Tag: Japan

In materials science, candidates for novel functional materials are usually explored in a trial-and-error fashion through calculations, synthetic methods, and material analysis. However, the approach is time-consuming and requires expertise. Now, researchers from Japan have used a data-driven approach to automate the process of predicting new magnetic materials. By combining first-principles calculations, Bayesian optimization, and monoatomic alternating deposition, the proposed method can enable a faster development of next-generation electronic devices.

Materials scientists are constantly on the lookout for new “functional materials” with favorable properties directed towards some application. For instance, finding novel functional magnetic materials could open doors to energy-efficient spintronic devices. In recent years, the development of spintronics devices like magnetoresistive random access memory—an electronic device in which a single magnetoresistive element is integrated as one bit of information—has been progressing rapidly, for which magnetic materials with high magnetocrystalline anisotropy (MCA) are required. Ferromagnetic materials, which retain their magnetization without an external magnetic field, are of particular interest as data storage systems, therefore. For instance, L10-type ordered alloys consisting of two elements and two periods, such as L10-FeCo and L10-FeNi, have been studied actively as promising candidates for next-generation functional magnetic materials. However, the combination of constituent elements is extremely limited, and materials with extended element type, number, and periodicity have rarely been explored.

What impedes this exploration? Scientists point at combinatorial explosions that can occur easily in multilayered films, requiring a great deal of time and effort in the selection of the constituent elements and material fabrication, as the major reason. Besides, it is extremely difficult to predict the function of MCA because of the complex interplay of various parameters including crystal structure, magnetic moment, and electronic state, and the conventional protocol relies largely on trial and error. Thus, there is much scope and need for developing an efficient route to discovering new high-performance magnetic materials.

On this front, a team of researchers from Japan including Prof. Masato Kotsugi, Mr. Daigo Furuya, and Mr. Takuya Miyashita from Tokyo University of Science (TUS), along with Dr. Yoshio Miura from the National Institute for Materials Science (NIMS), has now turned to a data-driven approach for automating the prediction and synthesis of new magnetic materials. In a new study, which was made available online on June 30, 2022 and published in Science and Technology of Advanced Materials: Methods on July 1, 2022, the team reported their success in the development of material exploration system by integrating computational, information, and experimental sciences for high MCA magnetic materials. Prof. Kotsugi explains, “We have focused on artificial intelligence and have combined it with computational and experimental science to develop an efficient material synthesis method. Promising materials beyond human expectation have been discovered in terms of electronic structure. Thus, it will change the nature of materials engineering!”

In their study, which was the result of joint research by TUS and NIMS and supported by JST-CREST, the team calculated MCA energy through first-principles calculations (a method used to calculate electronic states and physical properties in materials based on the laws of quantum mechanics) and performed Bayesian optimization to search for materials with high MCA energy. After examining the algorithm for Bayesian optimization, they found promising materials five times more efficiently than through the conventional trial-and-error approach. This robust material search method was less susceptible to influences from irregular factors like outliers and noise and allowed the team to select the top three candidate materials—(Fe/Cu/Fe/Cu), (Fe/Cu/Co/Cu), and (Fe/Co/Fe/Ni)—comprising iron (Fe), cobalt (Co), nickel (Ni), and copper (Cu).

The top three predicted materials with the largest MCA energy values were then fabricated via the monoatomic alternating stacking method using the laser-driven pulsed deposition technique to create multilayered magnetic materials consisting of 52 layers, namely [Fe/Cu/Fe/Cu]13, [Fe/Cu/Co/Cu]13, and [Fe/Co/Fe/Ni]13. Among the three structures, [Fe/Co/Fe/Ni]1 showed an MCA value (3.74 × 106 erg/cc) much above that of L10-FeNi (1.30 × 106 erg/cc).

Furthermore, using the second-order perturbation method, the team found that MCA is generated in the electronic state, which has not been realized in previously reported materials. This attests to the suitability of employing Bayesian optimization to identify electronic states that are likely impossible to envision through human experience and intuition alone. Thus, the developed method can autonomously search for suitable elements to design functional magnetic materials. “This technique is extendable to advanced magnetic materials with more complicated electronic correlations, such as Heusler alloys and spin-thermoelectric materials,” observes Prof. Kotsugi.

With these findings, the study sets the groundwork for automating the synthesis of hitherto-unexplored high-performance functional materials, which could enable the production of high-speed, energy-saving electronic devices and even pave the way for a carbon-neutral society!

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Reference

Title of original paper: Autonomous synthesis system integrating theoretical, informatics, and experimental approaches for large-magnetic-anisotropy materials

Journal: Science and Technology of Advanced Materials: Methods

DOI: https://doi.org/10.1080/27660400.2022.2094698

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 Masato Kotsugi from Tokyo University of Science

Professor Masato Kotsugi graduated from Sophia University, Japan, in 1996 and then received a PhD from the Graduate School of Engineering Science at Osaka University in 2001. He joined the Tokyo University of Science in 2015 as a lecturer and is currently a Professor at the Faculty of Advanced Engineering, Department of Materials Science and Technology. Prof. Kotsugi and students at his laboratory conduct cutting edge research on high-performance materials with the aim of creating a green energy society. He has published over 118 refereed papers and is currently interested in solid-state physics, magnetism, synchrotron radiation, and materials informatics.

