Tag: Tokyo University of Science

Annealing processors are more energy efficient and quicker at solving mathematical optimization problems than PCs. Researchers at Tokyo University of Science have now developed a new approach to realizing scalable fully coupled annealing processors. These quantum-inspired systems can model the interactions between magnetic spins and use it to solve complex optimization problems. The new method greatly outperforms modern CPUs and shows potential for applications in drug discovery, artificial intelligence, and materials science.

Have you ever been faced with a problem where you had to find an optimal solution out of many possible options, such as finding the quickest route to a certain place, considering both distance and traffic? If so, the problem you were dealing with is what is formally known as a “combinatorial optimization problem.” While mathematically formulated, these problems are common in the real world and spring up across several fields, including logistics, network routing, machine learning, and materials science.

However, large-scale combinatorial optimization problems are very computationally intensive to solve using standard computers, making researchers turn to other approaches. One such approach is based on the “Ising model,” which mathematically represents the magnetic orientation of atoms, or “spins,” in a ferromagnetic material. At high temperatures, these atomic spins are oriented randomly. But as the temperature decreases, the spins line up to reach the minimum energy state where the orientation of each spin depends on its neighbors. It turns out that this process, known as “annealing,” can be used to model combinatorial optimization problems such that the final state of the spins yields the optimal solution.

Researchers have tried creating annealing processors that mimic the behavior of spins using quantum devices, and have attempted to develop semiconductor devices using large-scale integration (LSI) technology aiming to do the same. In particular, Professor Takayuki Kawahara’s research group at Tokyo University of Science (TUS) in Japan has been making important breakthroughs in this particular field.

In 2020, Prof. Kawahara and his colleagues presented at the 2020 international conference, IEEE SAMI 2020, one of the first fully coupled (that is, accounting for all possible spin-spin interactions instead of interactions with only neighboring spins) LSI annealing processors, comprising 512 fully-connected spins. Their work appeared in the journal IEEE Transactions on Circuits and Systems I: Regular Papers. These systems are notoriously hard to implement and upscale owing to the sheer number of connections between spins that needs to be considered. While using multiple fully connected chips in parallel was a potential solution to the scalability problem, this made the required number of interconnections (wires) between chips prohibitively large.

In a recent study published in Microprocessors and Microsystems, Prof. Kawahara and his colleague demonstrated a clever solution to this problem. They developed a new method in which the calculation of the system’s energy state is divided among multiple fully coupled chips first, forming an “array calculator.” A second type of chip, called “control chip,” then collects the results from the rest of the chips and computes the total energy, which is used to update the values of the simulated spins. “The advantage of our approach is that the amount of data transmitted between the chips is extremely small,” explains Prof. Kawahara. “Although its principle is simple, this method allows us to realize a scalable, fully connected LSI system for solving combinatorial optimization problems through simulated annealing.”

The researchers successfully implemented their approach using commercial FPGA chips, which are widely used programmable semiconductor devices. They built a fully connected annealing system with 384 spins and used it to solve several optimization problems, including a 92-node graph coloring problem and a 384-node maximum cut problem. Most importantly, these proof-of-concept experiments showed that the proposed method brings true performance benefits. Compared with a standard modern CPU modeling the same annealing system, the FPGA implementation was 584 faster and 46 times more energy efficient when solving the maximum cut problem.

Now, with this successful demonstration of the operating principle of their method in FPGA, the researchers plan to take it to the next level. “We wish to produce a custom-designed LSI chip to increase the capacity and greatly improve the performance and power efficiency of our method,” Prof. Kawahara remarks. “This will enable us to realize the performance required in the fields of material development and drug discovery, which involve very complex optimization problems.”

Finally, Prof. Kawahara notes that he wishes to promote the implementation of their results to solve real problems in society. His group hopes to engage in joint research with companies and bring their approach to the core of semiconductor design technology, opening doors to the revival of semiconductors in Japan.

Make sure to watch out for these groundbreaking annealing processors in the future!

Heat dissipation is essential for maintaining the performance of electronic devices. However, efficient heat dissipation is a major concern for thin-film electronics since conventional heat sinks are bulky. Researchers from Japan found a solution to this problem in sea squirts or ascidians. They prepared flexible nanocomposite films using an ascidian-derived cellulose nanofiber matrix and carbon fiber fillers. The prepared films demonstrate excellent anisotropic in-plane heat conduction and the carbon fiber fillers inside are reusable.

The last few decades have witnessed a tremendous advance in electronics technology, with the development of devices that are thinner, lightweight, flexible, and robust. However, as the devices get thinner so does the space for accommodating the internal working components. This has created an issue of improper heat dissipation in thin-film devices, since conventional heat sink materials are bulky and cannot be integrated into them. Thus, there is a need for thermal diffusion materials that are thin and flexible and can be implemented in thin-film devices for efficient heat dissipation.

