watershed Ecology Lab in the Graduate School of Life Sciences at Tohoku University, run by Associate Professor Hiromi Uno. Please share this posting with any interested individuals who meet the below qualifications.   Number of positions and Job title: 1 Assistant Professor   Affiliation: Watershed Ecology Lab, Ecological Dynamics Section, Department of Ecological Developmental Adaptability Life Sciences, Graduate School of Life Sciences, Tohoku University   Research Field: Watershed Ecology   Required qualifications: Applicant must have a doctoral degree in the biological sciences, environmental sciences, or related field (or should provide proof they are expecting to graduate before this position begins).   In the Watershed Ecology Lab, we aim to proceed field-based research to unveil ecological dynamics in watershed scale, ranging from lands, rivers, to estuaries. We seek applicants who can contribute to developing an interdisciplinary research group for the watershed ecology together with other members of the group including associate professor Hiromi Uno and assistant professor Wataru Makino. The research object can be either aquatic or terrestrial, and either animals or plants. Potential research topics include but not limited to river and riparian ecology, estuarine ecology, wetland use by animals or birds, nutrient-ecosystem dynamics, movement of animals with genetic, isotopic or telemetry techniques. Candidates would conduct independent internationally recognized research as well as interdisciplinary research together with other members of the lab as well as various researchers in the department. Ability to safely carry out fieldwork together with other researchers and students are desired. In addition to research, the candidate would teach one or two undergraduate field courses and mentor undergraduate and graduate students.    Working hours: Full-time, expected regular hours of 9:00 AM - 5:00 PM  Term: Until March 2029. (Possibility of reappointment. Maximum 8 years in total)  Location: Watershed Ecology Lab, Aobayama Campus, Graduate School of Life Sciences at Tohoku University  Compensation: Annual salary system (according to the rules of Tohoku University)  Application deadline: May 10 (Friday), 2024 Start date: August 1, 2024 or at earliest convenience    Application documents for submission: (English or Japanese) (1) Curriculum vitae (Format provided by Tohoku University: https://c.bureau.tohoku.ac.jp/jinji-top/external/resume_cv/)  (2) List of research achievements (including conference presentations)  (3) List of research funds and awards acquired  (4) Summary of research activities to date (1-2pages in A4, OK to include figures)  (5) Summary of desired future research and teaching statement (1-2pages in A4, OK to include  figures) (6) Diversity Statement. Your experiences and thoughts regarding DEI (Diversity, Equality &  Inclusion), and how you would contribute to the promotion of DEI on campus (1 page in A4) * (7) Names, emails, and relationship to the applicant of 2 individuals who can provide  recommendation letters During the selection process, applicants may be asked for an interview.  (8) Three primary research papers   *For the maintenance of the welcoming environment, commitment of every one of the campus  members is crucial. In the Diversity Statement, please state how you yourself can contribute to  the promotion of the DEI on campus either directly or indirectly.   Please arrange (1) through (8) into a single PDF file and send to the search committee (lif-saiyo@grp.tohoku.ac.jp). You will receive a confirmation upon submission. Submitted  documents will only be used for the purposes of this application, and personal information will  not be shared with any third parties.   Please send any inquiries to: The search committee. Email: lif-saiyo@grp.tohoku.ac.jp The title of the email should be “Assistant Professor at Watershed Ecology_NAME”   Note: Tohoku University promotes activities to increase Diversity, Equity and Inclusion (DEI) and  encourages people of varied talents from all backgrounds to apply for position s at the  university. Tohoku University’s website about the DEI Declaration is here:  https://dei.tohoku.ac.jp/en/. To promote the diversity of the campus community, Tohoku  University shall prioritize the hiring of applicants from minor groups deemed qualified for each  job opening, based on the impartial evaluation.     Laboratory of Watershed Ecology https://www.lifesci.tohoku.ac.jp/en/research/fields/laboratory---id-45420.html (after April 1st) Unveiling ecosystem processes of watersheds at the interface of land and ocean        The forest, stream, and marine ecosystems within a watershed are intricately interconnected. Water, sediment, and wood regimes originating from the forest significantly influence stream and coastal environments. Numerous animals, including fishes and shrimps, migrate between the ocean and streams, while aquatic insects, amphibians, birds, bats, and mammals traverse between forests and streams. These migratory animals serve to bridge two spatially distinct ecosystems by transporting resources and/or interacting with other community members. Dynamic and heterogeneous watershed landscape allow diverse organisms to co-exist in nature.   While the spatial couplings of ecosystems are often considered surprising, they are supported by ecosystem processes facilitated by watershed connectivity. We investigate these ecosystem processes within watersheds using field-based approaches such as direct observations, surveys, and field manipulative experiments.   Unfortunately, the majority of ecosystems on our planet have been degraded. However, biota have evolved and adapted to thrive in natural environments. By studying how biota live and interact with each other in natural ecosystems, we aim to better understand nature and provide essential foundational information for humans to coexist with nature. Our research group visits pristine natural ecosystems around the world to study the broader scope of nature, collaborating with scientists from various backgrounds.   PDF https://www.lifesci.tohoku.ac.jp/ Habenular Astrocytes Tuning Anxiety with the ‘Marble Blues’ 2024-02-15T15:00:00+09:00 Anxiety is often attributed to an unconscious assessment of the environment and detection of potential danger. Whilst moderate anxiety is therefore advantageous for survival, excessive anxiety can lead to psychiatric disorders.     Now, researchers at Tohoku University have shed light on the intricate interactions between neurons and astrocytes within the habenula, a region of the brain associated with emotional processing. By subjecting mice to a scenario involving a floor scattered with marbles, the researchers observed behavioral responses indicative of anxiety.     The findings were detailed in the journal, Neuroscience Research, on February 10, 2024.     The habenula are a pair of small nuclei located above the thalamus. It is one of the few brain regions that controls both dopaminergic and serotonergic systems. As these neuromodulators play essential roles in a wide range of motivational and cognitive functions, habenula neuronal circuits are potentially relevant to controlling anxiety.     “Anxiety may appear to be an irrational emotion having only negative impacts on our life,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “However, well-tuned anxiety is a guide provided by our unconsciousness which allows us to navigate the hidden dangers. Such tuning may be accomplished by the actions of the habenula.”     Mice perceive smooth glass marbles as potentially harmful objects due to their unfamiliarity. Mice tend to bury marbles in saw dust bedding to keep these uncomfortable objects out of sight. Here, the researchers created a chamber filled with marbles to create an inescapable, maximum anxiety environment.     They noticed increased neuronal activity in the theta band (5 to 10 Hz) frequency, an increase in local brain blood volume, and acidification occurring in the astrocytes of the habenula when the mice were placed in the all-marble cage. When the habenular astrocytes were artificially alkalized to counter the acidification, the theta band neuronal activity diminished. When the mice were allowed to choose between the brightly lit all-marble cage and a dark and comfortable cage, the mice naturally chose to stay in the dark cage. However, when the habenular astrocytes were optogenetically alkalized, the mice ventured more into the bright cage.     Astrocytes are non-neuronal cells that occupy approximately half of the brain. They have been shown to control the local ionic and metabotropic environment in the brain. Astrocytes also release transmitters that can affect neuronal activity in the vicinity. The results of this study suggest that the theta band habenular neuronal activity is regulated by the activity of astrocytes. Thus, habenular astrocytes were considered to play a role in regulating anxiety.     Lead study investigator, Wanqin Tan, says that future treatment of anxiety disorders may be realized by developing a therapeutic strategy that adjusts astrocyte activity in the habenula. “Habenular astrocytes tune the ‘marble blues.’ Based on this, we expect that methods to cope with anxiety could be developed.”    Habenular astrocytes tuning the marble blues. Mice usually do not prefer novel objects and the presence of smooth glass marbles makes them uneasy and anxious. In the marble burying test, the number of marbles buried in the sawdust bedding is counted and administration of anti-anxiety drugs has been shown to reduce the buried number. However, with the floor filled with marbles, the mouse is faced with inescapable anxiety. Theta-band neuronal activity is observed in the habenula when the mouse is in such an anxiogenic environment. With optogenetic alkalinization of habenular astrocytes, the theta-band neuronal activity becomes dissipated. These experiments suggest the role of habenular astrocytes in regulating the tone of anxiety. * The animal in this figure is not a real photograph but a drawn picture and is depicted for the sole purpose of presenting the circumstantial image of the research only.  ©Wanqin Tan, Ko Matsui       Habenular astrocyte acidification in the anxiogenic environment. (A) Fluorescence sensor protein E2GFP is sensitive to changes in the intracellular pH. The green emission in response to purple light excitation does not change much with changes in the pH; however, the orange emission is largely decreased with pH acidification. E2GFP was selectively expressed in astrocytes and fluorescence fluctuation in the habenula was analyzed using the fiber-photometry method. (B) When the mouse was placed in the anxiogenic all-marble cage, ~ 8 Hz theta-band neuronal activity was detected in the local field potential recorded using a pair of electrodes placed in the habenula. With the optical fiber placed in the habenula, green emission fluorescence showed a downward deflection when the mouse was placed in the all-marble cage. This is the result of an increase in the local brain blood volume. The expansion of the blood vessel diameter likely obstructs the emitted fluorescence from reaching the optical fiber for detection. The orange emission showed a larger downward deflection compared to the green emission. This shows that intracellular pH in the habenular astrocytes was acidified and the local brain blood volume increased when the mice were anxious.  ©Wanqin Tan, Ko Matsui       Optogenetic alkalinization of habenular astrocytes results in the reduction of anxiety. (A) Archaerhodopsin-T (ArchT) is a light-activated outward proton pump. Photoactivation of ArchT expressed in cell membranes results in intracellular alkalinization. ArchT was selectively expressed in astrocytes and the optical fiber placed in the habenula was used for photoactivation of ArchT. When the mouse was placed in an anxiogenic, all-marble cage environment, theta-band neuronal activity was detected. Photoactivation of the ArchT in the habenular astrocytes led to the reduction of the theta-band. (B) Mice normally prefer a dark room with comfortable bedding. When the mouse was placed in a two-way chamber with a dark room and a bright room with an all-marble floor, the mouse tended to stay in the dark room. However, when the ArchT in the habenular astrocytes were photoactivated, the mouse ventured to the bright room and traveled more in the bright room. These results suggest that when the acidic reaction of the habenular astrocytes is countered by optogenetic alkalinization, anxiety can be reduced.  ©Wanqin Tan, Ko Matsui     Publifation Details: Title: Anxiety control by astrocytes in the lateral habenula Authors: Wanqin Tan, Yoko Ikoma, Yusuke Takahashi, Ayumu Konno, Hirokazu Hirai, Hajime Hirase, Ko Matsui Journal: Neuroscience Research DOI: https://doi.org/10.1016/j.neures.2024.01.006 Embargo date: February 10, 2024   Contact: Ko Matsui, Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/ https://www.lifesci.tohoku.ac.jp/ Team explores role of STING – stimulator of interferon genes – in body’s innate immune system 2024-01-18T09:59:00+09:00 When pathogens attack the body, the innate immune system goes to work protecting against the invading disease. The innate immune system is the first line of defense. It detects precisely what the virus or bacteria is and then activates the proteins that fight the pathogens. Wanting to better understand how the body’s innate immune system works, a team of scientists undertook a study of STING, a protein that plays a vital role in innate immunity. The team provides quantitative results, showing how STING, an acronym for stimulator of interferon genes, works in innate immune signaling.    Their work is published in the journal Nature Communications on Jan 11th, 2024. A graphical illustration of cholesterol- and palmitoylation-dependent STING clustering at the TGN. ©Institute for Glyco-core Research   Type I interferons are signaling proteins that respond when they detect the presence of viruses. They play an essential role in the body’s immune system, communicating between cells as they fight against pathogens. STING is critical for the type I interferon response to pathogen- or self-derived DNA in the cytosol, the fluid portion of a cell. While STING plays an important role in the body’s successful protection against infections, dysregulated STING activity leads to the excessive production of inflammatory mediators that can have a detrimental effect on surrounding cells and tissues. Recent studies have made the connection between STING and a number of autoinflammatory and neurodegenerative diseases.   “STING was discovered as a protein that induces innate immune signals in response to virus-derived non-self DNA. The STING innate immune response has recently been reported to play an important role in cancer immune responses and to contribute to inflammatory pathologies in aging, autoinflammatory, and neurodegenerative diseases, making it a highly attractive target for disease therapy,” said Kenichi G.N. Suzuki, a professor at the Institute for Glyco-core Research, Gifu University and a chief at the Division of Advanced Bioimaging, National Cancer Center Research Institute.                              Research suggests that STING may function as a scaffold to activate the TANK-binding kinase 1 (TBK1). TBK1 is a signaling molecule that is activated by receptors when a viral infection occurs. Scaffold proteins do the important job of regulating key signaling pathways. However, up to this point, scientists have lacked direct cellular evidence proving that STING activated the TBK1.    To analyze the STING cluster, the research team used a live-cell imaging procedure called photoactivated localization microscopy or PALM. They performed this single-molecule imaging of STING with enhanced time resolutions down to 5 milliseconds. They determined that STING becomes clustered at the trans-Golgi network. The trans-Golgi network, or TGN, is a pathway in the body that directs proteins to the correct subcellular destination.   The team also proved that STING palmitoylation facilitated the STING clustering. Palmitoylation describes a protein modification process in the body. This palmitoylation of STING is required for the cluster formation of STING at the TGN. The Golgi lipid order, along with STING palmitoylation, is essential for the STING signaling. The team examined the role of cholesterol, a lipid that plays an essential role in generating the lipid order in STING’s signaling and clustering.   They used a cholesterol biosensor and an environmentally sensitive probe for lipid membranes, to further demonstrate that cholesterol plays a role in the palmitoylated STING-formed clusters that activate TBK1 at the TGN.   The team specifically examined the formation of STING clusters as it relates to COPA syndrome. COPA syndrome is a disorder of immune dysregulation characterized by an increase in type I interferon-stimulated genes. This autoimmune disorder can impact multiple systems in the body.   The team’s imaging of TBK1 revealed that the increase in the clustering enhances the association of TBK1. “We provide quantitative proof-of-principle for the signaling STING scaffold, reveal the mechanistic role of STING palmitoylation in the STING activation, and resolve the long-standing question of the requirement of STING translocation for triggering the innate immune signaling,” said Tomohiko Taguchi, a professor in the Graduate School of Life Sciences, Tohoku University.   Looking ahead, the team sees potential for this work helping the fight against disease. “In the present study, we showed that inhibition of cholesterol transport to TGN markedly suppressed the STING innate immune response. Therefore, based on the results of this study, it is expected that reducing cholesterol levels will be a new tool to treat the diseases associated with STING inflammation,” said Suzuki.   Haruka Kemmoku, Kanoko Takahashi, Kojiro Mukai, Yasunori Uchida, Yoshihiko Kuchitsu, and Tomohiko Taguchi from Tohoku University; Toshiki Mori, Koichiro M. Hirosawa, and Yasunari Yokota from Gifu University; Fumika Kiku and Hiroyuki Arai from the University of Tokyo; Yu Nishioka and Masaaki Sawa from Carna Biosciences, Inc.; Takuma Kishimoto and Kazuma Tanaka from Hokkaido University; and Kenichi G.N. Suzuki from Gifu University and the National Cancer Center, Tokyo.    This work was funded by JSPS KAKENHI, JSPS Research Fellowship for Young Scientists, AMED-PRIME, JST CREST, Subsidy for Interdisciplinary Study and Research concerning COVID-19 (Mitsubishi Foundation), National Cancer Center Research and Development Fund, Takeda Science Foundation, The Uehara Memorial Foundation, Mizutani Foundation for Glycoscience, Daiichi Sankyo Foundation of Life Science, Research Foundation for Opto-Science and Technology, The Naito Foundation, Grant for Basic Science Research Projects from the Sumitomo Foundation, SGH Cancer Research Grant, Research Grant of the Princess Takamatsu Cancer Research Fund, and the Nagoya University CIBoG program from MEXT WISE program.   #   INSERT BOILERPLATE   Suggested EurekAlert! Summary: When pathogens attack the body, the innate immune system goes to work protecting against the invading disease. The innate immune system is the first line of defense. It detects precisely what the virus or bacteria is and then activates the proteins that fight the pathogens. Wanting to better understand how the body’s innate immune system works, a team of scientists undertook a study of STING, a protein that plays a vital role in innate immunity. ### About iGCORE: Institute for Glyco-core Research (iGCORE) is a cutting-edge integrative glycoscience institute that brings together researchers from two universities - Nagoya University and Gifu University under the Tokai National Higher Education and Research System - with outstanding achievements in the fields of glycan synthesis, imaging, glycobiology, and glycomedicine. Through our research, iGCORE is committed to gaining a deeper understanding of the fundamental nature of life, ultimately paving the way for groundbreaking innovations in medicine, such as personalized prevention and early detection of pre-disease.   About The National Cancer Center Research Institute: The National Cancer Center Research Institute is one of the largest cancer research institutions in Japan, with over 350 staff, including postgraduate students and research assistants. The Institute covers 20 research areas with 9 independent units, as well as the Fundamental Innovative Oncology Core, established as a common platform serving the entire Center. From highly original basic research to the development of therapeutic and diagnostic drugs, the Institute conducts a wide range of activities in collaboration with other units within the Center.   Expert Contact: Kenichi G.N. Suzuki, Ph.D., Professor. Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, Japan. Division of Advanced Bioimaging, National Cancer Center Research Institute, Tokyo, Japan. e-mail: suzuki.kenichi.b7@f.gifu-u.ac.jp   Tomohiko Taguchi, Ph.D., Professor. Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan. e-mail: tomohiko.taguchi.b8@tohoku.ac.jp   Media Contact: Yutaka Nibu, Ph.D. Institute for Glyco-core Research (iGCORE), Tokai National Higher Education and Research System yutaka.nibu@igcore.nagoya-u.ac.jp   https://www.lifesci.tohoku.ac.jp/ Cutting-edge Biodiversity Models Will Help Assess Nature’s Vital Contributions to People 2023-12-13T11:00:00+09:00 People depend on nature in a multitude of ways. Crop pollination, pest management, storm buffering, and carbon capturing are all part of nature’s contributions to people (NCP). But these contributions are subject to change—species that make vital contributions may migrate or even go extinct due to climate change or habitat loss. Forecasting these changes is challenging, but also essential to ensure that humans are adequately prepared to respond.      Part of what makes this so challenging is that current NCP estimates typically rely on data incorporating the physical environment and omit information on species. Given that biodiversity is a cornerstone of NCP, many scientists recognize that biodiversity information can help us better assess the current and future state of NCP.      In a new opinion paper published in Trends in Ecology and Evolution, lead author Jamie M. Kass, associate professor and head of the Macroecology Lab at Tohoku University’s Graduate School of Life Sciences, and an international team of colleagues argue that recent advances in biodiversity modeling and mapping have great potential for improving NCP estimates.     “Modeling and mapping of biodiversity advance at a rapid pace, making it difficult for researchers outside the field to keep up,” points out Kass. “Our paper overviewed the current challenges in predicting NCP and explained how two major biodiversity modeling strategies can help: species distribution models and macroecological models.”      Species distribution models predict species’ range limits and habitat suitability based on environmental variables like climate and land use. Macroecological models also use environmental variables but instead predict biodiversity patterns such as the richness of species in an area or how much ecological communities change across a region.       “In the paper we noted that increased adoption of these modeling strategies could allow for a more reliable assessment of the spatial distribution of NCP, for example, by predicting distributions of service-providing species with high biodiversity likely to be important for NCP,” adds Kass.     To illustrate their point, the authors outlined how multiple advances for these modeling approaches can be employed to predict different dimensions of pollinator diversity, as well as abundance patterns for predators of crop pests and maps of the associated analytical uncertainty.      The authors conclude these advances will help us forecast changes in NCP that human societies rely on and also meet international goals for biodiversity conservation.      The work for this paper was done in partnership with Keiichi Fukaya (National Institute for Environmental Studies, Japan), Wilfried Thuiller (Université Grenoble Alpes, France), and Akira S. Mori (The University of Tokyo).   Edible wild foods like oyster mushrooms (left) and pollination provided by bees (right) are two examples of nature's contributions to people whose distributions can be predicted using biodiversity models. ©Keiichi Fukaya       Example workflows that utilize advances in biodiversity modeling to predict nature’s contributions to people (NCP) linked to species and ecological communities. ©Trend in Ecology & Evolution       Publication Details: Title: Biodiversity modeling advances will improve predictions of nature’s contributions to people Authors: Jamie M. Kass, Keiichi Fukaya, Wilfried Thuiller, Akira S. Mori Journal: Trends in Ecology and Evolution DOI: https://doi.org/10.1016/j.tree.2023.10.011     Contact Name: Jamie M. Kass Affiliation: Tohoku University     Email: kass@tohoku.ac.jp Website: https://www.lifesci.tohoku.ac.jp/en/research/fields/laboratory.html?id=45417 Twitter: ndimhypervol   https://www.lifesci.tohoku.ac.jp/ Glial Tone of Aggression 2023-12-05T15:00:00+09:00 Aggression is often associated as a negative emotion. Uncontrolled aggression can lead to conflict, violence and negative consequences for individuals and society. Yet that does not that mean that aggression serves no purpose. It is an instinctive behavior found in many species that may be necessary for survival. The key is managing and channeling aggression.     In a recent study using mice, researchers at Tohoku University have demonstrated that neuron-glial interactions in the cerebellum set the tone of aggression, suggesting that future therapeutic methods could rely on adjusting glial activity there to manage anger and aggression.     The findings were detailed in the journal, Neuroscience Research, on November 24, 2023.     Scientists have recently recognized the role of the cerebellum in non-motor functions such as social cognition. A malfuctioning cerebellum can occur in autism spectrum disorders and schizophrenia, leading to social interaction difficulties. In particular, it has been reported that a region of the cerebellum, known as the vermis, is associated with aggression in humans. Therefore, the researchers investigated the possibility that Bergmann glial cells in the cerebellar vermis regulate the volume of aggression in mice.     Schematic diagram of the mechanism of cerebellar glial cell activity in regulating aggression. Gliotransmitter could be released in response to intracellular Ca2+ concentration increase in the cerebellar Bergmann glial cells. Excitatory transmitters such as glutamate would increase the cerebellar Purkinje cell activity. The only output nerve fiber from the cerebellum is the axon of the Purkinje cell (PC). PC activity leads to inhibitory GABA input to the deep cerebellar nuclei (DCN). Excitatory neuronal contacts from the DCN to the ventral tegmental area (VTA) have recently been identified. Dopaminergic neurons in the VTA have been reported to have a significant influence on social behavior, including aggression. Therefore, if the schematic pathway as described works, then an increase in Ca2+ concentration in cerebellar glial cells would be expected to increase PC activity and suppress DCN and VTA activity, leading to reduced aggression. This could lead to an early breakup of fights. On the other hand, a decrease in Ca2+ concentration in cerebellar glial cells would decrease PC activity and increase DCN and VTA activity, which would increase aggression and lead to dominance in fight situations. ©Yuki Asano, Ko Matsui   “Cells in the brain can be divided into neurons and glia, and although glia occupy approximately half of the brain, their participation in the brain’s information processing, plasticity, and health has long been an enigma,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “Our newly created fiber photometry method provides a gateway for understanding the physiology of glia.”     Matsui and his colleagues employed the resident-intruder model, where one mouse (the intruder) goes into the territory of another mouse (the resident). When the unfamiliar male mouse enters the cage, quite commonly, a series of fights break out between the resident male mouse and the intruder. Each combat round lasted about 10 seconds, and these rounds were repeated at a frequency of approximately one per minute. The superiority and inferiority of the resident and intruder dynamically switched within each combat round.        Theta band local field potential (LFP) in the cerebellum upon combat breakup. LFPs were recorded between two electrodes implanted in the mouse cerebellum. In the particular combat round shown, the intruder mouse approached the resident mouse (the recorded mouse), and a fight broke out immediately after contact. Signals recorded during the combat were not analyzed as they contained electrical signals from muscle movements from intense exercise. After the combat breaks up, both mice became stationary. The LFPs in the cerebellum showed oscillations in the frequency range of 4 - 6 Hz (theta band). In separate experiments, when theta band electrical stimulation was delivered via the same cerebellar electrode immediately after the start of the fight, the combat often broke up quickly. It was also shown that ChR2 photostimulation of cerebellar glial cells results in theta band LFP in the cerebellum and also causes the fight to break up early. ©Yuki Asano, Ko Matsui   The fiber photometry method revealed that intracellular Ca2+ levels in cerebellar glia decreased or increased in conjunction with the superiority or inferiority of the fight, respectively. When the combat broke up, the researchers observed 4 to 6 Hz theta band local field potentials in the cerebellum, along with a sustained increase in Ca2+ levels in the glia. Optogenetic stimulation of cerebellar glia induced the emergence of the theta band, casuing an early breakup of the fighting.     Glia have been shown to control the local ionic and metabotropic environment in the brain and also to release transmitters that can affect neuronal activity in the vicinity. The results of this study suggest that the theta band cerebellar neuronal activity is regulated by the activity of Bergmann glial cells, thereby demonstrating that cerebellar glial cells play a role in regulating aggression in mice.     Lead study investigator, Yuki Asano, says that future anger management strategies and clinical control of excessive aggression and violent behavior may be realized by developing a therapeutic strategy that adjusts glial activity in the cerebellum. “Imagine a world without social conflict. By harnessing the innate ability of the cerebellar glia to control aggression, the peaceful future could be become reality.”     Fiber optic measurement of the local brain environment of the cerebellum. We measured three types of fluorescence (fYFP, dYFP, and fCFP) by inserting an optical fiber into the cerebellum and sending two types of excitation light. By comparing the three fluorescence waveforms, we can estimate the fluctuation of Ca2+ concentration in glial cells, pH fluctuation, and local brain blood volume. Analysis of Ca2+ concentration fluctuations in glial cells during combats revealed that Ca2+ levels decreased significantly when the recorded resident mice fought back and attacked the intruder mice. When the recorded mice were chased from behind by the intruder mice, Ca2+ in the glial cells increased significantly. In addition, the Ca2+ levels remained high even after the fight broke up. These results suggest that cerebellar glial cell activity is linked to mouse aggression. ©Yuki Asano, Ko Matsui     Publication Details: Title: Glial tone of aggression Authors: Yuki Asano, Daichi Sasaki, Yoko Ikoma, Ko Matsui Journal: Neuroscience Research DOI: https://doi.org/10.1016/j.neures.2023.11.008     Contact: Ko Matsui, Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/       https://www.lifesci.tohoku.ac.jp/ The seminar by Dr. Satoshi Ogawa (JSPS PD Researcher, RIKEN) 2023-11-07T13:00:00+09:00 Title : How do Orobanchaceae parasitic plants grow their roots toward host roots?   Talks : Dr.Satoshi Ogawa (JSPS PD Researcher, Center for Sustainable Resource Science,  RIKEN, Japan (Ken Shirasu Laboratory))   Data : Tuesday, November 28. 15:00-16:00   Venue : Hybrid (On-site): Katahira campus, Life Sciences Project Research Laboratory, Meeting Room 103 (On-line): https://us06web.zoom.us/meeting/register/tZIpf-itpj8qE9UyweEDPxZBMd9EUOUeLhIA   Abstract Orobanchaceae root parasitic plants deprive their host plants of nutrients and water by establishing connections between their roots and those of host roots. Some species are devastating for major crops, causing annual losses of several billion dollars. To prevent infestation by these parasites, it is crucial to understand the molecular mechanisms that regulate parasitism. Orobanchaceae parasitic plants have evolved the ability to direct their root growth towards hosts, known as host tropism, to ensure accurate parasitism. However, the underlying molecular mechanisms remained largely elusive. To characterize host tropism, we used the model facultative root parasite Phtheirospermum japonicum, capable of surviving with or without hosts. We showed that host-derived strigolactones (SLs) act as chemoattractants for host tropism. Furthermore, we demonstrated that SLs trigger an asymmetric auxin response in P. japonicum roots, which is impaired under ammonium-rich conditions. We have also identified SL receptors that contribute to host tropism. In parallel with host tropism, I will present another recently uncovered molecular basis modulating parasitism in Orobanchaceae parasites.       