Nagoya City University

26/05/2025

Numerical simulations reveal the origin of barred olivine crystals in early solar system
For the first time, researchers replicated the formation of barred olivine—a unique mineral texture found in chondrules—using phase-field numerical simulations, shedding light on planet formation processes.

Summary Text
A research team has, for the first time, successfully replicated the formation of barred olivine—a unique crystalline texture found in chondrules from meteorites and asteroids—using numerical simulations. The results offer critical clues to the conditions in the early solar system and could reshape existing theories on planet formation.

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Researchers from Nagoya City University, Tohoku University, and other institutions have used numerical simulations to replicate how a peculiar mineral texture called barred olivine forms inside chondrules—millimeter-sized spherical particles found in meteorites. These chondrules are considered time capsules from the early solar system, and barred olivine is a rare mineral texture not seen in Earth rocks.

Associate Professor Hitoshi Miura of Nagoya City University and the team was the first to reproduce this texture using numerical simulations and theoretically elucidate its formation process.

Using a phase-field model, the team simulated the rapid cooling of molten chondrules in a vacuum-like environment and found that the formation of barred olivine requires a cooling rate exceeding 1°C per second—faster than previously assumed. Their results indicate that conventional experimental conditions may underestimate how quickly chondrules cooled in space.

This work not only provides a new theoretical model for crystal growth under early solar system enrivonments but also has significant implications for understanding how planetary building blocks formed. The team is now preparing a microgravity experiment aboard the International Space Station to further validate their findings.

The study was published in Science Advances.

Reference
Journal：Science Advances
DOI：10.1126/sciadv.adw1187

Author
Miura Hitoshi

Nagoya City University

13/05/2025

New Insights into X-ray Sterilization: Dose Rate Matters
Nagoya City University researchers reveal that X-ray sterilization efficiency dramatically changes depending on dose rate and bacterial nutrient conditions.

Summary Text
Scientists investigate the inactivation efficacy of X-ray and assess the effective management of X-ray sterilization.

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Radiation sterilization technology destroys the DNA and cellular structures of bacteria and microorganisms using electromagnetic waves with far higher energy than ultraviolet radiation. This technique has become indispensable for sterilization in various fields, including medical devices (e.g., disposable syringes, catheters, artificial joints), pharmaceuticals (e.g., raw materials, tissue grafts), and food products (e.g., sprout inhibition in potatoes).

Traditionally, it has been believed that the effectiveness of radiation sterilization depends solely on the total irradiation dose. However, this assumption has now been challenged by a research team led by Professor Matsumoto and Associate Professor Iwata at Nagoya City University.

In their study, the team varied the X-ray dose rate significantly while keeping the total irradiation dose constant, using Escherichia coli as a model organism. The results revealed striking differences depending on the nutritional environment of the bacteria:
(a) In a nutrient-poor environment, long-term irradiation at a low dose rate (i.e., low-intensity X-rays) was more effective than short-term irradiation at a high dose rate.
(b) Conversely, in a nutrient-rich environment, short-term irradiation at a high dose rate achieved more than ten times the sterilization efficiency compared to long-term irradiation at a low dose rate.

These findings were further analyzed using stochastic differential equations—a cutting-edge mathematical tool—enabling a quantitative understanding of the mechanisms by which radiation damages bacterial and cellular structures.

This research not only provides a scientific foundation for optimizing sterilization and disinfection protocols using radiation, but also introduces a novel framework for designing irradiation strategies that can selectively eliminate rapidly proliferating lesion cells (e.g., cancer cells) while minimizing damage to healthy tissue. These insights hold great promise for the development of safer, more effective, and patient-friendly radiation therapies using X-rays and proton beams.

Reference
Journal：Scientific Reports
DOI：10.1038/s41598-025-96461-1

Author
Matsumoto Takahiro

Nagoya City University

23/01/2025

Discovery of the significance of birth in the maintenance of quiescent neural stem cells
Birth-induced alteration of glutamine metabolism is required for the acquisition of quiescence and long-term maintenance of postnatal neural stem cells. Preterm birth impairs this cellular process, leading to decreased postnatal neurogenesis.

