Biology subjects

Araki, S.

Publications and source records attributed to Araki, S..

5 recordsLinked to original sources

bioRxiv2026

IL-17A Mediates Cardiac Hypertrophy in Chronic Kidney Disease through the IL-23/Th17 Axis.

Background: Chronic kidney disease (CKD) is a major risk factor for cardiovascular morbidity, promoting left ventricular hypertrophy (LVH) prior to overt heart failure. The mechanisms underlying early cardiac remodeling in CKD remain incompletely understood. The IL-23/Th17/IL-17A inflammatory axis has emerged as a key mediator of cardiovascular pathology; however, its role in CKD-associated cardiac remodeling remains unclear. This study aimed to elucidate the contribution of this pathway to the early cardiac changes in CKD. Methods: Using a 5/6 nephrectomy (5/6Nx) mouse model of CKD, we evaluated cardiac structure, mitochondrial function, and inflammatory signaling. Cardiomyocyte transcriptomes were analyzed by RamDA-seq to identify molecular alterations. Circulating cytokines were profiled longitudinally, and IL-17A neutralization experiments were performed to assess causality. In addition, serum IL-12p40 concentrations were measured in patients with CKD and correlated with their renal function and cardiac remodeling indices. Results: At 16 weeks post-5/6Nx, mice developed LVH with preserved systolic function, accompanied by increased oxidative stress and mitochondrial structural abnormalities, but without significant myocardial fibrosis. Transcriptomic analysis identified oxidative phosphorylation as the most significantly downregulated pathway in cardiomyocytes. Despite increased mitochondrial DNA copy number and elevated PGC-1 expression, ATP production and mitochondrial respiratory chain proteins were reduced, indicating mitochondrial dysfunction. Circulating IL-12p40 and IL-23 levels increased progressively, concurrent with expansion of splenic Th17 cells and elevated cardiac IL-17A expression. Recombinant IL-17A directly impaired mitochondrial respiration in cultured cardiomyocytes. In vivo, IL-17A neutralization attenuated LVH, reduced oxidative stress, and partially restored mitochondrial protein expression without improving renal function. In patients with CKD, serum IL-12p40 levels correlated inversely with estimated glomerular filtration rate and positively with left ventricular mass index, supporting clinical relevance. Conclusions: Activation of the systemic IL-23/Th17/IL-17A axis contributes to early CKD-associated cardiac remodeling by promoting oxidative stress and mitochondrial dysfunction. Circulating IL-12p40 may serve as a biomarker of cardiorenal remodeling, and the IL-23/IL-17A pathway represents a potential therapeutic target.

physiology↗

bioRxiv2025

Design Guidelines for Dry Electrode Tip Geometry in Electroencephalography Measurements: A Proposal Based on the Scalp's Mechanical Response

In electroencephalography (EEG) measurements using dry electrodes, a trade-off between signal stability and user comfort is a critical barrier to long-term, wearable applications. While various approaches have been proposed to address this issue, the mechanical impact of electrode tip geometry has not been adequately quantified, and most existing evaluations predominantly rely on subjective assessments. To address this gap with a quantitative, mechanics-based framework, the current study aimed to identify an optimized electrode tip geometry that minimizes mechanical stress on the scalp even under tilted contact conditions. Finite element analysis was conducted using strain energy density (SED)-- a mechanical index known to correlate with neural impulse activity--as a quantitative indicator of the mechanical influence of tip geometry on the skin. Six types of electrode tip geometries, ranging from flat to hemispherical, were defined based on the ratio of fillet radius to prong radius. These geometries were analyzed under inclination angles from 0{degrees} to 5{degrees}, and their peak SED values were compared. Additionally, a geometry optimization using an iterative search algorithm was performed to minimize peak SED under the 5{degrees} tillt. The findings revealed that intermediate fillet geometries with gently rounded edges more effectively reduce peak SED under inclined conditions. Optimization further identified a geometry ratio of [Formula] as the most effective tip geometry for minimizing mechanical loading under the specified conditions. These results offer a potential geometric design guideline for dry EEG electrodes that can help maintain user comfort across varying inclination angles.

