Behind the chemically-induced suppression of fearful memories

Fearful events negatively impact the brain. For instance, war veterans often go through post-traumatic stress disorder months after the cessation of the triggering event. Now, in a study led by Tokyo University of Science researchers, the precise mechanism of suppression of such fearful memories has been uncovered. Using a mouse model, the researchers identified the associated biochemical pathways, thus paving the way for the development and clinical evaluation of therapeutic compounds such as KNT-127.

Tragic events like wars, famines, earthquakes, and accidents create fearful memories in our brain. These memories continue to haunt us even after the actual event has passed. Luckily, researchers from Tokyo University of Science (TUS) have recently been able to understand the hidden biochemical mechanisms involved in the selective suppression of fearful memories, which is called fear extinction. The researchers, who had previously demonstrated fear extinction in mice using the chemically synthesized compound “KNT-127,” have now identified the underlying mechanism of this compound’s action. Their findings have been published recently in Frontiers in Behavioral Neuroscience.

Prof. Akiyoshi Saitoh, lead author of the study, and Professor at TUS, muses, “Drugs that treat fear-related diseases like anxiety and posttraumatic stress disorder must be able to help extinguish fear. We previously reported that KNT-127, a selective agonist of the d-opioid receptor or DOP, facilitates contextual fear extinction in mice. However, its site of action in the brain and the underlying molecular mechanism remained elusive. We therefore investigated brain regions and cellular signaling pathways that we assumed would mediate the action of KNT-127 on fear extinction.”

“We investigated the molecular mechanism of KNT-127-mediated suppression of fearful memories. We administered KNT-127 to specific brain regions and identified the brain regions involved in promoting fear extinction via delta receptor activation,” elaborates Dr. Daisuke Yamada, co-author of the study, and Assistant Professor at TUS.

Using a mouse model, the research team performed fear conditioning test on laboratory mice. During fear conditioning, mice learn to associate a particular neutral conditioned stimulus with an aversive unconditioned stimulus (e.g., a mild electrical shock to the foot) and show a conditioned fear response (e.g., freezing).

After the initial fear conditioning, the mice were re-exposed to the conditioning chamber for six minutes as part of the extinction training. Meanwhile, the fear-suppressing therapeutic “KNT-127” was microinjected into various regions of the brain, 30 minutes prior to re-exposure. The treated brain regions included the basolateral nucleus of the amygdala (BLA), the hippocampus (HPC), and the prelimbic (PL) or infralimbic subregions (IL) of the medial prefrontal cortex. The following day, the treated mice were re-exposed to the chamber for six minutes for memory testing. The fear-suppressing “KNT-127” that infused into the BLA and IL, but not HPC or PL, significantly reduced the freezing response during re-exposure. Such an effect was not observed in mice that did not receive the KNT-127 treatment, thus confirming the fear-suppressing potential of this novel compound.

Chemical compounds known to inhibit the actions of key intracellular signaling pathways like PI3K/Akt and MEK/ERK pathways reversed the therapeutic effect, thereby suggesting the key roles of these two pathways in influencing KNT-127-mediated fear extinction.

The first author of the study, Ayako Kawaminami, who is currently pursuing research at TUS, says, “The selective DOP antagonist that we used for pretreatment antagonized the effect of KNT-127 administered into the BLA and IL. Further, local administration of MEK/ERK inhibitor into the BLA and of PI3K/Akt inhibitor into the IL abolished the effect of KNT-127. These findings strongly indicated that the effect of KNT-127 is mediated by MEK/ERK signaling in the BLA, by PI3K/Akt signaling in the IL, and by DOPs in both brain regions. We have managed to show that DOPs play a role in fear extinction via distinct signaling pathways in the BLA and IL.”

PTSD and phobias are thought to be caused by the inappropriate or inadequate control of fear memories. Currently, serotonin reuptake inhibitors and benzodiazepines are prescribed during therapy. However, many patients do not derive significant therapeutic benefits from these drugs. Therefore, there is an urgent need for the development of new therapeutic agents that have a different mechanism of action from existing drugs.

Dr. Hiroshi Nagase, a Professor at University of Tsukuba and a coauthor of the study, concludes, “We have succeeded in creating KNT-127 by successfully separating convulsion- and catalepsy-inducing actions, which has so far been extremely difficult. Our findings will provide useful and important information for the development of evidence-based therapeutics with a new mechanism of action, that is targeting DOP.”