Summary Text
A research group led by Kazunobu Sawamoto, a professor at Nagoya City University and National Institute for Physiological Sciences, and Koya Kawase, a pediatric doctor at Nagoya City University Hospital, has elucidated the significance of birth in the maintenance of neural stem cells. These findings enhance our understanding of the pivotal role of birth in regulating tissue homeostasis and regenerative capacities.

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A research group led by Kazunobu Sawamoto, a professor at Nagoya City University and National Institute for Physiological Sciences, and Koya Kawase, a pediatric doctor at Nagoya City University Hospital, has elucidated the significance of birth in the maintenance of neural stem cells (NSCs).

Birth is one of the most significant life events for animals. The transition from the intrauterine to the extrauterine environment causes various metabolic changes in individuals. Despite its significance, the role of birth in the developmental process remains incompletely understood. In the adult mammalian brain, NSCs are retained in the ventricular-subventricular zone(V-SVZ), where they continue to generate new neurons. The majority of postnatal NSCs are maintained in a quiescent state, enabling their long-term maintenance. In various tissues, metabolic profiles of the stem cell niche and of the stem cells themselves play a critical role in determining whether the cells remain quiescent or transition to an active, differentiated state. However, how birth-associated metabolic changes affect the fate of tissue stem cells, especially NSCs, is largely unknown.

Sawamoto’s group focused on metabolic changes in radial glia (RG), the embryonic NSCs. The researchers performed metabolomics and single cell RNA-seq in the V-SVZ of full-term birth mice and preterm birth mice. They found that normal term birth triggers RG to become quiescent, which involves alteration of glutamine metabolism, resulting from increased expression of Glul, a gene encoding an enzyme that converts glutamate to glutamine. Importantly, they found that this cellular process is impaired by preterm birth.

“To understand the role of birth in the maintenance of quiescent NSCs, we evaluated the effects of preterm birth on postnatal neurogenesis,” Sawamoto said.

Next, the team histologically analyzed the changes in the neurogenic activity of RG. They showed that RG transiently enter a neurogenic state via mTORC1 signaling in preterm birth mice. However, they also found that neurogenesis at the young-adult stage was decreased due to depletion of the NSC pool in preterm birth mice. Furthermore, they analyzed human autopsy brains and found that postnatal neurogenesis in the V-SVZ is decreased by preterm birth not only in mice but also in humans.

“Considering that postnatal neurogenesis plays an important role in brain development and plasticity in humans, the reduction in postnatal neurogenesis may be a cause of worse neurodevelopmental outcome in preterm infants,” Kawase said.

Finally, to examine the role of birth-induced upregulation of Glul in RG, they generated Glul-knockdown and -overexpression lentiviruses and infected them to RG in vivo. Their experiments demonstrated that sufficient upregulation of Glul in RG at an appropriate time of birth is critical for the maintenance of quiescent NSCs.

“We have uncovered the significance of birth in the maintenance of quiescent NSCs. Considering that glutamine metabolism also regulates the functions of tissue stem cells other than NSCs, our findings enhance our understanding of the pivotal role of birth in tissue homeostasis and regenerative capacities,” Sawamoto commented.

The full findings of the study are published in the Science Advances.
Article title: Significance of birth in the maintenance of quiescent neural stem cells. DOI:10.1126/sciadv.adn6377

In addition to Kazunobu Sawamoto and Koya Kawase, co-authors of this research article include researchers from Nagoya City University, National Institute for Physiological Sciences, Kindai University, University of Copenhagen, Children’s National Hospital, and National Institute of Advanced Industrial Science and Technology.

