Biology subjects

Oshima, K.

Publications and source records attributed to Oshima, K..

9 recordsLinked to original sources

bioRxiv2026

Asymmetric Neurogenomic States Emerge in Winners and Losers After Social Competition

Winner and loser effects can influence future aggressive behavior following social competition, but their neurogenomic basis remains poorly understood. Using Betta splendens, we integrated behavioral analyses, whole-brain RNA sequencing, and genomic coexpression network analyses to investigate how social experiences influence enduring behavioral and molecular states. Winners showed increased attack frequency, whereas losers prolonged aggressive latency, indicating effects on distinct behavioral aspects. Winners and losers initially shared acute responses in terms of both gene expression and network coordination but subsequently diverged through outcome-specific patterns of network reorganization, despite few persistent differentially expressed genes. This divergence was asymmetric and involved multiple components: immune-related networks showed notable contrasts, with winners displaying anticipated postconflict coordination but losers instead showing discoordination, whereas neuroendocrine and purinergic networks diverged over distinct temporal scales. These findings highlight transcriptomic network-level remodeling as a potential key feature of the winner-loser effect.

animal behavior and cognition↗

bioRxiv2026

Dual targeting of astrocytic and endothelial GLUT1 enables functional rescue in GLUT1 deficiency syndrome

Glucose transporter 1 deficiency syndrome (GLUT1-DS) is a severe neurometabolic disorder caused by impaired brain glucose transport. Because GLUT1 has been classically viewed as predominantly localized to blood-brain barrier endothelial cells, gene therapy strategies have largely focused on endothelial GLUT1 restoration. However, whether this endothelial-centered model fully explains disease pathogenesis and therapeutic rescue has remained unclear. Using enhanced detection in mouse brain and human postmortem tissue, we show that GLUT1 is broadly expressed in astrocytes as well as endothelial cells, extending beyond perivascular endfeet into astrocytic somata and processes. Conditional Glut1 haploinsufficiency in either astrocytes or endothelial cells reproduced GLUT1-DS-like reductions in cerebrospinal fluid glucose availability and brain parenchymal glucose responses, together with cognitive and motor impairments. To determine the therapeutic consequence of this revised cellular model, we used complementary endothelial- and astrocyte-directed AAV delivery to restore GLUT1 in systemic Glut1 haploinsufficient mice. Single-compartment restoration produced partial benefit, whereas dual-compartment restoration more robustly improved cerebrospinal fluid glucose availability and cognitive function. These findings indicate that endothelial GLUT1 restoration alone is insufficient for robust rescue and redefine GLUT1-DS as a multicellular disorder of the neurovascular unit.

neuroscience↗

bioRxiv2023

A potential pathway that links intron retention with the physiological recovery by a Japanese herbal medicine

Our previous experiments with klotho mice (i.e., klotho knockout mice) showed that aberrant intron retention (IR) occurs in a pre-symptomatic state of aging and can be restored to the normal state by administration of Juzentaihoto (JTT), a formula of the Japanese herbal medicine (referred to as kampo; Okada et al., 2021). To explain that this phenomenon is not just a specific example observed in klotho mice, but is due to a universal cause that may be common in a pre-symptomatic state, we re-analyzed the data for genes that were differentially expressed in the klotho liver in response to JTT. Our data showed that AMPK signaling was activated in these mice, resulting in inhibition of anabolic pathways including protein synthesis and activation of catabolic pathways including lipolysis in various organs. These data were consistent with the observation that klotho mice appeared to be in a perpetual state of pseudo-starvation, i.e., based on their overall metabolic profile. The abnormally increased incidence of IR (IncIR) in the liver of klotho mice could be classified into three types according to their transcriptional status, revealing that each of all the three types of IncIR was caused by AMPK activation, a consequence of the pseudo-starvation state exhibited by these mice. Furthermore, we showed that both the transcriptional drift variance and the IR drift variance can be useful for visually assessing recovery from the pseudo-starvation state of klotho mice after administration of JTT. With these data, we propose a novel pathway linking intron retention to changes in the physiological state such as starvation, resulting in the maintenance of cellular homeostasis.

