Biology subjects

Shimada, S.

Publications and source records attributed to Shimada, S..

15 recordsLinked to original sources

bioRxiv2026

Avatar-Induced Postural Responses during a Virtual Full-Body Illusion

Body ownership over an artificial body can alter perceptual and autonomic responses, but its influence on online postural control remains less understood. We investigated whether ownership-related body-avatar correspondence modulates postural responses to an unexpected change in avatar posture. Thirty-six healthy male participants were randomly assigned to an Embodiment condition, in which body-avatar correspondence was maintained, or a Disruption condition, in which the avatar's arm temporarily moved independently of the participant before the critical event. During a standing virtual-reality session with synchronous visuotactile stimulation, the avatar unexpectedly leaned forward. We introduced Avatar-Induced Postural Response (AIPR), an event-related index of anterior-posterior center-of-pressure displacement following the avatar's movement. Ownership-related questionnaire ratings were higher in the Embodiment condition, whereas self-location-related ratings did not differ between conditions. AIPR was greater in the Embodiment condition and was greater than zero only in this condition. AIPR was also positively correlated with skin conductance responses in the Embodiment condition, but was not associated with questionnaire ratings. These findings suggest that an unexpected change in avatar posture can influence the participant's own postural regulation when ownership-related body-avatar correspondence is maintained. AIPR may provide a complementary behavioral index of a postural-control component of avatar embodiment not fully reflected in explicit subjective reports.

neuroscience↗

bioRxiv2026

Region-specific cortico-striatal transcriptomic remodeling following early postnatal dopaminergic disturbance

Dopamine signaling plays critical roles in postnatal brain development, yet the molecular consequences of early dopaminergic disturbance remain incompletely understood. Here, we investigated transcriptomic alterations in the prefrontal cortex (PFC) and striatum (STR) of mice subjected to early postnatal dopaminergic disturbance by 6-hydroxydopamine (6-OHDA) treatment. Using bulk RNA sequencing (RNA-seq) and weighted gene co-expression network analysis (WGCNA), we identified 369 differentially expressed genes (DEGs) in the PFC, 493 DEGs in the STR, and 32 co-expression modules with region-specific expression patterns. Functional enrichment analyses showed that PFC DEGs were associated with cortical development, plasma membrane signaling, and transcriptional regulation, whereas STR DEGs were enriched for striatal development, locomotion, extracellular matrix organization, and amphetamine response. Co-expression network analysis further identified module-specific enrichments related to developmental, synaptic, metabolic, immune-related, and transcriptional programs. DEG sets from both regions also overlapped with genes implicated in attention-deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Together, these findings reveal region-specific cortico-striatal transcriptomic remodeling following early postnatal dopaminergic disturbance and identify molecular programs that may link developmental dopaminergic perturbation to later behavioral phenotypes. HighlightsO_LIEarly dopaminergic disturbance reshapes cortico-striatal transcriptomes C_LIO_LIPFC changes were linked to developmental and transcriptional programs C_LIO_LISTR changes were linked to locomotion and extracellular matrix programs C_LIO_LINetwork analysis revealed region-specific developmental and synaptic programs C_LI

neuroscience↗

bioRxiv2026

Brief online mindfulness meditation training modulates heart rate variability during post-stress meditation

Mindfulness-based interventions are increasingly delivered online, yet evidence for short programs often relies on self-report outcomes. We tested whether a brief online mindfulness meditation training produces detectable changes in autonomic regulation during a standardized stress-to-meditation sequence. Healthy adults with no meditation experience were randomized to a four-week online mindfulness meditation program (MG) or an active health-management program (CG). Before and after training, participants completed a laboratory session consisting of rest, a mental arithmetic stress task, guided focused-attention breathing meditation, and post-rest while ECG was recorded. Across the training period, both groups showed reduced negative affective symptoms, but only the mindfulness group showed an increase in the Observing facet. Critically, frequency-domain HRV indices during the laboratory protocol showed a group-specific post-training pattern: MG exhibited lower LF/HF and higher normalized HF power (nHF) compared with pre-training, and MG differed from CG in the post-training session. Within MG, training-related improvement in FFMQ Non-reactivity was positively associated with nHF during the post-stress meditation period. These findings indicate that a brief online mindfulness program can modulate HRV during a stress-to-meditation context and that post-stress autonomic modulation during meditation covaries with acceptance-related skill acquisition.

neuroscience↗

bioRxiv2026

Avatar facial expressions enhance social presence and inter-brain synchronization in virtual reality

