Biology subjects

Nishimura, I.

Publications and source records attributed to Nishimura, I..

5 recordsLinked to original sources

bioRxiv2024

Silicon Nitride Induces Osteoconduction Via Activated Mitochondrial Oxidative Phosphorylation and Neovascularization

Silicon nitride (Si3N4: SiN) is a thermodynamically stable ceramic material with excellent mechanical properties, and wear and corrosion resistance for industrial applications. SiN has been proposed for orthopedic and dental implant applications owing to its enhanced osteoconduction. However, the biological mechanisms underlying SiN-induced bone formation have not been fully elucidated. In this study, SiN significantly increased in vitro mineralization of human bone marrow mesenchymal stromal cells (BM-MSC) and in vivo peri-implant bone volume in mouse femurs compared to conventionally used titanium (Ti) implants. RNA sequencing of BM-MSC cultured on SiN disks revealed that functional gene clusters associated with mitochondrial oxidative phosphorylation were significantly elevated. SiN in an aqueous solution has been shown to release ammonium/ammonia, which may provide a source for glutamine-dependent energy production, and BM-MSC upregulated the expression of a key enzyme, glutamate-ammonia ligase under osteogenic conditions. Additionally, SiN increased the expression of functional gene clusters involved in vascular formation. The upregulation of HIF1a in vitro and increased VEGFR3-positive blanching vascular structures in vivo implied that SiN induced neovascularization. This study revealed an important mechanism through which SiN stimulated osteoconduction by unique glutamine-driven mitochondrial oxidative phosphorylation and established oxygen and nutrient supply by neovascularization, leading to stable osseointegration.

bioengineering↗

bioRxiv2023

Mouse gingival single-cell transcriptomic atlas: An activated fibroblast subpopulation guides oral barrier immunity in periodontitis

Periodontitis, one of the most common non-communicable diseases, is characterized by chronic oral inflammation and uncontrolled tooth supporting alveolar bone resorption. Its underlying mechanism to initiate aberrant oral barrier immunity has yet to be delineated. Here, we report a unique fibroblast subpopulation activated to guide oral inflammation (AG fibroblasts) identified in a single-cell RNA sequencing gingival cell atlas constructed from the mouse periodontitis models. AG fibroblasts localized beneath the gingival epithelium and in the cervical periodontal ligament responded to the ligature placement and to the discrete application of Toll-like receptor stimulants to mouse maxillary tissue. The upregulated chemokines and ligands of AG fibroblasts linked to the putative receptors of neutrophils in the early stages of periodontitis. In the established chronic inflammation, neutrophils together with AG fibroblasts appeared to induce type 3 innate lymphoid cells (ILC3s) that were the primary source of interleukin-17 cytokines. The comparative analysis of Rag2-/- and Rag2{gamma}c-/-mice suggested that ILC3 contributed to the cervical alveolar bone resorption interfacing the gingival inflammation. We propose that AG fibroblasts function as a previously unrecognized surveillant to initiate gingival inflammation leading to periodontitis through the AG fibroblast-neutrophil-ILC3 axis.

pathology↗

bioRxiv2022

Abrupt shifts in the plant species richness and community composition along an aridity gradient in the Mongolian grasslands

Aridity, edaphic variables related to aridity, and livestock grazing are major drivers of plant community composition across dryland grasslands. With accounting these factors, little is known about differences in determinants and changing patterns along aridity gradients with different average of aridity. Thus, the comparative investigations of communities without and with grazing in semi-arid and arid regions are suitable to clarify the difference in compositional responses along aridity gradients between potential vegetations and degraded ones with grazing. We investigated compositional changes of communities without/with grazing in semi-arid (north) /arid (south) regions across Mongolia. The compositional changes based on Bray-Curtis dissimilarity were investigated by generalized dissimilarity modeling, including geographic distance, aridity, soil pH, and sand and clay contents as independent variables. The determinants and changing patterns of community composition were compared among the four groups. Aridity had significant impacts on community composition regardless of the regions and the absence/presence of grazing. However, without the dependency on grazing, the difference in response patterns was observed between the regions. The compositional change was steeper especially at the upper edge of aridity rather than the lower edge in the arid region. This indicates the vulnerability of plant communities to aridity shifts due to future climate change in desert steppe of Mongolia. In addition, regardless of the regions, the effects of soil pH on community composition were eliminated by grazing. Because soil pH indirectly affected by aridity shifts can have impacts on community composition of potential vegetations without grazing, the long-term monitoring of vegetation dynamics needs observations of both of communities without and with grazing.

ecology↗

bioRxiv2021

Therapeutic downregulation of neuronal PAS domain 2 (Npas2) promotes surgical skin wound healing

Attempts to minimize scarring remain among the most difficult challenges facing surgeons, despite the use of optimal wound closure techniques. Previously, we reported improved healing of dermal excisional wounds in circadian clock neuronal PAS domain 2 (Npas2)-null mice. In this study, we performed high-throughput drug screening to identify a compound that downregulates Npas2 activity. The hit compound (Dwn1) suppressed circadian Npas2 expression, increased murine dermal fibroblast cell migration, and decreased collagen synthesis in vitro. Based on the in vitro results, Dwn1 was topically applied to iatrogenic full-thickness dorsal cutaneous wounds in a murine model. The Dwn1-treated dermal wounds healed faster with favorable mechanical strength and developed less granulation tissue than the controls. The expression of type I collagen, Tgf{beta}1, and -smooth muscle actin was significantly decreased in Dwn1-treated wounds, suggesting that hypertrophic scarring and myofibroblast differentiation are attenuated by Dwn1 treatment. NPAS2 may represent an important target for therapeutic approaches to optimal surgical wound management.

bioengineering↗

bioRxiv2021

Local adaptation mediated niche expansion in correlation with genetic richness

As a central issue in evolution and ecology, the quantitative relationship among the genome, adaptation and the niche was investigated. Local adaptation of five Escherichia coli strains carrying either the wild-type genome or reduced genomes was achieved by experimental evolution. A high-throughput fitness assay of the ancestor and evolved populations across an environmental gradient of eight niches resulted in a total of 80 fitness curves generated from 2,220 growth curves. Further analyses showed that the increases in both local adaptiveness and niche broadness were negatively correlated with genetic richness. Local adaptation caused common niche expansion, whereas niche expansion for generality or speciality was decided by genetic richness. The order of the mutations accumulated stepwise was correlated with the magnitude of the fitness increase attributed to mutation accumulation. Pre-adaptation probably participated in coordination among genetic richness, local adaptation and niche expansion.

evolutionary biology↗