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Fujioka, T.

Publications and source records attributed to Fujioka, T..

7 recordsLinked to original sources

Sex differences in task engagement and lapse rate during reward learning plateaus

Our understanding of sex differences in reward learning has been limited due to the predominant study of males. Here, we evaluated sex differences in flexible learning in two domains: the learning of stimulus-and action-based associations and their reversals. During action-based learning, rats selected between two identical visual stimuli presented on a touchscreen, where the spatial location predicted a higher probability of reward. For stimulus-based learning, rats chose between two distinct visual stimuli presented in pseudorandom spatial locations, one of which was associated with a higher probability of reward. Reversal phases involved switching reward contingency between the two actions or stimuli. We found that females did not differ in their discrimination or reversal learning accuracy compared to males, yet they collected fewer rewards and were more likely to omit trials than males in both domains. To gain a detailed understanding of differences across conditions, we modeled animals trial-by-trial choices using reinforcement learning (RL) models and examined their steady-state behavior to capture transitions between distinct behavioral states. Although the estimated parameters of the best-fitting RL model revealed some sex differences, the model that incorporated transitions between different behavioral states provided a better overall fit to the data. This model also revealed that across all reversal phases, females exhibited a higher transition-specific lapse rate than males, indicating greater task disengagement once there was no need for further learning. Together, our fine-grained analysis of behavior adds to a growing literature on sex differences in flexible reward learning.

animal behavior and cognition↗

Genomic prediction models based on a large-scale recombinant population allow quick breeding of high-yield rice

Rapid development of cultivars with optimal genome-wide allele combinations is essential for addressing agricultural challenges. However, constructing desired genotypes through conventional cross-breeding requires many generations, calling for a more efficient methodology. Here, we present a rapid breeding strategy that combines a large-scale recombinant population as starting material with interpretable genomic prediction models trained on that population. This approach enables efficient construction of target genotypes optimized for multiple traits in cultivars. To validate our strategy in rice (Oryza sativa), we established a nested association mapping population of 2,787 recombinant inbred lines derived from an elite cultivar 'Hitomebore' and 19 diverse donors. We built highly accurate genomic prediction models using this population. We then used the models to estimate haplotype-specific effects and account for trade-offs among yield-related traits, and selected optimal lines and designed breeding schemes. Crossbreeding based on these schemes produced rice lines with the target genotypes for multiple yield-related traits, supporting the predicted effects and validating the effectiveness of our strategy. This genomic breeding approach provides a general framework for rapidly breeding cultivars able to meet the challenges posed by a changing environment.

genetics↗

Sensory Entrained TMS (seTMS) enhances motor cortex plasticity

Neural excitability fluctuates with sensory events, creating windows of opportunity to enhance brain stimulation. Repetitive transcranial magnetic stimulation (TMS), including intermittent theta burst stimulation (iTBS), is a promising treatment for neurological and psychiatric disorders, but does not account for fluctuations in neural excitability, likely contributing to variable outcomes. Sensory Entrained TMS (seTMS) leverages sensorimotor oscillations to enhance corticospinal responses, but the sustained effects as a repetitive protocol are unknown. We extended seTMS to iTBS measuring motor-evoked potentials (MEPs) as a physiological readout in a randomized crossover study comparing standard iTBS with sensory entrained iTBS (se-iTBS, n=20). se-iTBS more than doubled the MEP effect (55% vs. 26% MEP enhancement) and persisted for at least 30 minutes. Notably, more than 80% of participants showed larger responses with se-iTBS at all time points. se-iTBS may provide a robust and practical framework for optimizing TMS that bridges electrophysiological mechanisms and clinical applications.

neuroscience↗

Sensory Entrained TMS (seTMS) enhances motor cortex excitability

Transcranial magnetic stimulation (TMS) applied to the motor cortex has revolutionized the study of motor physiology in humans. Despite this, TMS-evoked electrophysiological responses show significant variability, due in part to inconsistencies between TMS pulse timing and ongoing brain oscillations. Variable responses to TMS limit mechanistic insights and clinical efficacy, necessitating the development of methods to precisely coordinate the timing of TMS pulses to the phase of relevant oscillatory activity. We introduce Sensory Entrained TMS (seTMS), a novel approach that uses musical rhythms to synchronize brain oscillations and time TMS pulses to enhance cortical excitability. Focusing on the sensorimotor alpha rhythm, a neural oscillation associated with motor cortical inhibition, we examine whether rhythm-evoked sensorimotor alpha phase alignment affects primary motor cortical (M1) excitability in healthy young adults (n=33). We first confirmed using electroencephalography (EEG) that passive listening to musical rhythms desynchronizes inhibitory sensorimotor brain rhythms (mu oscillations) around 200 ms before auditory rhythmic events (27 participants). We then targeted this optimal time window by delivering single TMS pulses over M1 200 ms before rhythmic auditory events while recording motor-evoked potentials (MEPs; 19 participants), which resulted in significantly larger MEPs compared to standard single pulse TMS and an auditory control condition. Neither EEG measures during passive listening nor seTMS-induced MEP enhancement showed dependence on musical experience or training. These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost-effective method for optimizing non-invasive brain stimulation outcomes.

