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Mt. Fuji is an active basaltic volcano near the Tokyo metropolitan area; future eruptions could thus have serious nationwide impacts. To better understand recent volcanism at Fuji Volcano, we here clarify temporal variations of eruption rate and magma composition since 5.6 ka based on time-series volumetric and geochemical data of eruptive products in a new stratigraphic sequence. Volcanic activity during the studied period consisted of (i) the emission of many lava flows that formed a new volcanic edifice between 5.6 and 3.45 ka, (ii) a period dominated by explosive events both at the summit and on the flanks of the volcano between 3.45 and 2.25 ka, and (iii) a period dominated by flank fissure eruptions since 2.25 ka. The eruption rate (dense-rock equivalent, DRE) was 3.5 km3 DRE/kyr during the edifice-building period, decreased to 0.8 km3 DRE/kyr during the explosive period, and then increased to 2.0 km3 DRE/kyr since 1.5 ka. Erupted magmas were dominantly basaltic and geochemically similar through time, except for increased Sr contents and decreased Ca/Sr ratios during the explosive period. Similarly, the geochemical properties of the parental magmas did not change greatly, although the Sr contents and Ca/Sr ratios of magmas erupted during the explosive period reflect the delayed fractionation of plagioclase due to the increased water contents of the parental magmas at that time.

We investigate the influence of polymer molecular weight on the properties of silver–methylcellulose (Ag–MC) nanocomposite films synthesized by the irradiation of a CO2 laser. Although the reduction power of MC with a smaller molecular weight turns out to be stronger than that with a larger molecular weight in the solution phase, we do not see such a clear difference when MC is in the matrix phase. For the 30 s irradiation at the laser power of 0.8 W, the size of Ag nanoparticles (NPs) in the two types of MC matrix is similar, and it is about 30 nm. However, for the longer irradiation time at the same laser power, aggregation of Ag NPs set in, and it is more serious for the Ag–MC film with MC of larger molecular weight. We also carry out the antibacterial test with the Ag–MC films, and find that the Ag–MC film synthesized at the lower laser power and shorter irradiation time generally exhibits a stronger antibacterial effect.

The Rho family small GTPases mediate cell responses through actin cytoskeletal rearrangement. We previously reported that PLEKHG2, a Rho-specific guanine nucleotide exchange factor, is regulated via interaction with several proteins. We found that PLEKHG2 interacted with non-receptor tyrosine kinase ABL1, but the cellular function remains unclear. Here, we show that the interaction between PLEKHG2 and ABL1 attenuated the PLEKHG2-induced serum response element-dependent gene transcription in a tyrosine phosphorylation-independent manner. PLEKHG2 and ABL1 were co-localized and accumulated within cells co-expressing PLEKHG2 and ABL1. The cellular fractionation analysis suggested that the accumulation involved actin cytoskeletal reorganization. We also revealed that the co-expression of PLEKHG2 with ABL1, but not BCR-ABL, suppressed cell growth and synergistically enhanced NF-κB-dependent gene transcription. The cell growth suppression was canceled by co-expression with IκBα, a member of the NF-κB inhibitor protein family. This study suggests that the interaction between PLEKHG2 and ABL1 suppresses cell growth through intracellular protein accumulation via the NF-κB signaling pathway.

Many methods for modification of an oligonucleotide with a peptide have been developed to apply for the therapeutic and diagnostic applications or for the assembly of nanostructure. We have developed a method for the construction of receptor-based fluorescent sensors and catalysts using the ribonucleopeptide (RNP) as a scaffold. Formation of a covalent linkage between the RNA and the peptide subunit of RNP improved its stability, thereby expanding the application of functional RNPs. A representative method was applied for the formation of Schiff base or dihydroxy-morpholino linkage between a dialdehyde group at the 3&prime, end of sugar-oxidized RNA and a hydrazide group introduced at the C-terminal of a peptide subunit through a flexible peptide linker. In this report, we investigated effects of the solution pH and contribution of the RNA and peptide subunits to the conjugation reaction by using RNA and peptide mutants. The reaction yield reached 90% at a wide range of solution pH with reaction within 3 h. The efficient reaction was mainly supported by the electrostatic interaction between the RNA subunit and the cationic peptide subunit of the RNP scaffold. Formation of the RNP complex was verified to efficiently promote the reaction for construction of the RNA-peptide conjugate.