Currently, several substrate materials can act as heat diffusers as thin films, but most diffuse heat in the in-plane direction isotropically. This, in turn, could create thermal interference with neighboring components of a device. “For a substrate on which multiple devices are mounted in high density, it is necessary to control the direction of thermal diffusion and find an effective heat removal path while thermally insulating between the devices. The development of substrate films with high anisotropy in in-plane thermal conductivity is, therefore, an important target,” explains Junior Associate Professor Kojiro Uetani from Tokyo University of Science (TUS) in Japan, who researches advanced materials for thermal conductivity and formerly belonged to SANKEN (The Institute of Scientific and Industrial Research), Osaka University.

In a recent study available online on 20 July 2022 and published in Volume 14, Issue 29 of ACS Applied Materials & Interfaces on 27 July 2022, Dr. Uetani and his team, comprising Assistant Professor Shota Tsuneyasu from National Institute of Technology, Oita College, and Prof. Toshifumi Satoh from Tokyo Polytechnic University, both in Japan, reported a newly developed nanocomposite film made of cellulose nanofibers and carbon fiber-fillers that demonstrated excellent in-plane anisotropic thermal conductivity.

Many polymer composites with thermally conductive fillers have been proposed to enhance thermal conductivity. However, there are few reports on materials with particulate or plate-like fillers that exhibit thermal conductivity anisotropy, which is important to prevent thermal interference between adjacent devices. Fibrous fillers such as carbon fibers (CF), on the other hand, can provide in-plane anisotropy in two-dimensional materials due to their structural anisotropy.

It is also important to select matrix with high thermal conductivity. Cellulose nanofibers (CNFs) extracted from the mantle of ascidians has been reported to exhibit higher thermal conductivity (about 2.5 W/mK) than conventional polymers, making it suitable for use as a heat-dissipating material. As indicated by the ability to write with a pencil on paper, cellulose has a high affinity for carbon materials and is easy to combine with CF fillers. For example, hydrophobic CF cannot be dispersed in water by itself, but in the presence of CNF, it is easily dispersed in water. Accordingly, the team chose bio-based ascidian—sea squirt—derived CNFs as the matrix.

For material synthesis, the team prepared an aqueous suspension of CFs and CNFs and then used a technique called liquid 3D patterning. The process resulted in a nanocomposite consisting of a cellulose matrix with uniaxially aligned carbon fibers. To test the thermal conductivity of the films, the team used laser-spot periodic heating radiation thermometry method.

They found that the material showed a high in-plane thermal conductivity anisotropy of 433% along with conductivity of 7.8 W/mK in the aligned direction and 1.8 W/mK in the in-plane orthogonal direction. They also installed a powder electroluminescent (EL) device on a CF/CNF film to demonstrate the effective heat dissipation. In addition, the nanocomposite film could cool two closely placed pseudo heat sources without any thermal interference.

Apart from the excellent thermal properties, another major advantage of the CF/CNF films is their recyclability. The researchers were able to extract the CFs by burning the cellulose matrix, allowing to be reused. Overall, these findings can not only act as a framework for designing 2D films with novel heat dissipating patterns but also encourage sustainability in the process. “The waste that we humans generate has a huge environmental impact. Heat transfer fillers, in particular, are often specialized and expensive materials. As a result, we wanted to create a material that does not go to waste after usage but can be recovered and reused for further applications,” concludes Dr. Uetani.

Indeed, with cooler smartphones and lower waste, it’s a win-win for everyone!

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Reference

DOI: https://doi.org/10.1021/acsami.2c09332

Title of original paper: Thermal Diffusion Films with In-Plane Anisotropy by Aligning Carbon Fibers in a Cellulose Nanofiber Matrix

Journal: Applied Materials & Interfaces

Authors: Kojiro Uetani1, Kosuke Takahashi2, Rikuya Watanabe3, Shota Tsuneyasu4, and Toshifumi Satoh3

Income inequality is at an all-time high worldwide. Now, researchers at the Tokyo University of Science have observed that overconfidence plays an important role in how people view their individual ability to earn. They found that overconfident people’s realization of the gap between their perceived ability and their income lowers their faith in the economy being fair and meritocratic. However, this does not translate into higher support for reducing income inequality.

Overconfidence in one’s ability is not uncommon among humans. It can be observed in areas ranging from driving ability and productivity to calculating returns on investment projects. Overconfidence can also lead people to think that they aren’t earning as much as they think they can. This consideration should encourage overconfident people to think that society is unfair. Furthermore, this effect should increase the support for more concentrated efforts, including government interventions, to reduce the income inequality and mitigate the perceived unfairness of society. However, is this really the case?

A new study by researchers from Tokyo University of Science and Princeton University seeks to answer this question. The research team, which included Junior Associate Professors Tomoko Matsumoto and Daiki Kishishita from Tokyo University of Science and Atsushi Yamagishi from Princeton University, aimed to find out how the preferences of overconfident people, specifically those concerning income inequality, change when they are made aware of a gap between their economic status and their self-evaluated ability. The study was made available online in the European Journal of Political Economy on 28 August, 2022.

