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

Fertilization is the starting point for creating new progeny. At this time, the highly differentiated oocyte and sperm fuse to form one zygote, which is then converted into a pluripotent early embryo. Recent studies have shown that the lysosomal degradation system via autophagy and endocytosis plays important roles in the remodeling of intracellular components during oocyte-to-embryo transition. For example, in Caenorhabditis elegans, zygotes show high endocytic activity, and some populations of maternal membrane proteins are selectively internalized and delivered to lysosomes for degradation. Furthermore, fertilization triggers selective autophagy of sperm-derived paternal mitochondria, which establishes maternal inheritance of mitochondrial DNA. In addition, it has been shown that autophagy via liquid-liquid phase separation results in the selective degradation of some germ granule components, which are distributed to somatic cells of early embryos. This review outlines the physiological functions of the lysosomal degradation system and its molecular mechanisms in C. elegans and mouse embryos.

The establishment of the Nobeyama Radio Observatory (NRO) in 1982 was an important event that greatly influenced the subsequent development of Japanese astronomy. The 45 m radio telescope and the Nobeyama Millimeter Array (NMA) pushed Japanese radio astronomy to the forefront of the world. As a plan beyond the Nobeyama telescopes, the Japanese radio astronomy community considered a large array to achieve unprecedented resolution at millimeter and submillimeter wavelengths under the project name of the Large Millimeter and Submillimeter Array (LMSA). After long and patient discussions and negotiations with the United States and Europe, the LMSA plan eventually led to the ALMA (Atacama Large Millimeter/submillimeter Array) as an international joint project, and the ALMA was inaugurated in 2013. This paper reviews the process from the establishment of the NRO to the realization of the ALMA, including planning of the LMSA, international negotiations, site survey, instrumental developments, and initial science results.

A bacterium with a "mouth"-like pit structure isolated for the first time in the history of microbiology was a Gram-negative rod, containing glycosphingolipids in the cell envelope, and named Sphingomonas sp. strain A1. The pit was dynamic, with repetitive opening and closing during growth on alginate, and directly included alginate concentrated around the pit, particularly by flagellins, an alginate-binding protein localized on the cell surface. Alginate incorporated into the periplasm was subsequently transferred to the cytoplasm by cooperative interactions of periplasmic solute-binding proteins and an ATP-binding cassette transporter in the cytoplasmic membrane. The mechanisms of assembly, functions, and interactions between the above-mentioned molecules were clarified using structural biology. The pit was transplanted into other strains of sphingomonads, and the pitted recombinant cells were effectively applied to the production of bioethanol, bioremediation for dioxin removal, and other tasks. Studies of the function of the pit shed light on the biological significance of cell surface structures and macromolecule transport in bacteria.

In eukaryotic cells, the genomic DNA is hierarchically organized into chromatin. Chromatin structures and dynamics influence all nuclear functions that are guided by DNA, and thus regulate gene expression. Chromatin structure aberrations cause various health issues, such as cancer, lifestyle-related diseases, mental disorders, infertility, congenital diseases, and infectious diseases. Many studies have unveiled the fundamental features and the heterogeneity of the nucleosome, which is the basic repeating unit of chromatin. The nucleosome is the highly conserved primary chromatin architecture in eukaryotes, but it also has structural versatility. Therefore, analyses of these primary chromatin structures will clarify the higher-order chromatin architecture. This review focuses on structural and functional studies of nucleosomes, based on our research accomplishments.

Pradimicins (PRMs) are an exceptional family of natural products that specifically bind d-mannose (Man). In the past decade, their scientific significance has increased greatly, with the emergence of biological roles of Man-containing glycans. However, research into the use of PRMs has been severely limited by their inherent tendency to form water-insoluble aggregates. Recently, we have established a derivatization strategy to suppress PRM aggregation, providing an opportunity for practical application of PRMs in glycobiological research. This article first outlines the challenges in studying Man-binding mechanisms and structural modifications of PRMs, and then describes our approach to address them. We also present our recent attempts toward the development of PRM-based research tools.