bioinformatics↗

bioRxiv2022

Host-derived protease promotes aggregation of Staphylococcus aureus by cleaving the surface protein SasG

Staphylococcus aureus is one of the leading causes of hospital acquired infections, many of which begin following attachment and accumulation on indwelling medical devices or diseased tissue. These infections are often linked to establishment of biofilms, but another often overlooked key characteristic allowing S. aureus to establish persistent infection is formation of planktonic aggregates. Such aggregates are physiologically similar to biofilms and protect pathogen from innate immune clearance and increase its antibiotic tolerance. The cell wall-associated protein SasG has been implicated in biofilm formation via mechanisms of intercellular aggregation, but the mechanism in the context of disease is largely unknown. We have previously shown that expression of cell wall-anchored proteins involved in biofilm formation is controlled by the ArlRS-MgrA regulatory cascade. In this work, we demonstrate that the ArlRS two-component system controls aggregation, by repressing expression of sasG by activation of the global regulator MgrA. We also demonstrate that SasG must be proteolytically processed by a non-native protease to induce aggregation, and that strains expressing functional full-length sasG aggregate significantly upon proteolysis by a mucosal-derived host protease found in human saliva. We used fractionation and N-terminal sequencing to demonstrate that human trypsin within saliva cleaves within the A domain of SasG to expose the B domain and induce aggregation. Finally, we demonstrated that SasG is involved in virulence during mouse lung infection. Together, our data point to SasG, its processing by host proteases, and SasG-driven aggregation as important elements of S. aureus adaptation to host environment.

microbiology↗

bioRxiv2021

Short 5'UTR enables optimal translation of plant virus tricistronic RNA via leaky scanning

Regardless of the general model of translation in eukaryotic cells, a number of studies suggested that many of mRNAs encode multiple proteins. Leaky scanning, which supplies ribosomes to downstream open reading frames (ORFs) by read-through of upstream ORFs, is the most major regulatory mechanism to translate polycistronic mRNAs. However, the general regulatory factors controlling leaky scanning and their biological relevance have rarely been elucidated, with exceptions such as the Kozak sequence. Here, we have analyzed the strategy of a plant RNA virus to translate three movement proteins from a single RNA molecule through leaky scanning. The in planta and in vitro results indicate that significantly shorter 5' UTR of the most upstream ORF promotes leaky scanning, potentially finetuning the translation efficiency of the three proteins in a single RNA molecule to optimize viral propagation. Moreover, in plant endogenous mRNAs, we found that shorter UTRs were more frequently observed in uORFs of polycistronic mRNAs. We propose that the promotion of leaky scanning induced by a short 5' UTR (LISH), together with the Kozak sequence, is a conserved gene regulation mechanism not only in viruses but also in eukaryotes.

plant biology↗

bioRxiv2021

Adolescent Stress Confers Resilience to Traumatic Stress Later in Life: Role of the Prefrontal Cortex

Stress during adolescence is usually associated with psychopathology later in life. However, under certain circumstances, developmental stress can promote an adaptive phenotype, allowing individuals to cope better with adverse situations in adulthood, thereby contributing to resilience. The aim of the study was to understand how adolescent stress alters behavioral and physiological responses to traumatic stress in adulthood. Sprague Dawley rats were subjected to adolescent chronic variable stress (adol CVS) followed by single prolonged stress (SPS) in adulthood. One week after SPS, animals were tested for acquisition, extinction, extinction recall and reinstatement of auditory-cued fear conditioning, with neuronal recruitment during reinstatement assessed by Fos expression. Patch clamp electrophysiology was performed to examine physiological changes associated with resilience. We observed that adol CVS blocked SPS-induced impairment of extinction learning (males) and enhancement fear reinstatement (both sexes). SPS effects were associated with a reduction of infralimbic (IL) cortex neuronal recruitment after reinstatement in males and increased engagement of the central amygdala in females, both of which were also prevented by adol CVS. We explored the mechanism behind reduced IL recruitment in male rats by studying the intrinsic excitability of IL pyramidal neurons. SPS reduced excitability of IL neurons and prior adol CVS prevented this effect, indicating that adolescent stress can impart resilience to the effects of traumatic stress by modification of IL output in males. Overall, our study suggests that prior stress exposure can limit the impact of a subsequent severe stress exposure in adulthood, effects that are mediated by sex-specific modification of infralimbic and amygdala signaling.

