Biology subjects

Otani, K.

Publications and source records attributed to Otani, K..

11 recordsLinked to original sources

bioRxiv2026

Right-lateralized prefrontal signature with successful Stroop-like interference control in early childhood

The Stroop effect is a canonical measure of executive control, yet its neural architecture has been defined largely in literate children and adults, where left frontal mechanisms have long been implicated in resolving verbal conflict. How the developing brain supports Stroop-like interference control before literacy and stable verbal responding are established remains unknown. Here we show that successful interference control in early childhood is associated with the selective engagement of right lateral prefrontal regions. We used multichannel functional near-infrared spectroscopy to measure prefrontal hemodynamics in 94 children aged 35-79 months during a color-pointing Stroop-like task, in which children pointed to colors in response to spoken color names. Stroop-like conflict elicited broad activation across bilateral lateral prefrontal regions, a conflict response already present from around 3 years of age and did not show a detectable age-related increase. By contrast, individual differences in accuracy under conflict were selectively associated with greater activation in the right dorsolateral and right rostrolateral prefrontal cortices, independent of age. These findings suggest that right lateral prefrontal regions play an important role in successful interference control in early childhood, indicating that preschool Stroop-like control is not merely a weaker form of the adult left-lateralized system.

neuroscience↗

bioRxiv2026

Dissociable pupil-linked arousal during overt and inner speech

Inner (covert) speech, the silent production of language in ones mind, plays a central role in human cognition and is known to activate speech-related cortical regions while also requiring executive and attentional resources. However, the conventional focus on cortical similarity or dissimilarity between inner and overt speech leaves unaddressed the question of whether arousal systems sustain cortical language processing. Here, using pupillometry across three controlled counting experiments, we show a dissociation between inner and overt speech. Overt speech consistently led to pupil dilation across all conditions. Inner speech, by contrast, produced a strikingly different profile: pupil constriction during simple counting, no deviation from baseline during noun-phrase counting, and clear dilation only under a high cognitive load, but with dilation remaining significantly less than that for overt speech in every condition. Covert verbal production thus proceeds at a reduced arousal cost, yet this cost scales flexibly with task demands rather than being fixed. This pupillometric dissociation reveals that inner and overt speech occupy fundamentally distinct arousal states, even when their cortical substrates partially overlap. These findings open a non-invasive window for tracking inner speech physiology across development, individual differences, and clinical populations in whom inner speech is altered.

neuroscience↗

bioRxiv2026

Emergent blink rate in early childhood is associated with neural origins of executive function

Executive function develops rapidly in early childhood and predicts later success in life, yet its neurobiological correlates during this period remain poorly understood. In adults, executive function is supported by prefrontal-striatal circuits under neuromodulatory control, including dopamine. Here, we show that spontaneous eye-blink rate (sEBR), a physiological output influenced by neuromodulatory systems, is associated with the developmental trajectory of executive function and prefrontal functional differentiation. We used fNIRS to monitor prefrontal cortex (PFC) activation in 113 children (35-80 months) during a cognitive flexibility task. With increasing age, the childrens task performance improved, and their PFC activation showed greater right-hemisphere and dorsal bias, reflecting functional differentiation. Importantly, higher sEBR was also associated with this right-dorsal PFC activation and with better task performance. The current findings demonstrate that emergent sEBR is associated with the neural origins of executive function development in young children. This highlights the potential of sEBR to serve as a unique and previously unrecognised indicator of this critical developmental neural mechanism.

neuroscience↗

bioRxiv2025

Anti-amyloid beta therapy resolves stroke recovery impairment caused by Alzheimer's disease

Stroke and dementia are common comorbidities and a growing concern causing disability in aging societies worldwide. Although anti-amyloid beta (anti-A{beta}) antibodies have recently been anticipated to relieve preclinical Alzheimers disease pathology, we discovered that post-stroke administration of anti-A{beta} antibodies restored neural repair for stroke recovery impeded by cerebral A{beta} accumulation. Neuronal recovery-associated gene expression for stroke recovery was considerably impaired even by slight A{beta} accumulation in murine and human brain. Slight A{beta} accumulation had less impact on neurons without stroke but caused a unique myeloid immunity after an ischemic stroke that enhanced the inflammatory cascades impeding neural repair for stroke recovery. Aducanumab administration after ischemic stroke prevented formation of this malignant myeloid immunity, resolving the impairment of post-stroke neural repair caused by cerebral A{beta} accumulation. Thus, our study has revealed the ability of anti-A{beta} therapies to restore functional recovery after a stroke with cerebral A{beta} accumulation.

