Biology subjects

Yamauchi, T.

Publications and source records attributed to Yamauchi, T..

At least 19 recordsLinked to original sources

bioRxiv2026

A genome-wide catalog of sites where peripheral DNA methylation reflects the brain

Epigenetic studies of psychiatric and neurological disorders rely largely on peripheral tissues, yet where peripheral DNA methylation (DNAm) reflects the brain remains unclear. We generated a paired brain and peripheral DNAm dataset from 148 donors in three cohorts and combined it with five published cohorts for consensus brain-peripheral correlations. By cross-validation across cohorts, we defined brain epigenome shared sites (BrESS), more than 100,000 CpGs per tissue at which peripheral DNAm reproducibly predicts brain DNAm. BrESS lay at promoters active in both brain and periphery and in housekeeping genes, and most were not explained by genetic effects. BrESS did not contribute to the heritability of seven disorders, and CpGs from epigenome-wide association studies of these disorders were not enriched at BrESS. Peripheral DNAm reflects the brain mainly in a regulatory compartment shared across tissues, outside which disease signals largely lie, and BrESS separate peripheral signals attributable to the brain from others.

neuroscience↗

bioRxiv2026

Developmental prefrontal myelination shapes inhibitory interneuron function and adult social behavior

Early-life adversity and abnormal myelination are implicated in psychiatric disorders, but how developmental myelination influences adult social cognition remains unclear. Here, we tested whether disrupting developmental myelination in the medial prefrontal cortex (mPFC) impairs adult social behavior. Using complementary genetic strategies in male mice, we suppressed Myelin Regulatory Factor (Myrf)-dependent myelination locally in the juvenile mPFC or broadly in oligodendrocyte-lineage cells. Both approaches selectively impaired adult social novelty preference while sparing sociability, locomotion, and affective behaviors. Focal prefrontal dysmyelination also reduced social dominance. Spatial transcriptomics revealed coupling between myelin-related genes and parvalbumin (PV) interneuron markers in the healthy mPFC, which was disrupted by developmental hypomyelination. Consistent with this transcriptional alteration, PV interneurons showed reduced high-frequency firing despite preserved intrinsic excitability. In the human prefrontal cortex, MBP-PV expression was correlated in controls but not in individuals with schizophrenia. These findings indicate that developmental prefrontal myelination contributes to PV interneuron maturation and suggest that disrupted oligodendrocyte-interneuron coordination may contribute to impaired social recognition.

neuroscience↗

bioRxiv2026

Neonatal social communication and single genes predict the variability of post-pubertal social behavior in a mouse model of paternal 15q11-13 duplication

Mental illnesses associated with high-risk copy number variations (CNVs) are characterized by incomplete penetrance and variable severity, with their underlying mechanisms remaining inadequately understood. We hypothesized that such phenotypic variability is evident from the neonatal stage and is, at least in part, attributable to individual differences in the expression levels of CNV-encoded genes in the brain. We conducted an analysis of the quantitative and functional structure of neonatal social communication, assessed post-pubertal social interaction, and evaluated the brain expression levels of genes within the same cohort of a mouse model of paternal human 15q11-13 duplication, a high-risk factor variably associated with neurodevelopmental disorders. Subsequently, computational methods were utilized to identify predictive variables for the variability of post-pubertal social interaction. Mice harboring the 15q11-13 duplication exhibited distinctive call sequences characterized by diverse connections, which lacked the incentive value necessary for effective social communication with mother mice. The neonatal call sequences and the expression levels of Magel2, along with, to a lesser extent, Herc2 and Ndn, in the prefrontal cortex of the 15q11-13 duplication model were predictive of post-pubertal social interaction. Our findings demonstrate that variability in post-pubertal social interaction--a dimensional characteristic of neurodevelopmental disorders--can be predicted by the variability of neonatal social communication and is influenced by the expression levels of specific CNV-encoded genes in the prefrontal cortex. This computational approach has the potential to predict the developmental trajectories of various dimensions of mental illness among CNV carriers in humans and to identify CNV-encoded driver genes in preclinical models, thereby providing potential mechanistic bases for the development of gene-based therapeutic strategies.

