Biology subjects

Oka, K.

Publications and source records attributed to Oka, K..

14 recordsLinked to original sources

bioRxiv2026

Diversity and stability of the gut microbiome of naked mole-rat (Heterocephalus glaber), the longest-lived rodent

The naked mole-rat is a subterranean rodent adapted to extreme hypoxia and low metabolic demands, with an exceptionally long lifespan relative to its small body size, while maintaining reproductive capacity. Using 16S rRNA gene sequencing of 24 samples and whole-metagenome sequencing of 11 samples from individuals up to 15 years of age, we characterized the gut microbiota and showed its complexity and distinctiveness compared with that of other rodents, including mice, squirrels, and rabbits. Although all animals were born and raised in a laboratory setting, the gut microbiota remained taxonomically stable across ages and retained key taxa previously reported in wild naked mole-rats (e.g., Treponema and Desulfovibrio). Metagenome-assembled genomes revealed the presence of archaeal methanogens and termite-gut-associated bacteria (e.g., Methanobacteria within Euryarchaeota and Avelusimicrobium within Elusimicrobiota), together with genes involved in hydrogen metabolism and archaeal methanogenesis. Compared with mice, the naked mole-rat gut microbiota was enriched in carbohydrate-active enzymes targeting plant cell-wall polysaccharides, resembling those found in ruminants. We also detected evidence of flagellates, ciliates, and fungi, which may further contribute to polysaccharide degradation and fermentation, potentially within the enlarged cecum. Together, this comprehensive analysis provides distinctive gut microbial features of the naked mole-rat that may be associated with the naked mole-rats low metabolic rate and exceptional longevity.

microbiology↗

bioRxiv2025

Genomic resources of Ascidiella aspersa and comparative analysis across tunicates reveal conserved class-level features and evolutionary diversification

BackgroundAscidiella aspersa is an invasive tunicate and one of the closest relatives of vertebrates. Despite its ecological nuisance, A. aspersa is anticipated to be a valuable model organism for developmental studies due to its remarkably transparent embryos. However, annotated genome assemblies and transcriptomic resources have not yet been fully established. Although several tunicate genomes have been sequenced, most lack annotations, and a comprehensive analysis across tunicates has not yet been conducted. ResultsWe performed de novo genome assembly and transcriptome analysis of A. aspersa, producing a high-quality 306.5 Mb genome assembly. The transcriptome was derived from nine different organs of adults and embryos at six developmental stages. Ab initio and homology-based gene predictions identified 24,504 genes with a BUSCO score of 92.2%. Functional annotation was added for 18,636 genes in the model. To understand the relative features of this species among tunicates, we conducted genome-wide comparative analysis using publicly available data from 35 other tunicate genomes across three classes, five orders, and 12 families, thus constructing gene models for 27 species with BUSCO scores >80%. Overall, phylogenetic analysis revealed a new hypothesis regarding the relationships among Phlebobranchia and Aplousobranchia families. Gene duplication analysis showed distinct contractions of gene families in some taxa with losses of specific DNA repair related genes that were shared among Thaliacea--these may have contributed to their evolutionary diversification. Tunicate genomes exhibited a high level of variation in genomic GC content (28.0%-42.7%). A. aspersa has the highest GC content in coding regions and the third position of codons among tunicate species, with changes in codon usage bias differing from other Ascidiidae species. We also constructed an online comparative tunicate genome database (TUNOME), that provides functional annotations of gene models and ortholog analyses based on these genomic and transcriptomic data. ConclusionsWe constructed genomic resources for A. aspersa and another 35 tunicate gene models. Comparative analysis reveals a variety in tunicate species genomes and characterizes class-level features. Our resources are expected to be a foundation for experimental studies involving non-model tunicates and for comparative analysis among tunicate species.

genomics↗

bioRxiv2025

Axial Rotation Comprises Concurrent Twisting and Bending, Each Differentially Regulated by TGF-β Signaling