Virtual reality (VR) has become a prominent medium for computer-mediated social interaction, yet the psychological and neural mechanisms underpinning avatar-mediated communication remain insufficiently understood. This study investigated how dynamically modulated avatar facial expressions shape interpersonal interaction in VR. Pairs of participants engaged in a collaborative creativity task while interacting via avatars whose facial expressions were either amplified, natural, or expressionless. We collected subjective measures of body ownership, social presence, and interpersonal attraction, while simultaneously recording neural activity using functional near-infrared-spectroscopy-based hyperscanning to assess inter-brain synchrony (IBS). Avatars displaying facial expressions, particularly amplified ones, significantly enhanced body ownership, social presence, and interpersonal attraction compared to expressionless avatars. At the neural level, visible avatar facial expressions were associated with IBS in the right temporo-parietal junction (TPJ) and the dorsolateral prefrontal cortex (dlPFC), regions that are commonly implicated in social-cognitive processes such as mentalizing and executive control. Although task performance did not differ across conditions, social presence was positively correlated with creative performance, suggesting that psychological connectedness supports collaborative creativity. Together, these findings indicate that avatar facial expressivity functions as a critical nonverbal social cue that facilitates affective and cognitive alignment between interaction partners. By linking subjective experience with inter-brain neural dynamics, this study provides empirical guidance for the design of virtual environments that promote social engagement and effective collaboration.

neuroscience↗

bioRxiv2025

High-Frequency Activity Encodes the Temporal Dynamics of Hierarchical Prediction Errors in Humans: An Electrocorticography Study

Prediction error refers to the discrepancy between expected and actual sensory input. Its hierarchical organization has been demonstrated through decomposed brain responses in the local-global paradigm, where temporal regularities are established locally at individual stimulus transitions and globally across multi-tone sequence structures. In macaques and marmosets, local and global prediction-error signals have both been found in high-frequency oscillations (60-150 Hz) recorded with ECoG. In humans, however, these signals have primarily been observed in a lower frequency range (30-100 Hz) using EEG. Here, we recorded human ECoG to achieve higher signal fidelity, enabling examination of neural oscillations above 100 Hz (high-frequency activity, HFA), which are believed to be closely linked to local spiking activity. Eight participants listened to auditory sequences that either followed their local and global regularities (local and global standards) or violated them (local and global deviants). Robust HFA responses were observed for the local deviants, but these responses were reduced when the deviants were expected based on the global regularity, indicating both levels of prediction-error processes contribute to the observed activity. Importantly, these HFA responses could be decomposed into two subcomponents: an early component reflecting local prediction-error signals localized to lateral auditory regions, and a late component reflecting global prediction-error signals prominent in both lateral auditory and frontal cortices. Together, these findings demonstrate that neural oscillations above 100 Hz encode hierarchical prediction errors not only in non-human primates but also in humans.

neuroscience↗

bioRxiv2025

Disrupted priming within draining lymph nodes drives immune quiescence in gastric cancer

The gastric mucosa is characterized by continuous innate immune surveillance and inflammatory signaling, yet a high proportion of gastric carcinomas (GCs) are recalcitrant to immune-directed therapies. The mechanisms by which GCs evade adaptive immune surveillance within the highly antigenic microenvironment of the gastric mucosa remains unknown. To address this, we collected patient-matched tumor tissue, distant normal tissue, metastasis, and draining lymph nodes to generate a large-scale single-cell immune profiling dataset from 64 patients (n=179 samples, >150,000 cells). From single cell analysis, we identified two distinct sources of impaired tumor surveillance within tumor draining lymph nodes. First, we observed that a significant fraction of tumor draining lymph nodes had undergone cytokine-driven reprogramming, leading to reduced dendritic cell homing and limited T cell priming. Second, T cells undergoing successful activation exhibited limited expansion and constrained differentiation, marked by expression of the quiescence-associated transcription factor Kruppel-like Factor 2 (KLF2). Overexpression of KLF2 in primary T cells limited both their differentiation and cytotoxic capacity. These findings implicate both impaired T cell priming and KLF2-dependent T cell quiescence in limiting T cell immunity in gastric adenocarcinoma. We suggest these findings represent an emerging model for immune silencing in tumors developing from tissues with chronic inflammation.

immunology↗

bioRxiv2025

Glucosylation of Endogenous Haustorium-inducing factors Underpins Kin Avoidance in Parasitic Plants