Reference
Journal：Science Advances
DOI：10.1126/sciadv.adn6377

Author
Kazunobu Sawamoto

Nagoya City University

13/12/2024

M87's Powerful Jet Unleashes Rare Gamma-ray Outburst

Summary Text
The international multi-instrument Event Horizon Telescope Collaboration (EHT) reveals new observations of a spectacular gamma-ray flare from the powerful relativistic jet emanating from the center of the M87 galaxy at multiple wavelengths, potentially leading to a better understanding of how and where particles are accelerated in these kinds of jets.
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Also known as Virgo A or NGC 4486, M87 is the brightest object in the Virgo cluster of galaxies, the largest gravitationally bound type of structure in the universe. It came to fame in April 2019 after scientists from EHT released the first image of a black hole in its center. Led by the EHT multi wavelength working group, a study published in Astronomy and Astrophysics Journal presents the data from the second EHT observational campaign conducted in April 2018, involving over 25 terrestrial and orbital telescopes. The authors report the first observation of a high-energy gamma-ray flare in over a decade from the supermassive black hole M87, based on nearly simultaneous spectra of the galaxy spanning the broadest wavelength range ever collected.

"We were lucky to detect a gamma-ray flare from M87 during this Event Horizon Telescope's multi-wavelength campaign. This marks the first gamma-ray flaring event observed in this source in over a decade, allowing us to precisely constrain the size of the region responsible for the observed gamma-ray emission. Observations—both recent ones with a more sensitive EHT array and those planned for the coming years—will provide invaluable insights and an extraordinary opportunity to study the physics surrounding M87’s supermassive black hole. These efforts promise to shed light on the disk-jet connection and uncover the origins and mechanisms behind the gamma-ray photon emission." says Giacomo Principe, one of the paper coordinators, a researcher at the University of Trieste associated with INAF and INFN. The article has been accepted for publication in Astronomy & Astrophysics.

The relativistic jet examined by the researchers is surprising in its extent, reaching sizes that exceed the black hole’s event horizon by tens of millions of times (7 orders of magnitude) - akin to the difference between the size of a bacterium and the largest known blue whale.

The energetic flare, which lasted approximately three days and suggests an emission region of less than three light-days in size (~170 AU, where 1 Astronomical Unit is the distance from the Sun to Earth), revealed a bright burst of high-energy emission—well above the energies typically detected by radio telescopes from the black hole region.

"The activity of this supermassive black hole is highly unpredictable – It is hard to forecast when a flare will occur. The contrasting data obtained in 2017 and 2018, representing its quiescent and active phases respectively, provide crucial insights into unraveling the activity cycle of this enigmatic black hole." says Kazuhiro Hada at Nagoya City University, who led radio observations and analysis of the multi-wavelength campaign.

"The duration of a flare roughly corresponds to the size of the emission region. The rapid variability in gamma rays indicates that the flare region is extremely small, only approximately ten times the size of the central black hole. Interestingly, the sharp variability observed in gamma rays was not detected in other wavelengths. This suggests that the flare region has a complex structure and exhibits different characteristics depending on the wavelength." explains Daniel Mazin at the Institute for Cosmic Ray Research, The University of Tokyo, a member of the MAGIC telescope team that detected the gamma ray flare.

The second EHT and multi-wavelength campaign in 2018 leveraged more than two dozen high-profile observational facilities, including NASA’s Fermi-LAT, HST, NuSTAR, Chandra, and Swift telescopes, together with the world’s three largest Imaging Atmospheric Cherenkov Telescope arrays (H.E.S.S., MAGIC and VERITAS). These observatories are sensitive to X-ray photons as well as high-energy very-high-energy (VHE) gamma-rays, respectively. During the campaign, the LAT instrument aboard the Fermi space observatory detected an increase in high-energy gamma-ray flux with energies up to billions of times greater than visible light. Chandra and NuSTAR then collected high-quality data in the X-ray band. The East Asian VLBI Network (EAVN) radio observations show an apparent annual change in the jet's position angle within a few microseconds of arc from the galaxy's core.

"By combining the information about the change in the jet direction, the brightness distribution of the ring observed by the EHT and the gamma-ray activity, we can better understand the mechanisms behind the production of the very-high-energy radiation." says Motoki Kino at Kogakuin University, a coordinator of the EAVN observations during the campaign.

Data also show a significant variation in the position angle of the asymmetry of the ring (the so-called event horizon of the black hole) and the jet’s position, suggesting a physical relation between these structures on very different scales. The researcher explains: “In the first image obtained during the 2018 observational campaign, it was seen that the emission along the ring was not homogeneous, thus presenting asymmetries (i.e., brighter areas). Subsequent observations conducted in 2018 and related to this paper confirmed the data, highlighting that the asymmetry's position angle had changed.”

