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Biology subjects

Oya, T.

Publications and source records attributed to Oya, T..

11 recordsLinked to original sources

Engineering a highly active thermophilic F1-ATPase by homolog-guided exploration and machine-learning-assisted prioritization

The rotary motor F1-ATPase has been extensively studied as a model molecular machine, yet rational engineering of its catalytic activity remains challenging because ATP hydrolysis is regulated by long-range intersubunit allostery and large conformational transitions. Here, we developed a homolog-guided engineering strategy to increase the maximum rotation rate of the thermophilic Bacillus PS3 F1-ATPase (TF1). Candidate mutation sites were first identified by comparing TF1 with the homologous enzymes bovine mitochondrial F1 (bMF1) and Paracoccus denitrificans F1 (PdF1), both of which exhibit higher maximum rotation rates than TF1. Systematic exploration of these sites identified four activity-enhancing hotspots, followed by focused hotspot exploration and machine-learning-assisted prioritization of combinatorial mutants. The best mutant, TF1({beta}Y313L/{beta}E332S), exhibited a 1.8-fold higher maximum rotation rate than TF1(WT) while retaining its functional thermostability. Interestingly, activity-enhancing substitutions were not limited to the residues conserved in both bMF1 and PdF1, indicating that the bMF1-PdF1 consensus substitutions effectively identify activity-enhancing hotspots rather than uniquely defining the optimal amino acid. Machine-learning-assisted exploration efficiently prioritized highly active mutants, although the predictive performance was limited by the relatively small training dataset and epistatic interactions among mutations. Kinetic and structural comparisons further provided mechanistic insights into the enhanced catalytic activity of the engineered mutant. Together, these results establish a practical strategy for engineering complex molecular motors by combining homolog-guided hotspot identification with focused hotspot exploration.

biophysics↗

Hierarchical neuronal processing in primary somatosensory cortex during action observation

Voluntary movement requires the central nervous system to transform and integrate visual and somatosensory information into coordinated motor outputs. Although mirror-like neuronal activity during both action execution and observation has been extensively described in premotor, motor, and parietal cortices, it remains unknown whether the primary somatosensory cortex (S1) also participates in the action observation network. Here, we recorded single-unit activity from cytoarchitectonically defined areas 3a, 3b, 1, and 2 in macaque S1 while monkeys either executed or observed grasping movements. Approximately one-third of neurons across S1 modulated their firing during action observation, with the proportion of responsive neurons increasing from area 3 to areas 1 and 2, consistent with the hierarchical organization of somatosensory processing. Most action observation neurons showed congruent activity during action execution and observation, suggesting that these responses may reflect top-down motor-related or integrated visuomotor signals and are unlikely to be explained by visual input alone. The higher prevalence of action observation neurons in areas 1 and 2 suggests that action observation-related signals preferentially influence later stages of somatosensory processing, potentially via cortico-cortical interactions with motor and parietal regions.

neuroscience↗

Multi-timescale neural adaptation underlying long-term musculoskeletal reorganization.

The central nervous system (CNS) can effectively control body movements despite environmental changes. While much is known about adaptation to external environmental changes, less is known about responses to internal bodily changes. This study investigates how the CNS adapts to long-term alterations in the musculoskeletal system using a tendon transfer model in non-human primates. We surgically relocated finger flexor and extensor muscles to examine how the CNS adapts its strategy for finger movement control by measuring muscle activities during grasping tasks. Two months post-surgery, the monkeys demonstrated significant recovery of grasping function despite the initial disruption. Our findings suggest a two-phase CNS adaptation process: an initial phase enabling function with the transferred muscles, followed by a later phase abandoning this enabled function and restoring a control strategy that, while potentially less conflicted than the maladaptive state, resembled the original pattern, possibly representing a good enough solution. These results highlight a multi-phase CNS adaptation process with distinct time constants in response to sudden bodily changes, offering potential insights into understanding and treating movement disorders. SIGNIFICANCE STATEMENTAfter major changes to the bodys mechanics, the nervous system adapts using strategies on multiple timescales. Our primate tendon transfer study shows that core muscle synergy groupings remain stable, reflecting a default to modular control. However, the activation of these synergies changes dramatically; an initial, rapid swap of their timing proves to be maladaptive, impairing motor function. This conflict is only resolved through the gradual development of slower, compensatory strategies over several weeks. This process highlights the fundamental tension the CNS faces when its reliance on stable motor modules conflicts with the need for flexible control, offering insights into neural plasticity and staged rehabilitation.

