Biology subjects

Kawashima, N.

Publications and source records attributed to Kawashima, N..

7 recordsLinked to original sources

bioRxiv2026

Transient cortical activity modulates somatosensory gating during postural control

Human somatosensory responses vary with movement-related gating as well as with fluctuations in ongoing cortical activity. During standing, both somatosensory responses and cortical activity change in response to postural demands. However, little is known regarding whether moment-to-moment fluctuations in cortical activity contribute to variation in somatosensory responses during different postural tasks. In this study, we investigated whether somatosensory-evoked potentials (SEPs) during postural control are associated with prestimulus cortical activity, focusing on oscillatory amplitudes and corticocortical connectivity. SEPs evoked by tibial nerve stimulation were recorded in 18 healthy adults under four postural conditions. Canonical correlation analysis (CCA) was used to extract single-trial SEP amplitudes from multichannel electroencephalography (EEG). The results showed that the early component of CCA-SEPs, N80, was significantly reduced according to postural demands. A higher prestimulus amplitude in the {beta}-frequency band in the central cortical regions was associated with a larger N80 amplitude. Moreover, modulation of -band corticocortical connectivity involving frontal and parietal regions covaried with N80 reduction. Clustering analysis using {beta}-amplitude and -connectivity as features further indicated that multivariate prestimulus cortical activity accounted for variability in N80 amplitude. These findings revealed that somatosensory responses vary through posture-related somatosensory gating and as a function of ongoing fluctuations in cortical activity. Clarifying the temporal dynamics of somatosensory processing will help elucidate the underlying physiological mechanisms of standing balance and contribute to the development of novel physiological assessments of postural impairments.

neuroscience↗

bioRxiv2026

Hog1/p38 and ZAKα drive Shwachman-Diamond syndrome and provide targets to improve cell growth

Shwachman-Diamond syndrome (SDS) is a ribosomopathy characterized by neutropenia, pancreatic insufficiency, skeletal defects, and predisposition to leukemia. Most cases result from biallelic SBDS mutations that impairing 80S ribosome and polysome assembly. In yeast lacking SDO1 (the SBDS ortholog), growth slows dramatically and the p38 ortholog Hog1 signaling is elevated by multiple types of stress. SBDS-deficient HeLa cells exhibited reduced proliferation and slowed cell cycling. The p38 kinase was constitutively activated in SBDS mutants and SDS patient-derived blood cells. Because ZAK detects ribosome dysfunction, its activation links ribosomal defects to stress kinase pathways in SDS. Suppressing p38 or its upstream activator ZAK restored cell growth and reduced stress signaling. These findings reveal an evolutionarily conserved-independent mechanism via p38 drives SDS pathophysiology and identifies stress kinases as potential therapeutic targets for ribosomal dysfunction.

cell biology↗

bioRxiv2025

In cellulo DNA assembly for targeted genomic integration and rearrangement in human cells

Although therapeutic genome editing holds great potential to remedy diverse inherited and acquired disorders, targeted installation of medium to large sized genomic modifications in therapeutically relevant cells remains challenging. We have developed an approach that permits DNA sequence assembly and integration in human cells leveraging CRISPR-targeted dual flap synthesis. This method, named prime assembly, allows for RNA-programmable site-specific integration of single- or double-stranded DNA fragments. Unlike homology-directed repair, prime assembly was similarly active in dividing and non-dividing cells. We applied prime assembly to perform targeted exon recoding, transgene integration, and megabase-scale rearrangements, including at therapeutically relevant loci in primary human cells. Prime assembly expands the capabilities of genome engineering by enabling the targeted integration of medium to large sized DNA sequences without relying on double-stranded DNA donors, nuclease-driven double strand breaks, or cell cycle progression.

molecular biology↗

bioRxiv2024

Inflammatory molecules in the glomerular endothelium in mild IgA-Nephropathy identified by single-cell and spatial transcriptome

Immunoglobulin A nephropathy (IgA-N) is a primary glomerulonephritis characterized by mesangial cell proliferation and expansion. It still leads to end-stage renal disease over the long course of the disease in many patients. Although glomerular endothelial cells (GE) have been implicated in the pathogenesis of IgA-N, their role remains poorly understood. We conducted single-cell and spatial transcriptomic analysis using human specimens with mild IgA-N compared with normal. We observed the significantly higher expression of several inflammation-associated molecules which have been reported and not reported to be involved in IgA-N pathogenesis, respectively. Furthermore, we show that several important molecules were also highly expressed in GE of IgA-N at protein level by tissue immunostaining. Our analysis suggests that the characteristic pathways identified in GE that involve these molecules are associated with the progression of IgA-N. These findings offer important insights on both the pathogenesis of IgA-N and its treatment at an early stage.

bioinformatics↗

bioRxiv2024

Corticocortical and Corticomuscular Connectivity Dynamicsin Standing Posture: Electroencephalography Study