Fighting fear with the right therapeutic is the need of the hour, as anxiety and stress increase globally, and the findings of this study could help us achieve this objective. We have our fingers crossed.

***

Reference

Title of original paper: Selective δ-Opioid Receptor Agonist, KNT-127, Facilitates Contextual Fear Extinction via Infralimbic Cortex and Amygdala in Mice

Journal: Frontiers in Behavioral Neuroscience

DOI: https://doi.org/10.3389/fnbeh.2022.808232

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan’s development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society”, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today’s most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Akiyoshi Saitoh from Tokyo University of Science

Dr. Akiyoshi Saitoh is serving as a Professor in the Department of Pharmacy, at the Tokyo University of Science, Japan. His research work primarily focuses on the role of the amygdala in the rodent fear extinction memory as well as on the development of novel opioid delta receptor agonists for combating depression and anxiety. Prof. Saitoh has published over 100 refereed papers so far. He also has a patent to his credit.

Rare bacterial strain isolated, sequenced

Certain types of bacteria are unable to survive and thrive outside host organisms. This makes their isolation and identification technically challenging. Recently, a researcher from Tokyo University of Science successfully isolated a new bacterial strain of the candidate bacterial group, Candidatus phylum Dependentiae, from a pond in the Noda campus of the university. This study marks the first time such a novel strain has been isolated from a Japanese environment.

The development of the field of metagenomics—the study of genetic material from environmental samples—has revolutionized how we observe and discover new species. Many bacteria cannot be independently cultivated in the lab. Sometimes this is because the medium they are grown in is not suitable, sometimes it is because these bacteria thrive only

in multispecies communities (such as many bacteria in our gut!) and sometimes this is because they can only grow in relation to another larger organism. A group of bacteria belonging to the final category are Candidatus phylum Dependentiae. Not much is known about this group because thus far, only three strains belonging to it have been isolated. But in a recent study, published in Microbiology Resource Announcements, Professor Masaharu Takemura from Tokyo University of Science (TUS) has succeeded in isolating the fourth such strain—Noda2021.

“Initially we sampled Risoukai Park in the Noda Campus of TUS with the aim of isolating a giant virus by screening it using a common laboratory host ‘Vermamoeba vermiformis.’ However, in the process of doing so we accidentally discovered this rare bacterium that also infects Vermamoeba,” says Dr. Takemura.

To isolate the new strain, Dr. Takemura first cultured a sample obtained from the pond in Risoukai Park and then added it to a culture of Vermamoeba. After growing the Vermamoeba for a few days, he extracted Noda2021 from this and then performed an analysis of its genetic material.

“We found that the Noda2021 strain consists of 1,222,284 base pairs with approximately 38.3% guanine and cytosine (GC) content and 1,287 genes. We then performed a 16S rRNA molecular phylogenetic analysis of the strain and found that it is relatively close to one of the other Candidatus phylum Dependentiae strains isolated so far, ‘Vermiphilus pyriformis,’” explains Dr. Takemura. He also examined the infected Vermamoeba cells under an electron microscope and found that Noda2021 sometimes exhibited a connected cellular structure within its host cells.

“This discovery is evidence that the pond in the Noda campus is microbiologically diverse and ecologically exciting,” says Dr. Takemura. This is also the first time such a strain has been isolated in Japan.

The isolation of this new strain of Candidatus phylum Dependentiae is sure to further our understanding of this curious bacterial group. According to Dr. Takemura, “This bacterium is located in the border region between giant viruses and microbacteria, so we expect it to provide some useful and unique information on the origin and ecological position of both these groups.”

Indeed, Tokyo University of Science’s Noda campus seems to have plenty of hidden treasures for budding microbiologists. We for one, cannot wait for the next discovery— accidental or otherwise!

***

Reference

DOI: https://doi.org/10.1128/mra.01123-21

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan’s development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society”, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today’s most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Masaharu Takemura from Tokyo University of Science

Dr. Masaharu Takemura is a Professor at the Tokyo University of Science. His research interests include giant virus biology, evolutionary cell biology, and the origin of the eukaryotic nucleus. Dr. Takemura also has a deep interest in biology education. He completed his Ph.D. from Nagoya University in 1998. He has published over 100 papers in internationally renowned journals thus far.