The GCOM-C (SHIKISAI) satellite was developed to understand the mechanisms of global climate change. The Second-generation Global Imager (SGLI) onboard GCOM-C is an optical sensor observing wavelengths from 380 nm to 12.0 μm in 19 bands. One of the notable features is that the resolution of the 1.63-, 10.8-, and 12.0-µm bands is 250 m, with an observation frequency of 2-3 days. To investigate the effective use and potential of the 250-m resolution of these SGLI bands in the study of eruptive activities, we analyzed four practical cases. As an example of large-scale effusive activity, we studied the 2018 Kilauea eruption. By analyzing the series of 10.8-μm band images using cumulative thermal anomaly maps, we could observe that the lava effused on the lower East Rift Zone, initially flowed down the southern slope to the sea, and then moved eastward. As an example of lava dome growth and generation of associated pyroclastic flows, the activity at Sheveluch between December 2018 and December 2019 was analyzed. The 1.63- and 10.8-µm bands were shown to be suitable for observing growth of the lava dome and occurrence of pyroclastic flows, respectively. We found that the pyroclastic flows occurred during periods of rapid lava dome expansion. For the study of an active crater lake, the activity of Ijen during 2019 was analyzed. The lake temperature was found to rise rapidly in mid-May and reach 38 °C in mid-June. We also analyzed the intermittent activities of small-scale Vulcanian eruptions at Sakurajima in 2019. The 1.63-µm band was useful for detecting activities that are associated with Vulcanian eruptions. Analytical results for these case studies demonstrated that the GCOM-C SGLI images are beneficial for observing various aspects of volcanic activity, and their real-time use may contribute to reducing eruption-related disasters.

The GCOM-C (SHIKISAI) satellite was developed to understand the mechanisms of global climate change. The Second-generation Global Imager (SGLI) onboard GCOM-C is an optical sensor observing wavelengths from 380 nm to 12.0 µm in 19 bands. One of the notable features is that the resolution of the 1.63-, 10.8-, and 12.0-µm bands is 250 m, with an observation frequency of 2–3 days. To investigate the effective use and potential of the 250-m resolution of these SGLI bands in the study of eruptive activities, we analyzed four practical cases. As an example of large-scale effusive activity, we studied the 2018 Kilauea eruption. By analyzing the series of 10.8-µm band images using cumulative thermal anomaly maps, we could observe that the lava effused on the lower East Rift Zone, initially flowed down the southern slope to the sea, and then moved eastward. As an example of lava dome growth and generation of associated pyroclastic flows, the activity at Sheveluch between December 2018 and December 2019 was analyzed. The 1.63- and 10.8-µm bands were shown to be suitable for observing growth of the lava dome and occurrence of pyroclastic flows, respectively. We found that the pyroclastic flows occurred during periods of rapid lava dome expansion. For the study of an active crater lake, the activity of Ijen during 2019 was analyzed. The lake temperature was found to rise rapidly in mid-May and reach 38 °C in mid-June. We also analyzed the intermittent activities of small-scale Vulcanian eruptions at Sakurajima in 2019. The 1.63-µm band was useful for detecting activities that are associated with Vulcanian eruptions. Analytical results for these case studies demonstrated that the GCOM-C SGLI images are beneficial for observing various aspects of volcanic activity, and their real-time use may contribute to reducing eruption-related disasters.

Receptor-based fluorescent sensors are the representative tool for quantitative detection of target ligands. The high substrate-selectivity originated from biomacromolecule receptor is one of the advantages of this tool, but a laborious trial and error is usually required to construct sensors showing satisfactory fluorescence intensity changes without diminishing the function of parent receptor. Ribonucleopeptide (RNP) provides a scaffold of fluorescent sensors to improve such issues. RNP receptors for the ligand of interest are constructed by applying in vitro selection for RNA-derived RNP library. Simple modification of the N-terminal of peptide in RNP by an appropriate fluorophore converts the RNP receptor into the fluorescent sensor with retaining the affinity and selectivity for the substrate. In this chapter, we introduce the protocols for construction of fluorescent RNP sensors through selection from a library of fluorophore-modified RNP complex or by a structure-based modular design. Furthermore, we describe the application of covalently linked RNP sensors for simultaneous detection of multiple ligands.

Rho family small GTPases (Rho) regulate various cell motility processes by spatiotemporally controlling the actin cytoskeleton. Some Rho-specific guanine nucleotide exchange factors (RhoGEFs) are regulated via tyrosine phosphorylation by Src family tyrosine kinase (SFK). We also previously reported that PLEKHG2, a RhoGEF for the GTPases Rac1 and Cdc42, is tyrosine-phosphorylated by SRC. However, the details of the mechanisms by which SFK regulates RhoGEFs are not well understood. In this study, we found for the first time that PLEKHG1, which has very high homology to the Dbl and pleckstrin homology domains of PLEKHG2, activates Cdc42 following activation by FYN, a member of the SFK family. We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1. We also found that the region containing the Src homology 3 and Src homology 2 domains of FYN is required for this interaction. Finally, we demonstrated that tyrosine phosphorylation of Tyr-720 and Tyr-801 in PLEKHG1 is important for the activation of PLEKHG1. These results suggest that FYN is a regulator of PLEKHG1 and may regulate cell morphology through Rho signaling via the interaction with and tyrosine phosphorylation of PLEKHG1.