The team also compared the observed broadband multi-wavelength spectra with theoretical emission models. "The flare in 2018 exhibited particularly strong brightening in gamma rays. It is possible that ultra-high-energy particles underwent additional acceleration within the same emission region observed in quiet states, or that new acceleration occurred in a different emission region." says Tomohisa Kawashima at the Institute for Cosmic Ray Research, who performed a simulation using a supercomputer installed at the National Astronomical Observatory of Japan.

“How and where particles are accelerated in supermassive black hole jets is a longstanding mystery. For the first time, we can combine direct imaging of the near event horizon regions during gamma-ray flares from particle acceleration events and test theories about the flare origins,” says Sera Markoff, a professor at the University of Amsterdam and co-author of the study.

This discovery paves the way for stimulating future research and potential breakthroughs in understanding the universe.

Reference
Journal：Astronomy and Astrophysics
DOI：https://doi.org/10.1051/0004-6361/202450497

Author
Kazuhiro Hada

https://www.nagoya-cu.ac.jp/english/research-news/202412131730/

Nagoya City University

27/11/2024

Passport Control for Glycan Maturation:Discovery of a Molecular Tag Enhancing Biopharmaceutical Quality

Summary Text
A new technology enhances critical modifications of glycoprotein glycans, specifically galactosylation and sialylation, by adding a “passport sequence” that promotes efficient transport through the secretory pathway. This approach improves the quality and efficiency of therapeutic glycoproteins, advancing the development of high-quality biopharmaceuticals.

Full Text
A collaborative research group, including researchers from Nagoya City University, National Institutes of Natural Sciences, and RIKEN has uncovered a groundbreaking molecular tool, the "passport sequence," that significantly improves the production efficiency and quality of glycoproteins, such as blood coagulation factor VIII and erythropoietin (EPO). This discovery holds great promise for the development of high-quality biopharmaceuticals.
The study focuses on a short, 10-amino-acid sequence called the "passport sequence," which facilitates the efficient trafficking of glycoproteins through the secretory pathway. When attached to target proteins, this sequence enhances their interactions with glycosylation enzymes in the Golgi apparatus, leading to significantly increased galactosylation and sialylation—critical modifications that impact protein stability and efficacy.
The researchers revealed that the passport sequence selectively interacts with a Golgi protein called NUCB1, which in turn promotes the function of the glycosyltransferase B4GALT1. This mechanism not only improves glycan maturation but also provides a novel strategy for controlling glycosylation in therapeutic glycoproteins, ultimately improving their pharmacokinetics and therapeutic properties.
The researchers emphasize "This discovery not only offers a new approach to enhancing the production and quality of biopharmaceutical glycoproteins but also provides deeper insights into the complex mechanisms underlying protein glycosylation,"

Reference
Journal：iScience
DOI：10.1016/j.isci.2024.111457

Author
Hirokazu Yagi and Koichi Kato

Nagoya City University

14/03/2024

Deciphering the tip of migrating neurons: Discovery of growth cone in migrating neurons involved in promoting neuronal migration and regeneration in the brain after injury

Summary Text
The structure and functions of the tip of migrating neurons remain elusive. Here, a research group led by Kazunobu Sawamoto, Professor at Nagoya City University and National Institute for Physiological Sciences, and by Chikako Nakajima and Masato Sawada, staff scientists in his laboratory, has elucidated that the PTPσ-expressing growth cone senses the extracellular matrix and drives neuronal migration in the injured brain, leading to functional recovery.

Full Text
The structure and functions of the tip of migrating neurons remain elusive. Here, a research group led by Kazunobu Sawamoto, Professor at Nagoya City University and National Institute for Physiological Sciences, and by Chikako Nakajima and Masato Sawada, staff scientists in his laboratory, has found that the PTPσ-expressing growth cone senses the extracellular matrix and drives neuronal migration in the injured brain, leading to functional recovery.