Understanding the use of bicycle sharing systems with statistics

Though bicycle sharing systems (BSSs) are popular in many big cities, it is necessary to actively rebalance the number of bicycles across the various ports with optimization algorithms. In a recent study, Tokyo University of Science researchers statistically analyzed the bicycle usage patterns in four real-world BSSs to obtain realistic benchmarks for testing these algorithms. Their findings can make BSS rebalancing more efficient through an understanding of the social dynamics of human movement.

Bicycle sharing systems (BSSs) are a popular transport system in many of the world’s big cities. Not only do BSSs provide a convenient and eco-friendly mode of travel, they also help reduce traffic congestion. Moreover, bicycles can be rented at one port and returned at a different port. Despite these advantages, however, BSSs cannot rely solely on its users to maintain the availability of bicycles at all ports at all times. This is because many bicycle trips only go in one direction, causing excess bicycles at some ports and a lack of bicycles in others.

This problem is generally solved by rebalancing, which involves strategically dispatching special trucks to relocate excess bicycles to other ports, where they are needed. Efficient rebalancing, however, is an optimization problem of its own, and Professor Tohru Ikeguchi and his colleagues from Tokyo University of Science, Japan, have devoted much work to finding optimal rebalancing strategies. In a study from 2021, they proposed a method for optimally rebalancing tours in a relatively short time. However, the researchers only checked the performance of their algorithm using randomly generated ports as benchmarks, which may not reflect the conditions of BSS ports in the real world.

Addressing this issue, Prof. Ikeguchi has recently led another study, together with PhD student Ms. Honami Tsushima, to find more realistic benchmarks. In their paper published in Nonlinear Theory and Its Applications, IEICE, the researchers sought to create these benchmarks by statistically analyzing the actual usage history of rented and returned bicycles in real BSSs. “Bike sharing systems could become the preferred public transport system globally in the future. It is, therefore, an important issue to address in our societies,” Prof. Ikeguchi explains.

The researchers used publicly available data from four real BSSs located in four major cities in USA: Boston, Washington DC, New York City, and Chicago. Save for Boston, these cities have over 560 ports each, for a total number of bicycles in the thousands.

First, a preliminary analysis revealed that an excess and lack of bicycles occurred across all four BSSs during all months of the year, verifying the need for active rebalancing. Next, the team sought to understand the temporal patterns of rented and returned bicycles, for which they treated the logged rent and return events as “point processes.”

The researchers independently analyzed both point processes using three approaches, namely raster plots, coefficient of variation, and local variation. Raster plots helped them find periodic usage patterns, while coefficient of variation and local variation allowed them to measure the global and local variabilities, respectively, of the random intervals between consecutive bicycle rent or return events.

The analyses of raster plots yielded useful insights about how the four BSSs were used in their respective cities. Most bicycles were used during daytime and fewer overnight, producing a periodic pattern. Interestingly, from the analyses of the local variation, the team found that usage patterns were similar between weekdays and weekends, contradicting the results of previous studies. Finally, the results indicated that the statistical characteristics of the temporal patterns of rented and returned bikes followed a Poisson process—a widely studied random distribution—only in New York City. This was an important find, given the original objective of the research team. “We can now create realistic benchmark instances whose temporal patterns of rented and returned bicycles follow the Poisson process. This, in turn, can help improve the bicycle rebalancing model we proposed in our earlier work,” explains Prof. Ikeguchi.

Overall, this study paves the way to a deeper understanding of how people use BSSs. Moreover, through further detailed analyses, it should be possible to gain insight into more complex aspects of human life, as Prof. Ikeguchi remarks: “We believe that the analysis of BSS data will lead not only to efficient bike sharing but also to a better understanding of the social dynamics of human movement.”

In any case, making BSSs a more efficient and attractive option will, hopefully, make a larger percentage of people choose the bicycle as their preferred means of transportation.

***

Reference

Title of original paper: Statistical analysis of usage history of bicycle sharing systems

Journal: Nonlinear Theory and Its Applications, IEICE

DOI: https://doi.org/10.1587/nolta.13.355

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan’s development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society”, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today’s most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Tohru Ikeguchi from Tokyo University of Science

Tohru Ikeguchi received M.E. and Ph.D. degrees from Tokyo University of Science, Japan. After working for nearly a decade as Full Professor at Saitama University, Japan, he worked at Tokyo University of Science as Full Professor at the Department of Management Science from 2014 to 2016. Since then, he has been a Full Professor at the Department of Information and Computer Technology in Tokyo University of Science. His research interests include nonlinear time series analysis, computational neuroscience, application of chaotic dynamics to solving combinatorial optimization problems, and complex network theory. He has published over 230 papers and proceedings.