He can be reached at [email protected]

Funding information

This work was partially supported by the Japan Society for the Promotion of Science (KAKENHI) Grant-in-Aid for Scientific Research (A) (21H04656) and (B) (20H02190), and the Japan Science and Technology Agency (JST) CREST (Grant No. JPMJCR21O1).

Researchers from Japan have developed novel complex-peptide hybrids, which can induce programmed cell death in apoptosis-resistant cancer cells

Inducing programmed cell death (PCD), such as apoptosis, is a widely used therapeutic option for the treatment of cancer. Unfortunately, many cancer cells become resistant to PCDs, and continue multiplying. In a new study, researchers from Tokyo University of Science synthesized new complex-hybrid compounds named triptycene-peptide hybrids (TPHs), which successfully induced a kind of PCD known as paraptosis in Jurkat cells—a type of lymphocytes. These paraptosis-inducing compounds can revolutionize cancer therapy in the future.

Apoptosis, a type of programmed cell death (PCD), is a biological process through which unwanted cells are eliminated in multicellular organisms. In most cells, certain proteins known as “caspases” trigger apoptosis. This process is especially important for the treatment of cancer, since inducing cell death in cancer cells can help in their elimination.

Other than apoptosis, several types of PCDs occur in cells, including paraptosis, necroptosis, and autophagy. Of these, paraptosis is the most recently identified type of PCD, which is caused by the influx of excess calcium in the cells, leading to cell death.

Cancer cells often become resistant to drugs that induce apoptosis and other types of PCDs. In such cases, inducing paraptosis, which is not dependent on caspases, could act as a promising anti-cancer treatment. Hence, the development of compounds that can induce paraptosis in cancer cells is crucial.

To this end, a team of researchers from the Tokyo University of Science, led by Prof. Shin Aoki in collaboration with Mr. Kohei Yamaguchi and Dr. Kenta Yokoi, conducted a study to develop novel complex-peptide hybrids with paraptosis-inducing potential. This study was made available online on 11 April 2022, and subsequently published in Volume 33 of the journal Bioconjugate Chemistry, on 20 April 2022.

“Previously, we synthesized an iridium complex-peptide hybrid compound and observed that it induced cell death in cancer cells, which was different from apoptosis. Since this compound was unlike other paraptosis-inducing compounds, we wanted to understand its mechanism of paraptosis induction. Our goal now is to synthesize new compounds and elucidate how they induce paraptosis in cells, before we share this crucial information with the public,” explains Prof. Aoki while discussing the team’s motivation behind this study.

The newly synthesized compounds were composed of a triptycene core—an aromatic hydrocarbon—with two or three cationic peptides made of the amino acids lysine and glycine (represented as KKKGG) through a C8 alkyl linker chain, at different positions of the triptycene units. As a result, three triptycene core hybrids (TPHs) were produced, namely, 5, syn-6, and anti-6.

The team subsequently performed experiments on Jurkat cells, a type of immortalized human lymphocytes used in research, to understand the type of PCD that occurred in these cells on treatment with syn-6 and anti-6. They found that death in these cells was inhibited by carbonyl cyanide m-chlorophenyl hydrazone (CCCP) which is an uncoupling reagent and an inhibitor of mitochondrial calcium uptake, RuRed, which is an inhibitor of the mitochondrial calcium channel), and 2-aminoethoxydiphenyl borate (2-APB), which is an inhibitor of D-inositol-1,4,5-trisphosphate receptor. However, cell death was not inhibited by inhibitors of the other types of PCDs.

Hence, they ruled out autophagy, necroptosis, and apoptosis, confirming that paraptosis is a major PCD pathway induced by syn-6 and anti-6 in Jurkat cells.

“Studies have indicated that the TPHs syn-6 and anti-6 induce the transfer of excess calcium from the endoplasmic reticulum (ER) to mitochondria, resulting in a loss of mitochondrial membrane potential. It is very likely that these phenomena are strongly related with the fusion of the ER with the mitochondria, followed by cytoplasmic vacuolization, resulting in cell death,” said Prof. Aoki, when asked why these two TPHs were selected for the study. The TPHs syn-6, and anti-6 are more hydrophilic than other TPHs, which could also be a reason for their high paraptosis-inducing anti-cancer potential.

Through additional imaging experiments, the team detected the presence of cytoplasmic vacuolization, elevated mitochondrial calcium concentrations, and the degradation of the ER in Jurkat cells treated with syn-6 and anti-6.
Based on previous findings, the team hypothesized that in Jurkat cells as well, the influx of calcium in the mitochondria might be facilitated by the close proximity of the ER and the mitochondria. As expected, they found that the ER and mitochondrial membranes were attached to one another, facilitating direct transfer of calcium.

These findings confirmed that Jurkat cells treated with syn-6 and anti-6 had undergone programmed cell death, owing to paraptosis. They also provide crucial information for the design of compounds that can be used as therapeutic agents against cancer and other diseases.

Here’s hoping that these promising findings contribute to the development of effective therapy against the ever-evolving cancer cells.