Neural stem cells are present in the postnatal mammalian brain and produce new neurons. New neurons migrate toward injured sites, and promoting neuronal migration results in functional recovery after brain injury. Nevertheless, there is an inhibitory effect on neuronal migration in the injured sites, the mechanisms of which need to be elucidated in order to improve recruitment of new neurons in the injured sites and thus to enhance the recovery after brain injury. The migrating neurons possess an axonal growth cone-like structure at their tip, but the role of this structure in neuronal migration has not been fully understood.

Sawamoto’s group focused on elucidating the function of the growth cone-like structure of migrating neurons of the mouse brain. The researchers used super-resolution microscopy to study the cytoskeletal dynamics and molecular features of the neuronal tip. They showed that the tip structure shares important functions with axonal growth cones. In short, the growth cone of cultured migrating neurons is responsive to external signals through tyrosine phosphatase receptor type sigma (PTPσ) to guide the directionality of migration and initiate the movement of their cell body. The growth cone responds to chondroitin sulfate (CS) through PTPσ and collapses, resulting in inhibition of neuronal migration. In the presence of CS, the growth cones can revert to their extended morphology when they interact with heparan sulfate (HS), thus re-enabling neuronal migration.

“To investigate whether the effect of HS in reversing the inhibitory effect of CS can promote neuronal migration in the injured brain, it was necessary to apply HS-containing biomaterial to the CS-rich injured brain,” Sawamoto said.

Next, they employed HS-containing gelatin-fiber nonwoven fabric, a biomaterial that provides structural scaffolds for cells such as migrating neurons. They showed that the applied HS-containing fibers promoted extension of growth cones and neuronal migration in the injured brain. Furthermore, implantation of the HS-enriched gelatin fabric promoted the regeneration of mature neurons and restored neurological functions. These results suggest that elucidating the molecular mechanisms of growth cone-mediated interaction with the local extracellular environment may enable the development of new regeneration technologies based on the promotion of neuronal migration.

Recent studies by other groups have shown that aging alters the physical properties of brain extracellular matrix, including CSPG.

“Given that the growth cone of migrating neurons serves as a primer for neuronal migration under inhibitory extracellular conditions, it is necessary to further investigate whether the growth cone-mediated treatment to recruit new neurons from the endogenous source to the damaged sites is also applicable to aged brains,” Nakajima commented.

The full findings of the study are published in Nature Communications.
Article title: Identification of the growth cone as a probe and driver of neuronal migration in the injured brain. DOI: 10.1038/s41467-024-45825-8

In addition to Kazunobu Sawamoto, Chikako Nakajima, and Masato Sawada, co-authors of this research article include researchers from Nagoya City University, National Institute for Physiological Sciences, Niigata University, Kyoto University, Doshisha University, Jichi Medical University, The Japan Wool Textile Co., Ltd., Nikke Medical Co., Ltd., Toray Research Center, Inc., New York University, Friedrich Schiller University Jena, University of Valencia, and University of Pennsylvania.

Author
Kazunobu Sawamoto

Nagoya City University

29/09/2023

Electric shock revealed that worms may have "emotions"

Summary Text
A research team has found that worms start moving at an unusually high speed when stimulated with alternating current even for a few seconds. Because of its several characteristics, the team considered that this phenomenon may be triggered by primitive "emotion". Worms are advantageous for genetic and cellular analysis, offering great potential to contribute to the detailed understanding of how basic emotions are generated in the brain.

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Brain research is one of the most crucial fields in modern life sciences, and "emotion" is one of its major topics. Studying emotions in animals has long been considered challenging with limited research mostly focused on 'fear' in mice and rats. However, since the 2010s, it has been increasingly reported in scientific papers that even crayfish and flies may have brain functions resembling emotions by focusing on several characteristics of their behavior, such as persistence and valence. For instance, when an animal experiences a dangerous situation like being attacked by a predator (a negative valence) even for a short period, the animal's behavior may be to stay in a safe place, ignoring normally attractive smells of food even if hungry, for a certain length of time (persistence), which can be regulated by a primitive form of emotion. However, the details of these fundamental "emotion mechanisms" remain largely undisclosed.