Funding information

This study was partially supported by JSPS KAKENHI Grant Numbers JP20H000596 and JP21H03514.

A better black hole laser may prove a circuitous ‘Theory of Everything’

The fundamental forces of physics govern the matter comprising the Universe, yet exactly how these forces work together is still not fully understood. The existence of Hawking radiation — the particle emission from near black holes — indicates that general relativity and quantum mechanics must cooperate. But directly observing Hawking radiation from a black hole is nearly impossible. So how can researchers study it to better understand how the forces integrate into a “Theory of Everything”?

According to Hiroshima University doctoral student Haruna Katayama, since researchers cannot go to the Hawking radiation, it must be brought to them. She proposed a quantum circuit that acts as a black hole laser using an analogue black hole and a white hole as a resonator to amplify weak Hawking radiation. The proposal was published in Scientific Reports.

“In the proposed circuit, the metamaterial element makes it possible for Hawking radiation to travel back and forth between horizons, and the Josephson effect plays an important role in amplifying Hawking radiation through the mode conversion at the horizons, mimicking the behavior between the black and white holes,” Katayama said.

The proposed laser also provides a future light source for quantum information technology.

High-performance organic optoelectronics with better crystallinity at semiconductor interface

Organic molecular interfaces with minimized structural mismatch and spontaneous electron transfer could open doors to high-efficiency optoelectronics

Organic semiconductors have garnered much attention in optoelectronics owing to their flexibility, which is allowed by weak interaction forces. However, this also makes for poor charge carrier mobility. In a new study, researchers from Japan combined organic semiconductor molecules with similar structures to produce interfaces with better crystal quality and charge transport efficiency, paving the way for the realization of high-mobility organic optoelectronics.

Semiconductor electronic devices can be made of either inorganic crystals, formed by the strong bonding of atoms and ions, or organic crystals, which demonstrate weaker bonds held together by van der Waals forces (weak electric forces of attraction between neutral atoms or molecules that do not share a chemical bond). These weak bonds make organic semiconductors viable for flexible optoelectronics applications such as wearable electronic devices and flexible solar cells. However, this very characteristic also lends them a disadvantage: organic semiconductors typically exhibit poor charge carrier mobility and, therefore, do not conduct electricity well.

It is well-known that single-crystalline semiconductors can conduct electricity much better compared to their non-crystalline forms. Moreover, crystals composed of organic molecules can be grown to have interfaces with little structural mismatch even when their structures are quite different. Is there a way to leverage these properties to improve the charge transport in organic semiconductors?

This is where researchers from Tokyo University of Science, Japan decided to step in. In a new study led by Associate Professor Yasuo Nakayama, the researchers attempted to enhance the charge transport efficiency by minimizing the crystal structure mismatch between the growing crystal layer and the substrate. “I wanted to confirm whether the quality of the crystals at the interface would be better if we combined materials with similar structures so that we could create a crystalline interface even with inorganic materials,” says Dr. Nakayama, speaking of his personal motivation for the research. The paper was made available online on 18 November 2021, and published in Volume 12, Issue 46 of The Journal of Physical Chemistry Letters on 25 November 2021.

The team designed a high-quality crystalline interface using a technique called “quasi-homo-epitaxial growth” to grow bis(trifluoromethyl)dimethylrubrene on a single crystal surface of rubrene. They used surface X-ray diffraction measurements to characterize the interface and demonstrated its high crystallinity resulting from minimized structure mismatch. This eliminated the mobility issue. Additionally, they probed its electronic structure using ultraviolet photoelectron spectroscopy, which revealed an abrupt step in the electronic energy levels across the interface. This allowed for spontaneous electron transfer across the interface, validating their strategy.

With these results, the team is now excited about the potential applications their findings could entail. “Our work could potentially open up an untested route for the realization of high-mobility organic semiconductor optoelectronics. Additionally, since organic semiconductors can be made into thin and light crystals, it is possible to print semiconductor devices on transparent films and fabrics for carrying and wearing,” speculates Dr. Nakayama. “Furthermore, it could also lead to highly efficient flexible solar cells with better performance than those of existing technologies.”

Those certainly are some fascinating consequences to look forward to!