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Reference

Title of original paper: Design, Synthesis, and Anticancer Activity of Triptycene–Peptide Hybrids that Induce Paraptotic Cell Death in Cancer Cells

Journal: Bioconjugate Chemistry

DOI: https://doi.org/10.1021/acs.bioconjchem.2c00076

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 Shin Aoki from Tokyo University of Science

Professor Shin Aoki is a professor of cancer biology & research at the Faculty of Pharmaceutical Sciences, Tokyo University of Science. He is engaged in the study of medicinal chemistry, pharmacology, bioinorganic chemistry, and supramolecular chemistry. He is a recipient of the Award of Japan Society of Coordination Chemistry for Young Scientists (1999); the AJINOMOTO Award in Synthetic Organic Chemistry, Japan (2001); and the Pharmaceutical Society of Japan Award for Young Scientists (2002). He is a graduate from the University of Tokyo with B. S. (1986), M.S. (1988), and Ph.D. (1992) degrees in pharmaceutical sciences. He holds a post doctorate degree from the Department of Chemistry, the Scripps Research Institute, USA.

Schiff base-metal complexes exhibit promising antibacterial and antioxidant properties. However, conventional methods for their preparation can be time-consuming. To reduce the reaction time and improve the quality and quantity of the products, researchers designed a new synthesis technique that uses microwave irradiation and methanol for the preparation of amino acid Schiff base copper complexes in just 10 minutes. The resulting products exhibit desirable properties, such as mild antioxidant activity and antibacterial activity against Escherichia coli.

Ever since their development in the late 19th century, Schiff bases have been a popular group of organic compounds, owing to their wide variety of desirable properties. The presence of both nitrogen and oxygen in their structure makes them versatile molecules with an array of applications, ranging from dyes and catalysts to environmental sensors and raw materials for chemical synthesis.

Recently, there has been growing interest in the biological activity of Schiff bases, as researchers have discovered that metal complex derivatives of Schiff bases can serve as antioxidant, antimicrobial, and anticancer agents. Among these compounds, studies have shown that amino acid Schiff base copper (Cu) complexes have the most promising antimicrobial properties; however, the reaction time taken to create these compounds can range from hours to days.

In a recent breakthrough published on 18 June 2022 in Applied Microbiology, a team of researchers led by Professor Takashiro Akitsu from the Tokyo University of Science reported a two-step synthesis procedure that produced amino acid Schiff base Cu (II) complexes within a mere 10 minutes! The team included Dr. Estelle Léonard and Dr. Antoine Fayeulle from ESCOM, TIMR (Integrated Transformations of Renewable Matter), Centre de Recherche Royallieu, University of Technology of Compiègne, France.

“Amino acid Schiff base Cu (II) complexes have the potential to be used as antimicrobial agents but their wider applications are being limited by conventional methods for synthesis that often takes several hours and sometimes days. With our research, we aim to overcome this challenge by making the synthesis process more facile,” comments Prof. Akitsu on the rationale behind their study.

The team used microwave irradiation to prepare these compounds, owing to its ability to greatly accelerate the reaction while providing controlled heating. This method also ensures higher yields, better purity, and fewer by-products. Additionally, they chose methanol as the solvent for the reactions. With a high loss tangent of 0.659, which determines the ability to convert microwave energy into heat, and a high microwave absorption rate, methanol was ideal for accelerating the reactions and lowered the global reaction time to 10 minutes.

To gauge the antibacterial properties of the compounds, the researchers tested them against various bacteria. They found that the one- and two-chlorine substituted complexes showed better action against bacteria, with remarkable activity against E. coli, than the molecules with no chlorine groups. The team also noted the presence of light antioxidant properties in the one- and two-chlorinated complexes. In the future, the team aims to check for the toxicity of these compounds toward kidney, liver, and skin cells.

This new synthesis technique minimizes the global reaction time, maximizes the reaction conditions, and produces high purity products with promising antibacterial activity. The insights from this study can be used as a framework for the development of fast and facile synthesis techniques for biologically active amino acid derivatives of Schiff base metal complexes. “Bacterial infectious diseases are a major threat to public health. Our study aims to contribute towards the improvement of health care systems in developing nations that are often affected by infectious epidemics,” concludes Prof Akitsu.

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Reference

Title of original paper: Synthesis, Identification and Antibacterial Activities of Amino Acid Schiff Base Cu(II) Complexes with Chlorinated Aromatic Moieties

Journal: Applied Microbiology

DOI: https://doi.org/10.3390/applmicrobiol2020032

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 Hokkaido. Established in 1881, the university has continually contributed to Japan’s development in science by 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 Takashiro Akitsu from Tokyo University of Science

Prof. Takashiro Akitsu is a professor in the Department of Chemistry, Faculty of Science, Tokyo University of Science (TUS), Japan. He graduated from Osaka University and obtained his Ph.D. in Physical and Inorganic Chemistry in 2000 and went on to study physical and bioinorganic chemistry at Stanford before moving to TUS. He joined the TUS as a Junior Associate Professor in 2008 and became a Professor in 2016. He has published 220 articles and book chapters and served as an editorial board member in many international peer-reviewed journals. His current research areas involve the study of imines, Schiff bases, coordination chemistry, and crystal structures.