“There is a large variation in the level of inequality in countries with similar levels of income redistribution, in terms of the degree to which people support or oppose income redistribution. We are interested in understanding why those who benefit economically from the implementation of income redistribution policies oppose such policies, and have focused on the nature of the ‘self-confidence overload’,” explains Dr. Matsumoto, explaining the rationale for their study.

To this end, the researchers conducted an online survey in the United States with 4,471 participants. The survey was framed in such a way that the questions reinforced a participant’s self-perceived income-ability gap randomly. The novelty of the study stems from the fact that previous studies have been lab-controlled experiments. However, this study tests the presented theory in a real economic environment using the actual income values of the participants.

The study yielded a number of surprising results. The researchers found that participants who stated that their income was lower than their ability to earn lose their confidence in meritocracy and their faith in the economy being fair. They view the economy and society as being unfair, which hinders them to earn to their full potential. The researchers also noted that people believed that negative income-ability gap was a result of an unfair economy and not an individual responsibility.

Upon realizing the negative income-ability gap, more left-wing participants were in favor of reducing income inequality than right-wing and centrist participants. However, people across the political spectrum did not favor government intervention as a way to reduce income inequality. Government intervention did not garner a lot of support even among left-wing participants with high trust in the government. Explaining this anomaly, Dr. Matsumoto says, “Scholars have previously argued that characteristics such as party ideology or family and personal values are major determinants of preferences for redistribution and changing a belief about social and economic environments may have a limited role. Their limited effect on preferences for reducing income inequality may stem from a similar mechanism.”

Interestingly, it was noted that people following a right-wing ideology showed higher support for ensuring that people get paid according to their ability than government intervention.

The researchers believe their findings would be relevant in countries apart from the United States, as overconfidence in one’s ability is prevalent across the world. However, they anticipate differences based on the population’s belief in the state of their economy. Addressing the implications of their findings, Dr. Matsumoto says, “I believe that identifying who is for and who is against reducing inequality will help to alleviate social conflicts in a society where inequality is growing and polarization is increasing.”

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Reference

DOI: https://doi.org/10.1016/j.ejpoleco.2022.102279

Title of original paper: Overconfidence, Income-ability Gap, and Preferences for Income Equality

Journal: European Journal of Political Economy

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Elimination of transformed cells that can initiate cancer is necessary to maintain tissue integrity. In a new study, scientists from Tokyo University of Science show how this mechanism is regulated by the cellular process “autophagy.” They found that intact autophagic vacuoles are indispensable in mediating competitive elimination of cancer cells. Conversely, perturbation of autophagy prevents cell elimination, thereby encouraging cancer cell propagation. These findings pave the way for development of novel anti-cancer therapies.

The maintenance of a healthy cell population is a dynamic process, whereby unhealthy cells are eliminated by a defense mechanism called “cell competition”. This process is crucial as unhealthy cells or cells that have accumulated detrimental “genetic mutations” (defects in genes) over time, can initiate the formation of cancer. Cell competition is achieved by healthy normal cells that surround mutant cancer cells through various mechanisms that trigger cell removal. In addition, epithelial cells (a type of cell that constitutes external and internal body surfaces such as skin and internal organs) adopt a cell-death-independent mechanism known as “apical extrusion” to recognize and eliminate transformed cells. While the role of apical extrusion in cell competition has been well elucidated, the regulatory mechanisms underlying this complex dynamic process remain elusive.

“Autophagy” is a process by which cells degrade and recycle cellular components. Dysregulation of autophagy has been implicated in various diseases, including several cancers. While autophagy is known to facilitate the growth and survival of cancer cells at advanced stages, previous studies have indicated that autophagy may have a preventive role in early stages of cancer. Does autophagy regulate the early destruction of cancer cells through cell competition?

Building on this hypothesis, Dr. Shunsuke Kon, a junior associate professor at Tokyo University of Science along with Eilma Akter and a team of researchers, has now explored the potential regulatory role of autophagy in cell competition, in a new study recently published in Cell Reports.

Probing deeper into the possible interplay between autophagy and cell competition, the researchers used cell lines, in which cell competition is triggered by RasV12 (a cancer-causing protein). Dr. Kon explains, “We have previously shown that when a small number of mutant cells are produced in the normal epithelial layer by activating the cancer-causing gene Ras, the mutant cells are eliminated into the lumen as loser cells. This happens as a result of cell competition between the normal epithelial cells and the Ras mutant cells.”

Using the RasV12-induced mosaic (healthy + mutant cancer cells) cell competition model and fluorescent-protein labeling, the team uncovered a fascinating set of results. They showed that the RasV12-transformed cells had an increased number of autophagosomes (structures containing degradable cytoplasmic contents). Further, they noted impairment of lysosomes, the structures that fuse with autophagosomes and mediate the breakdown of their contents; which likely, caused the increase in autophagosomes. This in turn, perturbed the “autophagic flux” (a measure of autophagic degradation) in RasV12-transformed cells.