 

***

 

Reference

Title of original paper: Quasi-Homoepitaxial Junction of Organic Semiconductors: A Structurally Seamless but Electronically Abrupt Interface between Rubrene and Bis(trifluoromethyl)dimethylrubrene

Journal: The Journal of Physical Chemistry Letters

DOI: https://doi.org/10.1021/acs.jpclett.1c03094

UiTM and Tokyo NODAI sign MoU

Universiti Teknologi MARA Malaysia (UiTM) expands its international collaboration by signing an MoU with the Tokyo University of Agriculture (Tokyo NODAI), conducted on December 6th, 2021.

The objectives of this signing ceremony are that the two universities could start visioning the knowledge, technological advancement, and viable resources sharing, focusing on integrated and smart solutions to achieve sustainable development goals (SDGs) in every aspect. This strategic partnership would be beneficial to reaffirm, strengthen, and leverage their comparative advantages to support high-quality and impactful research, education, and culture through effective and accountable governance, digitalization, resilience to energy and environmental challenges, women’s empowerment and good infrastructures.

The Rector of UiTM Pahang Branch expressed his gratitude for the commitment of both universities in taking a step further for the collaboration.

“The collaboration will have positive repercussions on promoting a knowledge-based economy, increasing the nation’s employment rate, improving innovation excellence, and attaining global recognition. This effort is also in line with UiTM Strategic Planning’s agenda towards becoming a globally renowned university of Science, Technologies, Humanities, and Entrepreneurship by 2025. These aspirations can be accomplished through conveying knowledge and instilling moral values in graduates who are capable of producing content and knowledge for the benefit of the society, industry, and nation.”, he added.

Moreover, Tokyo NODAI agrees that this collaboration could bring enormous benefits for both universities through the active involvement of students and staff in research and innovations as well as academics and cultural perspectives.

UiTM and Tokyo NODAI embarked on the collaborative journey earlier this year with the organization of two exciting events, namely “Continually striving to advance agriculture: Return student to the farm, a hope for the world” on January 26th, 2021, and “Virtual colloquium for education and research collaboration” on September 29th, 2021. The MoU signing event further solidifies the relationship, which is hoped to mutually benefit and enhance the exchange of knowledge and research collaborations for both institutions.

The signatories were UiTM Pahang Branch’s Rector, Professor Ts Dr Mohd Ilham Adenan and Professor Dr Hiroya Ohbayashi as the Dean of Faculty of Regional Environment Science, Tokyo University of Agriculture. The ceremony was witnessed by UiTM Pahang Branch’s Deputy Rector, Associate Professor Dr Wan Mohd Nazri Wan Abdul Rahman (Research & Industrial Linkages), Associate Professor Dr Nazirah Ramli (Academic Affairs), Dr Mohd Kamal Azman Jusoh (Student Affairs), and Nor Yusnita Mohamed Yusoff (Bursary). Also present in the virtual ceremony was the Head of Faculty of Globalization from Tokyo University of Agriculture, Professor Dr Iwao Uehara.

This initiative is aligned with the Sustainable Development Goals (SDGs) No.17, which focuses on strengthening and revitalizing the global partnership.

A close look into the regulation of CCL17

New insight into a key protein could lead to novel treatments for diseases such as contact dermatitis and asthma

The CCL17/TARC chemokine is involved in many immune-mediated diseases, and is a well-known biomarker of atopic dermatitis. However, the proteins that regulate CCL17 expression are not clear. Recently, scientists from Japan conducted experiments on cultures of dendritic cells focusing on PU.1, a key protein regulating gene expression in immune cells. Further experiments on mice showed that externally regulating PU.1 can alleviate certain asthma symptoms, hinting at potential therapeutic targets for hyperimmune diseases.

Allergies and many other types of immune system-related diseases originate from an interplay of complex chemical pathways that affect cell behavior, distribution, and development. One prominent example is the CCL17/TARC chemokine, a protein that contributes to allergy by attracting certain types of white blood cells, such as T cells and eosinophils. Despite the important and proven roles of CCL17/TARC in allergic diseases like contact dermatitis, not much is known about the transcription factors (proteins that regulate gene expression) involved in regulating the expression of the CCL17 gene.

To address this knowledge gap, a team of scientists from Japan conducted a detailed study, the results of which were published in Allergy, focusing on PU.1, a transcription factor known to regulate gene expression in various types of immune cells. Prof. Chiharu Nishiyama from Tokyo University of Science (TUS), who headed the study, explains why they targeted this specific protein: “A long time ago, we discovered that forced expression of PU.1 in certain types of blood cell lineages causes them to change into dendritic cells. Since then, I have developed a deep interest in the fact that PU.1 is a master transcription factor that regulates dendritic cell differentiation and gene expression.”