Contact: Plant Development Prof. KYOZUKA Junko E-mail:junko.kyozuka.e4(at)tohoku.ac.jp   https://www.lifesci.tohoku.ac.jp/ Nutrients drive cellular reprogramming in the intestine 2023-09-11T13:00:00+09:00 Researchers have unveiled an intriguing phenomenon of cellular reprogramming in mature adult organs, shedding light on a novel mechanism of adaptive growth. The study, which was conducted on fruit flies (Drosophila), provides further insights into dedifferentiation - where specialized cells that have specific functions transform into less specialized, undifferentiated cells like stem cells.   Until now, dedifferentiation has primarily been associated with severe injuries or stressful conditions, observed during tissue regeneration and diseases like tumorigenesis. However, the researchers have unearthed a previously unknown facet: enteroendocrine cells (EEs) within the intestinal epithelium undergo dedifferentiation into intestinal stem cells (ISCs) in response to nutritional changes, such as recovery from starvation.   “Through meticulous experimentation, we identified a subset of enteroendocrine cells residing in the adult midgut of Drosophila, which exhibit dedifferentiation into ISCs when nutrient levels fluctuate,” states Hiroki Nagai, first author of the study and a postdoc who was previously based at Tohoku University’s Frontier Research Institute for Interdisciplinary Sciences (FRIS). “By utilizing in vivo lineage tracing of EEs and single-cell RNA sequencing, we pinpointed the dedifferentiating EE subpopulation and developed a genetic system for selectively removing ISCs derived from dedifferentiation, a process known as ablation.”     A brief summary of this study: the Drosophila adult midgut rapidly grows in size upon recovery from starvation (adaptive growth). ©Hiroki Nagai et al.     Remarkably, the ablation experiments demonstrated that dedifferentiation is vital for ISC expansion and subsequent intestinal growth following food intake. Previous studies using mice relied on massive stem cell ablation to induce dedifferentiation. Yet, in the current research, stem cells were not lost but instead increased in response to nutritional stimuli. This crucial distinction demonstrates that dedifferentiation is not limited to regenerative contexts but significantly contributes to organ remodeling during environmental adaptations.   Furthermore, the team unraveled the molecular mechanism driving nutrient-dependent dedifferentiation: a deficiency in dietary glucose and amino acids activates the JAK-STAT signaling pathway in EEs, facilitating the conversion of EEs into ISCs during post-starvation recovery. When combined with findings from other studies, this implies that the nutrient-dependent dedifferentiation could be an evolutionary conserved mechanism across species.     A detailed summary of this study: the Drosophila adult midgut rapidly grows in size upon the first food intake after eclosion or upon refeeding after starvation. ©Hiroki Nagai et al.     Yuichiro Nakajima, also formerly based at FRIS and corresponding author of the paper, states that this could lead to being able to control artificial cellular reprogramming in vivo. “If we figure out specific nutrients and the detailed signaling that induce dedifferentiation, we could control cell fate plasticity by nutritional intervention and/or pharmacological treatments”   Looking ahead, they hope to focus on examining cell fate plasticity under physiological conditions beyond nutrition, such as reproduction, temperature, light, and exercise. Doing so may uncover novel mechanisms underlying environmental adaptations.     Representative image of a dedifferentiating EE which is brightly shining like a star.This is a fluorescent confocal microscope image in which the dedifferentiating EE is shown as a cell with white color (center left). Green indicates expression of stemness marker, magenta marks cells that are originally derived from EEs, and blue indicates expression of EE marker. The white color (green + magenta) means that this cell lost identity as EEs and converted into a stem cell. ©Hiroki Nagai et al.   LINK: Tohoku University The Frontier Research Institutes for Interdisciplinary Sciences, Tohoku Univ     Publication Details: Title: Nutrient-driven dedifferentiation of enteroendocrine cells promotes adaptive intestinal growth in Drosophila Authors: Hiroki Nagai, Luis Augusto Eijy Nagai, Sohei Tasaki, Ryuichiro Nakato, Daiki Umetsu, Erina Kuranaga, Masayuki Miura, and Yu-ichiro Nakajima Journal: Developmental Cell DOI: 10.1016/j.devcel.2023.08.022     Contact: Yuichiro Nakajima, Graduate School of Pharmaceutical Sciences, The University of Tokyo Email: nakaji97g.ecc.u-tokyo.ac.jp Website: https://idenut.f.u-tokyo.ac.jp/   https://www.lifesci.tohoku.ac.jp/ Advanced Technology Reveals Intricate Details of Zinc Transportation in Cells 2023-09-01T09:00:00+09:00 A group of researchers has unearthed the secrets behind a tiny but crucial protein that shuttles zinc ions (Zn2+) within our bodies. The discovery offers a deeper understanding of how our cells maintain optimal health.   Zn2+ may be small, but they play a mighty role in our cells. Zinc enables enzyme catalysis, protein folding, DNA binding, and regulating gene expression, with about 10% of the proteins in our body reliant on Zn2+ to function effectively.   The study, which was published in the journal Nature Communication on August 8, 2023, focused on the Golgi apparatus - a cellular compartment that processes, sorts and distributes cells to their final destination. Within the Golgi, three distinct zinc transporter (ZnT) complexes - ZnT4, ZnT5/6, and ZnT7 - collaborate to usher Zn2+ ions from the cellular interior (cytosol) into the Golgi. While these complexes have long been known to play pivotal roles, the precise mechanisms governing Zn2+ transport within them have remained an enigma.   "We concentrated our study on the transport protein hZnT7," says Kenji Inaba, a corresponding author of the study and professor at Tohoku University's Institute of Multidisciplinary Research for Advanced Materials Sciences. "The study built upon our previous research that hZnT7 plays a vital role in Zn2+ uptake into the cis-Golgi cisterna and regulates the localization, traffic and function of the chaperone protein ERp44."   Cryo-EM map of human ZnT7 in complex with Fab at 2.2 a resolution. ©Han Ba Bui and Kenji Inaba   To reveal more about hZnT7, Inaba and his colleagues employed an advanced technique called cryo-electron microscopy (cryo-EM). Two cryo-EM machines, one from Tohoku University and one from the University of Tokyo, could capture detailed images of hZnT7 in action. By using a Fab fragment from a monoclonal antibody that specifically binds hZnT7 the researchers succeeded in determining the cryo-EM structures of hZnT7 at near-atomic resolutions, gaining critical insights into the mechanisms of Zn2+ transport.   Comparative analysis between hZnT7 and other zinc transporters, including human ZnT8 and bacterial YiiP, exposed distinct structural features of hZnT7. The existence of hZnT7 as a homodimer with varying Zn2+-bound configurations holds particular significance. Notably, hZnT7 boasts an elongated cytosolic histidine-rich loop (His-loop) that interfaces with the transmembrane metal-binding site, a vital feature governing zinc transfer. During Zn2+ recruitment via the His-loop, hZnT7 undergoes intricate conformational rearrangements, shedding light on an unparalleled mechanism of zinc transport.       Conformational transition of the hZnT7 protomer during the Zn2+ transport from the cytosol to the Golgi lumen. ©Han Ba Bui and Kenji Inaba   It is widely known that hZnT7 is a key player in dietary zinc absorption and controlling body fat. When zinc levels drop in certain parts of the body, it can lead to issues like prostate cancer development in mice and disruptions in how our bodies process insulin.   Inaba adds their findings will result in greater understandings of the molecular processes with certain pathogens. "With it reported that abnormalities in Golgi-resident ZnT transporters result in fatal diseases such as diabetes, cancers, and immunodeficiency, it's essential to understand the pathogenic mechanisms of these diseases at the molecular and cellular level."   The histidine-rich loop segment is inserted into the cytosolic cavity and coordinated to Zn2+ at the transmembrane metal-binding site for efficient Zn2+ uptake. ©Han Ba Bui and Kenji Inaba     Publication Details: Title: Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus Authors: Han Ba Bui, Satoshi Watanabe, Norimichi Nomura, Kehong Liu, Tomoko Uemura, Michio Inoue, Akihisa Tsutsumi, Hiroyuki Fujita, Kengo Kinoshita, Yukinari Kato, So Iwata, Masahide Kikkawa & Kenji Inaba Journal: Nature Communications Date of Publication: August 8th, 2023 DOI: 10.1038/s41467-023-40521-5   Link Tohoku University Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Graduate School of Science and Faculty of Science Tohoku University     Contact: Kenji Inaba Institute of Multidisciplinary Research for Advanced Materials Email: kenji.inaba.a1(at)tohoku.ac.jp Website: http://www2.tagen.tohoku.ac.jp/lab/inaba/html/   https://www.lifesci.tohoku.ac.jp/ How the Tropical Red Swamp Crayfish Successfully Invaded the Cold Regions of Japan 2023-08-24T16:40:00+09:00 https://www.cn.chiba-u.jp/en/news/press-release_e230802/ Researchers Unearth a New Process By Which Algae Pass on Nurtirients to their Coral Host 2023-08-23T11:00:00+09:00 Researchers have identified a new pathway by which sugar is released by symbiotic algae. This pathway involves the largely overlooked cell wall, showing that this structure not only protects the cell but plays an important role in symbiosis and carbon circulation in the ocean.   The findings were reported in the journal eLife on August 18, 2023.   It is widely known that microalgae enjoy a symbiotic relationship with cnidarians such as corals and sea anemones. The algae use the sun light to produce sugars and other carbohydrates and pass them on to the coral. In return, the coral provides nutrients and shelter to the algae. This fertile coral reefs form in the nutrient-poor tropical oceans and partially addresses the Darwin paradox.     Yet this symbiotic relationship is both delicate and complex; the slightest change in temperature, pollution or water chemistry can have adverse impacts, leading to coral bleaching or other negative effects on the ecosystem. Scientist still do not understand many of the intricate processes at play when it comes to this relationship, but doing so is crucial for the preservation of coral reefs and the biodiversity they support.     “We discovered that the release of sugar occurs when the algal cell begins degrading its own cell wall,” explains Shinichiro Maruyama, lead-author of the research and an associate professor at the University of Tokyo’s Graduate School of Frontier Sciences. “This breakdown of the cell wall happens even when a symbiotic host is absent and gets enhanced when conditions become more acidic.”     Symbiotic algae live in special compartments within coral cells - symbiosomes - or the guts of marine animals. These environments are generally acidic, and the researchers interpret the sugar release as the algal response to environmental changes in nature.     