Axial rotation (AR), a morphogenetic movement that reshapes the body axis, is widely observed in chordates, including mice and rats. AR involves complex three-dimensional deformations; however, its geometric characteristics and regulatory mechanisms remain poorly understood. Here, using the chordate Ciona robusta (Ciona intestinalis type A), we demonstrate that AR consists of two components--leftward bending and clockwise twisting along the anterior-posterior axis--differentially regulated by TGF-{beta} signaling. A comparison between chorionated and dechorionated embryos revealed that dechorionation randomized the bending direction, while twisting remained consistently clockwise. Inhibition of TGF-{beta} signaling with SB431542 randomized both deformations. Quantitative analysis of twisting angles indicated uniform clockwise twisting along the axis, peaking during the tailbud stage and proceeding in the tail region, independent of the tip, trunk, or myofibril patterning. Although overall twisting was reduced under TGF-{beta} inhibition, the tail exhibited disorganized twisting. The sum of absolute twisting-angle differences in every 10 m remained comparable to the wild type (WT). This suggests that twisting is intrinsically generated, while TGF-{beta} signaling aligns local twisting into a coordinated global direction. Our findings dissected the mechanisms of AR in Ciona and highlight the multilayered regulation underlying the morphogenesis of the chordate body plan and providing a foundation for understanding its biomechanical and molecular bases.

developmental biology↗

bioRxiv2025

A probiotic bacterium modulates antitumor γδ T-cell responses in lung cancer

The link between the intestinal microflora and cancer outcomes has been recognized for over a decade. Several recent studies have demonstrated that the gut microbiome is associated with the efficiency of T-cell checkpoint blockade therapy for cancer raising interest in strategies to harness this effect via consumption of live microorganisms (probiotics). The probiotic Clostridium butyricum strain MIYAIRI 588 (CBM588) enhances both response rates and overall survival in patients receiving immune checkpoint blockade therapy for non-small cell lung cancer and metastatic renal cell carcinoma but the mechanism underpinning this benefit remains unclear. Here, we show that CBM588 spores induce a population of V{gamma}9V{delta}2 T-cells from the peripheral blood of healthy donors and lung cancer patients. A subset of these T-cells responded to, and directly lysed, cancer cell lines via a butyrophilin 3A-dependant mechanism. In patients taking CBM588 alongside checkpoint blockade, peripheral V{delta}2 T-cells expressed the activation marker CD69 more frequently than those receiving checkpoint blockade alone and the frequency of V{delta}2CD69 cells increased following initiation of CBM588 treatment (p = 0.0041). Our findings provide a potential mechanism by which the manipulation of the intestinal microflora might directly contribute to cancer prognosis by activating immune effector cells with intrinsic anticancer properties.

immunology↗

bioRxiv2025

Genome assembly and annotation of the naked mole rat Heterocephalus glaber reared in Japan

The naked mole rat (NMR, Heterocephalus glaber) is a eusocial rodent that is native to northeastern Africa. NMRs exhibit extraordinary traits such as longevity, resistance to age-related decline, and remarkable hypoxia tolerance. Although the reference genome of this species has been determined because of its unique characteristics, the significance or role of intraspecific genomic variations remains unknown. In this study, we used PacBio long-read sequencing to generate a genome assembly of NMR reared in Japan. The assembled genome is 2.56 Gb. Benchmarking Universal Single-Copy Orthologs (BUSCO) revealed high completeness (95.2%). BRAKER3 estimated 26,714 protein-coding genes, and we successfully added functional annotations for 26,232 protein-coding genes using the functional annotation workflow. We identified 417 gene models that were previously undetectable in the reference genome of this species. We also identified structural and amino acid sequence variations between our assembly and the reference genome, suggesting the presence of intraspecific genomic variations. This new genomic resource could help uncover the molecular mechanisms underlying the behavioral and physiological traits of NMR.

genomics↗

bioRxiv2024

Exploring 3-Aminobenzoic Acid as a Therapeutic Dietary Component for Enhancing Intestinal Barrier Integrity in Ulcerative Colitis