Next, they showed that the accumulated autophagosomes and the impaired lysosomes facilitated apical elimination of the transformed (cancer) cells via cell competition. These results suggest that the intact or “non-degradable” autophagosomes are important for the elimination process. Interestingly, when the researchers ablated the autophagy gene, ATG-5 in RasV12-induced cells, they noted impairment in autophagy mediated cell competition and elimination of the transformed cells. Similarly, autophagy impaired cells exhibited resistance to elimination in a mouse model, and eventually led to chronic pancreatitis or inflammation of ducts in the pancreas, thus, corroborating their earlier findings.

Together, these findings highlight the role of autophagy in competitive elimination of mutant cancer cells and tissue homeostasis (balance). The study sheds light on the role of autophagy in cancer prevention during early stages and opens avenues for the development of novel anti-cancer therapeutics.

In this context, Dr. Kon remarks, “The development of anti-cancer drugs targeting autophagy is being intensely pursued worldwide. Since the role of autophagy has been found to differ depending on the stage of cancer progression, anti-cancer strategies that take into account the stage of cancer progression can enhance treatment efficacy.”

Autophagy is surely emerging as the unsung hero that aids the removal of cancer-causing rogue cells!

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Reference

DOI: https://doi.org/10.1016/j.celrep.2022.111292

Title of original paper: Non-degradable autophagic vacuoles are indispensable for cell competition

Journal: Cell Reports

An analysis of baby names published in municipality newsletters between 1979 and 2018 by Assistant Professor Yuji Ogihara of Tokyo University of Science and Atsuki Ito of Hitotsubashi University revealed that the rates of unique names increased in Japan over 40 years, suggesting a rise in uniqueness-seeking and individualism. This increase was observed from the 1980s, indicating that this phenomenon is not new. Their research provides important insights into changes in Japanese names and culture.

Previous research has analyzed baby names displayed by private companies and indicated that the rates of unique names increased in Japan between 2004 and 2018 (Ogihara, 2021; Ogihara et al., 2015). However, changes over a longer period were not analyzed because of the lack of a comprehensive and systematic database on baby names in Japan, unlike in other nations such as the United States and China. Therefore, it was unclear whether this increase in unique names was recent or had occurred before the 2000s. There was a possibility that the increase in unique names were found only after the 2000s.

Examining whether the rates of unique names increased for a longer period provides a betternunderstanding of not only historical changes in names and naming practices, but also cultural changes toward greater individualism which emphasizes uniqueness and independence.

To this end, Assistant Professor Yuji Ogihara of Tokyo University of Science and Atsuki Ito of Hitotsubashi University collected baby names from municipality newsletters and investigated historical changes in the rates of unique names in Japan over a longer period. Municipalities share important information such as major events (e.g., sports activities, lecture meetings), services (e.g., educational, medical), and basic statistics (e.g., financial, population) in newsletters. In these newsletters, the names of persons who are born, die, and marry in each municipality are listed.

For their study, the researchers collected municipality newsletters that fulfilled some criteria. The municipalities surveyed were geographically diverse. They were located all over Japan, from the southern part (Kyushu) to the northern part (Hokkaido). Some municipalities were located near the coast, while others were inland. The municipalities were also demographically diverse. They were located in both rural and urban areas.

The researchers analyzed 58,485 baby names published in these municipality newsletters between 1979 and 2018. They calculated the rates of the names that were not duplicated in each of the municipalities in each year. Then, they analyzed their historical changes. Furthermore, they calculated the rates of unique names not only within a given year (e.g., 2000) but also within a three-year unit (the target year, the year before it, and the year after it; e.g., 1999, 2000, 2001), and performed the same analysis.

They found that the rates of unique names increased within both time frames. Thus, unique names increased not only after the 2000s, but also from the 1980s for 40 years. This result shows that parents increasingly gave unique names to their babies and that Japanese culture increasingly emphasized uniqueness and independence for the 40 years, providing further evidence of the rise in uniqueness-seeking and individualism in Japan. This finding is also consistent with prior studies showing the rise in individualism in other aspects such as family structure and values.

Moreover, the findings reported in previous research (Ogihara, 2021; Ogihara et al., 2015) were replicated in this study: unique names increased in Japan in the 2000s and 2010s. In addition, the rates of unique names increased more rapidly for girls than for boys. This result may suggest that parents came to have stronger hope for their daughters to become unique and independent than for their sons. This means that the same phenomena were observed in a dataset different from that analyzed in previous research, indicating that the finding of an increase in unique names in Japan is robust. These findings were made available online on April 28, 2022, and published on June 21, 2022, in volume 3 of the international journal Current Research in Ecological and Social Psychology.

This study reveals an increase in the rates of unique names in Japan via an analysis of baby names published in municipality newsletters. Unique names increased from at least the 1980s in Japan. It shows that Japanese culture has changed toward greater individualism which emphasizes uniqueness and independence. Therefore, this research contributes to the understanding of changes in not only Japanese names and naming practices but also Japanese culture.