Funding information

This research was funded by TIMR UTC‐ESCOM, and this work was supported by a

Grant‐in‐Aid for Scientific Research (A) KAKENHI (20H00336).

The novel terminator-assisted solid-phase complementary DNA amplification and sequencing (TAS-Seq) method provides high-precision data on gene expression

Single-cell RNA sequencing (scRNA-seq) is one of the most important methods to study biological function in cells, but it is limited by potential inaccuracies in the data it generates. Now, a research team from Japan has developed a new method called terminator-assisted solid-phase complementary DNA amplification and sequencing (TAS-Seq), which overcomes these limitations and provides higher-precision data than existing scRNA-seq platforms.

The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized the fields of medicine and biology by providing the ability to study the inner workings of thousands of cells at one go. But scRNA-seq methods are limited by potential inaccuracies in determining cell composition and inefficient complementary DNA (cDNA) amplification—a process by which a double-stranded DNA that ‘complements’ the single-stranded RNA is generated and replicated millions of times—by the commonly-used template-switching reaction.

Recently, a research team from Japan, led by Assistant Prof. Shigeyuki Shichino and Prof. Kouji Matsushima of Tokyo University of Science, has developed a new and improved technique for scRNA-seq. The new method, terminator-assisted solid-phase cDNA amplification and sequencing (TAS-Seq), uses simple materials and equipment to provide higher-precision scRNA-seq data than current, widely-used technologies. “Our technique, TAS-Seq, combines genetic detection sensitivity, robustness of reaction efficiency, and accuracy of cellular composition to enable us to capture important cellular information,” reveals Assistant Prof. Shichino. The study was published in Communications Biology on June 27, 2022. The research team also included Associate Prof. Satoshi Ueha of Tokyo University of Science, Prof. Taka-aki Sato of the University of Tsukuba, and Prof. Shinichi Hashimoto of Wakayama Medical University.

TAS-Seq uses a template independent enzyme for cDNA amplification called terminal transferase (TdT). But TdT is difficult to handle. To surmount this challenge, the research team included dideoxynucleotide phosphate (ddNTP) as a ‘terminator’ for the cDNA amplification reaction. “ddNTP spike-in, specifically dideoxycytidine phosphate (ddCTP), stops the excessive extension of polyN-tail by TdT in a stochastic manner, and greatly reduces the technical difficulties of the TdT reaction,” explains Assistant Prof. Shichino. TAS-Seq also uses a nanowell/bead-based scRNA-seq platform, which allows the isolation of single cells in tissue samples, thereby decreasing cell sampling bias and improving the accuracy of cell composition data.

The research team then verified the efficiency of TAS-Seq and compared it to the current, widely used scRNA-seq techniques, 10X Chromium V2 and Smart-seq2, using murine and human lung tissue samples. They found that TAS-Seq could not only detect more genes overall, but also identify more highly variable genes, when compared to major scRNA-seq platforms. Assistant Prof. Shichino says, “We found that TAS-Seq may outperform 10X Chromium V2 and Smart-seq2 in terms of gene detection sensitivity and gene drop-out rates, indicating that TAS-Seq might be one of the most sensitive high-throughput scRNA methods. We can detect genes across a wide range of expression levels more uniformly and also detect growth factor and interleukin genes more robustly.”

An added advantage of the new method is that TAS-Seq is less susceptible to batch effects. TAS-Seq data was also highly correlated with flow-cytometric data on the tissue samples, indicating that it can generate highly accurate cell composition data.

Speaking on the future, Assistant Prof. Shichino reveals, “We have already completed development of TAS-Seq2, an improved, extensively-optimized version of TAS-Seq. TAS-Seq2 has 1.5 to 2 times more sensitive gene detection in mouse spleen cells.” The research team has also established ImmunoGenetics, a venture company from Tokyo University of Science, to provide scRNA-seq services using TAS-Seq and TAS-Seq2.

scRNA-seq is an important tool for medical and biology researchers. The development of TAS-Seq and TAS-Seq2 will lead to the discovery of new therapeutic targets for diseases and advancements in the field of ‘spatial transcriptomics,’ which also relies on solid-phase cDNA synthesis. It will also accelerate the development of single-cell omics technology, thereby promoting our understanding of the principles of biology and disease development and progression.

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Reference

Title of original paper: TAS-Seq is a robust and sensitive amplification method for bead-based scRNA-seq

Journal: Communications Biology

DOI: https://doi.org/10.1038/s42003-022-03536-0

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 Assistant Professor Shigeyuki Shichino and Professor Kouji Matsushima from Tokyo University of Science

Assistant Prof. Shigeyuki Shichino is part of the Research Institute for Biomedical Sciences, Tokyo University of Science. His research focuses on system genome science, including transcriptome, single-cell, and interactome network, and experimental pathology, including lung fibrosis, macrophage/fibroblast biology, and single-cell RNA sequencing. He has published 21 papers.

Prof. Kouji Matsushima is part of the Research Institute for Biomedical Sciences, Tokyo University of Science. His research focuses on inflammation, immunology, and cancer immunotherapy. He was conferred a Lifetime Honorary Membership Award by the International Cytokine and Interferon Society in 2019. In 2021, he won the Takeda Prize for Medical Science.