The researchers also found the sugar release is mediated by the enzyme cellulase, which is known for its usage in breaking down the cell walls in land plants. When the alga gets treated with a cellulase inhibitor, the amount of sugar released outside of the cell decreases, indicating that the degradation of sugar chains by cellulase is directly related to the increase in sugar release in acidic conditions.     “Our findings suggest that the algal-coral interaction is more complex than ever thought, providing an important piece of the jigsaw puzzle when it comes to carbon cycling in marine environments,” adds Maruyama.     For their next steps, Maruyama and his team will begin clarifying the molecular mechanisms of sugar release, cell wall maintenance, and regulation of enzymatic reactions. Already, they have embarked on a project to disclose the whole diversity of molecules secreted from symbiotic algae, which will further provide insights into what kind of ‘molecular language’ is exchanged between symbionts and hosts.   Coral reef ecosystem supported by symbiosis with microalgae    A model of the pathways of sugar secretion from coral symbiotic algae     Pocillopora coral in symbiosis with microalgae     Publication Details Title:Environmental pH signals the release of monosaccharides from cell wall in coral symbiotic alga Authors: Yuu Ishii, Hironori Ishii, Takeshi Kuroha, Ryusuke Yokoyama, Ryusaku Deguchi, Kazuhiko Nishitani, Jun Minagawa, Masakado Kawata, Shunichi Takahashi, Shinichiro Maruyama* Journal: eLife DOI: https://doi.org/10.7554/eLife.80628   Link Tohoku University Graduate School of Science and Faculty of Science Tohoku University Graduate School of frontier sciences, the University of Tokyo     Contact Name: Shinichiro Maruyama Affiliation: Laboratory of Integrated Biology Department of Integrated Biosciences Graduate School of Frontier Sciences The University of Tokyo Email: shinichiro.maruyama@k.u-tokyo.ac.jp Website: https://www.ib.k.u-tokyo.ac.jp/english/faculty/integrated_biology/       https://www.lifesci.tohoku.ac.jp/ Glial control of parallel memory processing 2023-06-27T12:00:00+09:00 Researchers at Tohoku University have discovered that there are two parallel processes involved in memory formation when a mouse performs a motor learning task. One process occurs during training and is called online learning, while the other happens during the resting period and is called offline learning. Online learning can be boosted or reduced by manipulating glial activity, but offline learning remains unaffected by these manipulations. Understanding the cellular mechanisms underlying these independent parallel memory formation processes may lead to the development of efficient rehabilitation after strokes, dementia treatment, or realizing extended intelligence.   The findings were detailed in the journal Glia on June 26, 2023.   We have long been aware that performance may not improve much during training, but increase the next day. Alternatively, excelling during training may not carry over to the next day. Here, the researchers have shown that online and offline learning are indeed separate parallel processes governed by distinct cellular mechanisms.   Glial cells in the brain occupy almost as much volume as neurons; however, they were simply thought to fill the gaps between neurons. Recently, glial cells have been shown to be involved in the information processing in the brain, albeit in quite a different manner than that of neurons. By releasing gliotransmitters, such as glutamate, glial cells can modulate the easiness of memory formation; a process termed meta-plasticity.   The researchers used the horizontal optokinetic response paradigm to understand the role of glial cells in online and offline learning. When mice were presented with a horizontally oscillating visual stimulus, their eyes followed the screen with a lesser amplitude relative to the presented stimulus. With prolonged and repeated presentation, the amplitude increased until their eyes could perfectly pursue the screen. The performance increase during the 15 min presentation was termed online learning and the increase during the 1-hour resting period, which the mice spent in the dark, was termed offline learning.     Parallel memory processing hypothesis. When a mouse is presented with an image that oscillates left and right, the mouse initially cannot follow the image well, but after repeated training, the visual pursuit of the image becomes more accurate. In this study, it was shown that there is online learning that progresses during training and offline learning that progresses slowly during post-training rest and that the function of glial cells in the brain is involved in each learning process. ©Teppei Kanaya, Ko Matsui     Light-activated proteins, channelrhodopsin-2 (ChR2) or archaerhodopsin (ArchT) were genetically expressed specifically in glial cells to manually control glial activity. When glutamate release from glial cells was facilitated by photo-activating ChR2, online learning was augmented. However, the benefit from glial modulation was short-lasting and the performance of eye movement soon became indistinguishable from control. When the glial activity was inhibited by ArchT, online learning was completely suppressed. Interestingly, offline learning proceeded normally even in the complete absence of online learning.   “Our data shows that short- and long-term memory formation is not a serial process, but rather it is a parallel and independent process,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “Agonizing over the performance gained during each training or study session is unnecessary, as long-lasting achievement depends on a totally separate process.”   The cellular mechanisms underlying glial modulation of online learning are now partially uncovered. Anion conducting channels expressed in glial cells mediate glutamate release, which leads to the augmentation of synaptic plasticity. The process of offline learning is less clear; however, the researchers have also found that ArchT optogenetic manipulation of glial activity during the resting period could facilitate offline learning.   “Glial cells apparently control the likelihood of plasticity to occur in the neural circuits, either during the online or offline learning process,” says the lead study investigator, Dr. Teppei Kanaya. “By uncovering the details of the cellular process, we may be able to control our rapid adaptation to changes in the environment or facilitate long-term achievements.”         Optical glial control of learning and memory. Optogenetic control of glial cell function in the brain during training could either enhance or inhibit online learning performance. Interestingly, regardless of the degree of online learning, offline learning was shown to progress at the same rate as the control group. The results indicate that online and offline learning are independent and parallel processes of memory formation. ©Teppei Kanaya, Ko Matsui       Cellular mechanisms of parallel memory formation. Both online learning, which proceeds during training, and offline learning, which proceeds during rest, are triggered by training. Offline learning proceeds slowly, independently, and in parallel with online learning. Using optogenetics technology to optically manipulate glial function, it has been shown that the amount of glutamate released from glial cells determines the degree of online learning. In addition, optical stimulation of ArchT expressed in glial cells during offline rest was shown to enhance offline learning. The degree of offline learning is controlled by a mechanism other than online learning. Glial cells appear to be involved in both online and offline learning. ©Teppei Kanaya, Ko Matsui       Publication Details Title: Glial modulation of the parallel memory formation Authors: Teppei Kanaya, Ryo Ito, Yosuke M. Morizawa, Daichi Sasaki, Hiroki Yamao, Hiroshi Ishikane, Yuichi Hiraoka, Kohichi Tanaka, and Ko Matsui Journal: Glia DOI: https://doi.org/10.1002/glia.24431   Contact Name: Ko Matsui Affiliation: Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/ https://www.lifesci.tohoku.ac.jp/ Researchers Shed Further Light onto Zinc Homeostasis in Cells 2023-05-29T14:00:00+09:00  A research group has unearthed how zinc transporter complexes regulate zinc ion (Zn2+) concentrations in different areas of the Golgi apparatus and revealed that this mechanism finely tunes the chaperone protein ERp44.   The findings, which were reported in the journal Nature Communications on May 9, 2023, reveal the crucial chemical and cellular biological mechanism at play behind zinc homeostasis, something necessary for avoiding fatal diseases such as diabetes, cancers, growth failures, and immunodeficiency.   As a trace element, zinc is essential for our health. Zn2+ are vital for enzyme catalysis, protein folding, DNA binding, and regulating gene expression, with nearly 10% of human proteome binding Zn2+ for their structural maturation and function.   Secretory proteins like hormones, immunoglobulins, and blood clotting factors are synthesized and folded in the endoplasmic reticulum (ER), a complex membrane network of tubules. Subsequently, they are transported to and matured in the Golgi apparatus, the organelle composed of multiple flattened sacs called cisternae, which sorts and processes proteins before directing them to a specific destination. Chaperone proteins are vital for maintaining protein homeostasis and preventing the formation of misfolded or aggregated proteins in these organelles.   The group’s previous research demonstrated that Zn2+ in the Golgi apparatus plays an essential part in protein quality control in the early secretory pathway comprising the ER and Golgi. This system is mediated by the ER-Golgi cycling chaperone protein ERp44.   In the Golgi apparatus, there exists three ZnT complexes: ZnT4, Znt5/6, and ZnT7. Yet, until now, mechanisms of how Zn2+ homeostasis is maintained in the Golgi apparatus has remained unclear.   “Using chemical biology and cell biology approaches together, we revealed that these ZnT complexes regulate the Zn2+ concentrations in the different Golgi compartments, namely cis, medial, and trans-Golgi cisternae,” says Kenji Inaba, a corresponding author of the study and professor at Tohoku University’s Institute of Multidisciplinary Research for Advanced Materials Sciences. “We also further elucidated the intracellular transport, localization, and function of ERp44 controlled by ZnT complexes.”     A fluorescence image of the ER and Golgi apparatus. Authors revealed that the Golgi-resident zinc transporters, ZnT4, ZnT5/6, and ZnT7, serve to maintain zinc homeostasis at the different Golgi cisternae. This mechanism finely tunes the localization, traffic and function of the ER-Golgi-cycling chaperone protein, ERp44. ©Yuta Amagai et al.       ERp44 captures immature secretory proteins at the Golgi apparatus to prevent their abnormal secretion. Previous studies have shown that mice with the expression of ERp44 suppressed suffer from heart failure and hypotension.   