Biology subjects

Nakanishi, S.

Publications and source records attributed to Nakanishi, S..

9 recordsLinked to original sources

bioRxiv2026

Circadian temperature compensation is intrinsically linked with metabolism and redox signaling

Circadian rhythms are a universal property of organisms, and a defining property of these oscillators is the ability to maintain a precise period at different temperatures. Indeed, the discovery in the 1950s of this property, known as "temperature compensation," was a watershed event in our understanding of biological timekeeping. Since that time, however, almost no general principles have emerged that uncover the mechanistic basis of how circadian timekeepers defy the rules" of temperature dependence of biochemical reactions. A genetic investigation of circadian temperature compensation revealed that the sensing of metabolism and ensuing modulation of the core mechanism preserves a constant circadian period. Intracellular redox sensing of metabolic rate is intrinsic to this compensation, and this relationship is conserved in bacterial and mammalian cells. These insights explain previously inexplicable observations of the interaction between redox reactions and circadian timekeeping. These results introduce a previously unknown linkage between temperature compensation and metabolism.

cell biology↗

bioRxiv2026

Metabolic diversity of microorganisms toward atypical sugar enantiomers

Life on Earth has long been regarded as homochiral, relying almost exclusively on a single enantiomer of sugars--typically the D-form. However, recent discoveries challenge this paradigm, including the identification of L-glucose-catabolizing bacteria and microbial L-glucoside hydrolases. Despite these findings, the metabolic diversity of organisms toward a broader range of atypical sugar enantiomers and their ecological relevance remains largely unexplored. This study aimed to identify and isolate microorganisms capable of catabolizing atypical enantiomers of diverse sugars. We performed enrichment cultures with either the D- or L-forms of glucose, fructose, xylose, and sorbose, using soil and activated sludge as microbial sources. Microbial growth was observed under all tested conditions, with the dominant taxa varying depending on the sugars supplied. Six phylogenetically distinct bacterial isolates exhibited the ability to catabolize atypical sugar enantiomers, two of which exhibited growth on all tested sugars. These findings uncover a previously unrecognized diversity in microbial sugar metabolisms, providing new insights into the environmental dynamics of atypical sugar enantiomers and offering a novel perspective on the principle of biological homochirality. Furthermore, this work lays a foundation for the development of biomanufacturing processes using racemic sugar mixtures synthesized via abiotic chemical reactions.

microbiology↗

bioRxiv2025

MiR-23b Neutralization In Brain Endothelium Promotes Blood-Brain Barrier Repair Through Wnt/Beta-catenin Dependent And Independent Mechanisms

Blood-brain barrier (BBB) disruption drives stroke and other CNS disorders pathology, yet restoring its integrity remains challenging. Using an unbiased anti-miR lentiviral screen, miR-23b was identified as a critical negative regulator of BBB integrity in brain endothelial cells (BECs). Targeted inhibition of miR-23b using anti-miR-23b, validated by Wnt-reporter, Wnt-rescue, and eCLIP analysis, demonstrates that BEC miR-23b silencing in BECs, enhances junctional protein expression and strengthens barrier function while suppressing transcellular transport. Global multi-omics analysis reveals that miR-23b acts as a robust driver of angiogenesis-specific genes and proteins. Conversely, anti-miR-23b induces the expression of factors essential for BBB stabilization and repair. Notably, anti-miR-23b enhances these protective barrier properties through the multi-faceted regulation of Wnt/{beta}-catenin, TGF-{beta}, Notch, and VEGF signaling mechanisms. Using a 3D microfluidic platform, anti-miR-23b was shown to foster BBB repair by accelerating vessel maturation and enhancing resilience against ischemic injury. Proof-of-concept studies show that BEC specific AAVBR1-anti-miR-23b gene therapy reinforces BBB tight junctions, reduces BBB leakage, and improves outcome measures in a transient middle cerebral artery occlusion (t-MCAO) stroke model. Thus, miR-23b is a critical regulator of cerebrovascular integrity, positioning anti-miR-23b as a promising RNA-based therapy to enhance BBB stability and repair in stroke and other CNS disorders.

neuroscience↗

bioRxiv2024

Isolation of bacteria that catabolize abiotically synthesized tetroses via the formose reaction

Sugars synthesized through abiotic processes, specifically the formose reaction, are promising candidates for next-generation feedstocks for biomanufacturing due to their significantly higher productivity compared to cultivated crops. One of the significant challenges associated with the utilization of abiotically synthesized sugars via the formose reaction is the presence of unusual sugars, which are not metabolized by typical microorganisms. This study aimed to identify microorganisms capable of catabolizing tetroses, which are among the unusual sugars present in the abiotically synthesized sugars. Four model bacteria commonly used in biomanufacturing, including Escherichia coli, were unable to catabolize tetroses and their growth was completely inhibited by 2 to 4 g/L of D-erythrose or 0.5 to 1 g/L of L-erythrulose. We successfully isolated eight phylogenetically diverse bacterial strains from river sediments, capable of utilizing D-erythrose and L-erythrulose as the sole carbon sources. These isolates exhibited higher tolerances to tetroses compared to the model bacteria. The isolates exhibited the ability to grow in high concentrations of the abiotically synthesized sugars, which inhibit the growth of typical microorganisms, and to consume tetroses contained therein. Further investigation into the molecular mechanisms of tetrose metabolisms in the isolates will facilitate the development of biomanufacturing processes utilizing the abiotically synthesized sugars.