Extracellular fluids, including blood, lymphatic fluid, and cerebrospinal fluid, are collectively called body fluids. The Na⁺ concentration ([Na⁺]) in body fluids is maintained at 135-145 mM and is broadly conserved among terrestrial animals. Homeostatic osmoregulation by Na⁺ is vital for life because severe hyper- or hypotonicity elicits irreversible organ damage and lethal neurological trauma. To achieve "body fluid homeostasis" or "Na homeostasis", the brain continuously monitors [Na⁺] in body fluids and controls water/salt intake and water/salt excretion by the kidneys. These physiological functions are primarily regulated based on information on [Na⁺] and relevant circulating hormones, such as angiotensin II, aldosterone, and vasopressin. In this review, we discuss sensing mechanisms for [Na⁺] and hormones in the brain that control water/salt intake behaviors, together with the responsible sensors (receptors) and relevant neural pathways. We also describe mechanisms in the brain by which [Na⁺] increases in body fluids activate the sympathetic neural activity leading to hypertension.

A global navigation satellite system (GNSS) buoy system for early tsunami warnings has been developed for more than 20 years. The first GNSS buoy system using a real-time kinematic algorithm (RTK) was implemented in the Nationwide Ocean Wave information network for Ports and HArbourS (NOWPHAS) wave monitoring system in Japan in 2008. The records of NOWPHAS were used to update the tsunami alert by the Japan Meteorological Agency (JMA), owing to the tsunami generated by the 2011 Tohoku-oki earthquake (Mw9.0). However, considering that the distance limit is less than 20 km for the RTK algorithm, a new system was designed by introducing a new positioning algorithm and satellite data transmission to place the buoy much farther from the coast. A new technique for the continuous monitoring of ocean-bottom crustal movements was also implemented in the new system. The new buoy system can be used for weather forecasting and ionospheric monitoring as well.

PRDI-BF1 and RIZ (PR) domain zinc finger protein 14 (PRDM14), first reported in 2007 to be overexpressed in breast cancer, plays an important role in breast cancer proliferation. Subsequent studies reported that PRDM14 is expressed in embryonic stem cells, primordial germ cells, and various cancers. PRDM14 was reported to confer stemness properties to cancer cells. These properties induce cancer initiation, cancer progression, therapeutic resistance, distant metastasis, and recurrence in refractory tumors. Therefore, PRDM14 may be an ideal therapeutic target for various types of tumors. Silencing PRDM14 expression using PRDM14-specific siRNA delivered through an innovative intravenous drug delivery system reduced the size of inoculated tumors, incidence of distant metastases, and increased overall survival in nude mice without causing adverse effects. Therapeutic siRNA targeting PRDM14 is now being evaluated in a human phase I clinical trial for patients with refractory breast cancer, including triple-negative breast cancer.

A year and a half has passed since the outbreak of the COVID-19 pandemic. Mathematical models to predict infection are expected and many studies have been conducted. In this study, a new interpretation was created that could reproduce the daily positive cases in Tokyo using only a simple SIR model. In addition, the data on the ratio of transfer to delta variants could also be simulated. It is anticipated that this interpretation will be a basis for the development of forecasting methods.

With the name "phenine" given to 1,3,5-trisubstituted benzene for a fundamental trigonal planar unit to weave nanometer-sized networks, a series of curved nanocarbon molecules have been designed and synthesized. Since the 6π-phenine units were amenable to modern biaryl coupling reactions mediated by transition metals, concise syntheses of >400π-nanocarbon molecules were readily achieved. In addition, the phenine design allowed for installing of heteroatoms and/or transition metals doped at specific positions of the large π-systems of the nanocarbon molecules. Fundamental tools were also developed to specify and describe the locations of defects/dopants, quantify pyramidalizations of trigonal panels and estimate molecular Gauss curvatures of the discrete surface. Unique features of phenine nanocarbons, such as stereoisomerism, entropy-driven molecular assembly and effects of dopants on electronic/magnetic characteristics, were revealed during the first half-decade of investigations.