Parasitic plants rarely attack themselves, suggesting the activity of a kin-avoidance mechanism. In the root parasitic plant Phtheirospermum japonicum, prehaustorium formation is triggered by host-secreted haustorium-inducing factors (HIFs), but it is unresponsive to its own root exudates. Here we report the identification of the spontaneous prehaustorium 1 (spoh1) mutant, which forms prehaustoria without external HIFs. spoh1 harbors a point mutation in the gene encoding UDP-glycosyltransferase GT72B1, an enzyme that glucosylates and thereby inactivates phenolic HIFs. Notably, PjGT72B1 possesses a different substrate specificity from its ortholog of the host Arabidopsis. Introduction of PjGT72B1 in Arabidopsis reduced HIF activity, indicating that HIF glucosylation regulates haustorium induction by hosts. Our findings suggest that parasitic plants have evolved kin-avoidance mechanisms through the glucosylation of endogenous HIFs.

plant biology↗

bioRxiv2024

A Nostalgia Brain-Music Interface for Enhancing Nostalgia, Well-Being, and Memory Vividness in Young and Elderly Individuals

Music-evoked nostalgia has the potential to assist in recalling autobiographical memories and enhancing well-being. However, nostalgic music preferences vary from person to person, presenting challenges for applying nostalgia-based music interventions in clinical settings, such as a non-pharmacological approach. To address these individual differences, we developed the Nostalgia Brain-Music Interface (N-BMI), a neurofeedback system that recommends nostalgic songs tailored to each individual. This system is based on prediction models of nostalgic feelings, developed by integrating subjective nostalgia ratings, acoustic features and in-ear electroencephalographic (EEG) data during song listening. To test the effects of N-BMI on nostalgic feelings, well-being, and memory recall, seventeen elderly and seventeen young participants took part in the study. The N-BMI was personalized for each individual, and songs were recommended under two conditions: the "nostalgia condition", where songs were selected to enhance nostalgic feelings, and the "control condition", to reduce nostalgic feelings. We found nostalgic feelings, well-being, and memory vividness were significantly higher after listening to the recommended songs in the nostalgia condition compared to the control condition in both groups. This indicates that the N-BMI enhanced nostalgic feelings, well-being, and memory recall across both groups. The N-BMI paves the way for innovative therapeutic interventions, including non-pharmacological approaches.

neuroscience↗

bioRxiv2023

High-Dimensional Spectral Cytometry Reveals Therapeutically Relevant Immune Subtypes in Gastric Cancer

Identification of locally advanced gastric cancer (GC) patients who might potentially benefit from immune-based strategies is limited by both the poor predictive quality of existing biomarkers, including molecular subtypes, tumor mutational burden, and PD-L1 expression, as well as inadequate understanding of the gastric cancer immune microenvironment. Here, we leveraged high-dimensional spectral cytometry to re-classify locally advanced gastric tumors based on immune composition. The gastric cancer microenvironment was comprised of a diverse immune infiltrate including high proportions of plasmablasts, macrophages, and myeloid-derived suppressor cells. Computational cell typing and sample clustering based on tiered broad immune and T-cell focused phenotyping identified three distinct immune subtypes. The most immunogenic subtype exhibited high proportions of activated CD4+ T-cells and plasmablasts and included tumors that would have been classified as non-immunogenic based on prior classifications. Analysis of gastric cancer patients treated with immune checkpoint blockade indicates that patients who responded to immunotherapy had a pre-treatment tumor composition that corresponded to higher immune scores from our analysis. This work establishes a novel immunological classification of gastric cancer including identification of patients and immune networks likely to benefit from immune-based therapies.

cancer biology↗

bioRxiv2023

The effects of excess salt intake on the kidney metabolism in Sprague-Dawley rats

In the present study, novel methods were developed which allowed continuous (24/7) measurement of blood pressure (BP) and renal blood flow (RBF) in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. The study determined the effects of a high salt (HS) diet upon whole kidney O2 consumption and the metabolomic profiles of normal Sprague Dawley (SD) rats. A separate group of rats was studied to determine changes in the cortex (Cx) and outer medulla (OM) tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to a 4.0% NaCl diet. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. Increased glycolysis was evident with the elevation of mRNA expression encoding key glycolytic enzymes and release of pyruvate and lactate from the kidney in the renal venous blood. Glycolytic production of NADH is used in either the production of lactate or oxidized via the malate aspartate shuttle. Aerobic glycolysis (e.g., Warburg-effect) may account for the needed increase in cellular energy. The study provides evidence that kidney metabolism responds to a HS diet enabling enhanced energy production while protecting from oxidate stress and injury.

physiology↗

bioRxiv2022

STREAMING-tag system reveals spatiotemporal relationships between transcriptional regulatory factors and transcriptional activity