neuroscience↗

bioRxiv2026

Direction-dependent bias in the perceived approach speed and its implications for robot motion design

Humans frequently interact with robots that approach from different directions; however, how the approach direction systematically biases the perceived speed remains unclear. Here, we demonstrate a robust direction-dependent bias in the perceived approach speed, whereby objects approaching from behind are consistently perceived as moving faster than those approaching from the front are. Across five experiments using both physical robots and immersive virtual reality, this bias manifests as a systematic shift in the point of subjective equality without corresponding changes in discrimination sensitivity, indicating a perceptual bias rather than altered precision. We further show that this effect can be explained by body-induced differences in interocular velocity that arise when observers orient themselves toward stimuli approaching from behind. This bias persists in virtual environments and for nonrobotic objects, suggesting that it is driven primarily by visual factors rather than multisensory cues or robot-specific appearance. Together, these findings provide a perceptual foundation for incorporating approach direction into the design and evaluation of the motion behavior of robots in human-centered environments.

neuroscience↗

bioRxiv2025

Correlates of head-fixed orienting movements in mouse superior colliculus and substantia nigra pars reticulata

Orienting movements are a critical component of the natural behavioral repertoire, but their underlying neural bases are not well understood. The deep superior colliculus (dSC) integrates input from several brain regions that influence the selection of targets for orienting movements and coordinates activity among brainstem motor nuclei to initiate and execute movement. Evidence suggests that one prominent dSC input, the substantia nigra pars reticulata (SNr), permits movement by disinhibiting its targets, but much is unknown about the relationship between SNr activity, dSC activity, and movement. Building on increasing application of the head-fixed mouse model to elucidate the neural basis of behavior, we examined neural activity recorded in dSC and SNr with high-density probes in mice performing several variants of a sensorimotor orienting task, from our labs and in data sets curated by the International Brain Laboratory. We found that dSC and SNr were active preceding and throughout movement, across task variants, suggesting that they were engaged by the required movements. Prior to movement, SNr activity reflected the outcome of the previous trial, consistent with a role in biasing movements towards the highest value target. However, the dependence of dSC activity on movement direction was weaker than in other directional orienting behaviors, and we found little evidence for strong suppression of dSC by SNr. These results complement and extend previous findings from other orienting tasks and suggest diverse roles for modulatory input from SNr to dSC in shaping motor behavior.

neuroscience↗

bioRxiv2025

Pain-stimulated ultrasound vocalizations and their impact on pain response in mice

Pain is a complex phenomenon encompassing both the physiological and psychological aspects of sensation and emotion, respectively. In recent years, pain has been clarified to arise even without direct injury, with emotional transmission as a cause. However, the specific mechanisms behind emotional transmission are still not well understood. In this study, sounds in the ultrasonic domain that were recorded during pain stimulation in mice were used as sound stress to examine the effects of psychological stress caused by exposure to ultrasound on tactile thresholds. We also examined the effects of psychological stress caused by the ultrasound on an inflammatory pain model of mice. The tactile threshold decreased the next and three days after sound stress exposure in mice. DNA microarray analysis of the mouse thalamus exposed to sound stress revealed increased expression of inflammation-related genes, Prostaglandin-endoperoxide synthase 2 and C-X-C motif chemokine ligand 1. Their respective inhibitors, loxoprofen and SB225002, significantly improved hyperalgesia induced by sound stress. When sound stress was applied to a mouse model of inflammatory pain in which pain thresholds were restored 14 days after complete Freunds adjuvant administration, prolonged pain and attenuated analgesic effects of loxoprofen were observed. These results suggest that sound stress not only induces inflammation in the brain that causes hyperalgesia but may also be partially responsible for exacerbating inflammatory pain, hence complicating treatment.

pharmacology and toxicology↗

bioRxiv2024

Multi-layered apoplastic barrier underlying the ability of Na+ exclusion in Vigna marina