Assistant Professor Ogihara plans to continue investigating the historical changes in names and naming practices in Japan. In the near future, he aims to examine whether these changes have continued in the last few years recently and how COVID-19 has affected naming practices in Japan.

Reference

DOI: https://doi.org/10.1016/j.cresp.2022.100046

As we move towards a more energy-efficient society, the need for high-capacity, cost-effective batteries is greater than ever. Magnesium is a promising material for such solid-state batteries owing to its abundance, but its practical application is limited by the poor conductivity of magnesium ions (Mg2+) in solids at room temperature. Recently, researchers from Japan have developed a novel Mg2+ conductor with a practically applicable superconductivity of 10-3 S cm-1, overcoming this decades-long roadblock.

The development of highly efficient energy storage devices that can store renewable energy is crucial to a sustainable future. In today’s world, solid-state rechargeable lithium ion (Li+) batteries are the state of the art. But lithium is a rare earth metal, and society’s dependence on the element is likely to lead to a rapid decline in resources and subsequent price hikes.

Magnesium ion (Mg2+)-based batteries have gained momentum as an alternative to Li+. The earth’s crust holds ample magnesium, and Mg2+-based energy devices are said to have high energy densities, high safety, and low cost. But the wide application of Mg2+ is limited by its poor conductivity in solids at room temperature. Mg2+ has poor solid-state conductivity because divalent positive ions (2+) experience strong interactions with their neighboring negative ions in a solid crystal, impeding their migration through the material.

This hurdle was recently overcome by a research team from the Tokyo University of Science (TUS). In their new study published online on 4 May 2022 and on 18 May 2022 in volume 144 issue 19 of the Journal of the American Chemical Society, they report for the first time, a solid-state Mg2+ conductor with superionic conductivity of 10−3 S cm−1 (the threshold for practical application in solid-state batteries). This magnitude of conductivity for Mg2+ conductors is the highest reported to date. According to Junior Associate Professor Masaaki Sadakiyo of TUS, who led the study, “In this work, we exploited a class of materials called metal–organic frameworks (MOFs). MOFs have highly porous crystal structures, which provide the space for efficient migration of the included ions.

Here, we additionally introduced a “guest molecule,” acetonitrile, into the pores of the MOF, which succeeded in strongly accelerating the conductivity of Mg2+.” The research group further included Mr. Yuto Yoshida, also from TUS, Professor Teppei Yamada from The University of Tokyo, and Assistant Professor Takashi Toyao and Professor Ken-ichi Shimizu from Hokkaido University. The paper was made available online on May 4, 2022 and was published in Volume 144 Issue 19 of the journal on May 18, 2022.

The team used a MOF known as MIL-101 as the main framework and then encapsulated Mg2+ ions in its nanopores. In the resultant MOF-based electrolyte, Mg2+ was loosely packed, thereby allowing the migration of divalent Mg2+ ions. To further enhance ion conductivity, the research team exposed the electrolyte to acetonitrile vapors, which were adsorbed by the MOF as guest molecules.

The team then subjected the prepared samples to an alternating current (AC) impedance test to measure ionic conductivity. They found that the Mg2+ electrolyte exhibited a superionic conductivity of 1.9 × 10−3 S cm−1. This is the highest ever reported conductivity for a crystalline solid containing Mg2+.

To understand the mechanism behind this high conductivity, the researchers carried out infrared spectroscopic and adsorption isotherm measurements on the electrolyte. The tests revealed that the acetonitrile molecules adsorbed in the framework allowed for the efficient migration of the Mg2+ ions through the body of the solid electrolyte.

These findings of this study not only reveal the novel MOF-based Mg2+ conductor as a suitable material for battery applications, but also provide critical insights into the development of future solid-state batteries. “For a long time, people have believed that divalent or higher valency ions cannot be efficiently transferred through a solid. In this study, we have demonstrated that if the crystal structure and surrounding environment are well-designed, then a solid-state high-conductivity conductor is well within research,” explains Dr. Sadakiyo.

When asked about the research group’s future plans, he reveals, “We hope to further contribute to society by developing a divalent conductor with even higher ionic conductivity.”

We look forward to seeing what they develop next!

Study finds that when exposed to 1,2-dichloropropane, cells show altered gene expression that induces cellular cascades promoting cancer

1,2-dichloropropane (1,2-DCP) is a solvent used in the printing industry. It was linked to cholangiocarcinoma in 2013, when printing company employees exposed to 1,2-DCP were diagnosed with the cancer. To understand the genes influencing cholangiocarcinoma development, scientists examined gene expression profiles in co-cultured cholangiocytes and macrophages exposed to 1,2-DCP. They found DNA repair genes in cholangiocytes and cell cycle genes in macrophages were upregulated, yielding novel insights on the pathogenesis of this elusive occupational hazard.