Transcription is a dynamic process that stochastically switches between the ON and OFF states. To detect the dynamic relationship among protein clusters of RNA polymerase II (RNAPII) and coactivators, gene loci, and transcriptional activity, we inserted an MS2 repeat, a TetO repeat, and inteins with a selection marker just downstream of the transcription start site (TSS). By optimizing the individual elements, we have developed the Spliced TetO REpeAt, MS2 repeat, and INtein sandwiched reporter Gene tag (STREAMING-tag) system. Clusters of RNAPII and BRD4 were observed proximally to the TSS of Nanog when the gene was transcribed in mouse embryonic stem cells. In contrast, clusters of MED19 and MED22 Mediator subunits were constitutively located near the TSS. Thus, the STREAMING-tag system revealed the spatiotemporal relationships between transcriptional activity and protein clusters near the gene. This powerful tool is useful for quantitatively understanding dynamic transcriptional regulation in living cells.

molecular biology↗

bioRxiv2021

Decrease of Functional Connectivity within the Default Mode Network by a Brief Training of Focused Attention on the Breath in Novices

Experienced meditators reduce the activity of the default mode network (DMN), a brain system preferentially active when people are not engaged in specific tasks. However, the neural modulation of the DMN in novices remain largely unexplored. By using electroencephalography, we investigated the DMN functional connectivity in two groups of novices: the meditation group practiced six consecutive days of focused attention on the breath; the control group practiced only on the first and last days. After the brief training, results showed a decrease in the DMN functional connectivity between the ventromedial prefrontal cortex and the posterior cingulate cortex in theta and alpha bands during the focused attention condition, in the meditation group compared to the control group. The change in DMN functional connectivity was significantly correlated with the increase in state-level mindfulness scores. These data elucidate DMN modifications already arising at the initial stages of mindfulness meditation training in novices.

neuroscience↗

bioRxiv2020

Pruriception and neuronal coding in nociceptor subtypes in human and nonhuman primates

In human, intradermal administration of {beta}-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1 respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (Macaca nemestrina), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22 and histamine, that activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.

neuroscience↗

bioRxiv2020

Zbtb16 regulates social cognitive behaviors and neocortical development.

Recent genetic studies have underscored the pleiotropic effects of single genes to multiple cognitive disorders. Mutations of ZBTB16 are associated with autism spectrum disorder (ASD) and schizophrenia (SCZ), but how the function of ZBTB16 is related to ASD or SCZ remains unknown. Here we show the deletion of Zbtb16 in mice leads to both ASD- and SCZ-like behaviors such as social impairment, repetitive behaviors, risk-taking behaviors, and cognitive impairment. To elucidate the mechanism underlying the behavioral phenotypes, we carried out histological studies and observed impairments in thinning of neocortical layer 6 (L6) and a reduction of TBR1+ neurons in the prefrontal cortex (PFC) of Zbtb16 KO mice. Furthermore, we found increased dendritic spines and microglia as well as developmental defects in oligodendrocytes and neocortical myelination in the PFC of Zbtb16 KO mice. Using a genomics approach, we identified the Zbtb16-transcriptome that includes genes involved in both ASD and SCZ pathophysiology and neocortical maturation such as neurogenesis and myelination. Co-expression networks further identified Zbtb16-correlated modules that are unique to ASD or SCZ respectively. Our study provides insight into the differential role of ZBTB16 in ASD and SCZ.

neuroscience↗

bioRxiv2017

Structure and function of the intermembrane space domain of mammalian FoF1 ATP synthase

Mitochondrial FoF1 ATP synthase is a membrane bound molecular machine central to cellular energy conversion and cristae architecture. Recently, a novel domain has been visualized in the intermembrane space region of mammalian ATP synthase. The complete three-dimensional (3D) structure, composition and function of this domain - which we term intermembrane space domain (IMD) - are unknown. Here, we present two distinct 3D structures of monomeric bovine FoF1 ATP synthase by single particle cryo-electron microscopy (cryo-EM) that differ by the presence and absence of the IMD. Comparison of both structures reveals the IMD to be a bipartite and weakly associated domain of FoF1 ATP synthase. The tubular sub-domain of the IMD appears to contact the rotor-ring region, its globular sub-domain is anchored in the membrane-bending kink of the ATP synthase. However, absence of the IMD does not impact the kink in the transmembrane region ruling out a functional role in membrane bending. By combining our structural analysis with chemical cross-linking and reported biochemical, genetic and structural data we identify 6.8PL and DAPIT as the subunits forming the intermembrane space domain. We compare the present structure of the mammalian IMD in the bovine FoF1 ATP synthase monomer with structures of dimeric FoF1 ATP synthase from yeast and ciliate showing that the IMD is a common, but structurally divergent feature of several mitochondrial ATP synthases. On the basis of our analysis we discuss potential functions of the novel domain in rotary catalysis, oligomerization and mitochondrial permeability transition.

biophysics↗