Additionally, many secretory zinc enzymes are related to various diseases, including metastasis of cancer cells and hypophosphatasia. These enzymes depend on the Golgi-resident ZnT complexes to acquire Zn2+ for enzymatic activity. Male mice with ZnT5 suppressed have experienced death caused by arrhythmias, so there is possible relevance of Zn2+ homeostasis to cardiovascular disease.   “Our findings will help us understand the mechanism by which disruptions of Zn2+ homeostasis in the early secretory pathway leads to the development of pathological conditions,” adds Inaba. The group are hopeful that the strategies employed in their study can paint a bigger picture of the mechanisms underlying the maintenance of intracellular Zn2+ homeostasis, recommending future studies that can measure Zn2+ in other organelles such as the mitochondria and nucleus.   The group are hopeful that the strategies employed in their study can paint a bigger picture of the mechanisms underlying the maintenance of intracellular Zn2+ homeostasis, recommending future studies that can measure Zn2+ in other organelles such as the mitochondria and nucleus.     <Publication Details> Title: Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface Authors: Y. Amagai, M. Yamada, T. Kowada, T. Watanabe, Y. Du, R. Liu, S. Naramoto, S. Watanabe, J. Kyozuka, T. Anelli, T. Tempio, R. Sitia, S. Mizukami, and K. Inaba*. Journal: Nature Communications DOI: 10.1038/s41467-023-38397-6   <Link> Tohoku University   <Contact> Kenji Inaba Institute of Multidisciplinary Research for Advanced Materials Email: kenji.inaba.a1@tohoku.ac.jp Website: http://www2.tagen.tohoku.ac.jp/lab/inaba/html/   https://www.lifesci.tohoku.ac.jp/ The seminar by Dr. Johan B. Quilbe (Aarhus Univ.) 2023-05-02T11:30:00+09:00 Title:Natural variation in Lotus japonicus as a key to elucidate the molecular mechanisms of root microbiome assembly.   Talks:Dr. Johan B. Quilbe (Department of Molecular Biology and Genetics, Aarhus University)   Data: Friday, May 12. 10:00 ~ 11:30   Venue (On-site) : Katahira campus, Life Sciences Project Research Laboratory, Lecture Room 104   Contact: Symbiosis Genomics Prof. SATO Shusei TEL 022-217-5688 E-mail:shusei.sato.c1(at)tohoku.ac.jp https://www.lifesci.tohoku.ac.jp/ Course Outline 2023 2023-05-02T00:00:00+09:00 Course outline 2023 has been updated. Please see below.       Graduate school of life sciences, Tohoku University 2023 (16.1MB) (Written in both Japanese & English)     https://www.lifesci.tohoku.ac.jp/ Jellyfish and Fruit Flies Shed Light on the Origin of Hunger Regulation 2023-04-11T13:00:00+09:00     Decades’ worth of research has shown that the motivation to feed, i.e., hunger and feelings of fullness, is controlled by hormones and small proteins called neuropeptides. They are found in a wide array of organisms like humans, mice and fruit flies. Such a widespread occurrence suggests a common evolutionary origin. To explore this phenomenon, a research group has turned to jellyfish and fruit flies, discovering some surprising results.       Although jellyfish shared a common ancestor with mammals at least 600 million years ago, their bodies are simpler; they possess diffused nervous systems called nerve nets, unlike mammals which have more concrete structures such as a brain or ganglia. Still, jellyfish possess a rich repertoire of behaviors, including elaborate foraging strategies, mating rituals, sleep and even learning. Despite their important position in the tree of life, these fascinating creatures remain understudied, and almost nothing is known about how they control their food intake.       The group, which was led by Hiromu Tanimoto and Vladimiros Thoma from Tohoku University’s Graduate School of Life Sciences, focused on Cladonema, a small jellyfish with branched tentacles that can be raised in a laboratory. These jellyfish regulate how much they eat based on how hungry they are.   The jellyfish Cladonema pacificum. ©Hiromu Tanimoto    “First, to understand mechanisms underlying feeding regulation, we compared the gene expression profiles in hungry and fed jellyfish,” said Tanimoto. “The feeding state changed the expression levels of many genes, including some that encode neuropeptides. By synthesizing and testing these neuropeptides, we found five that reduced feeding in hungry jellyfish.”      The researchers then honed in on how one such neuropeptide—GLWamide—controls feeding. A detailed behavioral analysis revealed that GLWamide inhibited tentacle shortening, a crucial step for transferring captured prey to the mouth. When the researchers labelled GLWamide, they found it was present in motor neurons located in the tentacle bases, and feeding increased GLWamide levels. This led to the conclusion that, in Cladonema, GLWamide acts as a satiety signal - a signal sent to the nervous system indicating that the body has had enough food.   The GLWamide (green) expressed in neurons surrounding the Cladonema eyelet (black circle). Nuclei shown in magenta. ©Vladimiros Thoma et al.    Yet the researchers’ quest to explore the evolutionary significance of this finding did not stop there. Instead, they looked to other species. Fruit flies’ feeding patterns are regulated by the neuropeptide myoinhibitory peptide (MIP). Fruit flies lacking MIP eat more food, eventually becoming obese. Interestingly, MIP and GLWamide share similarities in their structures, suggesting they are related through evolution.      “Since the functions of GLWamide and MIP have been conserved despite 600 million years of divergence, this led us to ponder whether it was possible to exchange the two,” said Thoma. “And we did exactly that, first giving MIP to jellyfish and then expressing GLWamide in flies that had no MIP.”      Amazingly, MIP reduced Cladonema feeding, just as GLWamide had. Furthermore, the GLWamide in flies eliminated their abnormal over-eating, pointing to the functional conservation of the GLWamide/MIP system in jellyfish and insects.      Tanimoto notes that their research highlights the deep evolutionary origins of a conserved satiety signal and the importance of harnessing a comparative approach. “We hope that our comparative approach will inspire focused investigation of the role of molecules, neurons and circuits in regulating behavior within a wider evolutionary context.”   Publications Details: Title: On the origin of appetite: GLWamide in jellyfish represents an ancestral satiety neuropeptide Authors: Vladimiros Thoma, Shuhei Sakai, Koki Nagata, Yuu Ishii, Shinichiro Maruyama, Ayako Abe, Shu Kondo, Masakado Kawata, Shun Hamada, Ryusaku Deguchi, Hiromu Tanimoto Journal: The Proceedings of the National Academy of Sciences (PNAS) DOI: https://doi.org/10.1073/pnas.2221493120   Link Tohoku University   Contact: Hiromu Tanimoto Graduate School of Life Sciences, Tohoku University Email: hiromut(at)m.tohoku.ac.jp Website: http://www.lifesci.tohoku.ac.jp/neuroethology/index.html     https://www.lifesci.tohoku.ac.jp/ Degree of Asexual Reproduction in Liverwort Plants is Hormonally Controlled 2023-03-31T16:00:00+09:00 Asexual, or vegetative, reproduction in plants is controlled by environmental conditions, but the molecular signaling pathways that control this process are poorly understood. Recent research suggests that the KAI2-ligand (KL) hormone is responsible for initiating and terminating the production of gemmae, or genetically identical plantlets, on liverwort plants based on the presence or absence of specific environmental factors.   A team of leading scientists from Tohoku University designed a research study to investigate the hormones and signaling pathways associated with vegetative reproduction in the liverwort plant Marchantia polymorpha. Through a series of gene knockout (loss of function) experiments, the researchers demonstrated that the MpKARRIKIN INSENSITIVE2 (MpKAI2)-dependent signaling pathway initiates gemma cup, the structure that surrounds gemmae plantlets, and gemmae formation in liverwort plants, and that KAI2-dependent signaling, initiated through KL hormone binding, determines the total number of gemmae produced in a gemma cup. The team additionally observed that switching off KAI2-dependent signaling in the liverwort plant stops gemma production through the accumulation of MpSMXL, a suppressor protein.   The team published the results of their study on March 1, 2023 in the journal Current Biology.   "We discovered that the plant hormone KAI2-ligand, KL, is a gemma initiation hormone, and the efficiency of vegetative reproduction is regulated by modulating KL signaling according to environmental conditions," said Junko Kyozuka, one of the research paper authors and professor at the Graduate School of Life Sciences at Tohoku University. Interestingly, the KL hormone has yet to be identified, but researchers have inferred its presence based on its ability to bind and activate the KARRIKAN INSENSITIVE2 (KAI2) signaling pathway.     Vegetative reproduction of M. polymorpha is controlled by KL signaling. KL works as a plant hormone inducing gemma initiation and controls the efficiency of vegetative reproduction by switching the KAI-dependent signaling pathway on and off. ©Komatsu et al.     Through their research, the team discovered that normal, wild-type liverwort plants consistently produce the same number of gemmae given the same environmental conditions, suggesting a genetic basis for this trait. The researchers discovered that KAI2-dependent signaling, initiated by KL binding, starts the process of gemma formation by breaking down the MpSMXL suppressor protein. Once the proper number of gemmae is produced, KAI2-dependent signaling is turned off, and the MpSMXL suppressor protein accumulates again, turning off gemma formation.   "Because vegetative reproduction is widespread in plants, this discovery also elucidates the origin of vigorous growth pattern[s] of plants," added Kyozuka. Importantly, the team also revealed the direction that gemmae are initiated in the gemma cup, which starts from the inner region of the gemma cup and moves out to the periphery.   In KL signaling (A), KAI2 functions as a receptor of an unknown plant hormone called KL. After binding with KL, KAI2 forms a complex with MAX2, an F-box protein, and SMXL, a repressor protein. SMXL is degraded by MAX2, leading to the de-repression of genes that were suppressed by SMXL, resulting in various responses. In KAI2 and MAX2 loss-of-function mutants (B), KL signaling does not occur, and gemma cups are not formed. In SMXL loss-of-function mutants (C), genes suppressed by SMXL are no longer repressed, mimicking KL signaling, and more gemmae are formed.©Komatsu et al.     While the current study has answered many important questions related to vegetative reproduction in the liverwort plant, many questions remain. The identity of the KL hormone remains unknown, and the environmental conditions responsible for KL regulation, and thus KAI2-dependent signaling, remain a mystery. The research team experimented with liverwort growth medium that lacked potassium (K), nitrate (N) or phosphorus (P) to observe the effect of nutrient deprivation on gemmae formation, but no effect was seen on normal, wild-type liverwort plants. The team plans to design future studies to determine the environmental factors that influence KL regulation and their individual effects.   