BackgroundDietary components and their metabolites produced by intestinal bacteria play a crucial role in maintaining intestinal epithelial integrity. Disrupted epithelial integrity increases permeability and leads to chronic inflammation in the colon, known as ulcerative colitis (UC), in genetically predisposed individuals. However, the gut microbial metabolites regulating epithelial permeability remain unexplored and their metabolism in UC patients is unclear. MethodsA library of 119 gut microbial metabolites was screened for their ability to reduce epithelial permeability in Caco2 cell monolayers. The diet containing 3-aminobenzoic acid (3-ABA) was identified using liquid chromatography with quadrupole time-of-flight mass spectrometry. The abundance of fecal 3-ABA was compared between UC patients and healthy individuals followed by 16S rRNA metagenomic analysis to estimate the gut microbial function in ABA degradation. The anti-inflammatory effect of 3-ABA was examined in a mouse model of dextran sodium sulfate-induced colitis. ResultsStimulation with 3-ABA reduced epithelial permeability and enhanced barrier integrity in Caco2 cells by modulating the tight junctional regulatory pathway. 3-ABA was abundant in beans and decreased in the feces of UC patients. Functional prediction analysis of gut microbiota revealed an accelerated degradation of ABA with significant up-regulation of mabA, a gene encoding a bacterial enzyme involved in 3-ABA degradation, in UC patients. Rectal and oral administration of 3-ABA ameliorated experimental colitis in mice. Conclusion3-ABA abundant in beans enhanced intestinal epithelial integrity and ameliorated experimental colitis in mice. Proactive intake of 3-ABA might be a novel treatment approach for UC.

molecular biology↗

bioRxiv2022

Genetically encoded sensors for analysing neurotransmission among synaptically-connected neurons

Anatomical connectome mapping in small areas of the nervous system as well as large-scale detection of neuronal activity patterns have been respectively achieved; however, it is still challenging to evaluate the functional connections among anatomically-connected neurons in a large-scale nervous system. We have developed a novel method to visualize neurotransmission named Split Protein HEmispheres for REconstitution (Sphere). By splitting a sensor into two fragments and expressing them in pre- and postsynaptic neurons separately, functional neurotransmitter sensors can be reconstituted only at the synapses between those neurons. We developed a Sphere-SF-iGluSnFR to measure glutamate levels, and further demonstrated that this system is functional in cultured cells, worms, and mouse brains. Moreover, this system is applicable to sensors other than glutamate, and colour variants have also been developed. This could allow for brain-wide imaging of functional synaptic transmission among particular neurons and identification of important neuronal circuits in the nervous system.

neuroscience↗

bioRxiv2021

Resistance to chemical carcinogenesis induction via a dampened inflammatory response in naked mole-rats

Naked mole-rats (NMRs) have a very low spontaneous carcinogenesis rate, which has prompted scientists to study their cancer resistance mechanisms in order to provide clues for human cancer prevention. Although cancer resistance in NMRs has been intensively investigated at the cellular level, it is still unknown how strongly resistant NMR individuals are to carcinogenesis and how NMR tissues respond to experimental carcinogenesis induction. Here, we show that NMRs exhibit extraordinary resistance against potent chemical carcinogenesis induction through a dampened inflammatory response. Although carcinogenic insults damaged skin cells of both NMRs and mice, NMR skin showed markedly lower immune cell infiltration and reduced induction of inflammatory genes. NMRs harbor loss-of-function mutations in receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) genes, which are essential for necroptosis, a type of necrotic cell death that activates strong inflammation. A necroptosis-inducing stimulus did not increase death of NMR cells. After carcinogenic insults, leakage of the HMGB1, a marker of necrotic cell death, was not increased in NMR skin. In mice, inhibition or knockout of RIPK3 reduced immune cell infiltration and delayed the onset of chemical carcinogenesis. Therefore, necroptosis deficiency may serve as a cancer resistance mechanism via attenuating the inflammatory response in NMRs. Our study sheds light on the importance of a dampened inflammatory response as a non-cell-autonomous cancer resistance mechanism in NMRs. Further in vivo study of the unusual tissue immune system and carcinogenesis resistance of NMRs may lead to the development of new strategies to prevent carcinogenesis in humans. Significance StatementIn contrast with intensive studies of cancer resistance mechanisms in naked mole-rats (NMRs) at the cellular level, little is known about how NMR individuals respond to carcinogenesis induction, despite the fact that cell-to-cell interactions in tissues regulate carcinogenesis in vivo. Here, we demonstrate that NMRs are remarkably resistant to chemical carcinogenesis induction and characteristically have attenuated tissue inflammatory responses to carcinogenic insults. NMRs have loss-of-function mutations in RIPK3 and MLKL genes and thus cannot activate necroptosis, a type of inflammation-inducing cell death. RIPK3 inhibition in mice reduced immune cell infiltration in response to carcinogenic insults and delayed the onset of chemical-induced carcinogenesis. Our results highlight the importance of studies on dampened tissue inflammatory responses to understand cancer resistance of NMRs.

