Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
99 巻, 8 号
選択された号の論文の6件中1~6を表示しています
Review series to celebrate our 100th volume
Reviews
  • Atsushi OHTSU, Koichi GOTO, Takayuki YOSHINO
    2023 年 99 巻 8 号 p. 241-253
    発行日: 2023/10/11
    公開日: 2023/10/11
    [早期公開] 公開日: 2023/08/09
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    We launched SCRUM-Japan platform for the cancer genome profiling (CGP) test screening followed by the enrollment to genomically-matched clinical trials in 2015. More than 30,000 tissue-based and 10,000 liquid-based CGP tests have already been performed for enrolling to a total of 127 industry-/investigator-initiated registration trials, which resulted in regulatory approvals of 12 new agents with 14 indications in Japan. Using the clinical-genomic database, a new driver gene was recently discovered with dramatic response by genomically-matched agent. Our comparative study with tissue-based CGPs revealed more usefulness of liquid biopsy in terms of less invasive manner, shorter turn-round time, and higher enrollment rate for matched treatments than tissue-based in gastrointestinal cancers. For detecting minimal/molecular residual disease (MRD) after surgery, post-surgical monitoring with tumor-informed liquid biopsy assay in association with two randomized control trials have also started in 2020 (CIRCULATE-Japan). The observational cohort study showed obvious efficacy of the MRD monitoring for predicting recurrence, leading to change clinical practice in patient selection who should receive adjuvant therapy in the near future.

  • Haruo KASAI
    2023 年 99 巻 8 号 p. 254-305
    発行日: 2023/10/11
    公開日: 2023/10/11
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    Recent research extends our understanding of brain processes beyond just action potentials and chemical transmissions within neural circuits, emphasizing the mechanical forces generated by excitatory synapses on dendritic spines to modulate presynaptic function. From in vivo and in vitro studies, we outline five central principles of synaptic mechanics in brain function: P1: Stability – Underpinning the integral relationship between the structure and function of the spine synapses. P2: Extrinsic dynamics – Highlighting synapse-selective structural plasticity which plays a crucial role in Hebbian associative learning, distinct from pathway-selective long-term potentiation (LTP) and depression (LTD). P3: Neuromodulation – Analyzing the role of G-protein-coupled receptors, particularly dopamine receptors, in time-sensitive modulation of associative learning frameworks such as Pavlovian classical conditioning and Thorndike’s reinforcement learning (RL). P4: Instability – Addressing the intrinsic dynamics crucial to memory management during continual learning, spotlighting their role in “spine dysgenesis” associated with mental disorders. P5: Mechanics – Exploring how synaptic mechanics influence both sides of synapses to establish structural traces of short- and long-term memory, thereby aiding the integration of mental functions. We also delve into the historical background and foresee impending challenges.

  • Sooyeon KIM, Latiefa KAMARULZAMAN, Yuichi TANIGUCHI
    2023 年 99 巻 8 号 p. 306-327
    発行日: 2023/10/11
    公開日: 2023/10/11
    [早期公開] 公開日: 2023/09/06
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    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 provide an outlook on this research field.

Original Article
  • Taku KITANOSONO, Tomoya KAWASE, Yasuhiro YAMASHITA, Shū KOBAYASHI
    2023 年 99 巻 8 号 p. 328-333
    発行日: 2023/10/11
    公開日: 2023/10/11
    [早期公開] 公開日: 2023/09/06
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    電子付録

    Catalytic asymmetric direct-type aldol reactions of ketones with aldehydes are a perennial puzzle for organic chemists. Notwithstanding the emergence of a myriad of chiral catalysts to address the inherent reversibility of the aldol products, a general method to access acyclic α-chiral ketones from prochiral aryl ketones has remained an unmet synthetic challenge. The approach outlined herein is fundamentally different to that used in conventional catalysis, which typically commences with an α-proton abstraction by a Brønsted base. The use of a chiral 2,2′-bipyridine scandium complex enabled the hydroxymethylation of propiophenone to be run under base-free conditions, which avails effectual suppression of hydrolytic deactivation of the Lewis acid catalyst. Intriguingly, the use of water as a reaction medium had an overriding effect on the progress of the reaction. The sagacious selection of sodium dodecyl sulfate and lithium dodecyl sulfate as surfactants allowed a variety of propiophenone derivatives to react in a highly enantioselective manner.

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