The new method can be used to construct copolymers comprising different metal species, which have potential uses in catalysis and drug discovery

Polymers with different metal complexes in their side chains are thought to be promising high-performance materials with a wide variety of applications. However, conventional fabrication methods are not suitable for constructing such polymers because controlling their resulting metal composition is complicated. Recently, scientists from Japan have developed a method to overcome this limitation and successfully produce multimetallic copolymers, which can be used as building blocks to create future hybrid materials.

From plastics to clothes to DNA, polymers are everywhere. Polymers are highly versatile materials that are made of long chains of repeating units called monomers. Polymers containing metal complexes on their side chains have enormous potential as hybrid materials in a variety of fields. This potential only increases with the inclusion of multiple metal species into the polymers. But conventional methods of fabricating polymers with metal complexes are not appropriate for the construction of multimetallic polymers, because controlling the composition of metal species in the resulting polymer is complex.

Recently, a research team, led by Assistant Professor Shigehito Osawa and Professor Hidenori Otsuka from Tokyo University of Science, has proposed a new method of polymerization that can overcome this limitation. Dr. Osawa explains, “The usual method of preparing such complexes is to design a polymer with ligands (molecular ‘backbones’ that join together other chemical species) and then add the metal species to form complexes on it. But each metal has a different binding affinity to the ligand, which makes it complicated to control the resulting structure. By considering polymerizable monomers with complexes of different metal species, we can effectively control the composition of the resulting copolymer.” The study was made available online on April 1, 2022, and published in Volume 58, Issue 34 of Chemical Communications on April 30, 2022.

When the monomers that make up a polymer are polymers themselves, the polymer is called a copolymer. For their study, the scientists designed a dipicolylamine acrylate (DPAAc) monomer. DPA was chosen because it is an excellent metal ligand and has been used in various biochemical applications. They then polymerized DPAAc with zinc (Zn) and platinum (Pt) to form two polymer chains with metal complexes—DPAZn(II)Ac and DPAPt(II)Ac. They then copolymerized the two monomers. They found that they could not only successfully create a copolymer, but that they could also control its metal composition by varying the feeding composition of the monomers.

Then they applied this copolymer as a building block to fabricate nanoparticles using plasmid deoxyribonucleic acid (DNA) as a template. Plasmid DNA was chosen as a template because the two constituent monomers are known to bind to it. The formation of the resulting nanoparticle polymer complexes with DNA (polyplexes) was confirmed using high-resolution scanning tunneling electron microscopy and energy-dispersive X-ray spectroscopy.

This technique—now a patent-pending technology—can be extended to a novel method for fabricating intermetallic nanomaterials. “Intermetallic catalytic nanomaterials are known to have significant advantages over nanomaterials containing only a single metallic species,” says Dr. Osawa.

The polyplexes formed in the study are DNA-binding molecules, which indicates that they could be used to develop anti-cancer drugs and gene carriers. The proposed fabrication method will also lead to advances in catalysis that move away from precious metals like platinum. “These multimetallic copolymers can serve as building blocks for future macromolecular metal complexes of many varieties,” concludes Dr. Osawa.

The findings of this study are sure to have far reaching consequences in the field of polymer chemistry.

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Reference

Title of original paper: Controlled polymerization of metal complex monomers – fabricating random copolymers comprising different metal species and nano-colloids

Journal: Chemical Communications

DOI: https://doi.org/10.1039/D1CC07265J

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 Assistant Professor Shigehito Osawa from Tokyo University of Science

Shigehito Osawa obtained a PhD in Materials Engineering from the University of Tokyo, Japan, in 2016. He worked as a Research Scientist at the Kawasaki Institute of Industrial Promotion from 2016 to 2018. He joined Tokyo University of Science afterwards, where he now serves as Assistant Professor at the Department of Applied Chemistry. His research interests are in the fields of polymer materials and polymer chemistry. He has published 24 peer-reviewed papers and has patent-pending technology currently under review. He is currently a member of the Water Frontier Research Center (WaTUS).

 

Funding information

This work was financially supported by Grants-in-Aids for Early Carrier Scientists (JSPS KAKENHI Grant Number 20K15346 to Shigehito Osawa) from the Japanese Society of the Promotion of Science (JSPS).

The development of new thin semiconductor materials requires a quantitative analysis of a large amount of reflection high-energy electron diffraction (RHEED) data, which is time consuming and requires expertise. To tackle this issue, scientists from Tokyo University of Science identify machine learning techniques that can help automate RHEED data analysis. Their findings could greatly accelerate semiconductor research and pave the way for faster, energy efficient electronic devices.

The semiconductor industry has been growing steadily ever since its first steps in the mid-twentieth century and, thanks to the high-speed information and communication technologies it enabled, it has given way to the rapid digitalization of society. Today, in line with a tight global energy demand, there is a growing need for faster, more integrated, and more energy-efficient semiconductor devices.

