Biology subjects

Kamiya, S.

Publications and source records attributed to Kamiya, S..

6 recordsLinked to original sources

bioRxiv2025

Cdc25-mediated activation of the small GTPase RasB is essential for hyphal fusion and symbiotic infection of Epichloë festucae

Epichloe festucae is a filamentous endophytic fungus that symbiotically colonizes the intercellular spaces of aerial tissues in perennial ryegrass (Lolium perenne) without causing disease symptoms. This mutualistic association enhances host resistance to both biotic and abiotic stresses. Balanced and coordinated growth of E. festucae with its host is essential for the establishment and long-term maintenance of the symbiotic relationship. Various E. festucae mutants defective in symbiosis with host plants have been isolated, and notably, many of these symbiosis-defective mutants also lack hyphal fusion ability under culture conditions, supporting a close functional connection between signal transduction required for hyphal fusion and symbiosis establishment. Using a plasmid insertional mutagenesis approach, we identified Cdc25 as an essential regulator of hyphal fusion in E. festucae. Cdc25 encodes a guanine nucleotide exchange factor (GEF) that activates the small GTPase Ras. The{Delta} cdc25 strain lost both hyphal fusion ability and the capacity to infect host plants. Furthermore, yeast two-hybrid assays revealed that Cdc25 specifically interacts with RasB, one of the five Ras proteins in E. festucae. Expression of constitutively active (CA) RasB in the{Delta} cdc25 strain restored both hyphal fusion and host infection, whereas expression of CA-RasB in the{Delta} mpkB deletion strain failed to rescue its defect in hyphal fusion, suggesting that the Cdc25-RasB signaling module acts upstream of the MAPK cascade. In pathogenic fungi, this signaling module is known to regulate infection-related morphogenesis. These findings indicate that E. festucae has evolutionarily repurposed the conserved Cdc25-RasB module to coordinate hyphal fusion and maintain a stable mutualistic interaction with its host.

microbiology↗

bioRxiv2023

Cell type specificity of mosaic chromosome 1q gain resolved by snRNA-seq in a case of epilepsy with hyaline protoplasmic astrocytopathy

STRUCTURED ABSTRACTO_ST_ABSIntroductionC_ST_ABSMosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathological finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown. MethodsWe present a child with pharmacoresistant epilepsy who underwent epileptic focus resections at age 3 and 5 years and was found to have mosaic chr1q gain and HPA. We performed single-nuclei RNA-sequencing (snRNA-seq) of brain tissue from the second resection. ResultssnRNA-seq showed increased expression of chr1q genes specifically in subsets of neurons and astrocytes. Differentially expressed genes associated with inferred chr1q gain included AKT3 and genes associated with cell adhesion or migration. A subpopulation of astrocytes demonstrated marked enrichment for synapse-associated transcripts, possibly linked to the astrocytic inclusions observed in HPA. DiscussionsnRNA-seq may be used to infer the cell type-specificity of mosaic chromosomal copy number changes and identify associated gene expression alterations, which in the case of chr1q gain may involve aberrations in cell migration. Future studies using spatial profiling could yield further insights on the molecular signatures of HPA.

neuroscience↗

bioRxiv2023

AtMYB50 regulates root cell elongation by upregulating PECTIN METHYLESTERASE INHIBITOR 8 in Arabidopsis thaliana

Plant root development is regulated by several signal transduction pathways. Among them, plant phytohormones, like auxin and cytokinin, are well characterized for their molecular mechanisms of action. Reactive oxygen species (ROS) play important roles as signaling molecules in controlling root development. Under these signal transduction pathways, the gene regulatory network, which is controlled by transcription factors, is the key to regulating root growth. We have previously reported an important transcription factor, UP BEAT1 (UPB1), that regulates ROS homeostasis at the root tip, further controlling the transition from cell proliferation to differentiation. Although UPB1 directly regulates the expression of several peroxidases that control ROS homeostasis, UPB1 still targets genes other than peroxidases. This indicates that UPB1 may regulate root growth through different ROS signals. Here, we investigated the function of the transcription factor MYB50, a direct target of UPB1, in Arabidopsis thaliana. We then examined whether UPB1 regulates MYB50 expression in the roots using an induction expression system and imaging of multiple fluorescent proteins. We also performed RNA-Seq analysis using MYB50 estradiol induction lines and ChIP-seq analysis to identify the MYB50 regulatory gene network. Integrating these analyses with UPB1 regulatory network revealed that MYB50 regulates the expression of PECTIN METHYLESTERASE INHIBITOR 8 (PMEI8). These data suggest that MYB50 is a new root growth regulator under the UPB1 gene regulatory network, which differs from the control of ROS homeostasis. Our study presents a model including a new transcriptional network under MYB50 into UPB1 regulatory root growth system and will provide novel insights into the cell elongation controlled by pectin modification.