The practical application of biosensors can be determined by evaluating the sensing ability of fluorophore-modified derivatives of a receptor with appropriate recognition characteristics for target molecules. One of the key determinants for successfully obtaining a useful biosensor is wide variation in the fluorophores attached to a given receptor. Thus, using a larger fluorophore-modified receptor library provides a higher probability of obtaining a practically useful biosensor. However, no effective method has yet been developed for constructing such a diverse library of fluorophore-modified receptors. Herein, we report a method for constructing fluorophore-modified receptors by using a chemical library of synthetic fluorophores with a thiol-reactive group. This library was converted into a library of fluorophore-modified adenosine-binding ribonucleopeptide (RNP) receptors by introducing the fluorophores to the Rev peptide of the RNP complex by alkylation of the thiol group. This method enabled the construction of 263 fluorophore-modified ATP-binding RNP receptors and allowed the selection of suitable receptor-based fluorescent sensors that target ATP.

PLEKHG2 is a Gβγ- and Gαs-dependent guanine nucleotide exchange factor for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways such as those for actin cytoskeletal reorganization and serum response element (SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the other FHL family members and found that the FHL1A specifically regulate the PLEKHG2 activity. Moreover, FHL1A further enhanced Gβγ- and PLEKHG2-induced SRE-dependent gene transcription, whereas FHL1A partially restored the attenuated PLEKHG2-induced SRE-dependent gene transcription by Gαs. Our results suggest that FHL1A specifically interacts with PLEKHG2 to regulate a function of PLEKHG2 that is modified by the interaction of Gβγ and Gαs.

Highly selective fluorescent sensors for ATP and ADP were constructed from RNA aptamers by applying a modular design of a ribonucleopeptide scaffold. These sensors allow facile and quantitative detection of ATP and ADP simultaneously in a solution and enable monitoring of the time-course changes of ATP and ADP concentrations in an enzymatic reaction.

It is well known that Rho family small GTPases (Rho GTPase) has a role of molecular switch in intracellular signal transduction. The switch cycle between GTP-bound and GDP-bound state of Rho GTPase regulates various cell responses such as gene transcription, cytoskeletal rearrangements, and vesicular trafficking. Rho GTPase-specific guanine nucleotide exchange factors (RhoGEFs) are regulated by various extracellular stimuli and activates Rho GTPase such as RhoA, Rac1, and Cdc42. The molecular mechanisms that regulate RhoGEFs are poorly understood. Our studies reveal that Dbl's big sister (DBS), a RhoGEF for Cdc42 and RhoA, is phosphorylated at least on tyrosine residues at 479, 660, 727, and 926 upon stimulation by SRC signaling and that the phosphorylation at Tyr-660 is particularly critical for the serum response factor (SRF)-dependent transcriptional activation of DBS by Ephrin type-B receptor 2 (EPHB2)/SRC signaling. In addition, our studies also reveal that the phosphorylation of Tyr-479 and Tyr-660 on DBS leads to the actin cytoskeletal reorganization by EPHB2/SRC signaling. These findings are thought to be useful for understanding pathological conditions related to DBS such as cancer and non-syndromic autism in future.

Recent development in the field of structural DNA nanotechnology has enabled the controlled self-assembly of biomacromolecules and nanomaterials. The precise and programmable base pairing of DNA is utilized to provide fully addressable nanoarchitectures of various shapes and geometries as ideal scaffolds to position the molecules of interest with nanometer-level precision. Proteins are particularly interesting class of molecules to assemble because of their huge functional variability. Although various methods to assemble proteins of interest (POI) on the DNA scaffold have been applied, a general methodology to assemble various kinds of proteins in their functional forms remains to be established. In this chapter, typical protein–DNA conjugation methods are intensively overviewed to reveal their characteristics. Among them, the recently developed DNA-binding–based adaptors have the potential to be an ideal protein–DNA conjugation method, and to locate several kinds of POIs at desired positions on the DNA scaffold with orthogonality and fast reaction kinetics to realize quantitative loading yields. By using a series of DNA-binding adaptors, an enzyme cascade reaction system was constructed on the DNA scaffold. The potential of DNA-binding adaptors as the ideal adaptor for covalently cross-linking multiple proteins to defined positions of DNA nanostructures was described from the kinetic aspect of reaction.