O_LISalt tolerance is important to tackle problems of soil salinization and ground water depletion. However, developing salt tolerant crops is facing difficulties due to limited potential in model plants and crop species. Thus, it is important to elucidate how coastal species, such as Vigna marina, adapt to saline environments. C_LIO_LIBy comparative transcriptome and histological analyses, this study elucidated one important aspect of how Vigna marina achieves salt exclusion and extraordinary salt tolerance. C_LIO_LIUnder salt stress, genes involved in casparian strip formation were specifically upregulated in JP247202 (V. marina). JP247202 reinforced apoplastic barrier with thick lignification in multiple layers of cells around endodermis. Also, disruption of lignification led to a dramatic increase of shoot Na+ accumulation and salt lesion in JP247202. Interestingly, despite the salt-induced apoplastic barrier, JP247202 maintained transport of essential ions including K+, Mg2+, and Ca2+. C_LIO_LIOur results revealed that lignification of multi-layered cells around endodermis was an important apoplastic barrier to the transport of Na+ to shoots in JP247202, while it did not restrict the transport of K+, Mg2+, and Ca2+. This feature, together with the ability of Na+ excretion by SOS1, enables V. marina to thrive in marine beaches. C_LI

plant biology↗

bioRxiv2024

Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via 7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.

cell biology↗

bioRxiv2023

Structural alterations in the amygdala and impaired social incentive learning in a mouse model of a genetic variant associated with neurodevelopmental disorders

Copy number variants (CNVs) are robustly associated with psychiatric disorders and their dimensions and changes in brain structures and behavior. However, as CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.2 CNV carriers have been identified in humans and mouse models, it is unknown how the genes in the 22q11.2 region individually contribute to structural alterations and associated mental illnesses and their dimensions. Our previous studies have identified Tbx1, a T-box family transcription factor encoded in 22q11.2 CNV, as a driver gene for social interaction and communication, spatial and working memory, and cognitive flexibility. However, it remains unclear how TBX1 impacts the volumes of various brain regions and their functionally linked behavioral dimensions. In this study, we used volumetric magnetic resonance imaging analysis to comprehensively evaluate brain region volumes in congenic Tbx1 heterozygous mice. Our data show that the volumes of anterior and posterior portions of the amygdaloid complex and its surrounding cortical regions were reduced in Tbx1 heterozygous mice. Moreover, we examined the behavioral consequences of an altered volume of the amygdala. Tbx1 heterozygous mice were impaired for their ability to detect the incentive value of a social partner in a task that depends on the amygdala. Our findings identify the structural basis for a specific social dimension associated with loss-of-function variants of TBX1 and 22q11.2 CNV.

neuroscience↗

bioRxiv2022

Human collision avoidance behavior against autonomous mobile robot

Currently, the probability of pedestrians on the streets of smart cities encountering autonomous mobile robots (AMRs) is increasing. Previous studies have discussed collision avoidance between humans as they cross paths. Their avoidance behavior toward AMRs, however, remains unclear. To address this, we experimentally investigated the avoidance direction a human would choose against an AMR approaching head-on. This experiment included recording human locomotion under such a scenario. Further, an AMR was programmed to approach from various starting points, including directly through the participants (head-on collision). The participants were directed to evade it by moving rightward or leftward, and their paths were tracked. We found that the participants did not strongly prefer either direction, suggesting that the avoidance direction is not solely determined by the participants attributes, such as their adherence to the traffic rules of their region. The probability of rightward evasion when the AMR approached head-on indicated that humans use different avoidance strategies when encountering other humans and obstacles. Moreover, the participants motion analysis revealed that they involuntarily twisted their waists in the avoidance direction before they evaded the AMR. These results suggest that this twist is the most important predictor of the avoidance direction. These findings could be encoded into the programs of AMRs to adapt these vehicles to our locomotory responses more organically.

neuroscience↗

bioRxiv2021

Transcriptional regulation of neonatal neural stem cells is a determinant of social behavior