neuroscience↗

Impact of rice GENERAL REGULATORY FACTOR14h (GF14h) on low-temperature seed germination and its application to breeding

Direct seeding is employed to circumvent the labor-intensive process of rice (Oryza sativa) transplantation, but this approach requires varieties with vigorous low-temperature germination (LTG) when sown in cold climates. To investigate the genetic basis of LTG, we identified the quantitative trait locus (QTL) qLTG11 from rice variety Arroz da Terra, which shows rapid seed germination at lower temperatures, using QTL-seq. We delineated the candidate region to a 52-kb interval containing GENERAL REGULATORY FACTOR14h (GF14h) gene, which is expressed during seed germination. The Arroz da Terra GF14h allele encodes functional GF14h, whereas Japanese rice variety Hitomebore harbors a 4-bp deletion in the coding region. Knocking out functional GF14h in a near-isogenic line (NIL) carrying the Arroz da Terra allele decreased LTG, whereas overexpressing functional GF14h in Hitomebore increased LTG, indicating that GF14h is the causal gene behind qLTG11. Analysis of numerous Japanese rice accessions revealed that the functional GF14h allele was lost from popular varieties during modern breeding. We generated a NIL in the Hitomebore background carrying a 172-kb genomic fragment from Arroz da Terra including GF14h. The NIL showed superior LTG compared to Hitomebore, with otherwise comparable agronomic traits. The functional GF14h allele from Arroz da Terra represents a valuable resource for direct seeding in cold regions. Author SummaryRice serves as a fundamental crop sustaining over half of the global population. With the rapid growth of the worlds population, it will become increasingly important to improve rice productivity. On the other hand, the aging of rice farmers in Japan has resulted in a constant labor shortage. To address this, direct seeding, in which seeds are sown directly in rice fields without going through the most labor-intensive part of the rice cultivation process, i.e., seedling production and transplanting, has been recommended. However, prevalent elite rice varieties are known to be unsuitable for direct seeding due to their poor seed germination ability under low-temperature conditions. In this study, we show for the first time that GF14h gene from the Portuguese variety Arroz da Terra improves seed germination at low temperatures (LTG). In addition, a novel cross-bred line was generated by introducing the GF14h-containing genomic segment from Arroz da Terra into Hitomebore, a widely cultivated variety in northern Japan. This line is expected to be used as a pre-breeding material to enhance LTG. This study will provide a genetic basis for LTG and contribute to basic and applied research progress.

plant biology↗

Retinoids rescue ceruloplasmin secretion and alleviate oxidative stress in Wilson's disease-specific hepatocytes

Wilsons disease (WD) is a copper metabolic disorder, which is caused by defective ATP7B function. Here, we have generated induced pluripotent stem cells (iPSCs) from WD patients carrying compound heterozygous mutations on ATP7B. ATP7B loss- and gain-of-functions were further manifested with ATP7B-deficient iPSCs and heterozygously-corrected R778L WD patient-derived iPSCs using CRISPR-Cas9-based gene editing. Transcriptome analysis identified abnormalities of retinoid signaling pathway and lipid metabolism in WD-specific hepatocytes. Although the expression level of ATP7B protein was variable among WD-specific hepatocytes, the expression and secretion of ceruloplasmin (Cp), which is a downstream copper carrier in plasma, were consistently decreased. Cp secretion-based drug screening identified all-trans retinoic acid (ATRA) as promising candidates for rescuing Cp secretion. ATRA also alleviated reactive oxygen species (ROS) production induced by lipid accumulation in WD-specific hepatocytes. Our patient-derived iPSC-based hepatic models provide potential therapeutics for liver steatosis in WD and other fatty liver diseases.

cell biology↗

Automatic Single-Cell Discrimination by Cellular Appearance using Convolutional Neural Network

Morphological images of cells contain extensive information, which help biologists to infer the type and state of cells to some degree based on their morphology. Convolutional Neural Network, a neural network architecture, is a powerful tool used for image recognition. However, whether it can be used to classify cells on the basis of their morphology remains unclear. In this study, we demonstrate that 10 different hematopoietic tumor cell lines with similar morphologies that biologists find difficult to distinguish can be classified with >90% accuracy using only their bright-field images when analyzed using a Convolutional Neural Network. This novel and simple system using bright-field images of cells could be a powerful analytical tool for cell type discrimination and could also be applied to the clinical diagnoses of hematopoietic tumors.

cell biology↗