microbiology↗

bioRxiv2023

A Novel Subtype of Myeloproliferative Neoplasms Driven by a MYC-Alarmin Axis

Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPNs) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for triple negative myelofibrosis (MF) patients whose MPNs lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in triple negative MF, and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves various hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs. SIGNIFICANCEThis study establishes that MYC expression is increased in triple negative MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in triple negative MPN.

cancer biology↗

bioRxiv2021

Coral symbionts exhibit a polycistronic flavodiiron gene leading to functional proteins in photosynthesis

Photosynthesis in cyanobacteria, green algae, and basal land plants is protected against excess reducing pressure on the photosynthetic chain by flavodiiron proteins (FLV) that dissipate photosynthetic electrons by reducing O2. In these organisms, the genes encoding FLV are always conserved in the form of a pair of two-type isozymes (FLVA and FLVB) that are believed to function in O2 photo-reduction as a heterodimer. While coral symbionts (dinoflagellates of the family Symbiodiniaceae) are the only algae to harbor FLV in photosynthetic red plastid lineage, only one gene is found in transcriptomes and its role and activity remain unknown. Here, we characterized the FLV genes in Symbiodiniaceae and found that its coding region is composed of tandemly repeated FLV sequences. By measuring the O2-dependent electron flow and P700 oxidation, we suggest that this atypical FLV is active in vivo. Based on the amino-acid sequence alignment and the phylogenetic analysis, we conclude that in coral symbionts, the gene pair for FLVA and FLVB have been fused to construct one coding region for a hybrid enzyme, which presumably occurred when or after both genes were inherited from basal green algae to the dinoflagellate. Immunodetection suggested the FLV polypeptide to be cleaved by a post-translational mechanism, adding it to the rare cases of polycistronic genes in eukaryotes. Our results demonstrate that FLV are active in coral symbionts with genomic arrangement that is unique to these species. The implication of these unique features on their symbiotic living environment is discussed.

plant biology↗

bioRxiv2020

A quantitative demonstration of NADP+/NADPH redox homeostasis in cyanobacterial cells

In photosynthetic organisms, it is recognized that the intracellular NADP+/NADPH ratio is regulated within an appropriate range for the cooperative function of a wide variety of physiological processes. However, despite its importance, there is large variability in the values of the NADP+/NADPH ratio quantitatively estimated to date. In the present study, the light-response of the NADP+/NADPH ratio was investigated by applying a novel NADP(H) extraction method using phenol / chloroform / isoamyl alcohol (PCI) in the cyanobacterium Synechocystis sp. PCC 6803. The light-response of NADP(H) observed using PCI extraction was qualitatively consistent with the NADPH fluorescence time course measured in vivo. Moreover, the results obtained by PCI extraction and the fluorescence-based methods were also consistent in a mutant lacking the ability to oxidize NAD(P)H in the respiratory chain, and exhibiting a unique NADPH light-response. These observations indicate that the PCI extraction method allowed quantitative determination of NADP(H) redox. Notably, the PCI extraction method showed that not all NADP(H) was oxidized or reduced by light-dark transition, indicating that some NADP(H) is not light-responsive. Specifically, 64% of total NADP(H) was observed as non-light-responsive in the wild-type cells. The variation of the intracellular NADP+/NADPH ratio is limited to a narrow range due to the presence of non-light-responsive NADP(H).

plant biology↗

bioRxiv2019

Time-of-day dependent responses of cyanobacterial cellular viability against oxidative stress

As an adaptation to periodic fluctuations of environmental light, photosynthetic organisms have evolved a circadian clock. Control by the circadian clock of many cellular physiological functions, including antioxidant enzymes, metabolism and the cell cycle, has attracted attention in the context of oxidative stress tolerance. However, since each physiological function works in an integrated manner to deal with oxidative stress, whether or not cell responses to oxidative stress are under circadian control remains an open question. In fact, circadian rhythms of oxidative stress tolerance have not yet been experimentally demonstrated. In the present work, we applied an assay using methyl viologen (MV), which generates reactive oxygen species (ROS) under light irradiation, and experimentally verified the circadian rhythms of oxidative stress tolerance in photosynthetic cells of the cyanobacterium Synechococcus elongatus PCC7942, a standard model species for investigation of the circadian clock. Here, we report that ROS generated by MV treatment causes damage to stroma components and not to the photosynthetic electron transportation chain, leading to reduced cell viability. The degree of decrease in cell viability was dependent on the subjective time at which oxidative stress was applied. Thus, oxidative stress tolerance was shown to exhibit circadian rhythms. In addition, the rhythmic pattern of oxidative stress tolerance disappeared in mutant cells lacking the essential clock genes. Notably, ROS levels changed periodically, independent of the MV treatment. Thus, we demonstrate for the first time that in cyanobacterial cells, oxidative stress tolerance shows circadian oscillation.

plant biology↗

bioRxiv2018

High prevalence of the antibody against Syncytin-1 in schizophrenia

Both genetic and environmental factors have been considered causative agents for schizophrenia (SZ). However, no single gene has been shown responsible for the development of SZ. Furthermore, the pathophysiological roles of environmental factors including psychological stress, autoimmunity, and microbial infection have not been fully understood. Previous studies have suggested the involvement of one of the human endogenous retroviruses (HERVs), HERV-W, in SZ. In this study, prevalence of antibodies against the HERV-W Syncytin-1 protein was examined using a newly developed ELISA test. Fifty percent of patients with SZ (24 out of 48 cases) were antibody-positive, with a specificity of greater than 95% (less than 5% of control cases, 3 out of 79). No significant effect of medication was evident, nor did any SZ cases become seropositive after diagnosis. These findings indicate a possible involvement of HERV-W expression in the development of SZ and support its applicability to laboratory diagnoses.

neuroscience↗