著者
Sooyeon KIM Latiefa KAMARULZAMAN Yuichi TANIGUCHI
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
pp.pjab.99.021, (Released:2023-09-06)

Studying the central dogma at the single-cell level has gained increasing attention to reveal hidden cell lineages and functions that cannot be studied using traditional bulk analyses. Nonetheless, most single-cell studies exploiting genomic and transcriptomic levels fail to address information on proteins that are central to many important biological processes. Single-cell proteomics enables understanding of the functional status of individual cells and is particularly crucial when the specimen is composed of heterogeneous entities of cells. With the growing importance of this field, significant methodological advancements have emerged recently. These include miniaturized and automated sample preparation, multi-omics analyses, and combined analyses of multiple techniques such as mass spectrometry and microscopy. Moreover, artificial intelligence and single-molecule detection technologies have advanced throughput and improved sensitivity limitations, respectively, over conventional methods. In this review, we summarize cutting-edge methodologies for single-cell proteomics and relevant emerging technologies that have been reported in the last 5 years, and we provide an outlook on this research field.
著者
Atsushi OHTSU Koichi GOTO Takayuki YOSHINO
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
pp.pjab.99.015, (Released:2023-08-09)

Cancer comprehensive genomic profiling (CGP) is a fundamental tool for promoting precision oncology in advanced solid tumors. In 2015, we launched the SCRUM-Japan platform for CGP test screening followed by enrollment in genomically-matched clinical trials. More than 30,000 tissue-based and 10,000 liquid-based CGP tests have already been performed for enrollment in a total of 127 industry-/investigator-initiated registration trials. So far, 12 new agents with 14 indications have achieved regulatory approval for health care coverage in Japan. Using the clinical-genomic database of this project, a new driver gene was recently discovered with a dramatic response to a genomically-matched agent. Liquid biopsies are a potentially powerful tool for establishing precision oncology. Our comparative study with tissue-based CGPs revealed the utility of liquid biopsy in terms of being less invasive, shorter turn-round time, and higher enrollment rate for genotype-matched treatment than tissue-based CGP in gastrointestinal cancers. Another major multilayer multi-omics study (MONSTAR-SCREEN-2) including whole exome/transcriptome tissue- and liquid-based analyses and multiplex immunohistochemistry, with artificial intelligence/machine learning was launched in 2020 for the purpose of novel biomarker and new oncology agent discovery/development in collaboration with 18 pharmaceutical companies.For detecting minimal/molecular residual disease (MRD) after surgery, post-surgical monitoring with tumor-informed liquid biopsy assays in association with two randomized controlled trials also started in 2020 (CIRCULATE-Japan). More than 5,000 patients have already been enrolled and the observational cohort study showed the clear utility of MRD monitoring for predicting recurrence, leading to changes in clinical practice in patient selection regarding who should receive adjuvant therapy in the near future.
著者
Satoshi KIDA
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.96, no.3, pp.95-106, 2020-03-11 (Released:2020-03-11)
参考文献数
87
被引用文献数
31

Memory retrieval is not a passive process. When a memory is retrieved, the retrieved memory is destabilized, similar to short-term memory just after learning, and requires memory reconsolidation to re-stabilize the memory. Recent studies characterizing destabilization and reconsolidation showed that a retrieved memory is not always destabilized and that there are boundary conditions that determine the induction of destabilization and reconsolidation according to certain parameters, such as the duration of retrieval and the memory strength and age. Moreover, the reconsolidation of contextual fear memory is not independent of memory extinction; rather, these memory processes interact with each other. There is an increasing number of findings suggesting that destabilization following retrieval facilitates the modification, weakening, or strengthening of the original memory, and the resultant updated memory is stabilized through reconsolidation. Reconsolidation could be targeted therapeutically to improve emotional disorders such as post-traumatic stress disorder and phobia. Thus, this review summarizes recent findings to understand the mechanisms and function of reconsolidation.
著者
Yasushi MIYASHITA
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.98, no.3, pp.93-111, 2022-03-11 (Released:2022-03-11)
参考文献数
113
被引用文献数
4