The mechanisms that dictate when gemma formation stops in liverwort plants also remain unknown. The research team removed gemmae from gemma cups that were actively producing gemmae and found that removal of gemmae didn't affect the timing of gemma initiation termination (roughly 10 days) or the total number of gemmae formed in the cup. This result suggested that the timing, rather than the number of gemmae in a gemma cup, is more likely to determine when gemma initiation ceases. However, the researchers could not rule out a role for gemmae quantity in the termination of gemmae initiation. The team plans to more fully investigate both hypotheses in future studies.   Other contributors include Aino Komatsu, Kyoichi Kodama, Yohei Mizuno and Mizuki Fujibayashi from the Graduate School of Life Sciences at Tohoku University in Sendai, Japan; and Satoshi Naramoto from the Graduate School of Life Sciences at Tohoku University in Sendai, Japan and the Department of Biological Sciences at Hokkaido University in Sapporo, Japan.       Marchantia polymorpha propagates through vegetative reproduction by forming gemmae in a gemma cup. Each gemma in gemma cups grows to a thallus, on which more gemma cups are formed. By repeating this process, Marchantia polymorpha can propagate vigorously. ©Komatsu et al.       Publications Details: Title: Control of vegetative reproduction in Marchantia polymorpha by the KAI2-ligand signaling pathway Authors: Aino Komatsu, Kyoichi Kodama, Yohei Mizuno, Mizuki Fujibayashi, Satoshi Naramoto, Junko Kyozuka Journal: Current Biology DOI: https://www.sciencedirect.com/science/article/abs/pii/S0960982223001628     Contact: Junko Kyozuka Graduate School of Life Sciences, Tohoku University Email: junko.kyozuka.e4(at)tohoku.ac.jp Website: https://www.lifesci.tohoku.ac.jp   https://www.lifesci.tohoku.ac.jp/ Cryo-electron Microscopy Captures Structure of a Protein Pump 2023-03-24T17:08:00+09:00 https://www.tohoku.ac.jp/en/press/cryoelectron_microscopy_captures_structure_of_protein_pump.html Research Team's Study Provides New Insights into How Brain Forms and Stores Long-Term Memory 2023-03-06T17:00:00+09:00 Wanting to better understand how the brain forms and stores long-term memory, an international team of scientists undertook a study of the brain's circuits. Their work sheds a new, updated light on the way the circuits in the brain work, providing fresh insights into the brain's long-term memory formation and storage.   Their work was published in the journal Cell Reports on January 20, 2023.   "In order to understand how we form memory, store memory, and recall memory, it is essential to unravel the complicated wiring of the memory circuits composed by the hippocampus and the entorhinal cortex," said Shinya Ohara, an assistant professor in the Graduate School of Life Sciences at Tohoku University. The hippocampus is the region of the brain that is primarily related to memory. The entorhinal cortex is the area of the brain that serves as a kind of network hub for navigation, memory, and perception of time. It is part of the brain's hippocampal memory system and serves as a gateway between the hippocampal formation and the neocortex, that part of the brain that controls higher brain function.   Scientists have long understood the general organization of this hippocampal and entorhinal circuit. In the early 1990s, scientists identified the basic wiring of this brain circuit. With these earlier studies, scientists thought that the hippocampus and the entorhinal cortex were connected by parallel identical circuits. However, the research team's findings bring new understanding of the memory circuits in the hippocampus and entorhinal cortex.   Previous (A) and updated circuit diagram (B) of the circuit from the hippocampus to the medial entorhinal cortex. We found that the ventral hippocampus efficiently sends out the information to the neocortex via the medial entorhinal cortex (blue arrows in B). ©Shinya Ohara et al.   The team conducted their study using anterograde tracing and in vitro electrophysiology in rodents. They discovered that the ventral hippocampus efficiently sends out information to the neocortex via the medial entorhinal cortex. Their study revealed that the ventral hippocampus - that part of the hippocampus related to stress and emotion - sends information to the medial entorhinal cortex layer Va neurons. The entorhinal cortex consists of six layers - this Va layer is one of the deep layers. When this information is received in the entorhinal cortex, it processes the information to the neocortex. This connectivity indicates that the ventral hippocampus controls the signal flow from the hippocampus to the neocortex, which supports long-term memory formation and storage.   Since the ventral hippocampus is well known for processing emotional information, the research team hypothesizes that this circuit may play an important role in memorizing emotional events. "For example, in our daily lives, we remember happy events or sad events very well. The neural mechanism of how the emotional events are memorized is largely unknown. The circuit which we identified in this study may play an important role in processing such emotional memories," said Ohara.   The circuit was examined by labeling the axons of hippocampal neurons (A). Ventral hippocampal neurons massively send their axons (cyan) to the medial entorhinal cortex which reaches the dorsal portion of layer Va (B, yellow arrowhead). ©Shinya Ohara et al.     Looking ahead, the team's next step is to test their hypothesis. They plan to selectively inactivate this pathway of the ventral hippocampal to medial entorhinal cortex layer Va while the animal performs a memory task. Generally, animals will approach a place where they experienced happy events while avoiding the places that caused bad memories. "We think that the animal will not be able to form such emotional memory when the ventral hippocampal-medial entorhinal cortex circuit is inactivated," said Ohara.   The research team includes Shinya Ohara who works for the Tohoku University Graduate School of Life Sciences, the NTNU Norwegian University of Science and Technology, and the Japan Science and Technology Agency; Märt Rannap, Andreas Draguhn, and Alexei V. Egorov from Heidelberg University medical faculty in Germany; Ken-Ichiro Tsutsui from Tohoku University Graduate School of Life Sciences, Japan; and Menno P. Witter from the NTNU Norwegian University of Science and Technology in Norway.   This work was a collaboration between three groups: Tohoku University, Heidelberg University, and Kavli Institute for Systems Neuroscience (NTNU). "This was a very fruitful collaboration in which Tohoku University and NTNU worked on the anatomy, visualizing the hippocampal- medial entorhinal cortex circuit, while colleagues at Heidelberg University worked on the electrophysiology to confirm the information flow within the hippocampal-medial entorhinal cortex circuit," said Ohara.     Publication Details: Title: Hippocampal-medial entorhinal circuit is differently organized along the dorsoventral axis in rodents Authors: Shinya Ohara, Märt Rannap, Ken-Ichiro Tsutsui, Andreas Draguhn, Alexei V. Egorov, Menno P. Witter Journal: Cell Reports DOI: 10.1016/j.celrep.2023.112001   Contact: Tohoku University Graduate School of Life Sciences Email: shinya.ohara.d3(at)tohoku.ac.jp Website: https://www.lifesci.tohoku.ac.jp/en/ https://www.lifesci.tohoku.ac.jp/ Acid glia in REM sleep: Stronger Acid Response in Epileptic Mice 2023-03-03T11:00:00+09:00 Researchers at Tohoku University have shown that astrocytes - star-shaped glial cells that control the local ionic and metabotropic environment of the brain - exhibit an acid response with REM sleep in mice. They theorize that the acid response could be the underlying drive for specific information processing and generating plasticity during sleep. They further discovered that REM response in astrocytes intensified in the epileptic brain, meaning studying brain environmental changes associated with REM sleep could potentially be employed as a biomarker for the severity of epileptogenesis.   The findings were detailed in the journal Brain on March 3, 2023.   Neurons are undoubtedly responsible for information processing in the brain. Astrocytes were not thought to be an essential component of the neural information circuit. However, recent findings suggest that the state of the mind, such as consciousness, sleep, memory formation, and meta-plasticity may all be controlled by astrocytes’ actions.   To understand the role of astrocytes in brain function, fluorescent sensor proteins were genetically expressed in the astrocytes of mice. The researchers implanted an optical fiber into the mice’s lateral hypothalamus, a part of the brain vital for controlling our state of being asleep or awake and whole-body metabolism.      Estimating brain environmental changes from optical signals detected during REM sleep. (A) Potentials recorded at the cerebral cortex (ECoG) and electromyograms (EMG) were recorded from experimental mice to identify the timing of REM sleep (left). At the same time, an optical fiber was inserted into the lateral hypothalamus and three different fluorescence waveforms (fCFP, fYFP, dYFP) were measured (right; fiber photometry method). (B) Fluorescence waveforms recorded from the lateral hypothalamus of mice genetically expressing FRET-type calcium (Ca2+) sensor protein in astrocytes. When Ca2+ increases, fCFP (blue fluorescence excited with purple) is expected to decrease and fYFP (yellow fluorescence excited with purple) is expected to increase. dYFP (direct yellow fluorescence excited with green) is considered to remain constant regardless of the Ca2+ concentration. In the present study, fYFP and fCFP did not show a mirror image reaction with REM sleep. In addition, dYFP fluorescence also changed, suggesting that factors other than Ca2+ that affect fluorescence has also changed. (C) When the intracellular pH becomes acidic, the fluorescence of both fYFP and dYFP decreases, while fCFP is expected to be less affected. In addition, if the vascular diameter near the optical fiber tip swells, an increase in the local blood flow occurs resulting in the fluorescent protein-free area to expand. When such an event occurs, the fluorescence of fYFP, dYFP, and fCFP are all expected to decrease. Considering these effects, we developed a method to extract changes in astrocyte intracellular Ca2+, pH, and local blood flow from the three measured fluorescence waveforms (fYFP, dYFP, and fCPF). During REM sleep, intracellular Ca2+ in astrocytes was shown to decrease, local blood flow (BBV) increased (indicated in the figure to reflect increased blood flow when the waveform shows downward deflection), and intracellular pH in astrocytes became more acidic. The astrocyte acidification in particular was unexpected. This is the first example showing that intracellular pH can fluctuate even under physiological conditions, despite the fact that intracellular pH is strongly buffered with bicarbonate.©Yoko Ikoma & Ko Matsui   Excitation light was sent through this fiber and the emitted fluorescence signals were recorded. Using a newly devised method, the researchers dissected the calcium concentration and pH of the astrocytes and the local brain blood volume changes from the recorded optical signals.   