Cortical involvements, including those in the sensorimotor, frontal, and occipitoparietal regions, are important mechanisms of neural control in human standing. Previous research has shown that cortical activity and corticospinal excitability vary flexibly in response to postural demand. However, it is unclear how corticocortical and corticomuscular connectivity is dynamically modulated during standing balance and over time. This study investigated the dynamics of this connectivity using electroencephalography (EEG) and electromyography (EMG). The EEG and EMG were measured in different 4 positions: sitting (ST), normal quiet standing (QS), one-leg standing (ON), and standing on a piece of wood (WD). For corticomuscular connectivity, we concentrated on sway-varying connectivity in the timing of peak velocity of postural sway in the anteroposterior direction. For the corticocortical connectivity, the time-varying connectivity was quantified, particularly in the {theta}-band connectivity which is linked to error identification, using a sliding-window approach. The study found that corticomuscular connectivity from the brain to the lower-limb muscle was strengthened during the sway peak in the {gamma}- and {beta}-frequency bands, while the connectivity strength from the muscle to the brain was decreased in the {theta}- and -band. For the time-varying connectivity, the {theta}-connectivity in all time-epoch was divided into 7 states including both posture-relevant and -irrelevant clusters. In one of the 7 states, the strong connectivity pairs were concentrated in the mid-central region and the proportion of epochs from the ON and WD conditions was significantly higher, indicating a functional role for posture balance. These findings shed light on electrodynamic connectivity which varies in response to postural demand. Those dynamics, particularly in the {theta}-band connectivity, can be used for ongoing monitoring and/or intervention for postural disability.

neuroscience↗

bioRxiv2024

MicroRNA-27a-5p downregulates the expression of proinflammatory cytokines in lipopolysaccharide-stimulated human dental pulp cells via NF-κB signaling pathway

AimTo investigate the effect of microRNA-27a-5p (miR-27a-5p) on the expression of proinflammatory cytokines in human dental pulp cells (hDPCs) stimulated by lipopolysaccharide (LPS). MethodologyExpression of miR-27a-5p was evaluated in LPS-stimulated hDPCs isolated from third molars of healthy patients by a TaqMan microRNA assay. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and a cytometric bead array were used to measure mRNA and protein expression levels, respectively, of proinflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemotactic protein 1 (MCP1). Luciferase assays and western blotting were conducted to assess nuclear factor {kappa}B (NF-{kappa}B) activity. Gene/protein expression of NF-{kappa}B signaling activators, i.e., transforming growth factor beta-activated kinase 1 binding protein 1 (TAB1), IL-1 receptor-associated kinase 4 (IRAK4), NF-{kappa}B p65 (RELA), and follistatin-like 1 (FSTL1), was evaluated by RT-qPCR and western blotting. Transfection of an miR-27a-5p mimic was performed using Lipofectamine RNAiMax reagent. Wildtype and mutated 3{square}-untranslated region (UTR) of TAB1-contained luciferase reporter vectors were co-transfected with the miR-27a-5p mimic. Small interfering RNA against TAB1 (siTAB1) was designed to block its expression. One-way analysis of variance and Students t-test were used to determine statistical significance ( = .05). ResultsLPS-stimulated hDPCs showed concurrent increases in the expression of miR-27a-5p and proinflammatory cytokines (IL-6, IL-8, and MCP1), and the increased expression was suppressed by NF-{kappa}B inhibitor BAY 11-0785. Transfection of the miR-27a-5p mimic downregulated expression of proinflammatory cytokines, NF-{kappa}B activity, and expression of NF-{kappa}B signaling activators (TAB1, IRAK4, RELA, and FSTL1) in LPS-stimulated hDPCs. Luciferase reporter assays revealed that miR-27a-5p bound directly to the 3{square}-UTR of TAB1. siTAB1 downregulated NF-{kappa}B activity and proinflammatory cytokine expression. Downregulation of proinflammatory cytokine expression, NF-{kappa}B activity, and NF-{kappa}B signaling activator expression (TAB1, IRAK4, and RELA) was also found in LPS-stimulated rat incisor pulp tissue explants following transfection with the miR-27a-5p mimic ex vivo. ConclusionsMiR-27a-5p, whose expression was induced by NF-{kappa}B signaling, negatively regulated the synthesis of proinflammatory cytokines via targeting NF-{kappa}B signaling. In particular, TAB1, a potent NF-{kappa}B activator, was targeted by miR-27a-5p. These results provide insights into the negative regulatory effects of miR-27a-5p, particularly those targeting the TAB1-NF-{kappa}B signaling pathway, on pulp inflammation.

pathology↗

bioRxiv2018

Cortical control of locomotor muscle activity through muscle synergies in humans: a neural decoding study

Walking movements are orchestrated by the activation of a large number of muscles. The control of numerous muscles during walking is believed to be simplified by flexible activation of groups of muscles called muscle synergies. Although significant corticomuscular connectivity during walking has been reported, the level at which the cortex controls locomotor muscle activity (i.e., muscle synergy or individual muscle level) remains unclear. Here, we examined cortical involvement in muscle control during walking by brain decoding of the activation of muscle synergies and individual muscles from electroencephalographic (EEG) signals using linear decoder models. First, we demonstrated that activation of locomotor muscle synergies was decoded from slow cortical waves with significant accuracy. In addition, we found that decoding accuracy for muscle synergy activation was greater than that for individual muscle activation and that decoding of individual muscle activation was based on muscle synergy-related cortical information. Taken together, these results provide indirect evidence that the cerebral cortex hierarchically controls multiple muscles through a few muscle synergies during walking. Our findings extend the current understanding of the role of the cortex in muscular control during walking and could accelerate the development of effective brain-machine interfaces for people with locomotor disabilities.

neuroscience↗