The cerebral cortex performs its computations with many six-layered fundamental units, collectively spreading along the cortical sheet. What is the local network structure and the operating dynamics of such a fundamental unit? Previous investigations of primary sensory areas revealed a classic “canonical” circuit model, leading to an expectation of similar circuit organization and dynamics throughout the cortex. This review clarifies the different circuit dynamics at play in the higher association cortex of primates that implements computation for high-level cognition such as memory and attention. Instead of feedforward processing of response selectivity through Layers 4 to 2/3 that the classic canonical circuit stipulates, memory recall in primates occurs in Layer 5/6 with local backward projection to Layer 2/3, after which the retrieved information is sent back from Layer 6 to lower-level cortical areas for further retrieval of nested associations of target attributes. In this review, a novel “dynamic multimode module (D3M)” in the primate association cortex is proposed, as a new “canonical” circuit model performing this operation.
著者
Hideki YORIMITSU Gregory J. P. PERRY
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.98, no.4, pp.190-205, 2022-04-11 (Released:2022-04-11)
参考文献数
83
被引用文献数
10

Biaryl synthesis continues to occupy a central role in chemical synthesis. From blockbuster drug molecules to organic electronics, biaryls present numerous possibilities and new applications continue to emerge. Transition-metal-catalyzed coupling reactions represent the gold standard for biaryl synthesis and the mechanistic steps, such as reductive elimination, are well established. Developing routes that exploit alternative mechanistic scenarios could give unprecedented biaryl structures and expand the portfolio of biaryl applications. We have developed metal-free C–H/C–H couplings of aryl sulfoxides with phenols to afford 2-hydroxy-2′-sulfanylbiaryls. This cascade strategy consists of an interrupted Pummerer reaction and [3,3] sigmatropic rearrangement. Our method enables the synthesis of intriguing aromatic molecules, including oligoarenes, enantioenriched dihetero[8]helicenes, and polyfluorobiaryls. From our successes in aryl sulfoxide/phenol couplings and a deeper understanding of sigmatropic rearrangements for biaryl synthesis, we have established related methods, such as aryl sulfoxide/aniline and aryl iodane/phenol couplings. Overall, our fundamental interests in underexplored reaction mechanisms have led to various methods for accessing important biaryl architectures.
著者
H. Kenji YOSHIHARA
出版者
日本学士院
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.84, no.7, pp.232-245, 2008-07-30 (Released:2008-07-30)
参考文献数
35
被引用文献数
5

This review article deals with a new element ‘nipponium’ reported by Masataka Ogawa in 1908, and with its scientific and science historical background. Ogawa positioned nipponium between molybdenum and ruthenium in the periodic table. From a modern chemical viewpoint, however, nipponium is ascribable to the element with Z=75, namely rhenium, which was unknown in 1908. The reasons for this corrected assignment of nipponium are (1) its optical spectra, (2) its atomic weight when corrected, (3) its relative abundance in molybdenite, the same being true with rhenium. Recently some important evidence was found among the Ogawa’s personal collection preserved by his family. Deciphering the X-ray spectra revealed that the measured spectra of the nipponium sample that Ogawa brought from University College, London clearly showed the presence of the element 75 (rhenium). Thus was resolved the mysterious story of nipponium, which had continued for almost a century. It is concluded that nipponium was identical to rhenium.(Communicated by Toshimitsu YAMAZAKI, M.J.A.)
著者
Yuji YAZAKI
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.93, no.6, pp.399-421, 2017-06-09 (Released:2017-06-12)
参考文献数
48
被引用文献数
1 2

In 1928, Klein and Nishina investigated Compton scattering based on the Dirac equation just proposed in the same year, and derived the Klein–Nishina formula for the scattering cross section of a photon. At that time the Dirac equation had the following unsettled conceptual questions: the negative energy states, its four-component wave functions, and the spin states of an electron. Hence, during their investigation struggles, they encountered various difficulties. In this article, we describe their struggles to derive the formula using the “Sangokan Nishina Source Materials” retained in the the Nishina Memorial Foundation.
著者
Toshio YANAGIDA Yoshiharu ISHII
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.93, no.2, pp.51-63, 2017-02-10 (Released:2017-02-10)
参考文献数
61
被引用文献数
4 13

Single molecule detection has contributed to our understanding of the unique mechanisms of life. Unlike artificial man-made machines, biological molecular machines integrate thermal noises rather than avoid them. For example, single molecule detection has demonstrated that myosin motors undergo biased Brownian motion for stepwise movement and that single protein molecules spontaneously change their conformation, for switching to interactions with other proteins, in response to thermal fluctuation. Thus, molecular machines have flexibility and efficiency not seen in artificial machines.
著者
Kumi YOSHIDA Kin-ichi OYAMA Tadao KONDO
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.97, no.2, pp.51-68, 2021-02-10 (Released:2021-02-10)
参考文献数
63
被引用文献数
5