The team conducted a series of detailed experiments to clarify, at the molecular level, the relationship that exists between CCL17, PU.1, and other associated transcription factors and promoters. They relied on small interfering RNAs (siRNAs), or short chains of nucleotides that interrupt the translation process (making proteins from a copied DNA segment into RNA) of a target protein with great precision, for their study.

After targeting PU.1 with siRNAs in dendritic cell cultures, they observed a decrease in expression not only for PU.1 and CCL17 but also IRF4 and IRF8, two partner molecules of PU.1.

Through further experiments in cell cultures followed by computational analysis, the team found that IRF4 and PU.1 work together synergistically to activate the transcription (copying of a DNA segment into RNA) of TARC in dendritic cells through the regulatory region of the CCL17 gene. Although this regulatory mechanism appears to be preserved across mammals, the scientists also discovered that the human CCL17 gene contains an additional promoter that is activated in keratinocytes, the most common type of cell found in the outermost layer of our skin.

Finally, the scientists tested the effects of PU.1 suppression in vivo using an asthmatic mouse as a model. They found that a simple intranasal administration of PU.1 siRNA helped reduce TARC secretion and the associated infiltration of white blood cells into the bronchioles, effectively reducing the extent of inflammation in the lungs.

These results highlight the importance of PU.1 in inflammatory processes and immune diseases and could pave the way to novel treatments. “I find it encouraging that we were able to report both basic research on genes as well as an applied approach that could lead to treatment for hyperimmune responses, such as contact hypersensitivity and asthma,” comments Prof. Nishiyama.

Hopefully, further research would help clarify the regulatory and transcriptional pathways of CCL17 even more, leading to a more comprehensive understanding of the complex panorama of immune diseases.

***

Reference

Authors: Naoto Ito (1), Fumiya Sakata (1), Masakazu Hachisu (1), Kazuki Nagata (1), Tomoka Ito (1), Kurumi Nomura (1), Masanori Nagaoka (1), Keito Inaba (1), Mutsuko Hara (2), Nobuhiro Nakano (2), Tadaaki Nakajima (1), Takuya Yashiro (1), and Chiharu Nishiyama (1).

Title of original paper: The Ccl17 gene encoding TARC is synergistically transactivated by PU.1 and IRF4 driven by the mammalian common promoter in dendritic cells

Journal: Allergy
DOI: https://doi.org/10.1111/all.15184

Novel way to prevent postoperative complication after pancreatic surgery

Scientists have developed a polymer-based hydrogel that can prevent pancreatic fistulae, a frequent complication of pancreatic surgery.

An unnatural connection between the pancreas and adjacent organs, called a pancreatic fistula, is a common complication of pancreatic surgery. This condition can lead to infection, sepsis and in some cases be fatal. So far, there are no effective methods that can stop these fistulae from developing after surgery. But, now, a team led by researchers from Tokyo University of Science have developed a novel hydrogel that can prevent pancreatic fistulae and thus, save lives.

Pancreatic fistulae, or ducts that grow from the pancreas to nearby organs such as the colon, are a frequent complication after pancreatic surgery. Studies have shown that the risk of pancreatic fistulae after surgery is as high as 50%. These fistulae cause a leakage of pancreatic fluid, which can then accumulate near the pancreas and form an abscess, become severely infected, and—in severe cases—lead to death. Repairing these fistulae is also a prolonged and complex process. They say prevention is better than cure, but despite multiple attempts, there are currently no effective prevention methods for pancreatic fistulae.

In a recent study, a team of scientists—including Professor Takehisa Hanawa, Dr. Yayoi Kawano and Mr. Hiroshi Mamada from Tokyo University of Science, as well as Dr. Akira Kemmochi and Dr. Takafumi Tamura from the University of Tsukuba—have developed a novel hydrogel that can prevent the formation of these postoperative pancreatic fistulae. The study was published in Polymers for Advanced Technologies.

“There are many polymers with chemical or biological synthesis, but their preparation and application can be somewhat complicated. Our research was inspired by a desire to develop a hydrogel that can be used simply and effectively in surgical settings as one of the ‘Patient-Friendly Formulations,’” says Prof. Hanawa.