1,2-Dichloropropane (1,2-DCP) is a solvent widely used in the printing industry. It rose to prominence when it was linked to the development of cholangiocarcinoma, or bile duct cancer, in the employees of an offset printing firm in Osaka in 2013. Thereafter, the International Agency for the Research on Cancer reclassified 1,2-DCP as being carcinogenic to humans, and many studies have since focused on occupational cholangiocarcinoma on exposure to 1,2-DCP.

Common cholangiocarcinoma develops in the cholangiocytes (or epithelial cells) of the bile duct and liver. On the other hand, occupational cholangiocarcinoma has markedly different features, such as the presence of non-characteristic precancerous lesions and inflammatory changes in the surrounding non-cancerous tissue. Research suggests that while 1,2-DCP primarily targets cholangiocytes, it indirectly damages their DNA in the presence of inflammatory cells called macrophages. However, the exact mechanism of 1,2-DCP-induced cholangiocarcinoma remains a mystery.

To solve this problem, in a new study, a group of researchers led by Professor Gaku Ichihara from Tokyo University of Science (TUS), identified the gene expression profiles of cholangiocytes co-cultured with macrophages and exposed to 1,2-DCP. Prof. Ichihara says, “Our findings identified the upregulation of genes tied to DNA repair and the cell cycle in cholangiocytes and macrophages, respectively. This suggests that the DNA damage, cell proliferation, and ultimately neoplasia occurring in the bile ducts is likely driven by the altered cell function induced by the abnormal gene expression.”

In the study, published in the journal Scientific Reports (published online on 02 July 2022), Prof. Ichihara, together with his colleagues Shigeyuki Shichino and Kouji Matsushimia at TUS, Kazuo Kinoshita from Shizuoka Graduate University of Public Health, and Sahoko Ichihara from Jichi Medical University School of Medicine, co-cultured cholangiocytes and macrophages that were exposed to varying concentrations of 1,2-DCP for 24 hours. The concentrations selected mirrored the occupational exposure of workers in a poorly ventilated environment.

Prof. Ichihara’s previous work had shown that in the presence of macrophages, 1,2-DCP induced the expression of activation-induced cytidine deaminase, which is a DNA-mutating enzyme, along with excess DNA damage and reactive oxygen species production in cholangiocytes. To delve deeper, the team used transcriptomics to study the gene expression patterns in the cells and identify the intracellular mechanisms driving carcinoma formation.

The data revealed that in the presence of 1,2-DCP, co-cultured cholangiocytes showed higher expression of base excision repair genes, whereas macrophages revealed upregulation of cell cycle genes. “The upregulation of DNA repair genes suggests an increase in DNA damage as 1,2-DCP concentration increases. Furthermore, macrophages could proliferate at a given site following 1,2-DCP exposure. Since they play an important role in the regulation of inflammatory responses by releasing cytokines and signaling molecules, their overstimulation could result in the persistent production of these compounds which ultimately influence various pathological states and cancer,” explains Prof. Ichihara.

The implications of the study are far-reaching in the fields of environmental toxicology and occupational cancer prevention. The team’s findings show that it is possible to pinpoint how potential carcinogens promote cancer without directly damaging DNA. Prof. Ichihara and his team are confident they can build on their findings and design further studies to fully understand the cross talk between cholangiocytes and macrophages and elucidate the mechanisms behind the erroneous DNA damage repair in cholangiocytes.

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Reference

Title of original paper: Transcriptome analysis of human cholangiocytes exposed to carcinogenic 1,2‑dichloropropane in the presence of macrophages in vitro

Journal: Scientific Reports

DOI: https://doi.org/10.1038/s41598-022-15295-3

 

Protein function and activity is determined by both their assembly and secondary structure. Abnormalities related to either protein aggregation or secondary structure can lead to neurodegenerative diseases. In a new study, an international research team reveal how fluoride nanoparticles, materials used in in vivo imaging, affect the assembly and structure of the amyloid β protein. Their results present a step towards better treatment and prevention of neurologic disorders like Alzheimer’s disease.

Self-assembly, or the association of individual units of a material into ordered structures or patterns, is a phenomenon of great research interest for materials scientists. One prominent example of self-assembly comes from the self-assembly of proteins in biological systems. The function and activity of proteins are governed by their assembly state. Additionally, the protein’s “secondary structure,” characterized by its folding into structures, such as a β-sheet, also plays a role. In fact, abnormalities in the protein secondary structures or their assembly can lead to various neurodegenerative diseases, including Alzheimer’s disease.

Nanoparticles (NPs) offer a promising route for the treatment and prevention of such diseases by allowing a controlled and targeted drug delivery. Additionally, inorganic NPs, such as fluoride NPs, are used in brain imaging applications. Compared to organic NPs, inorganic NPs are considered a better candidate for developing high functional materials. But, there is much concern regarding their bio-toxicity. While their interactions with bioproteins have been studied, the mechanism underlying these interactions are not well understood.