However, modern semiconductor processes have already reached the nanometer scale, and the design of novel high-performance materials now involves the structural analysis of semiconductor nanofilms. Reflection high-energy electron diffraction (RHEED) is a widely used analytical method for this purpose. RHEED can be used to determine the structures that form on the surface of thin films at the atomic level and can even capture structural changes in real time as the thin film is being synthesized!

Unfortunately, for all its benefits, RHEED is sometimes hindered by the fact that its output patterns are complex and difficult to interpret. In virtually all cases, a highly skilled experimenter is needed to make sense of the huge amounts of data that RHEED can produce in the form of diffraction patterns. But what if we could make machine learning do most of the work when processing RHEED data?

A team of researchers led by Dr. Naoka Nagamura, a visiting associate professor at Tokyo University of Science (TUS) and a senior researcher of National Institute for Materials Science (NIMS), Japan, has been working on just that. In their latest study, published online on 09 June 2022 in the international journal Science and Technology of Advanced Materials: Methods, the team explored the possibility of using machine learning to automatically analyze RHEED data. This work, which was supported by JST-PRESTO and JST-CREST, was the result of joint research by TUS and NIMS, Japan. It was co-authored by Ms. Asako Yoshinari, Prof. Masato Kotsugi also from TUS, and Dr. Yuma Iwasaki from NIMS.

The researchers focused on the surface superstructures that form on the first atomic layers of clean single-crystal silicon (one of the most versatile semiconductor materials). depending on the amount of indium atoms adsorbed and slight differences in temperature. Surface superstructures are atomic arrangements unique to crystal surfaces where atoms stabilize in different periodic patterns than those inside the bulk of the crystal, depending on differences in the surrounding environment. Because they often exhibit unique physical properties, surface superstructures are the focus of much interest in materials science.

First, the team used different hierarchical clustering methods, which are aimed at dividing samples into different clusters based on various measures of similarity. This approach serves to detect how many different surface superstructures are present. After trying different techniques, the researchers found that Ward’s method could best track the actual phase transitions in surface superstructures.

The scientists then sought to determine the optimal process conditions for synthesizing each of the identified surface superstructures. They focused on the indium deposition time for which each superstructure was most extensively formed. Principal component analysis and other typical methods for dimensionality reduction did not perform well. Fortunately, non-negative matrix factorization, a different clustering and dimensionality reduction technique, could accurately and automatically obtain the optimal deposition times for each superstructure. Excited about these results, Dr. Nagamura remarks, “Our efforts will help automate the work that typically requires time-consuming manual analysis by specialists. We believe our study has the potential to change the way materials research is done and allow scientists to spend more time on creative pursuits.”

Overall, the findings reported in this study will hopefully lead to new and effective ways of using machine learning technique for materials science—a central topic in the field of materials informatics. In turn, this would have implications in our everyday lives as existing devices and technologies are upgraded with better materials. “Our approach can be used to analyze the superstructures grown not only on thin-film silicon single-crystal surfaces, but also metal crystal surfaces, sapphire, silicon carbide, gallium nitride, and various other important substrates. Thus, we expect our work to accelerate the research and development of next-generation semiconductors and high-speed communication devices,” concludes Dr. Nagamura.

We certainly hope to see more such discoveries in the future that can automate complex data analysis and ease the workload of scientists!

***

Reference

Title of original paper: Skill-agnostic analysis of reflection high-energy electron diffraction patterns for Si(111) surface superstructures using machine learning

Journal: Science and Technology of Advanced Materials: Methods

DOI: https://doi.org/10.1080/27660400.2022.2079942

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 Masato Kotsugi from Tokyo University of Science

Dr. Masato Kotsugi graduated from Sophia University, Japan, in 1996 and then received a PhD from the Graduate School of Engineering Science at Osaka University in 2001. He joined the Tokyo University of Science in 2015 as a lecturer and became a full Professor in the Department of Materials Creation Engineering in 2021. Prof. Kotsugi and students at his laboratory conduct cutting edge research on high-performance materials with the aim of creating a green energy society. He has published over 110 refereed papers and is currently interested in solid-state physics, magnetism, synchrotron radiation, and materials informatics.

About Dr. Naoka Nagamura from National Institute for Materials Science

Dr. Naoka Nagamura is a visiting Associate Professor at Tokyo University of Science, Japan and a senior researcher at the Research Center for Advanced Measurement and Characterization at National Institute for Materials Science, Japan. She obtained her Ph.D. from the University of Tokyo, Japan in 2011 and did a postdoctoral stint there from 2011–2013. Her research interests include graphene, synchrotron radiation X-ray analysis, operando analysis, imaging, photoemission spectroscopy, and surface and interface analysis. She has published 34 papers so far with over 500 citations to her credit.

Funding information

This study was supported by JSPS KAKENHI Grant No. 19H02561; JST-CREST Grant No. JPMJCR21O1; and JST-PRESTO Grant Nos. JPMJPR20T7 and JPMJPR17NB.

Hydrogen peroxide (H2O2) is an important chemical, with a wide variety of applications. However, the current method used to manufacture H2O2 is expensive and generates a considerable amount of waste, making it an unsustainable approach. In this study, a group of researchers from Japan produced H2O2 from waste coffee grounds and tea leaves, and then demonstrated its industrial use. Their novel method proved to be simple, cost-effective, and most importantly, sustainable.