An international research team from Nagoya City University (Japan) and Mills College at Northeastern University (USA) has revealed the possibility that the roundworm Caenorhabditis elegans possesses basic "emotions." They used the worms because worms have been used for detailed analysis of basic functions such as perception, memory, and even decision-making at cellular and genetic levels. The team initially discovered that when worms are subjected to alternating current stimulation, worms start moving at an unexpectedly high speed. Interestingly, the team also found that this "running" response persisted for 1-2 minutes even after the electrical stimulation for a few seconds was terminated. In animals in general, when a stimulus is stopped, the response to that stimulus usually ceases immediately. (Otherwise, the perception of stimuli such as sounds or visual scenes would linger.) Therefore, the reaction of "continuing to run even after the stimulus stops" is exceptional.

Furthermore, during and after the electric stimulation, the team found that the worms ignore their food bacteria, which provide crucial environmental information. This suggests that while the presence or absence of their food bacteria is usually crucial, the danger posed by electrical shocks, a survival-threatening stimulus, is even more important. In other words, when worms sense the dangerous stimulus of an electrical shock, their highest survival priority is to escape from that location. To achieve this, the brain's functioning seems to persistently change, including ignoring the usually significant "food" in order to escape danger. This suggests that the phenomenon of "worms continuing to run due to short-term electrical stimulation" reflects basic "emotions."

Furthermore, through genetic analysis, particularly leveraging the advantages of worms, the team revealed that mutants unable to produce neuropeptides, equivalent to our hormones, exhibited a longer duration of continuous running in response to electrical stimulation compared to normal worms. This result indicates that the continuous state in response to danger is regulated to end at the appropriate time. Indeed, if we experience excitement or fear that persists for a very long period, it disrupts our daily lives. Therefore, the findings suggest that our emotions, such as "excitement," "happiness," or "sadness," induced by stimuli, may not be naturally destined to fade away with time, but are controlled by an active mechanism involving genes.

This study demonstrates that using worms can offer detailed insights into the genetic mechanisms underlying primitive "emotions". Many of the genes at work in worms are known to have counterparts in humans and other organisms, so studying worms can offer significant clues about the genes involved in the basis of "emotions." Specifically, conditions like depression, classified as mood disorders, can be interpreted as states where negative emotions are excessively and persistently maintained due to the inability to effectively process experienced stimuli. If novel genes related to emotions are discovered through worm research, these genes could potentially become targets for new treatments of emotional disorders.

Author : Kotaro Kimura

https://www.nagoya-cu.ac.jp/english/research-news/202309261400/

30/03/2021

New AI-based versatile software for tracking many cells in 3D microscope videossubtitle

Automatic tracking of cells in microscope videos will contribute to basic life science research and drug discovery by easily analyzing critical cellular activities.

summary

The first deep-learning software was developed as a versatile tool for tracking cells and extracting their signals from ~100 cells in a moving worm brain, in a zebrafish heart, and ~1,000 cultured cancer cells in 3D microscope videos. The method demonstrates significant improvements in tracking capabilities on various metrics including the possible number of tracked objects, robustness, and computing requirements.

Full Text

In modern basic life science research as well as in drug discovery, recording and analyzing the images of cells over time using 3D microscopy has become extremely important. Once the images have been recorded, the same cell in different images at different time points has to be accurately identified ("cell tracking") because the living cells captured in the images are in motion. However, tracking many cells automatically in 3D microscope videos has been considerably difficult. In the Kimura laboratory at the Nagoya City University, Dr. Chentao Wen and colleagues developed the 1st AI-based software called 3DeeCellTracker that can run on a desktop PC and automatically track cells in 3D microscope videos. Using the software, they were able to measure and analyze the activities of ~100 cells in the brain of a moving microscopic worm, in a naturally beating heart of a young small fish, and ~1000 cancer cells cultured in 3D under laboratory conditions, which were recorded with different types of cutting-edge microscope systems. This versatile software can now be used across biology, medical research, and drug development to help monitor cell activities.

Cell tracking in 3D space by AI

Workflow of the method

Cells of various organisms are recorded as 3D videos with state-of-the-art microscope systems (top), the cells in 3D videos obtained are automatically tracked by the AI technology (middle), and the activity of each cell is measured and analyzed (bottom).

Nagoya City University