An international team of scientists from Tokyo University of Science (TUS) in Japan and Nazarbayev University in Kazakhstan has now addressed this issue. In their study, which was made available online on June 2, 2022, and was published in Volume 5, Issue 6 the journal ACS Applied Bio Materials on June 20, 2022, the team investigated a section of the amyloid β peptide (a protein found in the plaques forming in the brains of patients with Alzheimer’s disease) in solution with fluoride ceramic (CeF3) NPs. The study was led by Junior Associate Professor Masakazu Umezawa and included contributions from Mr. Naoya Sakaguchi from TUS and Assistant Professors Mehdi Amouei Torkmahalleh and Dhawal Shah from Nazarbayev University.

The team used a technique called “Fourier transform infrared spectroscopy” (FTIR) to directly monitor the effect of the NP surface on the peptide bonds. “We found that, near the nanoparticle surface, peptides are more likely to form β-sheets. This comes as an effect of hydrophobicity. The parts of the peptide that repelled by the water solution stick to the nanoparticles, and form aggregates more easily,” explains Dr. Umezawa.

In addition, the team investigated the effect of other surrounding ions in the solution. “What we found was very surprising. Even without the nanoparticles, the environment affected the rate of secondary structure formation,” says Dr. Umezawa, “This effect, resulting from a combination of electrostatic interaction and hydrogen bonding, was exaggerated upon adding nanoparticles. With a careful choice of ions and nanoparticles, the β-sheet formation can be either suppressed or promoted. This implies that the process can be controlled and engineered to eradicate adverse effects.”

The experimental results were complemented with molecular dynamics simulations performed by the Nazarbayev University team. This, in turn, helped design and guide the experiments as well as provide insights into the results.

With this deeper understanding of the interaction between proteins and NPs, the study paves the way for controlled protein folding processes. With such control, any protein deformations could be eliminated, and positive interactions and structural changes could be promoted. This could lead to a better prevention and treatment protocol for Alzheimer’s disease and, eventually, to a better quality of life for aged adults.

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Reference

Title of original paper: Changes in the Secondary Structure and Assembly of Proteins on Fluoride Ceramic (CeF3) Nanoparticle Surfaces

Journal: ACS Applied Bio Materials

DOI: https://doi.org/10.1021/acsabm.2c00239

Colorectal tumors are a common adverse effect of chronic inflammation of the intestine. In a new study, researchers from Japan and China demonstrate that mice models with dendritic cell immunoreceptor (DCIR) protein deficiency are resistant to colonic tumors induced by dextran sodium sulfate and azoxymethane. Further, they identify an antibody that reduces colitis severity and colonic tumor growth, highlighting the potential of DCIR as a therapeutic target.

Inflammatory bowel disease (IBD) is an umbrella term for two diseases, Crohn’s disease and ulcerative colitis, that are characterized by the prolonged inflammation of the gastrointestinal tract. This condition often leads to the development of colorectal tumors. Understanding the pathogenesis of IBD is, therefore, crucial to mitigate the incidence of colonic tumors.

It turns out that innate immune receptors, particularly those expressed in the gut, such as C-type lectin receptors (CLRs), are responsible for the development of IBD. However, CLRs also play a vital role in the regulation of gut microbiota and defense against pathogens. As a result, a balance needs to be struck to maintain intestinal homeostasis.

Dendritic cell immunoreceptor (DCIR) is one such CLR that is responsible for maintaining homeostasis of the immune and skeletal systems. Previous studies have suggested that DCIR negatively regulates both innate and acquired immune responses. Blocking DCIR could, therefore, potentially boost immunity against colon tumor. However, its role in intestinal immunity has remained unclear.

Against this backdrop, a research group led by Professor Yoichiro Iwakura of Tokyo University of Science (TUS) in Japan has now shed light on this issue. In their study, to be published online on 02 August 2022 in the international journal Cell Reports, the group studied the development of colitis and colon tumor in mice models deficient in DCIR.

To this end, the group fed the mice with drinking water containing dextran sodium sulfate (DSS), a synthetic sulfated polysaccharide, and azoxymethane (AOM), a neurotoxic chemical, to induce colon tumors similar to that observed in humans with IBD.

To their surprise, they found that the mice lacking DCIR showed reduced colitis severity and AOM-DSS–induced colorectal tumor growth. Moreover, compared to the wild-type mice (control), the DCIR-deficient mice showed lower body weight loss as well as reduced proinflammatory cell infiltration in the colon.

What do these observations imply? Prof. Iwakura explains, “Our findings point to the fact that intestinal carcinogenesis and inflammation are facilitated by DCIR signalling, which points to the possibility that blocking DCIR might prevent ulcerative colitis and colon cancer.”

Corroborating this possibility, the study further revealed that the use of an antibody called “anti-NA2” against asialo-biantennary-N-glycans (NA2), a ligand (binding molecule) to DCIR, reduced DSS colitis symptoms and prevented colorectal tumor growth.

The researchers are excited by these findings. Speaking about the practical applications of their study, Prof. Iwakura says, “Our results suggest that therapeutics targeting DCIR and its ligands could be used to effectively treat autoimmune diseases, IBD, and cancer, which have been traditionally difficult to treat.”