Recent studies argued that unconscious visual information could access the working memory, however, it is still unclear whether the central executive could be activated unconsciously. We investigated, using a delayed match-to-sample task, whether the central executive is an unconscious process. In the experiment of the present study, participants were asked to compare the locations of two given visual targets. Both targets (or one of the two targets, depending on the experimental condition) were masked by a visual masking paradigm. The results showed an above-chance-level performance even in the condition that participants compared two unconscious targets. However, when the trials with the non-visual conscious experience of the target were removed from the analysis, the performance was no longer significantly different from chance level. Our results suggest that the central executive could be activated unconsciously by some level of stimulus signal, that is still below the threshold for a subjective report.

Summary What is known and objective We evaluated the effectiveness of warning letters published by the pharmaceutical regulatory agency in Japan on communication of drug safety and risk by quantitative analysis of the national health insurance claims database (NHICD). We then explored what factors may have affected risk communication. Methods We measured the implementation rate of the hepatitis virus-monitoring test among methotrexate (MTX)-treated patients; a warning letter had been issued regarding the use of MTX, as it apparently activates the hepatitis virus. Data from the NHICD, which include 99·3% of Japanese residents, were used. A total of 4 933 481 patients with rheumatoid arthritis (RA) (January–June, 2010) were the focus of this study. Results The implementation rate of the hepatitis virus-monitoring test increased from 1·4% before to 1·8% after the warning letter announcement. Logistic regression analysis suggested that the installation of a drug information management room is one of the important factors affecting risk communication. Further analysis revealed that the hepatitis virus monitoring rates in hospitals without drug information management rooms increased from 2·3% to 4·1% due to the issue of the warning letter. What is new and conclusion The warning letter from the regulatory agency plays an important role in risk communication in hospitals without drug information management rooms.

Functional screening of structurally diverse libraries consisting of proteins or nucleic acids is an effective method to obtain receptors or aptamers with unique molecular recognition characteristics. However, further modification of these selected receptors to exert a newly desired function is still a challenging task. We have constructed a library of structurally diverse ribonucleopeptides (RNPs) that are modified with a catalytic group, in which the catalytic group aligns with various orientations against the ATP binding pocket of RNA subunit. As a proof-of-principle, the screening of the constructed RNP library for the catalytic reaction of ester hydrolysis was successfully carried out. The size of both the substrate-binding RNA library and the catalytic group modified peptide library are independently expandable, and thus, the size of RNPs library could be enlarged by a combination of these two subunits. We anticipate that the library of functionalized and structurally diverse RNPs would be expanded for various other catalytic reactions.

Long-distance lateral magma transport away from volcanic centers in island arcs is emerging as a common phenomenon where the regional stress regime is favorable. It should also be recognized as an important factor in the construction and growth of island arcs, and a potential trigger for devastating eruptions. In this contribution, we report on recent investigations into the magma dynamics of Izu-Oshima volcano, an active basaltic volcano with an extensive fissure system. Izu-Oshima is flanked by numerous, subparallel NW–SE trending submarine ridges extending up to 22 km to the NW and the SE from the central vent. During a recent submersible survey we have identified that these ridges are fissures which erupted basaltic spatter and lava flows. Furthermore, lavas are petrographically similar along each ridge, while there are noticeable differences between ridges. The subparallel ridges are observed to transect a series of seamounts – the Izu-Tobu monogenetic volcanoes – which are dispersed across this area of the rear-arc. However, there are consistent petrographic and chemical differences between these seamounts and the ridges, indicating that they have different magma sources, yet, they are essentially bounding each other in dive tracks. The most appropriate scenario for their development is one where the Izu-Tobu Volcanoes are fed by an “in-situ” underlying source, while the NW–SE ridges are fed by lateral magma transport from Izu-Oshima. Magma erupted from each ridge is of a consistent geochemistry along its length, but has experienced crystal fractionation and some plagioclase accumulation. Compositions of the ridges are also very similar to lavas from the subaerial cones that can be traced down the flanks of Izu-Oshima. This implies that pairs of subaerial cones and submarine ridges represent the locus of magma transport events away from the storage system beneath Izu-Oshima. Hence, magma from this crustal reservoir moved upward to feed the on-edifice cones, as well as laterally to supply submarine fissures and dykes to a distance of 22 km.