Hydrangea (Hydrangea macrophylla) is a unique flower because it is composed of sepals rather than true petals that have the ability to change color. In the early 20th century, it was known that soil acidity and Al3+ content could intensify the blue hue of the sepals. In the mid-20th century, the anthocyanin component 3-O-glucosyldelphinidin (1) and the copigment components 5-O-caffeoylquinic, 5-O-p-coumaroylquinic, and 3-O-caffeoylquinic acids (2–4) were reported. Interestingly, all hydrangea colors from red to purple to blue are produced by the same organic components. We were interested in this phenomenon and the chemical mechanisms underlying hydrangea color variation. In this review, we summarize our recent studies on the chemical mechanisms underlying hydrangea sepal color development, including the structure of the blue complex, transporters involved in accumulation of aluminum ion (Al3+), and distribution of the blue complex and aluminum ions in living sepal tissue.
著者
Shuhei OKUBO
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.96, no.2, pp.50-69, 2020-02-10 (Released:2020-02-10)
参考文献数
77
被引用文献数
10

This report highlights the usefulness and applicability of various gravimetric methods for studying earthquakes and volcanic activities. A high-resolution gravity anomaly map of Japan reveals areas with very steep horizontal gradients, where potential seismic faults are likely to be buried. Such traditional geoprospecting is coupled with novel cosmic-ray radiography to produce a fine-resolution (<100 m) three-dimensional density structure of a volcano. On the other hand, temporal gravity changes provide invaluable information about the process of earthquake faulting, volcanic eruptions, caldera formation, etc. Specifically, in this report we present our previous work on gravity research for solid earth science: (1) the first detection of coseismic gravity changes, (2) the virtual visualization of the rising and falling of magma in a conduit of Asama volcano, and (3) the large-scale lateral movement of magma during the Miyake-jima eruption in 2000.
著者
Hirokazu KAWAGISHI
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.95, no.1, pp.29-38, 2019-01-11 (Released:2019-01-11)
参考文献数
29
被引用文献数
3 33

2-Azahypoxanthine (AHX, 1) and imidazole-4-carboxamide (ICA, 2) were isolated from a fairy-ring-forming fungus Lepista sordida. AHX was converted into a metabolite 2-aza-8-oxo-hypoxanthine (AOH, 3) in plants. It was found out that these three compounds, named as fairy chemicals (FCs), endogenously exist in plants and are biosynthesized via a new purine metabolic pathway. FCs provided tolerance to the plants against various stresses and regulated the growth of all the plants. In addition, FCs increased the yield of rice, wheat, and other crops in the greenhouse and/or field experiments.
著者
Tatsuro MATSUMOTO
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.58, no.8, pp.249-252, 1982 (Released:2006-10-10)
参考文献数
14
被引用文献数
1
著者
Takeshi TOKUDOME Kenji KANGAWA
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.95, no.8, pp.459-467, 2019-10-11 (Released:2019-10-11)
参考文献数
38
被引用文献数
15

Ghrelin, a growth hormone-releasing peptide first discovered in rat stomach in 1999, is a ligand for the growth hormone secretagogue receptor. It participates in the regulation of diverse processes, including energy balance and body weight maintenance, and appears to be beneficial for the treatment of cardiovascular diseases. In animal models of chronic heart failure, ghrelin improves cardiac function and remodeling; these findings have been recapitulated in human patients. In other animal models, ghrelin effectively diminishes pulmonary hypertension. Moreover, ghrelin administration early after myocardial infarction decreased the frequency of fatal arrhythmia and improved survival rate. In ghrelin-deficient mice, endogenous ghrelin protects against fatal arrhythmia and promotes remodeling after myocardial infarction. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system have not been fully elucidated, its beneficial effects appear to be mediated through regulation of the autonomic nervous system. Ghrelin is a promising therapeutic agent for cardiac diseases.
著者
Masamitsu FUTAI Ge-Hong SUN-WADA Yoh WADA Naomi MATSUMOTO Mayumi NAKANISHI-MATSUI
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.95, no.6, pp.261-277, 2019-06-11 (Released:2019-06-11)
参考文献数
87
被引用文献数
64