neuroscience↗

Spinal and cortical premotor control of primate dexterous hand movements

Skilled hand movements are an evolutionary advance in primates. Phylogenetically distinct corticospinal pathways are involved in hand control: "newer" direct corticomotoneuronal (CM) pathways and "older" indirect corticospinal pathways mediated by spinal premotor interneurons (PreM-INs). However, the functional differences of these pathways remain unclear. Here we show that CM cells and PreM-INs have distinct physiological properties for the activation of hand muscles and provide different types of movement control signals while monkeys perform a precision grip task. Spike-triggered averaging of electromyographic activity indicated that PreM-INs coactivate a larger number of muscles, whereas CM cells more selectively control fewer muscles. The firing activity of PreM-INs was tightly correlated with their target muscle activity and had a greater contribution to generating hand muscle activity. In contrast, CM cell activity diverged temporally from the target muscle activity and had a smaller contribution to its generation. On the basis of these results, we hypothesize that PreM-INs produce gross muscle activity by activating synergistic muscles, whereas CM cells fine-tune target muscle activity. This idea was supported by dimensional reduction analyses of hand muscle activity, as PreM-IN activity was specifically correlated with lower dimensional control of muscle activity, and CM cell activity was correlated with higher dimensional control. These results indicate that the two pathways have distinct functions, synergistic control and fine tuning of hand muscle activity, both of which are essential for the development of dexterous hand movement in primates.

neuroscience↗

Formation of brain-wide neural geometry during visual item recognition in monkeys

Neural dynamics assumes to reflect computations that relay and transform information in the brain. Previous studies have identified the neural population dynamics in many individual brain regions as a trajectory geometry, preserving a manifest of computational motifs. However, whether these populations share particular geometric patterns across brain-wide neural populations remains unclear. Here, by mapping neural dynamics widely across temporal/frontal/limbic regions in the cortical and subcortical structures of monkeys, we show that 10 neural populations, including 2,500 neurons, propagate visual item information in a stochastic manner. We found that visual inputs predominantly evoked rotational dynamics in the higher-order visual area, TE and its downstream striatum tail, while curvy/straight dynamics appeared frequently downstream in the orbitofrontal/hippocampal network. These geometric changes were not deterministic but rather stochastic according to their respective emergence rates. Our meta-analysis results indicated that visual information propagates as a heterogeneous mixture of stochastic neural population signals in the brain.

neuroscience↗

Modulation of somatosensory signal transmission in the primate cuneate nucleus during voluntary hand movement

Successful extraction of tactile and kinematic information is crucial for appropriate motor actions in daily life. To achieve this objective, sensory signals should be effectively regulated during motor actions. This regulation is understood both empirically and conceptually, but it is not well known where and how it is implemented in the central nervous system. Here, we show that, during voluntary movement, sensory signals are already attenuated in the primate cuneate nucleus, an early processing site in the ascending lemniscus pathway. The degree of suppression was comparable with the one reported in the cortex, suggesting that psychological attenuation of somatosensation could be ascribed to the cuneate. The results also revealed that this sensory attenuation was of descending origin, suggesting that cortical sensory prediction signals could regulate cuneate sensory transmission for extracting meaningful, and attenuate unnecessary, signals for movement regulation. This recurrent sensory modulation mechanism between cortical and subcortical areas may generalize to other sensory modalities and cognitive processes.

neuroscience↗

Myomatrix arrays for high-definition muscle recording

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous systems actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ("Myomatrix arrays") that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a "motor unit", during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous systems motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and in identifying pathologies of the motor system.

neuroscience↗

Comparison of neural population dynamics in the regression subspace between continuous and categorical task parameters

