Biology subjects

Kinoshita, N.

Publications and source records attributed to Kinoshita, N..

7 recordsLinked to original sources

bioRxiv2026

Ancient Ryukyu Jomon contributed to past and current genetic structure of Japanese populations

Characterized by the earliest use of pottery, the Jomon culture was a unique Neolithic culture that spread throughout the Japanese Archipelago. Previous archaeological evidence suggests that Jomon hunter-gatherers colonized the southernmost islands, the Ryukyu Archipelago, by approximately 7,000 years before present (YBP). However, genetic characteristics of the Ryukyu Jomon population and its contribution to the modern population have not been elucidated yet. In this study, we newly sequenced 273 modern and 25 ancient (6,700-900 YBP) whole genomes collected across the Ryukyu Archipelago. Our analysis demonstrated a genetic differentiation between the Hondo (Japanese mainland) and Ryukyu Jomon, dating back to [~]6,900 YBP. After the divergence from the Hondo Jomon, the Ryukyu Jomon experienced severe bottlenecks, with an effective population size of [~]2,000. Admixture between the Ryukyu Jomon and migrants from the historic Hondo population occurred [~]1,000 YBP, which corresponds to the widespread adoption of iron tools and agriculture in the Central Ryukyus. Different demographic histories between modern Hondo and Ryukyu populations resulted in different rates of Jomon ancestry in these populations. By providing a new perspective on the peopling of the Ryukyu Archipelago, this study significantly enhances our understanding of cultural transitions in the region.

evolutionary biology↗

bioRxiv2025

Competitive elimination of ZO-1/ZO-2-deficient cells regulates epithelial barrier homeostasis

Epithelia cover the body and form a barrier to segregate the internal body from the external environment. Epithelial tissues contact the external environment and are exposed to various stresses that are potentially deleterious for the epithelial barrier1. However, how focal epithelial barrier defects are detected and repaired to maintain epithelial barrier homeostasis remains poorly understood. We co-cultured ZO-1/ZO-2 double-knockout (DKO) MDCK II cells, which lack tight junctions, with wild-type MDCK II cells, to understand how epithelial cells respond to focal epithelial barrier defects. When co-cultured with wild-type cells, ZO-1/ZO-2 DKO cells were selectively eliminated by induction of apoptosis. The elimination depended on a purse-string-like contraction of supracellular actomyosin cables formed at the clone boundary, regulated by ROCK. Furthermore, Hippo signaling and adherens junctions in the surrounding wild-type cells were required to eliminate ZO-1/ZO-2 DKO cells. These results demonstrate that selective elimination of ZO-1/ZO-2-deficient cells by cell competition regulates epithelial barrier homeostasis. In briefOtani et al. reveal that epithelial barrier homeostasis is regulated by cell competition-mediated elimination of ZO-1/ZO-2-deficient cells. Supracellular actomyosin cables form at the clone boundary and constrict in a purse-string-like manner to eliminate the loser cells. Mechanosensing in the winning cells is required to eliminate the loser cells. HighlightsO_LIZO-1/ZO-2-deficient cells are eliminated by cell competition C_LIO_LIActomyosin cables form in the winning cells at the clone boundary C_LIO_LIA purse-string-like contraction of actomyosin cables compresses the losing cells C_LIO_LIMechanosensing in the winning cells is important to eliminate the loser cells C_LI

cell biology↗

bioRxiv2024

ZO-1 shuttles between tight junctions and podosomes by riding ERK activation waves during collective cell migration

Collective cell migration is essential in various physiological processes, including embryonic development, wound healing, and cancer metastasis. However, the mechanisms by which individual cells achieve coordinated movement remain elusive. Here, we demonstrate that zonula occludens-1 (ZO-1), a scaffolding protein of tight junctions (TJs), dynamically translocates to form cell-to- extracellular matrix (ECM) adhesion complexes, podosomes, at the basal cell surface during migration. The translocation of ZO-1 is regulated by extracellular signal-regulated kinase (ERK) activity and its interaction with F-actin. ZO-1 at podosomes contributes to traction force generation and cell invasion, while ZO-1 at TJs mediates intercellular propagation of ERK activation, facilitating collective cell migration. These findings elucidate the versatile roles of ZO-1 in cell adhesion and movement, providing insights into the mechanisms coordinating the discrete movements of individual cells into a cohesive and directed collective cell migration.