Coffee and tea are two of the most popular beverages around the world. The extensive consumption of these drinks produces large amounts of coffee grounds and tea leaves, which are typically discarded as waste. These unused biomass resources, however, have the potential to produce several useful chemicals. Tea and coffee contain a group of compounds called polyphenols, which can produce hydrogen peroxide (H2O2).

H2O2 has a lot of industrial value; this chemical plays a critical role in the oxidation of several compounds. The oxidation process is typically catalyzed by an enzyme called P450 peroxygenase, but it can’t occur unless H2O2 is present. These oxidation reactions are used to produce many chemicals of note.

Now, H2O2 is currently produced through an unsustainable method called the anthraquinone process, which is not only energy-intensive but also produces a lot of waste, highlighting the need for a greener, environmentally friendly alternative. While there are other methods which use enzymes or light to produce H2O2, these are expensive because they require catalysts and additional reagents.

Keeping these issues in mind, a group of scientists from Japan—including Associate Professor Toshiki Furuya and Mr. Hideaki Kawana from Tokyo University of Science, and Dr. Yuki Honda from Nara Women’s University, Japan—has found an alternative way to produce H2O2. Their product comes from an unlikely source—the leftovers of brewed tea and coffee, called spent coffee grounds (SCG) or tea leaf residue (TLR)!

“Given their polyphenol content, we predicted that SCG and TLR could be used to produce hydrogen peroxide,” says Dr. Furuya. Proving their prediction to be true, their study—published in ACS Omega on June 1, 2022—details their successful production of H2O2 using these underutilized biomass resources.

The team’s production method involved adding coffee grounds and tea leaves to a sodium phosphate buffer, then incubating this solution while shaking it. In the presence of the buffer, SCG and TLR interacted with molecular oxygen to produce H2O2.

The team also explored the scope of using this H2O2 to synthesize other chemicals of industrial importance. The newly-synthesized H2O2 aided in the production of Russig’s blue. Moreover, in the presence of peroxygenase (an enzyme that catalyzes an oxidation reaction using H2O2), TLR- and SCG-derived H2O2 was allowed to react with a molecule called styrene to produce styrene oxide—which has several applications in medicine—and another useful compound, phenylacetaldehyde.

These results prove that the team’s new approach of using SCG and TLR to produce H2O2 proved to be simple, cost-effective, and environmentally friendly, compared to the traditional anthraquinone process. Hailing these promising results, Dr. Furuya says, “Our method can be used to produce hydrogen peroxide from materials that would otherwise have been discarded. This could further result in new ways to synthesize industrial chemicals like styrene oxide, opening up new applications for these unused biomass resources.”

These findings thus open up a new way towards the sustainable production of H2O2, from the most unexpected sources: tea and coffee waste!

***
Reference

Title of original paper: Sustainable Approach for Peroxygenase-Catalyzed Oxidation Reactions Using Hydrogen Peroxide Generated from Spent Coffee Grounds and Tea Leaf Residues

Journal: ACS Omega

DOI: https://doi.org/10.1021/acsomega.2c02186

Chondroitin sulfate proteoglycans (CSPGs), commonly obtained from salmon nasal cartilage, are a key ingredient of various health foods. As the popularity of health foods increases, scientists are searching for alternative sources of CSPGs. Now, researchers from Japan have analyzed the PGs and their CS structures in the head cartilage of 10 edible bony fishes, including sturgeons. Their findings point to several new fishes that can serve as alternatives to salmon as a source of CSPGs.

Aggrecan, a major component of proteoglycan (PG) having chondroitin sulfate (CS) in cartilaginous tissues, has become increasingly popular as an ingredient in health food. In fact, proteoglycans from salmon nasal cartilage demonstrate biological properties such as antiaging, inhibition of angiogenesis, and attenuation of inflammatory responses. Commercially available chondroitin sulfate proteoglycans (CSPGs) have only been prepared from salmon nasal cartilage. Although the head cartilage was found in other edible bony fishes, there is little information on the composition of core proteins and their CS structures in the head cartilage.

Now, in a new study published in the International Journal of Biology Macromolecules, a team of researchers led by Associate Professor Kyohei Higashi of Tokyo University of Science, and Dr. Naoshi Dohmae and Dr. Takehiro Suzuki of the RIKEN Center for Sustainable Resource Science tackles this question. “We found that composition of PGs and their CS structure in the skull of the Siberian sturgeon and Russian sturgeon were similar to that in the salmon nasal cartilage,” reports Dr. Higashi. The fishes for the study were provided by Mr. Atsuhi Nakamura from Miyazaki Prefectural Fisheries Research Institute. This study was made available online on March 23, 2022 and was published in Volume 208 of the journal on May 31, 2022.

All the fishes examined contained abundant CSPGs in the head cartilage. Comprehensive analysis of CS structure in PGs derived from 10 bony fishes revealed that the structure of CS derived from Perciformes were similar to that of CS derived from cartilage of terrestrial animals. On the other hand, the structure of CS from skull of sturgeons was similar to that of CS from salmon nasal cartilage. In addition, they also found that aggrecan, a major CSPG in the cartilaginous tissue, was conserved in 10 bony fishes. In fact, the aggrecan protein from LOC117428125 and LOC117964296 genes registered in the National Center for Biotechnology Information database was found to be abundant in the skull of sturgeons. Furthermore, compositions of other PGs, collagens, and matrix proteins in the skull of sturgeons were similar to that of salmon nasal cartilage.

