Proceedings of the Japan Academy. Series B, Physical and Biological Sciences最新文献

This review outlines research on chemical biology using mainly microbial metabolites for agricultural applications. We established the RIKEN Natural Products Depository (NPDepo), housing many microbial metabolites, to support academic researchers who focus on drug discovery. We studied methods to stimulate secondary metabolism in microorganisms to collect various microbial products. The switch of secondary metabolism in microorganisms changes depending on the culture conditions. We discovered compounds that activate biosynthetic gene clusters in actinomycetes and filamentous fungi. Using these compounds, we succeeded in inducing the production of active compounds. Two approaches for screening bioactive compounds are described. One is phenotypic screening to explore antifungal compounds assisted by artificial intelligence (AI). AI can distinguish the morphological changes induced by antifungal compounds in filamentous fungi. The other is the chemical array method for detecting interactions between compounds and target proteins. Our chemical biology approach yielded many new compounds as fungicide candidates.

The formation of autophagosomes is a pivotal step in autophagy, a lysosomal degradation system that plays a crucial role in maintaining cellular homeostasis. After autophagy induction, phase separation of the autophagy-related (Atg) 1 complex occurs, facilitating the gathering of Atg proteins and organizes the autophagosome formation site, where the initial isolation membrane (IM)/phagophore is generated. The IM then expands after receiving phospholipids from endomembranes such as the endoplasmic reticulum. This process is driven by the collaboration of lipid transfer (Atg2) and scrambling (Atg9) proteins. The IM assumes a cup shaped morphology and undergoes closure, resulting in the formation of a double membrane-bound autophagosome. The Atg8 lipidation system is hypothesized to be a pivotal factor in this process. This review presents an overview of the current understanding of these processes and discusses the basic mechanisms of autophagosome formation.

Herein, the first English article demonstrating the Yagi-Uda antenna is introduced. The article was originally published in the Proceedings of the Imperial Academy of Japan in 1926.

Cell proliferation is a fundamental characteristic of organisms, driven by the holistic functions of multiple proteins encoded in the genome. However, the individual contributions of thousands of genes and the millions of protein molecules they express to cell proliferation are still not fully understood, even in simple eukaryotes. Here, we present a genome-wide translation map of cells during proliferation in the unicellular alga Cyanidioschyzon merolae, based on the sequencing of ribosome-protected messenger RNA fragments. Ribosome profiling has revealed both qualitative and quantitative changes in protein translation for each gene during cell division, driven by the large-scale reallocation of ribosomes. Comparisons of ribosome footprints from non-dividing and dividing cells allowed the identification of proteins involved in cell proliferation. Given that in vivo experiments on two selected candidate proteins identified a division-phase-specific mitochondrial nucleoid protein and a mitochondrial division protein, further analysis of the candidate proteins may offer key insights into the comprehensive mechanism that facilitate cell and organelle proliferation.

Thrombomodulin (TM) is an important regulator of intravascular blood coagulation and inflammation. TM inhibits the procoagulant and proinflammatory activities of thrombin and promotes the thrombin-induced activation of protein C (PC) bound to the endothelial PC receptor (EPCR). Activated PC (APC) inactivates coagulation factors Va and VIIIa, thereby inhibiting blood clotting. Additionally, APC bound to EPCR exerts anti-inflammatory and cytoprotective effects on vascular endothelial cells. TM also protects cells in blood vessels from inflammation caused by pathogen-associated and damaged cell-associated molecules. Excessive anticoagulant, anti-inflammatory, and tissue regenerative effects in the TM-PC pathway are controlled by PC inhibitor. A recombinant TM drug (TMα), a soluble form of natural TM developed from the cloned human TM gene, has been evaluated for efficacy in many clinical trials and approved as a treatment for disseminated intravascular coagulation (DIC) caused by diseases such as sepsis, solid tumors, hematopoietic tumors, and trauma. It is currently widely used to treat DIC in Japan.

Chloroplasts are photosynthetic organelles that evolved through the endosymbiosis between cyanobacteria-like symbionts and hosts. Many studies have attempted to isolate intact chloroplasts to analyze their morphological characteristics and photosynthetic activity. Although several studies introduced isolated chloroplasts into the cells of different species, their photosynthetic activities have not been confirmed. In this study, we isolated photosynthetically active chloroplasts from the primitive red alga Cyanidioschyzon merolae and incorporated them in cultured mammalian cells via co-cultivation. The incorporated chloroplasts retained their thylakoid structure in intracellular vesicles and were maintained in the cytoplasm, surrounded by the mitochondria near the nucleus. Moreover, the incorporated chloroplasts maintained electron transport activity of photosystem II in cultured mammalian cells for at least 2 days after the incorporation. Our top-down synthetic biology-based approach may serve as a foundation for creating artificially photosynthetic animal cells.

The tremendous tidal force that is linked to the supermassive black hole (SMBH) at the center of our galaxy is expected to strongly subdue star formation in its vicinity. Stars within 1'' from the SMBH thus likely formed further from the SMBH and migrated to their current positions. In this study, spectroscopic observations of the star S0-6/S10, one of the closest (projected distance from the SMBH of ≈0''.3) late-type stars were conducted. Using metal absorption lines in the spectra of S0-6, the radial velocity of S0-6 from 2014 to 2021 was measured, and a marginal acceleration was detected, which indicated that S0-6 is close to the SMBH. The S0-6 spectra were employed to determine its stellar parameters including temperature, chemical abundances ([M/H], [Fe/H], [α/Fe], [Ca/Fe], [Mg/Fe], [Ti/Fe]), and age. As suggested by the results of this study, S0-6 is very old (≳10 Gyr) and has an origin different from that of stars born in the central pc region.

In the late 1970s, crude interferon samples were found to exhibit anti-tumour activity. This discovery led to the interferon as a "magic drug" for cancer patients. Many groups, including those in Tokyo, Zürich, and San Francisco, attempted to identify human interferon cDNAs. Tadatsugu Taniguchi was the first to announce the cloning of human interferon-β cDNA in the December 1979 issue of Proc. Jpn. Acad. Ser. B. This was followed by the cloning of human interferon-α by a Zürich group and interferon-γ by a group in Genentech in San Francisco. Recombinant interferon proteins were produced on a large scale, and interferon-α was widely used to treat C-type hepatitis patients. The biological functions of interferons were quickly elucidated with the purified recombinant interferons. The molecular mechanisms underlying virus-induced interferon gene expression were also examined using cloned chromosomal genes. The background that led to interferon gene cloning and its impact on cytokine gene hunting is described herein.

Calcium ions (Ca²⁺) play critical roles in various biological phenomena. The free Ca²⁺ concentration in the cytoplasm of a resting cell is at the 10^-7 M level, whereas that outside the cell is 10^-3 M, creating a 10,000-fold gradient of Ca²⁺ concentrations across the cell membrane, separating the intracellular and extracellular solutions.^1),2) When a cell is activated by external stimuli, the intracellular Ca²⁺ concentration increases to levels of 10^-6-10^-5 M through Ca²⁺ entry from the extracellular solution via plasma membrane Ca²⁺ channels and/or Ca²⁺ release from intracellular stores. This transient increase in Ca²⁺ functions as an important signal mediated by Ca²⁺ sensors. Thus, Ca²⁺ signals are transmitted to intracellular loci such as distinct, localized targets of Ca²⁺ sensors. Among numerous Ca²⁺ sensors present in cells, calmodulin is a highly conserved and ubiquitous Ca²⁺ sensor.³⁾.