Rare gene variants confer a high level of penetrance to neurodevelopmental disorders, but their developmental origin and cellular substrates remain poorly understood. To address this limitation, we explored the role of TBX1, a gene encoded in a rare copy number variant, in cell and mouse models. Here, we report that neonatal Tbx1 deficiency contributes to defective peripubertal social behavior and impairs the proliferation of neonatal neural stem/progenitor cells. Moreover, TBX1 transcriptionally regulates genes linked to post-embryonic neurogenesis and neurodevelopmental disorders associated with other rare gene variants. Our data indicate a precise time window and cell type through which the social dimension is altered by a gene encoded in a rare CNV and provide a potential common mechanistic basis for a group of neurodevelopmental disorders. One-Sentence SummaryTbx1, a gene affecting neonatal stem cell proliferation, influences peripubertal social behavior.

neuroscience↗

bioRxiv2021

Activation of innate immune signalling during development predisposes to inflammatory intestine and shortened lifespan

Early-life inflammatory response is associated with risks of age-related pathologies. How transient immune signalling activity during animal development influences life-long fitness is not well understood. Using Drosophila as a model, we find that activation of innate immune pathway IMD signalling in the developing larvae increases adult starvation resistance, decreases food intake, and shortens organismal lifespan. Interestingly, lifespan is shortened by the IMD activation in the larval gut and fat body, while starvation resistance and food intake are altered by that in neurons. The adult flies developed with IMD activation show sustained IMD activity in the gut, despite complete tissue renewal during metamorphosis. The inflammatory adult gut is associated with a greater amount of Gluconobacter sp., characteristic gut microbiota increased in response to immune activation. Removing gut microbiota by antibiotics attenuates the increase of IMD activity and rescues the shortened lifespan. This study demonstrates a tissue-specific programming effect of early-life immune activation on the adult physiology and organismal lifespan.

genetics↗

bioRxiv2021

Tbx1, a 22q11.2-encoded gene, is a link between alterations in fimbria myelination and cognitive speed in mice

Copy number variants (CNVs) have provided a reliable entry point to identify structural correlates of atypical cognitive development. Hemizygous deletion of human chromosome 22q11.2 is associated with impaired cognitive function; however, the mechanisms by which numerous genes encoded in this CNV contribute to cognitive deficits via diverse structural alterations in the brain remain unclear. This study aimed to determine the cellular basis of the link between alterations in brain structure and cognitive functions in a mouse model. The heterozygosity of Tbx1, a 22q11.2 gene, altered the composition of myelinated axons in the fimbria, reduced oligodendrocyte production capacity, and slowed the acquisition of spatial memory and cognitive flexibility. Our findings provide a cellular basis for specific cognitive dysfunctions that occur in patients with loss-of-function TBX1 variants and 22q11.2 hemizygous deletion. TeaserA risk gene for autism alters myelin composition in the hippocampal connection and slows cognitive speed.

neuroscience↗

bioRxiv2020

Multimodal-Multisensory Experiments: Design and Implementation

The human mind is multimodal. Yet most behavioral studies rely on century-old measures of behavior - task accuracy and latency (response time). Multimodal and multisensory analysis of human behavior creates a better understanding of how the mind works. The problem is that designing and implementing these experiments is technically complex and costly. This paper introduces versatile and economical means of developing multimodal-multisensory human experiments. We provide an experimental design framework that automatically integrates and synchronizes measures including electroencephalogram (EEG), galvanic skin response (GSR), eye-tracking, virtual reality (VR), body movement, mouse/cursor motion and response time. Unlike proprietary systems (e.g., iMotions), our system is free and open-source; it integrates PsychoPy, Unity and Lab Streaming Layer (LSL). The system embeds LSL inside PsychoPy/Unity for the synchronization of multiple sensory signals - gaze motion, electroencephalogram (EEG), galvanic skin response (GSR), mouse/cursor movement, and body motion - with low-cost consumer-grade devices in a simple behavioral task designed by PsychoPy and a virtual reality environment designed by Unity. This tutorial shows a step-by-step process by which a complex multimodal-multisensory experiment can be designed and implemented in a few hours. When conducting the experiment, all of the data synchronization and recoding of the data to disk will be done automatically.

neuroscience↗

bioRxiv2020

Massive occurrence of benthic plastic debris at the abyssal seafloor beneath the Kuroshio Extension, the North West Pacific

