Biology subjects

Osaki, H.

Publications and source records attributed to Osaki, H..

8 recordsLinked to original sources

bioRxiv2025

Evaluation of therapeutic effect of baloxavir marboxil against high pathogenicity avian influenza virus infection in duck model

Since 2020, high pathogenicity avian influenza virus (HPAIV) infections in wild birds have been frequently reported. Because HPAIV infection has occasionally caused outbreaks in captive rare birds, application of antiviral drugs for treatment purposes against them has been considered from the perspective of conservation medicine. In this study, the therapeutic efficacy of baloxavir marboxil (BXM) was evaluated using a duck model to help establish the post-infection treatment for rare birds. Sixteen four-week-old ducks were divided into four groups and intranasally inoculated with the HPAIV strain A/crow/Hokkaido/0103B065/2022 (H5N1). BXM was orally administered once daily at doses of 12.5, 2.5, 0.5, and 0 mg/kg to each of the four groups from 2 to 6 days post-infection. Blood samples were collected at 2, 8, and 24 hours after the initial BXM administration to measure the plasma concentrations of its active form, baloxavir acid (BXA). All ducks were monitored until 14 days post-infection, and their oral and cloacal swabs were collected for virus recovery. All eight ducks administered with 12.5 or 2.5 mg/kg of BXM survived, demonstrating a significant reduction in virus recovery compared to the 0 mg/kg group. Pharmacokinetic/pharmacodynamic (PK/PD) analysis of BXA suggested that parameters such as Cmax and AUC0-24hr were correlated with the suppression of virus shedding. These findings demonstrated that BXM administration within 48 hours post-HPAIV infection in ducks effectively reduced mortality and virus shedding. The comparison of PK parameters may help estimate efficient BXM dosing strategies in rare birds. HighlightBXM prevented death of HPAIV-infected ducks when given within 48 hr of inoculation. Doses of 2.5 mg/kg rapidly suppressed and eliminated infectious virus shedding. AUC0-24hr and Cmax correlated with suppression of virus shedding.

microbiology↗

bioRxiv2025

Microfluidic platforms for probing spontaneous functional recovery in hierarchically modular neuronal networks

Inherent capacity to flexibly reorganize after injury is a hallmark of brain networks, and recent studies suggest that functional consequences of focal damage are strongly influenced by the networks non-random connectivity. Although many of these insights have been derived from animal models and computational simulations, experimental platforms that enable bottom-up investigations of the structure-function relationships underlying damage and recovery processes remain limited. In this study, we used polydimethylsiloxane microfluidic devices to construct hierarchically modular neuronal networks that mimic the architectural features of the mammalian cortex. Laser microdissection was employed to selectively sever intermodular connections, enabling controlled damage to either hub or peripheral connections. Damage to hub connections led to delayed recovery, requiring more than three days for correlations to re-emerge. In contrast, peripheral damage resulted in faster recovery. Experiments that induced repeated injury to neuronal networks further demonstrated that recovery primarily occurred through the formation of alternative pathways rather than restoration of the original connections. These findings highlight how topological features of neuronal networks shape their response to injury and subsequent reorganization, providing mechanistic insights into the intrinsic self-repair capacity of biological systems.

neuroscience↗

bioRxiv2024

Fight, Retreat, Repeat: Field observation of male-male agonistic behavior in the wood-feeding cockroach, Panesthia angustipennis spadica (Dictyoptera: Blattodea: Blaberidae)

Conflict is one of the most critical factors affecting the behavior of animals related to their reproduction and survival, with aggressive interactions being central to acquiring resources or mating partners. This phenomenon is more common among males than females, impacting reproduction strategy and beginning of biparental care. Investigating such interactions in species closely related to social species can be illuminating, offering valuable insights into the factors that influence the emergence and maintenance of more complex social behaviors. In this context, we present a field study of male-male agonistic behavior in the wood-feeding cockroach, Panesthia angustipennis. Panesthia is the closest genus to the subsocial genus Salganea, which is known for its biparental care. Our field observations reveal a characteristic behavior where one male pushes a rival away from a female. The victorious male repeatedly returns to a specific site near the female, suggesting a strategy to minimize unnecessary conflict or protect the female. This behavior provides insights into the potential evolutionary strategies that may have evolved in the common ancestor shared by Salganea and Panesthia. Notably, the displaced males persistently reengage, highlighting the high resource value attributed to females and the consequential intensity of male competition. This study not only sheds light on the aggressive and pacifist tendencies in P. angustipennis but also contributes to understanding the evolutionary development of social structures in Salganea. Further experimental investigations into the aggressive behaviors of P. angustipennis will enhance our comprehension of the factors shaping the evolution of sociality in these species.