Like the name suggests, hydrogels are three-dimensional polymer networks that can hold a large amount of water. This makes them useful in a wide variety of fields, from agriculture to wound healing in medicine. These hydrogels can be prepared in one of two ways. One, using chemical techniques such as chemical reactions or electron beam crosslinking, and the other using physical methods such as the freezing-thawing (F/T) cycle method. The polymer solution is prepared and then frozen, which makes the water present in the solution gather as ice. This allows the hydrogel particles to link together. The solution is then thawed and frozen again until the desired level of linkage is achieved in the hydrogel.

In this study, the research team prepared two polyvinyl alcohol (PVA) hydrogels using of two types of PVAs, Poval® and Exceval®. They then studied then evaluated a critical hydrogel property called swelling behavior. Hydrogels absorb water, which makes them swell. This swelling can at times cause the hydrogel to rupture. They found that the Exceval® hydrogel showed a lower swelling degree, increased elasticity, and superior gel strength to the one made with Poval®. These properties implied that the Exceval® could potentially be used in the abdominal cavity after pancreatic surgery.

The research team then prepared hydrogels that contained tartrazine, a common dye used to study the drug-release behavior of hydrogels, and nefamostat mesylate (NM), a drug that is used to treat pancreatitis. They found that the drug-release behavior of both hydrogels depended on the number of F/T cycles used in their preparation.

Finally, the research team tested the hydrogel in vivo in a pancreatic fistula rat model. They found that rats with the hydrogel showed lower levels of pancreatic enzymes in the blood and abdominal fluid, indicating that the leakage of pancreatic fluid was controlled. They inferred that the hydrogel was capable of absorbing pancreatic juices and intra-abdominal fluid, and of preventing pancreatic fistula.

The research team mentions that the results of animal experiments using the gel prepared in this study have been published in the Journal of Hepato-Biliary-Pancreatic Sciences.

“Since the hydrogel prepared in this study also has the ability to absorb liquid, we believe that it can be applied, not only to the body, but also to cancerous skin ulcers and wounds, where it can absorb secretions and release medicines for treatment,” explains Prof. Hanawa.

With its adjustable properties, excellent swelling behavior and high absorption abilities, the novel Exceval® hydrogel shows great promise for clinical applications for the prevention of pancreatic fistulae.

***

Reference
Title of original paper: Development and evaluation of novel hydrogel for preventing postoperative pancreatic fistula
Journal: Polymers for Advanced Technologies
DOI: https://doi.org/10.1002/pat.5496

Clear as (Quasi) Crystal: scientists discover the first ferromagnetic quasicrystals

Long-range magnetic order has been observed in quasicrystals, strange solids that show forbidden crystal symmetries, for the first time

Since the discovery of quasicrystals (QCs), solids that mimic crystals in their long-range order but lack periodicity, scientists have sought physical properties related to their peculiar structure. Now, an international group of researchers led by Tokyo University of Science, Japan, report for the first time a long-range magnetic order in QCs with icosahedral symmetry that turn ferromagnetic below certain temperatures. This groundbreaking discovery opens doors to future research on these exotic materials.

In 1984, a routine examination of an aluminum-manganese alloy revealed a curious anomaly that was previously thought to be crystallographically impossible– a five-fold rotational symmetry. This was the discovery (later recognized by Nobel Prize) of a “quasicrystal” (QC), a curious solid that shows long-range ordering similar to crystals but lacks their periodicity. Rather, the order is “quasiperiodic,” which leads to some exotic symmetries absent in crystals. Ever since then, QCs have been the subject of enormous scientific interest.

But their potential applications remain uncertain since no physical property signifying their long-range quasiperiodic order, such as long-range magnetic order, has been observed. Until now, that is.

In a new study published in the Journal of the American Chemical Society, a global team of scientists led by Professor Ryuji Tamura of Tokyo University of Science (TUS), Japan, Professor Taku J. Sato of Tohoku University, Japan, and Professor Maxim Avdeev of the Australian Nuclear Science and Technology Organisation and University of Sydney, Australia, have reported the first-ever observation of long-range ferromagnetic order in icosahedral quasicrystals (i QCs or QCs with 5-fold rotational symmetry). Ms. Asuka Ishikawa and Dr. Shintaro Suzuki, members of the Tamura Laboratory at TUS, also made invaluable contributions to the project.

“This successful synthesis of ferromagnetic i QCs is the culmination of more than 10 years of research in our laboratory,” says Prof. Tamura, “Nobody knows what kind of peculiar behavior they will further reveal or how they can be exploited for the advancement of technology, but now we have finally taken the first step. Elucidating the properties of these ferromagnetic QCs will contribute greatly to the development of science.”