The deep-sea is considered to be an ultimate sink for marine plastic debris. The abyssal (3500-6500 m) covers the bulk of the deep ocean floor yet little is known about the extent of plastic debris on the abyssal seafloor. We undertook a quantitative assessment of debris presents on the abyssal seafloor (5700-5800 m depth) beneath the Kuroshio Extension current system in the Northwest Pacific, which is one of the major transit points for massive amounts of debris sourced from Asia that are entering the North Pacific Ocean. The dominant type of debris was single-use plastics-mainly bags and food packaging. The density of plastic debris (average 4561 items km-2) in the abyssal zone was the highest recorded for an abyssal plain, suggesting that the deep-sea basin of the Northwest Pacific is a significant reservoir of plastic debris.

ecology↗

bioRxiv2020

Effective neoantigen vaccination correlates with generation of antigen-specific CX3CR1+CD8+ T cells mediated by CD40 and CD80/86 signaling in cDC1s

The use of tumor mutation-derived neoantigen represents a promising approach for cancer vaccines. Preclinical and early-phase human clinical studies have shown the successful induction of tumor neoepitope-directed responses; however, overall clinical efficacy of neoantigen vaccines has been limited. One major obstacle of this strategy is the prevailing lack of sufficient understanding of the mechanism underlying the generation of neoantigen-specific CD8+ T cells. Here, we report a correlation between antitumor efficacy of neoantigen/toll-like receptor 3 (TLR3)/CD40 vaccination and the generation of antigen-specific CD8+ T cells expressing CX3C chemokine receptor 1 (CX3CR1) in a preclinical model. Mechanistic studies using mixed bone marrow chimeras identified that CD40 and CD80/86, but not CD70 signaling in Batf3-dependent conventional type 1 dendritic cells (cDC1s) is required for antitumor efficacy of neoantigen vaccine and generation of neoantigen-specific CX3CR1+ CD8+ T cells. Although CX3CR1+ CD8+ T cells exhibited robust in vitro effector function, depletion of this subset did not alter the antitumor efficacy of neoantigen/TLR3/CD40 agonists vaccination, suggesting that the expanded CX3CR1+ CD8+ T cell subset represents the post-differentiated in vivo effective CX3CR1-negative CD8+ T cell subset. Taken together, our results reveal a critical role of CD40 and CD80/86 signaling in cDC1s in antitumor efficacy of neoantigen-based therapeutic vaccines, and implicate the potential utility of CX3CR1 as a circulating predictive T-cell biomarker in vaccine therapy.

immunology↗

bioRxiv2020

A circulating T-cell differentiation marker to predict response to immune checkpoint inhibitors

Immune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers; however, durable response is limited to only a subset of patients. Discovery of blood-based biomarkers that reflect dynamic change of the tumor microenvironment, and predict response to ICI will markedly improve current treatment regimens. Here, we investigated a role of CX3C chemokine receptor 1 (CX3CR1), a marker of T-cell differentiation, in predicting response to ICI therapy. Successful treatment of tumor-bearing mice with ICI increased the frequency and T-cell receptor clonality of the peripheral CX3CR1+CD8+ T-cell subset that included an enriched repertoire of tumor-specific and tumor-infiltrating CD8+ T cells. Furthermore, an increase in the frequency of the CX3CR1+ subset in circulating CD8+ T cells early after initiation of anti-PD-1 therapy correlated with response and survival in patients with non-small cell lung cancer (NSCLC). Taken together, these data support T-cell CX3CR1 expression as a blood-based dynamic biomarker to predict response to ICI therapy.

immunology↗

bioRxiv2020

Structural basis of ethnic-specific variants of PAX4 associated with type 2 diabetes

Recently, we conducted genome-wide association studies of type 2 diabetes (T2D) in a Japanese population, which identified 20 novel T2D loci that were not associated with T2D in Europeans. Moreover, nine novel missense risk variants, such as those of PAX4, were not rare in the Japanese population, but rare in Europeans. We report in silico structural analysis of ethnic-specific variants of PAX4, which suggests the pathogenic effect of these variants.

genetics↗