animal behavior and cognition↗

bioRxiv2023

Role of the medial agranular cortex in unilateral spatial neglect

Unilateral spatial neglect (USN) results from impaired attentional networks and can affect various sensory modalities, such as visual and somatosensory. The rodent medial agranular cortex (AGm), located in the medial part of the forebrain from rostral to caudal direction, is considered a region associated with spatial attention. The AGm selectively receives multisensory input with the rostral AGm receiving somatosensory input and caudal part receiving visual input. Our previous study showed slower recovery from neglect with anterior AGm lesion using the somatosensory neglect assessment. Conversely, the functional differences in spatial attention across the entire AGm locations (anterior, intermediate, and posterior parts) are unknown. Here, we investigated the relationship between the severity of neglect and various locations across the entire AGm in a mouse stroke model using a newly developed program-based analysis method that does not require human intervention. Among the various lesion positions, acute severity was higher with the lesion in the intermediate rostrocaudal position. On the other hand, the recovery from USN-like behavior after this phase tended to be slower in cases with more rostral lesions in the AGm. Additionally, no motor paralysis was observed in any of the mice with lesions in each AGm. These results suggest that the intermediate rostrocaudal position of the AGm may significantly influence selection of the direction, regardless of the areas to which it is connected. On the contrary, recovery from USN-like behavior may be dependent on the areas to which it is connected. HighlightsLesion of the rodent medial agranular cortex (AGm) results in unilateral spatial neglect (USN). In the acute phase, the severity was higher with lesions in the intermediate AGm position. Recovery from somatosensory USN tended to be slower with rostral AGm lesions. Recovery from USN may depend on sensory modalities associated with the connected areas. Our results revealed location-dependent differences in attentional functions within the AGm.

animal behavior and cognition↗

bioRxiv2022

Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 co-activation

Initial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). The main reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. To study mechanisms of resistance, we investigated immediate epigenetic and transcriptional responses following BET inhibition, and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback loop that attenuates inhibition, or even increases expression, of specific transcriptional modules. This adaptation is most marked at key AML maintenance genes and is mediated by p300, suggesting a rational therapeutic opportunity by combining BET- and p300- inhibition. p300 activity is required during all steps of adaptation. However, the transcriptional programs that p300 regulates to induce resistance to BETi differ between AML subtypes. Remarkably, in some AMLs, p300 regulates a series of transitional transcriptional patterns that allow homeostatic adjustments during earlier stages of resistance to BET-inhibitors. In consequence, p300 remains crucial throughout all stages of resistance in sensitive AML-subtypes, although its importance declines following the development of chronic resistance to BET inhibitors in some other AMLs. Altogether, our study elucidates the mechanisms that underlie an "acute" state of resistance to BET inhibition, achieved through p300 activity, and how these mechanisms remodel to become "chronic". Importantly, however, our data also suggest that a sequential treatment with BET- and p300 inhibition may prevent resistance development, thereby improving outcomes. Key pointsO_LIA mechanistic feedback to p300 enables acute tolerance to BET inhibition. C_LIO_LIp300 regulates transcriptional networks that lead to chronic resistance to BET inhibition. C_LIO_LISequential BET-, followed by p300-inhibition, is synthetically lethal in AML, and is optimally deployed during earlier stages of resistance to BET inhibitors. C_LI

cancer biology↗

bioRxiv2021

Genomic imprinting drives eusociality

The origin of eusociality, altruistically foregoing personal reproduction to help others, has been a long-standing paradox ever since Darwin. Most eusocial insects and rodents likely evolved from subsocial precursors, in which older offspring "helpers" contribute to the development of younger siblings without a permanent sterile caste. The driving mechanism for the transition from subsociality (with helpers) to eusociality (with lifelong sterile workers) remains an enigma because individuals in subsocial groups are subject to direct natural selection rather than kin selection. Our genomic imprinting theory demonstrates that natural selection generates eusociality in subsocial groups when parental reproductive capacity is linked to a delay in the sexual development of offspring due to sex-antagonistic action of transgenerational epigenetic marks. Focusing on termites, our theory provides the missing evolutionary link to explain the evolution of eusociality from their subsocial wood-feeding cockroach ancestors, and provides a novel framework for understanding the origin of eusociality.

evolutionary biology↗

bioRxiv2021

Distinct nociresponsive region in mouse primary somatosensory cortex

Nociception, somatic discriminative aspects of pain, is represented in the primary somatosensory cortex (S1), as is touch, but the separation and the interaction of the two modalities within S1 remain unclear. Here, we show the spatially-distinct tactile and nociceptive processing in the granular barrel field (BF) and the adjacent dysgranular region (Dys) in mouse S1. Simultaneous recording of the multiunit activity across subregions reveals that Dys responses are selective to noxious input whereas those of BF are to tactile input. At the single neuron level, nociceptive information is represented separately from the tactile information in Dys layer 2/3. In contrast, both modalities are converged in a layer 5 neuron in each region. Interestingly, the two modalities interfere with each other in both regions. We further demonstrate that Dys, but not BF, activity is critically involved in neuropathic pain and pain behavior, and thus provide evidence that Dys is a center specialized for nociception in S1.

neuroscience↗

bioRxiv2019

Layer-specific sensory processing impairment in the primary somatosensory cortex after motor cortex infarction

Primary motor cortex (M1) infarction occasionally causes sensory impairment. Because sensory signal plays an important role in motor control, sensory impairment compromises recovery and rehabilitation from motor disability. Despite the importance of sensory-motor integration for rehabilitation after M1 infarction, the neural mechanism of the sensory impairment is poorly understood. We show that the sensory processing in the primary somatosensory cortex (S1) was impaired in the acute phase of M1 infarction and recovered in a layer-specific manner in the subacute phase. This layer dependent recovery process and the anatomical connection pattern from M1 to S1 suggested the functional connectivity from M1 to S1 plays a key role in the impairment of sensory processing in S1. The simulation study demonstrated that the loss of inhibition from M1 to S1 in the acute phase of M1 infarction could cause the sensory processing impairment in S1, and the complementation of inhibition could recover the temporal coding. Taken together, we revealed how focal stroke of M1 alters cortical network activity of sensory processing, in which inhibitory input from M1 to S1 may be involved.

physiology↗