Sure enough, this study could open doors to novel therapeutic strategies for treating colorectal tumors, improving not only the lives of patients with IBD but also our understanding of the pathogenesis of human diseases.

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Reference

Title of original paper: Blocking DCIR mitigates colitis and prevents colorectal tumors by enhancing the GM-CSF-STAT5 pathway

Journal: Cell Reports

DOI: https://doi.org/10.1016/j.celrep.2022.111158

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 Yoichiro Iwakura from Tokyo University of Science

Professor Yoichiro Iwakura has been the director of the Center for Animal Disease Models at the Tokyo University of Science (TUS) since 2013, and has published numerous papers since his graduation from Kyoto University in 1970. He started researching interferon proteins at the university’s Institute for Virus Research before moving to the Sloan-Kettering Cancer Institute in the United States to analyze the developmental mechanism of early mouse embryos. In 1985, he moved to the University of Tokyo where he generated more than 100 lines of gene-modified mice as the director of the Center for Experimental Medicine to analyze the pathogenesis of infectious and autoimmune diseases.

He retired from the University of Tokyo and became an Emeritus Professor in 2012. He then moved to TUS. He has been a visiting professor for many universities, including Dalian Medical University in China and Chiba University in Japan. His work involves the development and analysis of animal disease models and research on autoimmune diseases and infectious diseases. He won the Hideyo Noguchi Memorial Award for Medical Science in 2015 and was selected as a highly cited researcher (Thomson Reuters and Clarivate Analytics) for six consecutive years from 2014.

In 2017, the Japanese party system took a dramatic turn when the major opposition party split, turning the election into a three-way contest. Long-dormant policy disagreements prompted legislators to switch parties. To understand why, researchers from Japan have recently analyzed post-electoral expert survey data. Their findings reveal both the reasons for the separation and the basis for party cohesion, offering valuable insights into party unity and cohesion.

The transformation of party politics in Japan has been marked by an array of sensational events, from the dominance of the Liberal Democratic Party (LDP) to party fragmentation. Individual legislators switch parties for a number of reasons, including policy considerations. The payoffs from “party switching” are closely linked to electoral and party systems, leading to a shift in the dynamics of party competition.

In Japan, such a situation of party switching was witnessed before the 2017 election. The founding leader of a new party, “Hope,” aggressively politicized an inactive debate regarding defense policy. Several members were persuaded to join the Hope, resulting in the collapse of the largest opposition group, “Minshin,” into three parties. However, there remains a lack of explanation as to why the long-dormant disagreement culminated in such a severe rupture.

To uncover the underlying rationale, a Japanese research group consisting of Junior Associate Professor Tomoko Matsumoto of Tokyo University of Science, Associate Professor Hiroki Kubo of Meiji Gakuin University, and Professor Kentaro Yamamoto of Hokkai-Gakuen University, examined responses on “issue position” and the “salience of party policies” from an expert survey conducted shortly after the 2017 general elections. Speaking of the motivation of the study, Dr. Matsumoto says, “The frequent breakdowns of opposition parties have created uncertainty among voters. By analyzing the expert survey, we hope to understand the structure of oppositional party policies in Japan.” Their seminal study was recently published in Japanese Journal of Political Studies.

The researchers began by assessing the expert responses using the “differential-item functioning (DIF)” analysis of “Aldrich-McKelvey” scaling. They next employed “Blackbox transpose” scaling to examine the multidimensional nature of the issue stances. One important point raised by this study is that traditional DIF analysis assumes diversity in responses is due to perceptional limitations and biases. However, the diversity in this case meant that the parties were unable to discern and convey their policy positions. As a result, a corrected version of the DIF analysis is required. “When we performed the corrected DIF analysis, we realized that the corrected value differed from the average value of the raw data obtained from the responses. In other words, the importance of using responses after rectification was reaffirmed,” reveals Dr. Matsumoto. “This is a huge revelation since online surveys are increasingly being used for scientific research.”

The results revealed a strong discord among the splinter parties over defense policy. However, their opinions on the environment, decentralization, and other policies clearly coincided. This was most likely the foundation for the main opposition camp’s unity. Furthermore, DIF analysis revealed considerable differences in expert responses on the relevance of defense policy. As a result, the rapid politicization of defense policy may have contributed to its relevance, which in turn led to the split.

Although the study showed that the major opposition separated over defense policy disagreements, it also showed that splinter opposition parties agreed on environmental and decentralization policies. Dr. Matsumoto concludes, “Our findings suggest that party switching is triggered not just by policy disagreement, but also by the decision of which policy is politicized. This may help us comprehend the future dynamics between the ruling and opposition parties.”

Party competition and party systems are critical facets of parliamentary democracies. These findings go a long way towards improving our understanding of these political structures.

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Reference

Title of original paper: Party Switching and Policy Disagreement: Scaling Analysis of Experts’ Judgement

Journal: Japanese Journal of Political Studies

DOI: https://doi.org/10.1017/S1468109922000160