bioengineering↗

bioRxiv2023

Transcription factor activity profiling reveals the role of REST and LEF1 in the recovery from depression

Psychophysiological disorders chronically impair brain functions, often accompanied by dysregulation of multiple genes, suggesting a multifaceted etiology behind the symptoms. To explore transcription factors (TFs) involved in such transcriptomic changes, we analyzed TF-activity profiles (TFAPs) from the brains of mice experienced chronic stress, and revealed alteration in TF-activity correlating with their pathophysiological phenotypes. We identified REST/NRSF and TCF/LEF associated with depressive phenotypes and discovered that neuropsychiatric drugs sertraline and lithium influence REST- and TCF/LEF-activity, both in vitro and in vivo, thereby affecting gene expression profiles. Pharmacological or genetic manipulation of REST- or TCF/LEF-activity in defeated mice impacts post-stress recovery from depressive phenotypes, with combined treatment further augmenting the outcomes. Our TFAP analysis enhances understanding of molecular mechanisms underpinning chronic diseases, aiding future therapeutic strategy development.

neuroscience↗

bioRxiv2022

3D-multiple immunoimaging using whole male organs in rice

The spatiotemporal regulation of proteins and RNAs is essential for the precise development of reproductive tissues in many organisms. The anther, a significant part of the male reproductive organ in plants, contains the somatic cell layers named the anther wall and germ cells located inside. The cell-to-cell communication between the soma and germ cells in the development of male and female tissues is reported, although the mechanism remains unknown in plants. Here, we successfully developed a simple 3D-organ-immunoimaging technique, which distinguishes each single cell from the four somatic cell layers and germ cells without the need for transformation, embedding, sectioning, or clearing in rice. The 3D-immunostaining method is also applicable to the intracellular localization of meiosis-specific proteins in meiocytes--namely MEL1, a germ cell-specific Argonaute in the cytoplasm, and ZEP1, a pachytene marker on meiotic chromosomes. Our study suggests that the 3D-multiple immunostaining method with single-cell and intracellular resolution will contribute to the organ-level elucidation of comprehensive molecular mechanisms and non-cell-autonomous systems.

plant biology↗

bioRxiv2017

EIF4A3 associated splicing and nonsense mediated decay defined by a systems analysis with novel small molecule inhibitors

Chemical biology approaches to the global functions of splicing reactions are gaining momentum, with an increasing repertoire of small molecule probes becoming available. Here we map the association of eIF4A3 with transcript expression, NMD and alternative splicing using a set of selective novel small molecule allosteric helicase inhibitors whose synthesis and chemical properties we have recently described. We show through analysis of dose monotonic transcriptional responses to increasing inhibition that both full length and NMD prone transcripts link eIF4A3 to normal functioning of cell division including chromosome segregation and cell cycle checkpoints, pointing to a conserved role of splicing and transcript quality processing in cell cycle functions. Cell cycle analysis and microscopy of inhibitor treated cells demonstrates chromosome mis-segregation and spindle defects, associated with a G2/M arrest, validating this observation. Through analysis of conserved alternative splicing patterns exhibiting monotonic responses, we find that eIF4A3 dependent alternative splicing involves exons that are longer and introns that are shorter than transcripts not modulated by eIF4A3. Moreover we observe conservation of over/under representation of RBP binding motif density over introns and exons implicated eIF4A3 modulated skipped exon and retained introns. The distribution of motif densities over 5 and branch intron sites and 5 exons is consistent with function of the exon-junction complex. Taken together we have defined a fraction of the transcrip-tome dependent on eIF4A3 functions and revealed a link between eIF4A3 and cell cycle regulation. The systems approach described here suggests additional avenues for therapeutic exploitation of eIF4A3 functions in cancer and related diseases.

genomics↗