Vacuolar-type ATPase (V-ATPase), initially identified in yeast and plant vacuoles, pumps protons into the lumen of organelles coupled with ATP hydrolysis. The mammalian counterpart is found ubiquitously in endomembrane organelles and the plasma membrane of specialized cells such as osteoclasts. V-ATPase is also present in unique organelles such as insulin secretory granules, neural synaptic vesicles, and acrosomes of spermatozoa. Consistent with its diverse physiological roles and unique localization, the seven subunits of V-ATPase have 2–4 isoforms that are organelle- or cell-specific. Subunits of the enzyme function in trafficking organelles and vesicles by interacting with small molecule GTPases. During osteoclast differentiation, one of the four isoforms of subunit a, a3, is indispensable for secretory lysosome trafficking to the plasma membrane. Diseases such as osteopetrosis, renal acidosis, and hearing loss are related to V-ATPase isoforms. In addition to its role as an enzyme, V-ATPase has versatile physiological roles in eukaryotic cells.
著者
Shin-ichi MAKINO Naoki AMANO Masashi SUZUKI
出版者
日本学士院
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.75, no.10, pp.311-316, 1999 (Released:2006-10-17)
参考文献数
5
被引用文献数
3 4

A new method is described for printing nucleotide sequences by assembling square microcells, representing nucleotides, into blocks, and by differentiating micro-cells following a color code, a gray scale, etc., corresponding to the four types of nucleotides. By printing micro-cells, whose sides are close to 250μm, using a laser printer, the complete sequence of a genome of the size close to 1M bases can be printed in the space of full size of A4, without loosing any original information. By enlarging the print using a magnifying glass or a photo-copy machine, the original sequence can be reconstituted, visually or mechanically. Overall and regional characteristics of genomes (e.g. distribution of gene-coding regions) can be analyzed using a plot of this type. The scheme for classifying micro-cells can be modified, in order to present different types of information such as distribution of purines and pyrimidines or that of different types of dinucleotide combinations through the genome.
著者
Motohide TAMURA
出版者
日本学士院
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.92, no.2, pp.45-55, 2016-02-10 (Released:2016-02-10)
参考文献数
66
被引用文献数
3 20

The first convincing detection of planets orbiting stars other than the Sun, or exoplanets, was made in 1995. In only 20 years, the number of the exoplanets including promising candidates has already accumulated to more than 5000. Most of the exoplanets discovered so far are detected by indirect methods because the direct imaging of exoplanets needs to overcome the extreme contrast between the bright central star and the faint planets. Using the large Subaru 8.2-m Telescope, a new high-contrast imager, HiCIAO, and second-generation adaptive optics (AO188), the most ambitious high-contrast direct imaging survey to date for giant planets and planet-forming disks has been conducted, the SEEDS project. In this review, we describe the aims and results of the SEEDS project for exoplanet/disk science. The completeness and uniformity of this systematic survey mean that the resulting data set will dominate this field of research for many years.
著者
Taro KUSAGAYA Hiroyuki K. M. TANAKA
出版者
日本学士院
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.91, no.9, pp.501-510, 2015-11-11 (Released:2015-11-11)
参考文献数
30
被引用文献数
21

In conventional muography observations using two detectors for muon tracking, the accidental coincidence of vertical electromagnetic showers generates identical trajectories to the muon tracks. Although muography has favorable properties, which allow direct density measurements inside a volcano, the measured density is lower than the actual value due to these fortuitous trajectories. We performed muography of Usu volcano, and confirmed that, in comparison with a use of two detectors, background noise levels were reduced by more than one order of magnitude using seven detectors for selecting linear trajectories. The resultant muographic image showed a high-density region underneath the central region of Usu volcano. This picture is consistent with the magma intrusion model proposed in previous studies. To clarify the three-dimensional location and actual size of the detected high-density body, multidirectional muographic measurements are necessary.
著者
Seiya UYEDA
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.89, no.9, pp.391-400, 2013-11-11 (Released:2013-11-11)
参考文献数
43
被引用文献数
22 29

Japan’s National Project for Earthquake Prediction has been conducted since 1965 without success. An earthquake prediction should be a short-term prediction based on observable physical phenomena or precursors. The main reason of no success is the failure to capture precursors. Most of the financial resources and manpower of the National Project have been devoted to strengthening the seismographs networks, which are not generally effective for detecting precursors since many of precursors are non-seismic. The precursor research has never been supported appropriately because the project has always been run by a group of seismologists who, in the present author’s view, are mainly interested in securing funds for seismology — on pretense of prediction. After the 1995 Kobe disaster, the project decided to give up short-term prediction and this decision has been further fortified by the 2011 M9 Tohoku Mega-quake. On top of the National Project, there are other government projects, not formally but vaguely related to earthquake prediction, that consume many orders of magnitude more funds. They are also un-interested in short-term prediction. Financially, they are giants and the National Project is a dwarf. Thus, in Japan now, there is practically no support for short-term prediction research. Recently, however, substantial progress has been made in real short-term prediction by scientists of diverse disciplines. Some promising signs are also arising even from cooperation with private sectors.(Contributed by Seiya Uyeda, M.J.A.)