plant biology↗

bioRxiv2022

Suppression of vitamin D metabolizing enzyme CYP24A1 provides increased sensitivity to chemotherapeutic drugs in breast cancer

Vitamin D is an essential nutrient for the human body that plays an important role in homeostasis and contributes to cell fate decision including proliferation, differentiation and cell viability. Accumulated epidemiological data suggest a relationship between vitamin D deficiency and carcinogenesis in various organs. However, the underlying mechanism remains to be further clarified. In this study, we showed that vitamin D metabolizing enzyme CYP24A1 promotes the oncogenic property of breast carcinoma cells. In addition, expression of CYP24A1 is elevated in invasive breast carcinoma and decreases the overall survival. Importantly, CYP24A1 suppression significantly enhances cell death sensitivity to two pharmacologically different acting anticancer drugs, cisplatin and gefitinib. The results of our study suggest the possibility of CYP24A1-inhibiting therapy for breast malignancy.

pathology↗

bioRxiv2021

Quantifying brain state transition cost via Schrödinger's bridge

Quantifying brain state transition cost is a fundamental problem in systems neuroscience. Previous studies utilized network control theory to measure the cost by considering a neural system as a deterministic dynamical system. However, this approach does not capture the stochasticity of neural systems, which is important for accurately quantifying brain state transition cost. Here, we propose a novel framework based on optimal control in stochastic systems. In our framework, we quantify the transition cost as the Kullback-Leibler divergence from an uncontrolled transition path to the optimally controlled path, which is known as Schrodinger bridge. To test its utility, we applied this framework to functional magnetic resonance imaging data from the Human Connectome Project and computed the brain state transition cost in cognitive tasks. We demonstrate correspondence between brain state transition cost and the difficulty of tasks. The results suggest that our framework provides a general theoretical tool for investigating cognitive functions from the viewpoint of transition cost. Author SummaryIn our daily lives, we perform numerous tasks with different kinds and levels of cognitive demand. To successfully perform these tasks, the brain needs to modulate its spontaneous activity to reach an appropriate state for each task. Previous studies utilized optimal control in deterministic systems to measure cost for brain state transition. However, there has not been a unified framework for quantifying brain state transition cost that takes account of stochasticity of neural activities. Here, we propose a novel framework for measuring brain state transition cost, utilizing the idea of optimal control in stochastic systems. We assessed the utility of our framework for quantifying the cost of transitioning between various cognitive tasks. Our framework can be applied to very diverse settings due to its generality.

neuroscience↗

bioRxiv2018

Genome-wide association meta-analysis identifies novel GP2 gene risk variants for pancreatic cancer in the Japanese population

The etiology of pancreatic cancer remains largely unknown. Here, we report the results of a meta-analysis of three genome-wide association studies (GWASs) comprising 2,039 pancreatic cancer cases and 32,592 controls, the largest sample size in the Japanese population. We identified 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P<5.0x10-8) and 4 suggestive loci (P<1.0x10-6) for pancreatic cancer. Of these risk loci, 16p12.3 is novel; the lead SNP maps to rs78193826 (odds ratio (OR)=1.46, 95% CI=1.29-1.66, P=4.28x10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant predicted to be highly deleterious. Additionally, the gene-based GWAS identified a novel gene, KRT8, which is linked to exocrine pancreatic and liver diseases. The identified GP2 gene variants were pleiotropic for multiple traits, including type 2 diabetes, hemoglobin A1c (HbA1c) levels, and pancreatic cancer. Mendelian randomization analyses corroborated causality between HbA1c and pancreatic cancer. These findings suggest that GP2 gene variants are associated with pancreatic cancer susceptibility in the Japanese population, prompting further functional characterization of this locus.

genetics↗