cancer biology↗

bioRxiv2021

Admp regulates tail bending by controlling the intercalation of the ventral epidermis through myosin phosphorylation.

The transient but pronounced ventral tail bending is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape (Lu et al., 2020). Here, we identify one key upstream regulator of ventral tail bending in the ascidian Ciona embryo. We show that during early tailbud stage, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin (pMLC) accumulated. We further show that interfering with the function of the BMP ligand Admp leads to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using a ultraviolet laser relaxes ventral tail bending. Based on these results, we propose a novel function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail. Summary StatementAdmp is an upstream regulator of tail bending in the chordate Ciona tailbud embryo, determining tissue polarity of the ventral midline epidermis by localizing phosphorylated myosin.

developmental biology↗

bioRxiv2021

One pair of motor neurons provokes early spontaneous motor behavior through periodic bursting in the chordate ascidian embryo

Vertebrate rhythmic motor behaviour is generated by the central pattern generator (CPG) located in the spinal cord. However, the development of the CPG has not been elucidated at the single-neuron level. We found that a single pair of motor neurons (A10.64/MN2) constitutes the CPG and regulates rhythmic early motor behaviour in the proto-chordate, Ciona. This pair of cells exhibited Ca2+ oscillation with an 80-sec interval at the mid-tailbud stage and 25 sec at the late tailbud stage. The Ca2+ oscillation occurred independently in a dissociated single cell. In the late tailbud stage, the Ca2+ oscillation began to coincide in phase with the ipsilateral tail muscle contraction, which corresponds to rhythmic early motor behaviour. Interestingly, the number and frequency of tail muscle contractions gradually coincided with spikes in the burst of membrane potential as the embryos developed toward late tailbud stage. Photoablation of A10.64/MN2 abolished the rhythmic early motor behaviour. These findings indicate that the early spontaneous rhythmic motor behaviour of Ciona is directly regulated by A10.64/MN2 as an essential component of the CPG. Our findings shed light on the development and evolution of chordate rhythmic behaviours.

developmental biology↗

bioRxiv2020

Senescent cell death as an aging resistance mechanism in naked mole-rat

Naked mole-rats (NMRs) are the longest-lived rodents, showing minimal aging phenotypes. An unsolved paradox is that NMRs exhibit low intracellular anti-oxidant defence despite minimal aging. Here, we explained a link between these “contradicting” features by a phenomenon termed “senescent cell death (SCD)”—Senescence induced cell death in NMR cells due to their inherent vulnerability to reactive oxygen species and unique metabolic system. In NMR skin, we observed few senescent cells during aging or after ultraviolet irradiation, suggesting suppression of senescent cell accumulation in NMR tissue. We discovered that senescent NMR-fibroblasts induce SCD through retinoblastoma protein activation accompanied by autophagy dysregulation, increased oxidative damage and accelerated H2O2-releasing metabolic pathways. During senescence, NMR cells showed resistance to metabolic remodelling unlike mice. Our findings provide mechanistic insights into how extraordinary aging resistance is accomplished in NMR. This will contribute to the development of senolytic drugs to regulate age-related diseases.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗

bioRxiv2020

Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a poikilothermic mammal

The naked mole-rat (NMR) is a poikilothermic mammal that forms eusocial colonies consisting of one breeding queen, several breeding kings, and subordinates. Despite their poikilothermic feature, NMRs possess brown adipose tissue (BAT), which in homeothermic mammals induces thermogenesis in cold environments. However, NMR-BAT thermogenic potential is controversial, and its physiological roles are unknown. Here, we show that NMR-BAT has beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential, which contributes to thermogenesis in the isolated queen in non-cold environments. NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity in vitro and in vivo. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment, it was insufficient to maintain the body temperatures of the NMRs. In a non-cold environment, NMRs are known to increase their body temperature by a heat-sharing behavior. Interestingly, we found that the body temperatures of NMRs isolated from the colony were also significantly higher than the ambient temperature. We also show that queens, but not subordinates, induce BAT thermogenesis in isolated, non-cold conditions. Our research provides novel insights into the role and mechanism of thermoregulation in this unique poikilothermic mammal.Competing Interest StatementThe authors have declared no competing interest.View Full Text

zoology↗

bioRxiv2018

Transcriptional Activation of a Cartilaginous Fish (Elephant Shark, Callorhinchus milii) Mineralocorticoid Receptor by Corticosteroids, Progestins and Spironolactone

We report the analysis of activation of full-length mineralocorticoid receptor (MR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates by corticosteroids and progesterone. Based on their measured activities, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone and 19-norprogesterone are potential physiological mineralocorticoids. However, aldosterone, the physiological mineralocorticoid in humans and other terrestrial vertebrates, is not found in cartilaginous or ray-finned fishes. Although progesterone activates ray-finned fish MRs, progesterone does not activate human, amphibian or alligator MRs, suggesting that during the transition to terrestrial vertebrates, progesterone lost the ability to activate the MR. Both elephant shark MR and human MR are expressed in the brain, heart, ovary, testis and other non-epithelial tissues, indicating that MR expression in diverse tissues evolved in the common ancestor of jawed vertebrates. Our data suggest that progesterone-activated MR may have unappreciated functions in elephant shark ovary and testis.

physiology↗

bioRxiv2017

Evolution of steroid specificity in human, chicken, alligator, frog and zebrafish mineralocorticoid receptors: Allosteric interactions affect steroid specificity

We studied the response to aldosterone, 11-deoxycorticosterone, 11-deoxycortisol, cortisol, corticosterone, progesterone, 19-norprogesterone and spironolactone of human, chicken, alligator, frog and zebrafish full-length mineralocorticoid receptors (MRs) and truncated MRs, lacking the N-terminal domain (NTD) and DNA-binding domain (DBD), in which the hinge domain and ligand binding domain (LBD) were fused to a GAL4-DBD. Compared to full-length MRs, some vertebrate MRs required higher steroid concentrations to activate GAL4-DBD-MR-hinge/LBD constructs. For example, 11-deoxycortisol activated all full-length vertebrate MRs, but did not activate truncated terrestrial vertebrate MRs and was an agonist for truncated zebrafish MR. Progesterone, 19-norProgesterone and spironolactone did not activate full-length and truncated human, alligator and frog MRs. However, at 10 nM, these steroids activated full-length chicken and zebrafish MRs; at 100 nM, these steroids had little activity for truncated chicken MRs, while retaining activity for truncated zebrafish MRs, evidence that regulation of progestin activation of chicken MR resides in NTD/DBD and of zebrafish MR in hinge-LBD. Zebrafish and chicken MRs contain a serine corresponding to Ser810 in human MR, required for its antagonism by progesterone, suggesting novel regulation of progestin activation of chicken and zebrafish MRs. Progesterone may be a physiological activator of chicken and zebrafish MRs.

physiology↗