Biology subjects

Yamada, G.

Publications and source records attributed to Yamada, G..

4 recordsLinked to original sources

bioRxiv2026

Differential physiological, behavioral, and medial prefrontal cortex transcriptomic responses to chronic restraint stress between BALB/c and C57BL/6J mice

Chronic stress is a major risk factor for psychiatric disorders such as depression and anxiety, yet the biological basis of individual differences in stress susceptibility and resilience remains poorly understood. Here, we examined physiological, behavioral, and medial prefrontal cortex (mPFC) transcriptomic responses to chronic restraint stress (CRS) in male BALB/c and C57BL/6J mice. After 21 days of CRS, BALB/c mice exhibited greater stress-related changes than C57BL/6J mice, including greater body weight loss, elevated serum corticosterone, reduced serum antioxidant capacity, and more pronounced depression-like behaviors. RNA sequencing showed largely strain-specific transcriptional changes in the mPFC. Strain x stress interaction analysis, followed by canonical pathway analysis using Ingenuity Pathway Analysis (IPA), identified strain-dependent molecular signatures. The most prominent differences involved extracellular matrix (ECM) organization and remodeling and neuroinflammatory signaling pathways, with greater predicted activation in BALB/c mice. IPA upstream regulator analysis further predicted multiple candidate regulators associated with these pathways, including TGF-{beta}/SMAD, C4a/C4b, and MAPK14. Among genes associated with these pathways, several ECM-related genes were preferentially upregulated in BALB/c mice, whereas activity-dependent immediate early genes were preferentially downregulated in C57BL/6J mice. These findings suggest that the strain-dependent mPFC transcriptional programs identified here may contribute to differential stress susceptibility and resilience.

neuroscience↗

bioRxiv2026

Cooperative regulation of NF-E2 related factor 1 protein stability and transcriptional activation by endoplasmic reticulum-associated degradation system mediator, Selenoprotein S/K.

NRF1 is a key mediator of the proteasome recovery pathway, yet its regulation by ER-resident factors is not fully elucidated. Here, we demonstrate that selenoproteins SELS and SELK are critical regulators for NRF1 protein dynamics. SELS stabilizes NRF1, while SELK induces its insolubilization. Their deficiency leads to a hyper-accumulation and increased nuclear localization of NRF1 under proteasome inhibition condition. This results in an augmented transcriptional response of proteasome subunits. These results indicate that SELS and SELK cooperatively gate NRF1 activity by controlling its retrotranslocation and solubility, highlighting a novel layer of selenoprotein-mediated quality control in the proteostasis network.

biochemistry↗

bioRxiv2026

Flow-driven lumen remodeling and valve opening in the vas deferens

Biological ducts must transport fluids while preserving structural integrity, yet how mechano-signaling coordinates wall deformation with luminal flow in vivo remains unclear. Here we combine intravital two-photon excitation microscopy, light-sheet imaging and FRET-based kinase biosensors to resolve ejaculation-like events in the mouse vas deferens. Acute phenylephrine stimulation elicits a sequence of luminal dynamics: an initial retrograde pressure-redistribution wave followed by a ballistic antegrade flow that propels dense sperm suspensions from proximal to distal duct. This contraction-driven flow opens a normally collapsed, wrinkled distal segment, driving progressive lumen expansion and unfolding of epithelial wrinkles. We show that the vas deferens actively modulates luminal geometry in response to these flow dynamics: ROCK activity in smooth muscle is required for global contraction and cAMP-associated signaling modulates this contractile response. By contrast, ERK activity in circumferential smooth muscle is dispensable for the ductal contraction but essential for active, flow-dependent remodeling of the distal lumen, forming the core of the mechano-signaling module that couples sperm flow to valve opening. These findings establish the vas deferens as an experimentally tractable model of ductal tissue hydraulics and reveal a mechano-signaling framework by which a tubular organ converts transient muscular input into robust, directional luminal transport. SIGNIFICANCE STATEMENTMale reproductive ducts must rapidly propel sperm-containing fluids forward, yet how they do so in living animals has remained unclear due to a lack of imaging studies. By combining real-time in vivo imaging and molecular activity reporters, we observe the mouse vas deferens at work and link each phase of ejaculation-like transport to specific signaling pathways. We find that ROCK activity is closely linked to the overall squeeze of the duct, cAMP-associated signaling modulates this contractile response, and ERK is uniquely required to open and remodel a normally closed distal valve in response to flow. This mechano-signaling framework offers a general blueprint for how tubular organs coordinate muscle contraction, tissue shape change, and directional luminal transport.

physiology↗

bioRxiv2025

High-Throughput Measurement of Oxidative Stress Indicators: d-ROMs and BAP Assays in a 384-Well Plate Format

The bodys oxidative balance is regulated by systems that produce and eliminate reactive oxygen species (ROS), and disruptions in this balance can contribute to the development of lifestyle-related diseases. d-ROMs and BAP tests, which evaluate oxidative balance using just 30 {micro}L of serum per sample in approximately 10 minutes, are widely used for this purpose. However, these methods are not suitable for large-scale studies due to their low-throughput and cost. To overcome these limitations, we established a simultaneous measurement system for multiple samples (144 samples) for measuring d-ROMs and BAP using a pipetting robot and a 384-well plate. The developed system demonstrated good linearity and reproducibility, while significantly reducing reagent and sample consumption. Measurement differences compared to the one of the currently available FREE Carrio Duo system ranged from -5% to 3% for d-ROMs and -12% to 8% for BAP, indicating high consistency with existing methods. Furthermore, the measurement time was substantially shortened from 24 hours (10 minutes x 144 samples) to at longest four hours, although the final color measurements for d-ROMs were performed one week later. This optimized semi-automated system enables the precise and efficient measurement of oxidative stress markers, making it suitable for large-scale studies.

biochemistry↗