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

Over the past decades, the understanding of sleep has evolved to be a fundamental physiological mechanism integral to the processing of different types of memory rather than just being a passive brain state. The cyclic sleep substates, namely, rapid eye movement (REM) sleep and non-REM (NREM) sleep, exhibit distinct yet complementary oscillatory patterns that form inter-regional networks between different brain regions crucial to learning, memory consolidation, and memory retrieval. Technical advancements in imaging and manipulation approaches have provided deeper understanding of memory formation processes on multi-scales including brain-wide, synaptic, and molecular levels. The present review provides a short background and outlines the current state of research and future perspectives in understanding the role of sleep and its substates in memory processing from both humans and rodents, with a focus on cross-regional brain communication, oscillation coupling, offline reactivations, and engram studies. Moreover, we briefly discuss how sleep contributes to other higher-order cognitive functions.

Tissue-resident macrophages perform indispensable functions in the development, maintenance, and repair of tissues. Microglia are the primary resident immune cells in the central nervous system (CNS), functioning as intracerebral macrophages distributed throughout the brain parenchyma. In addition to microglia, there is another, less well-characterized type of macrophage known as CNS border-associated macrophages (CAMs), and the existence of these cells has been recognized for several decades. With recent advances in research technologies, an increasing number of studies have focused on CAMs, and our understanding of them has begun to improve. In this article, we review the cellular characteristics and functions of CAMs that have been elucidated thus far, with a particular focus on the similarities and differences between CAMs and microglia.

Why and how do we age? This physiological phenomenon that we all experience remains a great mystery, largely unexplained even in this age of scientific and technological progress. Aging is a significant risk factor for numerous diseases, including cancer. However, underlying mechanisms responsible for this association remain to be elucidated. Recent findings have elucidated the significance of the accumulation of senescent cells and other inflammatory cells in organs and tissues with age, and their deleterious effects, such as the induction of inflammation in the microenvironment, as underlying factors contributing to organ dysfunction and disease development. Cellular senescence is a cellular phenomenon characterized by a permanent cessation of cell proliferation and secretion of several proinflammatory cytokines (senescence associated secretory phenotypes). Notably, the elimination of senescent cells from aging individuals has been demonstrated to alleviate age-related organ and tissue dysfunction, as well as various geriatric diseases. This review summarizes the molecular mechanisms by which senescent cells are induced and contribute to age-related diseases, as well as the technologies that ameliorate them.

This review examines the molecular mechanisms controlling the development and homeostasis of the musculoskeletal system through gene expression regulation. It introduces key discoveries from basic transcriptional control to advanced mechanotransduction pathways, focusing on our contributions including the EMBRYS database for transcription factor expression analysis and the identification of RP58 in muscle development and Mohawk (Mkx) in tendon formation. We also elucidated the role of miR-140 as a critical regulator in cartilage development and homeostasis. This microRNA is specifically expressed in cartilage, promotes chondrogenesis, and is involved in protective mechanisms against cartilage degenerative diseases such as osteoarthritis. Our discovery of the PIEZO1-Mkx pathway provides a molecular mechanism linking mechanical stimuli to gene expression in tendons, explaining tissue adaptation and differences in motor abilities. Understanding these pathways offers new therapeutic strategies for tendon and ligament injuries, age-related decline, and cartilage diseases. Currently, we are proposing the concept of "tenopenia" to complement sarcopenia, addressing the mechanisms of age-related tendon deterioration. This integrated approach to the musculoskeletal system as an environment-responsive entity advances both fundamental science and clinical applications aimed at maintaining mobility throughout life.

Transcription is an essential biological process that underlies all cellular and organismal activities. In eukaryotes, RNA polymerase II (RNAPII) transcribes every protein-coding gene and many non-coding genes, playing a central role in gene expression. Transcription generally occurs in three steps: RNAPII initiates transcription from a gene promoter, elongates RNA as it traverses the gene body, and terminates transcription at the end of the gene. Dynamic interactions with multiple accessory factors allow RNAPII to form functional transcription complexes and accomplish these processes in chromatin. Recent progress in structural biology has illuminated the structural and mechanistic details of RNAPII functions, particularly promoter-proximal pausing, nucleosome transcription, and transcription termination. This review provides a survey of these advances and discusses future directions.

It is now accepted that the pathogenesis of type 2 diabetes in East Asians including Japanese differs distinctly from that in Caucasians. Many non-obese individuals in Japan develop type 2 diabetes and present clinically with insufficient insulin secretion rather than a large increase in the insulin resistance. To understand the pathophysiology of this non-obese diabetes, we studied Goto-Kakizaki rats, a unique model of spontaneous non-obese diabetes, and identified mitochondrial dysfunction in pancreatic β-cells as a factor in decreased insulin secretion. Looking for a clinical treatment option, we focused on the incretins because of their glucose-dependent insulin stimulatory effect. Our findings have contributed to the understanding of incretin action and the development of incretin-associated therapeutics and shed light on the nature of East Asian diabetes and its optimal clinical treatment.

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.

Clusters of galaxies can be identified from the peaks in weak lensing aperture mass maps constructed from weak lensing shear catalogs. Such purely gravitational cluster selection differs considerably from traditional cluster selection based on the baryonic properties of clusters. In this review, we present the basics and applications of weak lensing shear-selected cluster samples. Detailed studies of the baryonic properties of shear-selected clusters shed new light on cluster astrophysics. The purely gravitational selection indicates that the selection function can be quantified more easily and robustly, which is crucial for deriving accurate cosmological constraints from the abundance of shear-selected clusters. Recent advances in shear-selected cluster studies are driven by the Subaru Hyper Suprime-Cam survey, in which more than 300 shear-selected clusters with a signal-to-noise ratio ＞ 5 were identified. It is argued that various systematic effects in cosmological analysis can be mitigated by carefully selecting the setup of the analysis, including the selection of kernel functions and the source galaxy sample.

Natural products that exhibit significant biological activity often possess complex molecular structures such as caged frameworks, strained motifs, inherent instability, and many stereogenic carbon centers, etc. Achievement of those total syntheses always requires the powerful methodologies and judicious strategies to fulfill the stereochemical requirements of the target compounds. Building on our successful stereo-controlled syntheses, we have established the concept of conformational constraint, which renders the approach of reactants under a controlled manner during the bond-forming process through the best orbital overlap. Important factors that affect the proper orientation of substrates are (i) acyclic allyl strain, (ii) stereoelectronic effect, (iii) chelation control, etc. Established methodologies include (i) heteroatom directed conjugate addition for diastereoselective C-C bond formation, (ii) 100% α-selective C-glycosidation by using alkynyl-silane, (iii) cobalt acetylene chemistry for medium-size ring formation, followed by its functional group transformation. The author has named such total concept as conformational constraint and has illustrated it with the finished examples of total syntheses. These examples are taken from maytansine, okadaic acid, tautomycin, tetrodotoxin, ciguatoxin, etc.