neuroscience↗

bioRxiv2021

The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation

BackgroundA hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early pro-inflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation. Methods and ResultsThe role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction (TAC) surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after TAC surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2-KO mice displayed a pro-inflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, TAC surgery led to the death of all mice by day 6 that was associated with myocardial hyper-inflammation and vascular leakage. ConclusionsTogether, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.

cell biology↗

bioRxiv2020

A unique neurogenomic state emerges after aggressive confrontations in males of the fish Betta splendens

Territorial defense involves frequent aggressive confrontations with competitors, but little is known about how brain-transcriptomic profiles change between individuals competing for territory establishment. Our previous study elucidated that brain-transcriptomic synchronization occurs in a pair-specific manner between two males of the fish Betta splendens during fighting, reflecting a mutual assessment process between them at the level of gene expression. Here we evaluated how the brain-transcriptomic profiles of opponents change immediately after shifting their social status (i.e., the winner/loser has emerged) and 30 min after this shift. We showed that unique and carryover hypotheses can be adapted to this system, in which changes in the expression of certain genes are unique to different fighting stages and in which the expression patterns of certain genes are transiently or persistently changed across all fighting stages. Interestingly, the specificity of the brain-transcriptomic synchronization of a pair during fighting was gradually lost after fighting ceased, because of the decrease in the variance in gene expression across all individuals, leading to the emergence of a basal neurogenomic state. Strikingly, this unique state was more basal than the state that existed in the before-fighting group and resulted in the reduced and consistent expression of genes across all individuals. In spite of the consistent and basal overall gene expression in each individual in this state, expression changes for genes related to metabolism, learning and memory, and autism still differentiated losers from winners. The fighting system using male B. splendens thus provides a promising platform for investigating neurogenomic states of aggression in vertebrates. Author summaryCompetitive interactions involve complex decision-making tasks that are shaped by mutual feedback between participants. When two animals interact, transcriptomes across their brains synchronize in a way that reflects how they assess and predict the others fighting ability and react to each others decisions. Here, we elucidated the gradual loss of brain-transcriptomic synchrony between interacting opponents after their interaction ceased, leading to the emergence of a basal neurogenomic state, in which the variations in gene expression were reduced to a minimum among all individuals. This basal neurogenomic state shares common characteristics with the hibernation state, which animals adopt to minimize their metabolic rates to cope with harsh environmental conditions. We demonstrated that this unique neurogenomic state, which is newly characterized in the present study, is composed of the expression of a unique set of genes, each of which was presumably minimally required for survival, providing a hypothesis that this state represents the smallest unit of neurogenomic activity for sustaining an active life.

molecular biology↗

bioRxiv2020

Intron retention as a new marker of the pre-disease state and its recovery to the normal state by a traditional Japanese multi-herbal medicine

Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. Using klotho mice at the pre-symptomatic state, we discovered that retained-introns accumulated in several organs including the liver and that among these retained introns in the liver a subset was recovered to the normal state by a Japanese traditional herbal medicine. This is the first report of IR recovery by a medicine. IR-recovered genes fell into two categories: those involved in liver-specific metabolism and in splicing. Metabolome analysis of the liver showed that the klotho mice were under starvation stress. In addition, our differentially expressed gene analysis showed that liver metabolism was actually recovered by the herbal medicine at the transcriptional level. By analogy with the widespread accumulation of intron-retained pre-mRNAs induced by heat shock stress, we propose a model in which retained-introns in klotho mice were induced by an aging stress and in which this medicine-related IR recovery is indicative of the actual recovery of liver-specific metabolic function to the healthy state. Accumulation of retained-introns was also observed at the pre-symptomatic state of aging in wild-type mice and may be an excellent marker for this state in general.

molecular biology↗