Neural population dynamics, presumably fundamental computational units in the brain, provide a key framework for understanding information processing in the sensory, cognitive, and motor functions. However, neural population dynamics is not explicitly related to the conventional analytic framework for single-neuron activity, i.e., representational models that analyze neuronal modulations associated with cognitive and motor parameters. In this study, we applied a recently developed state-space analysis to incorporate the representational models into the dynamic model in combination with these parameters. We compared neural population dynamics between continuous and categorical task parameters during two visual recognition tasks, using the datasets originally designed for a single-neuron approach. We successfully extracted neural population dynamics in the regression subspace, which represent modulation dynamics for both continuous and categorical task parameters with reasonable temporal characteristics. Furthermore, we combined the classical optimal-stimulus analysis paradigm for the single-neuron approach (i.e., stimulus identified as maximum neural responses) into the dynamic model, and found that the most prominent modulation dynamics at the lower dimension were derived from these optimal responses. Thus, our approach provides a unified framework for incorporating knowledge acquired with the single-neuron approach into the dynamic model as a standard procedure for describing neural modulation dynamics in the brain.

neuroscience↗

Phosphate starvation response precedes drought response in field-grown plants

Drought severely damages crop production, even under conditions so mild that the leaves show no signs of wilting. However, it is unclear how field-grown plants respond to mild drought. Here, we show through 6 years of field trials that ridges are a useful experimental tool to mimic mild drought stress in the field. Mild drought reduces inorganic phosphate levels in the leaves to activate the phosphate starvation response in soybean plants in the field. Using Arabidopsis thaliana and its mutant plants grown in pots under controlled environments, we demonstrate that phosphate starvation response (PSR) occurs before abscisic acid response under progressive mild drought and that PSR plays a crucial role in plant growth under mild drought. Our observations in the field and laboratory using model crop and experimental plants provide insight into the molecular response to mild drought in field-grown plants and the relationship between nutrition and drought stress response.

plant biology↗

Root xylem in three woody angiosperm species is not more vulnerable to embolism than stem xylem

AimsSince plants are compartmentalised organisms, failure of their hydraulic transport system could differ between organs. We test here whether xylem tissue of stems and roots differ in their drought-induced embolism resistance, and whether intact roots are equally resistant to embolism than root segments. MethodsEmbolism resistance of stem and root xylem was measured based on the pneumatic technique for Acer campestre, A. pseudoplatanus and Corylus avellana, comparing also intact roots and root segments of C. avellana. Moreover, we compared anatomical features such as interconduit pit membrane between roots and stems. ResultsWe found a higher embolism resistance for roots than stems, although a significant difference was only found for A. pseudoplatanus. Interconduit pit membrane thickness was similar for both organs of the two Acer species, but pit membranes were thicker in roots than stems of C. avellana. Also, embolism resistance of an intact root network was similar to thick root segments for C. avellana. ConclusionOur observations show that root xylem is not more vulnerable to embolism than stem xylem, although more species need to be studied to test if this finding can be generalised. We also demonstrated that the pneumatic method can be applied to non-terminal plant samples.

ecology↗

Distinct sensorimotor feedback loops for dynamic and static control of primate precision grip

Volitional limb motor control involves dynamic and static muscle actions. It remains elusive how such distinct actions are controlled through separated or shared neural circuits. Here we explored the potential separation for dynamic and static controls in the primate hand actions, by investigating the neuronal coherence between local 1eld potentials (LFPs) of the spinal cord and the forelimb electromyographic activity (EMGs), and LFPs of the motor cortex and the EMGs during the performance of a precision grip in macaque monkeys. We observed the emergence of beta-range coherence with EMGs at spinal cord and motor cortex in the separated phases; spinal coherence during the grip phase and cortical coherence during the hold phase. Further, both of the coherence were influenced by bidirectional interactions with reasonable latencies as beta oscillatory cycles. These results indicate that dedicated feedback circuits comprising spinal and cortical structures underlie dynamic and static controls of dexterous hand actions.

neuroscience↗