There are four major types of magnetic order: ferromagnetism, antiferromagnetism, paramagnetism, and diamagnetism. The discovery of antiferromagnetic and ferromagnetic transitions in approximant crystals (APs)—crystals with a somewhat similar structure to the related QCs that can be studied using conventional techniques—inspired the research group to look for magnetically ordered i QCs. For their research, the team prepared alloys of gold (Au), gallium (Ga) and gadolinium (Gd) and gold, gallium, and terbium (Tb). Using conventional X-ray diffraction, they observed the formation of an icosahedral quasicrystal phase for both Au-Ga-Gd and Au-Ga-Tb.

They then investigated the properties of the two i QCs using magnetic susceptibility and specific heat measurements. They found that both alloys showed a ferromagnetic phase transition at 23 K (Gd i QC) and 16 K (Tb i QC), a signature of long-range magnetic order. To further validate these results, they performed neutron diffraction experiments using ECHIDNA (ANSTO, Australia) and ISSP-GPTAS (JRR-3, Japan), and looked at the neutron diffraction patterns of the i QCs at different temperatures. They observed prominent Bragg peaks below their respective transition temperatures, confirming the ferromagnetic nature of the i QCs.

Attempts to synthesize magnetic i QCs until now have all ended in “spin-glass-like freezing,” characterized by a disordered magnetic state. Against this backdrop, the discovery of long-range ferromagnetic order in this study has consequences far beyond the landscape of the physical properties of materials and opens doors to tailored magnetic materials. “The crystal symmetry of ferromagnetic QCs is much higher than that of conventional periodic crystals, which makes it possible to apply them as ultrasoft magnetic materials,” says Prof. Tamura.

With the decades-long quest for long-range magnetic order in i QCs finally at an end, the world is now eagerly waiting to see what this groundbreaking discovery entails. With such superlative research pioneering the way, it won’t be long before we find out!

NITUC-UiTM Students Leadership and Networking Seminar 2.0

The NITUC (Japan)-UiTM (Malaysia) Students Leadership And Networking Seminar 2.0 was successfully organized for the second time by the National Institute of Technology, Ube College, Japan and Universiti Teknologi MARA (UiTM), Malaysia, specifically the Department of International Affairs (DIA), in collaboration with UiTM Global Ambassador (UGLAM) and the SPE – UiTM Student Chapter from 4th June 2021 for 8 weeks. The closing ceremony took place on 19th July 2021, graciously attended by Dr. Hajah Zainab Haji Mohd Noor (The Director of Department of International Affairs (DIA) UiTM Global), Prof. Dr. Hatamura Manabu (Director of International Office NIT Ube College (NITUC), staffs of Department of International Affairs (UiTM), UiTM lecturers, UiTM Global Ambassadors (UGLAM) and students from both UiTM and NITUC.

This program was smoothly handled by two student leaders representing UiTM and NITUC; Ahmad Sirhan bin Azlin and Nagatomi Shoichiro, respectively. They were assisted by the previous appointed student leaders of this program, Shalin Sellehuddin and Ena Kidani, together with project managers Ts. Dr. Nur Hashimah Alias (Coordinator Summer Program, DIA, UiTM Global and advisor of UGLAM) and also Ms. Siti Aisyah Mohktar (lecturer from NITUC). Not to mention the committee members, notably Nur Farah Hanani Binti Mohamad Azhari, Ezzanie Balqhis Binti Basir, Muhammad Faris Bin Mohd Fadhir, and Muhammad Ali Murtadha bin Mustafa, who made significant contributions in terms of multimedia and technical assistance. Due to the success of the student groups in organizing this program, the number of participants had increased in 2021 compared to 2020 with 32 groups and 70 individuals from both Malaysia and Japan drawn from various faculties.

The primary objective of this program is to develop leadership skills, expand networking, and improve communication skills in both English and Japanese for the participants. The topics include greetings, traditional clothes or costumes, popular tourism spots and festivals, food and delicacies, public figures as role models, and global issues such as climate change. Furthermore, during the closing ceremony, participants delivered their recorded group project presentation in Japanese and English. Lastly, this program hopes to develop a stronger network to place UiTM and NITUC in the international arena and make an impact globally by pushing the boundaries through networking activities. Subsequently, this program encourages students to think globally and create more partnerships with international partners for mutual benefit and future undertakings.