neuroscience↗

bioRxiv2024

Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product

Circulating Tumor Cells (CTCs), interrogated by sampling blood from patients with cancer, contain multiple analytes, including intact RNA, high molecular weight DNA, proteins, and metabolic markers. However, the clinical utility of tumor cell-based liquid biopsy has been limited since CTCs are very rare, and current technologies cannot process the blood volumes required to isolate a sufficient number of tumor cells for in-depth assays. We previously described a high-throughput microfluidic prototype utilizing high-flow channels and amplification of cell sorting forces through magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.83 liters from patients with metastatic cancer, with a median of 2,799 CTCs purified per patient. Isolation of many CTCs from individual patients enables characterization of their morphological and molecular heterogeneity, including cell and nuclear size and RNA expression. It also allows robust detection of gene copy number variation, a definitive cancer marker with potential diagnostic applications. High-volume microfluidic enrichment of CTCs constitutes a new dimension in liquid biopsies.

bioengineering↗

bioRxiv2023

Atf3 controls transitioning in female mitochondrial cardiomyopathy as identified by single-cell transcriptomics

Oxidative phosphorylation defects results in mitochondrial diseases, with cardiac involvement markedly impacting prognosis. However, the mechanisms underlying the transition from compensation to dysfunction in response to metabolic deficiency remain unclear, impeding the development of effective treatments. Here, we employed single-nucleus RNA sequencing (snRNA-seq) on hearts from mitochondrial cardiomyopathy (MCM) mice with cardiac-specific Ndufs6 knockdown (FS6KD). Pseudotime trajectory analysis of cardiomyocytes from early stage of female FS6KD hearts revealed dynamic cellular state transitioning from compensation to severe compromise, coincided with transient upregulation of a critical transcription factor, activating transcription factor 3 (Atf3). Genetic ablation or adeno-associated virus-mediated Atf3 knockdown in FS6KD mice effectively delayed cardiomyopathy progression in a female-specific manner. Notably, human MCM snRNA-seq revealed a similar transition, including the dynamic expression of ATF3. In conclusion, our findings highlight a fate-determining role of Atf3 in female MCM progression, providing a promising therapeutic candidate for the currently intractable disease.

cell biology↗

bioRxiv2022

Predictive coding during action observation - an Electrocorticographic study

Predictive coding is a theoretical framework that has received much attention for its ability to generate testable hypotheses on how multiple brain regions integrate information during cognitive functions. Given relatively large sensorimotor delays, during social interactions, predicting the behavior of others is crucial to enable joint actions or provide competitive advantages. The action observation network (AON) has been extensively studied, but how information is integrated across its main nodes remains poorly understood. Here we leverage the high spatial and temporal resolution of intracranial Electrocorticography (ECoG), to characterize how the key nodes of the AON - including precentral, supramarginal and visual areas - exchange information. We found more top-down beta oscillation from precentral to supramarginal contacts during the observation of predictable actions while more bottom-up gamma oscillation from visual to supramarginal contacts were measured for unpredictable actions. These results, in line with predictive coding, provide critical evidence towards an understanding of how nodes of the AON integrate information to process the actions of others.

neuroscience↗

bioRxiv2022

Plant specific armadillo repeat kinesin directs organelle transport and microtubule convergence to promote tip growth

Tip growth is essential for plant growth and reproduction. However, it remains elusive how highly polarized tip-growing cells coordinate the organization of intracellular components. Here, we show that plant-specific armadillo-repeat containing kinesin, MpARK, mediates organelle transport and microtubule convergence in tip growing rhizoids in the early diverging land plant Marchantia polymorpha. MpARK is required for anterograde transport of organelles to maintain their position. Furthermore, MpARK participates in the formation of microtubule foci at the rhizoid apex to stabilize growth direction. MpARK-dependent rhizoid growth is essential for plant anchorage and soil holding capacity. Thus, ARK might be a principal organelle transporter and intracellular organizer in the primitive rooting cells for the adaptation to terrestrial environments. Our findings suggest that ARK is functionally comparable to canonical anterograde kinesins in animals and fungi.