Elaborating on the findings of this study, Dr. Kyohei Higashi says, “Head cartilage from bony fishes is an underutilized resource and is typically discarded after food processing. The PGs, especially from the sturgeon, are similar in CS structure to the salmon nasal cartilage, showing that the sturgeon has a lot of potential to be an alternative source of CSPGs for health food formulations.”

The researchers hope with further studies to evaluate the biological properties of sturgeon PG, bony fishes could become an important source for CS as well as PGs.

***

Reference

Title of original paper: Comprehensive analysis of chondroitin sulfate and aggrecan in the head cartilage of bony fishes: Identification of proteoglycans in the head cartilage of sturgeon

Journal: International Journal of Biological Macromolecules

DOI: https://doi.org/10.1016/j.ijbiomac.2022.03.125

 

 

Animals often use highly specific signals to warn their herd about approaching predators. Surprisingly, similar behaviors are also observed among plants.

Shedding more light on this phenomenon, Tokyo University of Science researchers have discovered one such mechanism. Using Arabidopsis thaliana as a model system, the researchers have shown that herbivore-damaged plants give off volatile chemical “scents” that trigger epigenetic modifications in the defense genes of neighboring plants. These genes subsequently trigger anti-herbivore defense systems.

In the wild, many species of animals, especially those with known predators, signal each other of imminent dangers using a variety of techniques, ranging from scent to sound. Now, thanks to multiple studies on the topic, we have reason to believe that plants, too, can sound an alarm under threat of an attack.

Prior studies have shown that when grown near mint plants, soybean and field mustard (Brassica rapa) plants display heightened defense properties against herbivore pests by activating defense genes in their leaves, as a result of “eavesdropping” on mint volatiles. Put simply, if mint leaves get damaged after a herbivore attack, the plants in their immediate vicinity respond by activating their anti-herbivore defense systems in response to the chemical signals released by the damaged mint plant. To understand this mechanism better, a team of researchers from multiple Japanese research institutes, including Tokyo University of Science, studied these responses in Arabidopsis thaliana, a model plant used widely in biological studies.

“Surrounding undamaged plants exposed to odors emitted from plants eaten by pests can develop resistance to the pests.

Although the induction of the expression of defense genes in odor-responsive plants is key to this resistance, the precise molecular mechanisms for turning the induced state on or off have not been understood. In this study, we hypothesized that histone acetylation, or the so-called epigenetic regulation, is involved in the phenomenon of resistance development,” explains Dr. Gen-ichiro Arimura, Professor at the Tokyo University of Science and one of the authors of the study. Their findings have recently been published in the journal Plant Physiology.

First, they exposed the plants to β-ocimene, a volatile organic compound often released by plants in response to attacks by herbivores like Spodoptera litura. Next, the researchers tried to determine the exact mechanism of action of volatile-chemical-activated plant defense.

The results were interesting—defense traits were induced in Arabidopsis leaves, presumably through “epigenetic” mechanisms, which refer to gene regulation that occurs because of external environmental influences. In this case, the volatile chemicals released by the damaged plants enhanced histone acetylation and the expression of defense gene regulators, including the ethylene response factor genes “ERF8” and “ERF104”. The team found a specific set of histone acetyltransferase enzymes (HAC1, HAC5, and HAM1) were responsible for the induction and maintenance of the anti-herbivore properties.

The researchers are ecstatic about their discovery of the role that epigenetics has to play in plant defense. According to them, the communication between plants via volatile compounds (known as the “talking plants” phenomenon) can potentially be applied to organic cultivation systems. This can increase the pest resistance of plants and effectively reduce our massive dependence on pesticides.

“The effective use of plants’ natural survival strategies in production systems will bring us closer to the realization of a sustainable society that simultaneously solves environmental and food problems,” concludes Dr. Arimura.

***

Reference

Title of original paper: Sustained defense response via volatile signaling and its epigenetic transcriptional regulation

Journal: Plant Physiology

DOI: https://doi.org/10.1093/plphys/kiac07About Professor Gen-ichiro Arimura from Tokyo University of Science

Dr. Gen-ichiro Arimura obtained his Ph.D. from Hiroshima University, Japan. He is serving as a Professor at the Tokyo University of Science’s Department of Biological Science and Technology. His primary research interest includes biological communications. His laboratory also conducts research on biological interaction networks and defense response systems in plants. Dr. Arimura has published over 60 refereed papers. He also has three patents to his credit.

Funding information

This work was financially supported in part by a Japan Society for the Promotion of Science (JSPS) KAKENHI (20H02951), JSPS -DST Joint Research Program (JPJSBP120217713), MEXT Grants-in-Aid for Scientific Research on Innovative Areas (20H04786 and 18H04786), and Japan Science and Technology Agency (JST) A-STEP (JPMJTM20D2), and Nagase Science and Technology Foundation to GA.