Cellular metabolism involves complex sequences of organized enzymatic reactions, known as metabolic pathways, that convert substrates into readily usable materials. In nature, these enzymatic complexes are organized in a well-defined manner so that the cascade reactions are more rapid and efficient than they would be if the enzymes were randomly distributed in the cytosol. Development of artificial enzyme cascades that resemble nature's organization of sequentially assembled enzymes is of current interest due to its potential applications, from diagnostics to the production of high-value chemicals. Nucleic acids and their nanostructures have been used to organize enzyme cascades and have been shown to enhance the efficiencies and rates of sequential reactions. Here we summarize the recent progress in the development of artificial enzyme cascades and sequential reactions by arranging enzymes on various DNA/RNA templates and discuss the future directions of this research endeavour.

A GTP aptamer was converted to a modular fluorescent GTP sensor by conjugation of RRE (Rev responsive element) RNA and successive complex formation with a fluorophore-modified Rev peptide. Structural changes associated with substrate binding in the RNA aptamer were successfully transduced into changes in fluorescence intensity because of the modular structure of ribonucleopeptides. A simple modular strategy involving conjugation of a fluorophore-modified ribonucleopeptide to the stem region of an RNA aptamer deduced from secondary structural information helps produce fluorescent sensors, which allow tuning of excitation and detection wavelengths through the replacement of the fluorophore at the N-terminal of the Rev peptide.

Helicopter-borne aeromagnetic surveys at two different times separated by three years were conducted to better understand the shallow subsurface structure of the Vulcano and Lipari volcanic complex, Aeolian Islands, southern Italy, and also to monitor the volcanic activity of the area. As there was no meaningful difference between the two magnetic datasets to imply an apparent change of the volcanic activity, the datasets were merged to produce an aeromagnetic map with wider coverage than was given by a single dataset. Apparent magnetisation intensity mapping was applied to terrain-corrected magnetic anomalies, and showed local magnetisation highs in and around Fossa Cone, suggesting heterogeneity of the cone. Magnetic modelling was conducted for three of those magnetisation highs. Each model implied the presence of concealed volcanic products overlain by pyroclastic rocks from the Fossa crater. The model for the Fossa crater area suggests a buried trachytic lava flow on the southern edge of the present crater. The magnetic model at Forgia Vecchia suggests that phreatic cones can be interpreted as resulting from a concealed eruptive centre, with thick latitic lavas that fill up Fossa Caldera. However, the distribution of lavas seems to be limited to a smaller area than was expected from drilling results. This can be explained partly by alteration of the lavas by intense hydrothermal activity, as seen at geothermal areas close to Porto Levante. The magnetic model at the north-eastern Fossa Cone implies that thick lavas accumulated as another eruption centre in the early stage of the activity of Fossa. Recent geoelectric surveys showed high-resistivity zones in the areas of the last two magnetic models.

Hyperphosphorylation of the microtubule-associated protein tau is believed to play a crucial role in the neurofibrillary tangles formation in Alzheimer’s disease brain. In this study, fibril formation of peptides containing the critical sequences for tau aggregation VQIINK and a plausible serine phosphorylation site of tau at its C-terminal was investigated. All the peptides formed fibrils with the typical cross-b structural core. However, stability of the fibrils was highly sensitive to the pH conditions for the phosphorylated VQIINK peptide, suggesting a regulatory role of phosphorylation for the amyloid-formation of tau.

A noncovalent RNA complex embedding an aptamer function and a fluorophore-labeled peptide affords a fluorescent ribonucleopeptide (RNP) framework for constructing fluorescent sensors. By taking an advantage of the noncovalent properties of the RNP complex, the ligand-binding and fluorescence characteristics of the fluorescent RNP can be independently tuned by taking advantage of the nature of the RNA and peptide subunits, respectively. Fluorescent sensors tailored for given measurement conditions, such as a detection wavelength and a detection concentration range for a ligand of interest can be easily identified by screening of fluorescent RNP libraries. The noncovalent configuration of a RNP becomes a disadvantage when the sensor is to be utilized at very low concentrations or when multiple sensors are applied to the same solution. Here, we report a strategy to convert a fluorescent RNP sensor in the noncovalent configuration into a covalently linked stable fluorescent RNP sensor. This covalently linked fluorescent RNP sensor enabled ligand detection at a low sensor concentration, even in cell extracts. Furthermore, application of both ATP and GTP sensors enabled simultaneous detection of ATP and GTP by monitoring each wavelength corresponding to the respective sensor. Importantly, when a fluorescein-modified ATP sensor and a pyrene-modified GTP sensor were co-incubated in the same solution, the ATP sensor responded at 535 nm only to changes in the concentration of ATP, whereas the GTP sensor detected GTP at 390 nm without any effect on the ATP sensor. Finally, simultaneous monitoring by these sensors enabled real-time measurement of adenosine deaminase enzyme reactions.