cell biology↗

bioRxiv2020

Extracellular DJ-1 induces sterile inflammation in the ischemic brain

Inflammation is implicated in the onset and progression of various diseases, including cerebral pathologies. Here we report that DJ-1, which plays a role within cells as an antioxidant protein, functions as a damage-associated molecular pattern (DAMP), and triggers inflammation if released from dead cells into the extracellular space. We first found that recombinant DJ-1 protein induces the production of various inflammatory cytokines in bone marrow-derived macrophages (BMMs). We further identified a unique peptide sequence in the G and H helices of DJ-1 that activates Toll-like receptor 2 (TLR2) and TLR4. In the ischemic brain, DJ-1 is released into the extracellular space from necrotic neurons within 24 hours after stroke onset and makes direct contact with the surfaces of infiltrating myeloid cells. Administration of an antibody against DJ-1 suppresses the expression of inflammatory cytokines in infiltrating immune cells and attenuates ischemic neuronal damage. Our results demonstrate a previously unknown function of DJ-1 as a DAMP and suggest that extracellular DJ-1 could be a therapeutic target to prevent inflammation in tissue injuries and neurodegenerative diseases. Significance statementDJ-1 has been thoroughly investigated as a cytoprotective antioxidant protein in neurons. However, here we demonstrate that extracellularly released DJ-1 triggers neurotoxic inflammation after ischemic stroke. Intracellular DJ-1 increases in response to oxidative stress in ischemic neurons, but if ischemic stresses result in necrotic cell death, DJ-1 is released extracellularly. Released DJ-1 interacts with TLR2 and TLR4 on the surface of infiltrating myeloid cells and triggers post-ischemic inflammation, leading to the exacerbated pathologies of ischemic stroke. Thus, extracellular DJ-1 is a previously unknown inflammatogenic DAMP, and may be a putative target for therapeutic intervention to prevent progression of inflammatory and neurodegenerative diseases.

immunology↗

bioRxiv2019

Quantitative Analysis of Effects of a Single 60Co Gamma Ray Point Exposure on Time-Dependent Change in Locomotor Activity in Rats

Fatigue is one of the earliest nonspecific symptoms of radiation exposure in humans, but its etiology, mechanism, and dose dependency remain unexplained. Investigating initial behavioral changes caused by irradiation of animals might provide important information to aid understanding of early health effects of radiation exposure and clinical features of radiation injury. Although previous studies in rodents suggested that radiation exposure leads to reduced activity, detailed properties of the effects were unrevealed due to a lack of proper statistical analysis, which is needed to better elucidate details of changes in locomotor activity. Ten-week-old male Wistar rats were subjected to single point external whole-body irradiation with 60Co gamma rays at 0, 2.0, 3.5, and 5.0 Gy (4 rats per group). Infrared sensors were used to continuously record locomotor activity of each rat. Cumulative number of movements during the night was defined as "activity" for each day. A non-linear mixed effects model accounting for individual differences and daily fluctuation of activity was applied to analyze the rats longitudinal locomotor data. Despite a small number of animals per group, our statistical method successfully revealed characteristics of the changes in locomotor activity after radiation exposure, showing that 1) reduction in activity occurred immediately--and in a dose-dependent manner--after irradiation and 2) recovery to pre-irradiation levels required almost one week, with the same recovery rate in each dose group. In addition to improving our understanding of radiation effects on locomotor activity, this statistical framework should be useful to analyze other data with similar structure.

pharmacology and toxicology↗

bioRxiv2018

Changes in clock gene expression in esophagus in rat reflux esophagitis

Background and AimsGastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Clock genes harmonize circadian rhythms by their periodic expression and regulate several physiological functions. However, the association between clock genes and GERD is still unknown. We investigated whether reflux esophagitis affects circadian variability of clock genes in the esophagus and other organs using a rat reflux esophagitis model.\n\nMethodsReflux esophagitis was induced in 7-week-old male Wistar rats. Sham-operated rats were used as controls. Rats were sacrificed at 09:00 (light period) and 21:00 (dark period) 3 days (acute phase) and 21 days (chronic phase) after induction of esophagitis. The expression levels of clock gene mRNAs such as Per1, Per2, Per3, Cryl, Cry2, Arntl, and Clock in the esophagus were investigated by qPCR. Arntl expression was examined in stomach, small intestine, colon, and liver tissues. Serum melatonin and IL-6 levels were measured by ELISA.\n\nResultsHistological examination of reflux esophagitis mainly revealed epithelial defects with marked inflammatory cell infiltration in the acute phase, and mucosal thickening with basal cell hyperplasia in the chronic phase. Circadian variability of clock genes, except Cry1, was present in the normal esophagus, and was completely disrupted in reflux esophagitis during the acute phase. The circadian variability of Per2, Per3, and Arntl returned to normal, but disruption of Per1, Cry2, and Clock was present in the chronic phase. Disruption of circadian variability of Arntl was observed in the esophagus, as well as in the stomach, small intestine, and liver tissues in reflux esophagitis during the acute phase. There were no significant differences in serum melatonin and IL-6 levels between control and reflux esophagitis animals in both acute and chronic phases.\n\nConclusionDisruption to circadian variability of clock genes may play a role in the pathogenesis of GERD.

pathology↗