cell biology↗

bioRxiv2023

Mechanical transapical coupling of endometrial epithelial cells during implantation

Epithelial cells lining the lumen of organs have an apical-basal polarity, and mechanical cell contacts are located in the lateral and basal regions. During early pregnancy in rodents, the luminal space of the uterus is closed, and opposing epithelial cells attach to each other at apical-apical surfaces. Here, we show that cells are mechanically coupled at the apical cell-cell contacts. The apical plasma membrane was intricately intertwined between opposing cells. Extracellular matrix and tight junction molecules were localized at apical contacts. Claudin inhibition resulted in impaired luminal closure, suggesting a functional requirement of claudins for the establishment of transapical coupling. The present results demonstrate a mechanical cell-cell interaction that occurs between apical-apical surfaces in addition to lateral and basal cell junctions. One Sentence SummariesTransapical coupling of epithelial cells mediated by extracellular matrix and tight junction molecules

cell biology↗

bioRxiv2020

Force-dependent remodeling of a tight junction protein ZO-1 is regulated by phase separation

Although the physiological importance of biomolecular condensates is widely recognized, how it is controlled in time and space during development is largely unknown. Here we show that a tight junction protein ZO-1 forms cytoplasmic condensates in the trophectoderm (TE) of the mouse embryo before E4.0. These disappear via dissolution, and ZO-1 accumulates at the cell junction as the blastocyst cavity grows and internal pressure on TE cells increases. In contrast, this dissolution was less evident in TE cells attached to the inner cell mass, as they receive weaker tensile forces. Furthermore, analyses using MDCK cells have demonstrated that the ZO-1 condensates are generated and maintained by liquid-liquid phase separation. Our study also highlights that the dynamics of these condensates depends on the physical environment via an interaction between ZO-1 and F-actin. We propose that the force-dependent regulation of ZO-1 condensation contributes to establishing robust cell-cell adhesion during early development.

cell biology↗

bioRxiv2020

Benefit of Drought on an Herbivore of Herbaceous Plants: Enemy Free Space and Reduced Competition

Plants grow under reduced water availability can have divergent effects on insect herbivores, in some instances producing benefits to them. However, the forces mediating these positive impacts remain mostly unclear. We conducted a manipulative field study using a specialist herbivore Pieris rapae, and its host plant, Rorippa indica, in two populations to identify how water availability impacts overall plant quality and multitrophic interactions. We observed that R. indica growing under low water availability led to higher survival of P. rapae larvae. The increase in survival of eggs and larvae was related to the reduced abundance of other herbivores and natural enemies. Water availability had differential impacts on members of the herbivore community through changes in plant quality. Low water availability decreased the quality of R. indica to most herbivores as indicated by reduced abundance in the field and decreased relative growth rate in feeding assays. In contrast, the performance of P. rapae larvae were not affected by differences in sympatric R. indica grown under different water availability. These results indicate that local P. rapae possess some physiological adaptation to overcome fluctuations in host quality. Our findings illustrate that reduced water availability is beneficial to a specialist herbivore, but detrimental to most other herbivores. Our work highlights the complex roles of the arthropod communities associated with plants in determining the impacts of water availability on insect herbivores.

ecology↗

bioRxiv2020

The anticoagulant nafamostat potently inhibits SARS-CoV-2 infection in vitro: an existing drug with multiple possible therapeutic effects

Although infection by SARS-CoV-2, the causative agent of COVID-19, is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked MERS-CoV S protein-initiated cell fusion by targeting TMPRSS2, and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on SARS-CoV-2 S protein, ACE2 and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an EC50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. These findings, together with accumulated clinical data regarding its safety, make nafamostat a likely candidate drug to treat COVID-19.

microbiology↗