A clear change in the optical signals associated with REM sleep was observed. A calcium decrease, pH decrease (i.e. acidification), and increase in local brain blood volume occurred. The researchers identified that acidification and blood volume changes produce a strong effect on the optical signals; thus, many of the previous studies using fiber photometry could have misinterpreted their recorded data.    Acidification was especially unexpected, as the intracellular solution of cells is highly buffered for pH. Strong acidification occurs upon ischemia but changes in pH were not assumed to occur under physiological conditions. This astrocyte acidification may drive the amplification of synaptic signals and may underlie memory formation during REM sleep.   Interestingly, changes in the local brain environment detected with the optical recordings preceded the signature change of the ensemble neuronal electrical activity detected with electroencephalogram by nearly 20 seconds. This suggests that astrocytes and vascular changes have control of the state of neuronal activity. Transition to REM sleep can also be predicted from these local brain environmental changes.     Brain environment change precedes REM sleep transition. By analyzing the frequency of the electroencephalogram (ECoG), it is possible to determine when the theta waves (6 - 9 Hz) increase and the delta waves (1 - 4 Hz) decrease, indicating the transition to REM sleep. On the other hand, a close examination of the timing of the downward deflection in dYFP fluorescence recorded by fiber photometry in the lateral hypothalamus reveals that it precedes the onset of REM sleep determined by ECoG by nearly 20 seconds. The measured fluorescence emitted from the dYFP is thought to decrease as the pH in astrocytes becomes more acidic and local blood volume (BBV) increases. These changes in the brain environment precede changes in brain neural activity, indicating that changes in astrocyte and vascular activity cooperate with neurons to influence brain functions such as REM sleep.©Yoko Ikoma & Ko Matsui     “During REM sleep, prior experiences are sorted and remembered or forgotten, and this process is likely perceived as dreams,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “Acidification in astrocytes may control the likelihood of plasticity to occur in the neural circuits.”   The researchers further studied how the properties of REM sleep change with epilepsy. Repeated stimulus to a mouse’s hippocampus produces a brain prone to hyperactivity and this “kindling” method has been used as a model of epileptogenesis. After kindling, spontaneously occurring REM sleep episodes were recorded. Surprisingly, very little astrocytic calcium decreases and local brain blood volume increases occurred with REM sleep, and a strong acid response was recorded from astrocytes.   “Our previous study has shown an increased acid response of astrocytes associated with intensified epileptic seizures,” says the lead study investigator, Dr. Yoko Ikoma. “Information is transmitted and processed with electrical signals in neurons. The pH of astrocytes may have control over these neuronal activities both in physiology and in disease.”   Monitoring of the bulk pH and local brain blood flow is possible in humans using fMRI. Ikoma says that these local brain environmental changes associated with REM sleep can potentially be used to diagnose the severity of epilepsy in human patients. “A therapeutic strategy designed to control astrocytes’ pH could potentially be used for preventing exacerbation of epilepsy.”     Caption: Acidification of astrocytes in the lateral hypothalamus during REM sleep is enhanced in the epileptic pathological brain. Analysis of fluorescent waveforms obtained by inserting an optical fiber into the lateral hypothalamus of mice revealed that acidification in astrocytes occurs during REM sleep. Repeated daily electrical stimulation of the hippocampus changes the brain into one prone to epileptic seizures. We analyzed the spontaneous REM sleep that occurs after the brain is transformed into an epileptic pathological brain. The results revealed that astrocytes become more acidic during REM sleep. By analyzing the environmental changes in the brain during REM sleep, it is hoped that a new strategy to diagnose the developmental level of epilepsy and to treat epilepsy pathology by controlling astrocyte acidity can be pioneered.©Yoko Ikoma & Ko Matsui     Publication Details: Title: Properties of REM sleep alterations with epilepsy Authors: Yoko Ikoma, Yusuke Takahashi, Daichi Sasaki, Ko Matsui Journal: Brain DOI: doi.org/10.1093/brain/awac499  https://doi.org/10.1093/brain/awac499   Contact:  Name: Ko Matsui Affiliation: Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University Email: matsui@med.tohoku.ac.jp Website: http://www.ims.med.tohoku.ac.jp/matsui/   https://www.lifesci.tohoku.ac.jp/ Optimized Amide Bond Reaction Using Heterocyclic Compounds and Carboxylic Acid 2023-02-16T15:00:00+09:00 A high-yield, one-pot, scalable reaction facilitates the production of biologically relevant amide compounds using less reactive nitrogen-containing heterocyclic compounds and carboxylic acid without the use of heat or special equipment.    Amide bonds are important functional groups in medicinal chemistry and account for roughly 16% of all reactions performed in drug-discovery research. Some amide bond reactions using pharmaceutically important nitrogen-containing heterocyclic compounds, such as indole, carbazole and pyrrole, rather than amines are not efficient using conventional production methods.  In a recent study, a team of leading chemists developed a novel one-pot reaction using 4-(N,N-dimethylamino)pyridine N-oxide (DMAPO) catalyst and di-tertbutyl dicarbonate (Boc2O) to efficiently form amide bonds using low-reactivity, nitrogen-containing heterocyclic compounds and carboxylic acid without special equipment or heat.     Conventional methods for N-acylation of heterocyclic, nitrogen-containing compounds are notoriously inefficient, producing low yields and often involving preactivated reagents, strong metal bases and clean-up steps. (Image credit: Atsushi Umehara)        N-acylation of nitrogen-containing heterocyclic compounds is more efficient using DMAPO and Boc2O rather than conventional methods, even with less reactive N-heterocyclic compounds.  The reaction requires no special equipment, heat or clean-up and can be performed in a single reaction vessel. (Image credit: Atsushi Umehara) Optimized reaction conditions for amide bond formation in nitrogen-containing heterocyclic compounds using carboxylic acid requires only 4-(N,N-dimethylamino)pyridine N-oxide (DMAPO) and di-tertbutyl dicarbonate (Boc2O) in a single reaction vessel. (Image credit: Atsushi Umehara)       In an effort to improve the efficiency of N-acylation, or amide bond formation, of nitrogen-containing heterocyclic compounds, or cyclic compounds composed of nitrogen and one or more other elements, a research team from Tohoku University previously reported the successful N-acylation of the heterocyclic compound indole with carboxylic acid using the Boc2O/4-(N,N-dimethylamino)pyridine (DMAP)/2,6-lutidine system.  The reaction, however, required a large excess of indole for a moderate yield of the desired product. In the current study, the research team instead used DMAPO as a catalyst and Boc2O to create a more efficient N-acylation reaction that: a) produced a high chemical yield with a 1:1 substrate ratio, b) possessed high functional group tolerance, c) allowed one-pot direct use of carboxylic acid, d) tolerated a wide variety of substrates, e) could be performed in mild and scalable conditions, and f) was simple to perform.       The team reported their results on January 13 in ChemCatChem.     “Generally, the [N-acylation] reaction is carried out by using a dehydrating condensation agent in the presence of an amine (primary amine, secondary amine or aniline), which is highly reactive with carboxylic acid. However, in reactions that use pharmaceutically important nitrogen-containing heterocyclic compounds such as indole, carbazole and pyrrole instead of amines, condensing agents do not efficiently promote the reaction,” said Atsushi Umehara, lead author of the paper and assistant professor at Graduate School of Life Sciences at Tohoku University in Sendai, Japan.  “This is due to the low reactivity of nitrogen-containing heterocyclic compounds. Therefore, preactivated derivatives such as acyl chlorides and acid anhydrides derived from carboxylic acids must be used, but this method is a two-step reaction involving reagent preparation and inefficient. The use of strong metal bases is also often required, and the narrow scope of substrate application is a challenge,” said Umehara.   The team recognized the utility of a more efficient N-acylation reaction for less reactive nitrogen-containing heterocyclic compounds, especially for pharmaceutical research.  Their optimized, one-pot reaction produces amide compounds at high yields by reacting compounds such as indole, carbazole and pyrrole with carboxylic acid, addressing a major pain point in medicinal chemistry.  “We have demonstrated the usefulness of this reaction in the synthesis of more than 120 amide compounds, achieving chemical yields of more than 85% for 104 compounds,” said Umehara.    Importantly, the reaction is efficient for heterocyclic compounds that demonstrate low reactivity under conventional reaction conditions, and the yields of the team’s new N-acylation reaction are high even at a 1:1 ratio of a nitrogen-containing heterocyclic compound to carboxylic acid.  The new one-pot reaction conditions also eliminate the tedious cleanup steps that were necessary when strong metal bases were required for other N-acylation reaction conditions, and the new protocol requires no heat or special equipment.   Given the accessibility of these novel amide bond reaction conditions, the team predicts the DMAPO/Boc2O-mediated system will be used frequently for amide bond formation in medicinal chemistry.  “We expect that the reaction developed in this research will be applied to the creation of a wide range of functional molecules in both industry and academia,” said Umehara.  Increasing the efficiency of these amide bond reactions will decrease the cost and time associated with amide compound development in both research and the pharmaceutical industry.   Other contributors include Soma Shimizu and Makoto Sasaki from the Graduate School of Life Sciences at Tohoku University in Sendai, Japan.       Publication Details: Title: DMAPO/Boc2O-Mediated One-Pot Direct N-Acylation of Less Nucleophilic N-Heterocycles with Carboxylic Acids Authors: Atsushi Umehara, Soma Shimizu, Makoto Sasaki Journal: ChemCatChem DOI: 10.1002/cctc.202201596   LINK: Tohoku University   Contact: Atsushi Umehara Graduate School of Life Sciences, Tohoku University Email: atsushi.umehara.e3(at)tohoku.ac.jp        https://www.lifesci.tohoku.ac.jp/ Effects of Cultivar and Cropping Type on Growth and Yield of Female and Male Asparagus Plants 2023-01-31T16:59:00+09:00 https://ashs.org/news/627989/Effects-of-Cultivar-and-Cropping-Type-on-Growth-and-Yield-of-Female-and-Male-Asparagus-Plants.htm?fbclid=IwAR1ugYswP4MTTtYm-xQjPoRy5b5xD8za8i2Ipv2LYwgBAmPWCP8LiOJqOBs