Biology subjects

Yamada, H.

Publications and source records attributed to Yamada, H..

At least 19 recordsLinked to original sources

bioRxiv2026

SPIN1 selectively silences evolutionarily young transposable elements through chromatin regulation

Mammalian genomes encode multiple transposable element (TE) silencing pathways that distinguish their targets through different molecular features, with KRAB zinc finger proteins recognizing DNA sequence, the HUSH complex sensing intronless transcripts, and the PIWI-piRNA pathway using small RNA guides. How chromatin state itself contributes to TE recognition remains less defined. Here we identify Spindlin1 (SPIN1), a three-Tudor-domain histone reader implicated in germline piRNA-directed DNA methylation, as a transcriptional repressor of evolutionarily young TEs in mouse embryonic stem cells. SPIN1 selectively binds LINE and ERV loci carrying H3K4me3 and H3K9me3, a chromatin signature enriched at young, transcription-permissive elements, and recognition of these marks by Tudor domains 1 and 2 is required for TE targeting. SPIN1 engages SPINDOC as a Tudor 1 and 3-dependent cofactor whose loss phenocopies SPIN1 depletion, and associates with the H3K9 methyltransferases SETDB1 and G9a. SPIN1 loss reduces H3K9me3 and is accompanied by increased chromatin accessibility, without altering DNA methylation. Thus, SPIN1 uses a histone-state-based mechanism to identify and repress young TEs in pluripotent cells, mechanistically distinct from its germline mode in which SPIN1 cooperates with the PIWI-piRNA pathway to promote DNA methylation, illustrating how a single histone reader engages distinct silencing machineries across cellular contexts.

molecular biology↗

bioRxiv2026

Subsecond whole-brain neural dynamics identified by hidden Markov modeling reflect value-based decision making in humans

Value-based decision making emerges from coordinated neural dynamics across distributed brain networks. Recent studies using noninvasive whole-brain measurements in humans have highlighted the importance of neural activity in the 2-10 Hz frequency band for value-based decision making. Using magnetoencephalography and hidden Markov model (HMM) analysis, we examined whether and how whole-brain neural dynamics in this frequency band, evolving on a timescale of a few hundred milliseconds, reflect value-based decision processes. Thirty-five healthy adults (females and males) made binary choices between risky and sure options. Trial-wise subjective values were estimated using behavioral economic modeling based on prospect theory. We found that HMM-derived trial-by-trial whole-brain neural dynamics (defined by 2-10 Hz amplitude envelopes in distributed brain regions and their interregional coupling) were associated with the subjective values of choice options in a manner distinct from simple perceptual- or motor-evoked activity. Notably, these trial-by-trial whole-brain dynamics covaried with the difference in subjective values between the chosen and unchosen options when the neural data were time-locked to participants responses, but not when time-locked to option onset. These findings revealed a crucial link between subsecond whole-brain neural dynamics and trial-by-trial decision variables, providing insights into how value-based decision processes unfold over time in the human brain.

neuroscience↗

bioRxiv2025

Desiccation-tolerant Acinetobacter as a robust chassis for gas-phase bioprocesses

BackgroundGas-phase bioprocesses that immobilize microbial cells on solid carriers enable efficient conversion of volatile or poorly water-soluble substrates, but they also expose cells to fluctuating humidity and transient desiccation that can compromise viability and catalytic performance. In Gram-negative bacteria, especially in pathogens, desiccation is known to impose multifactorial stress, including loss of cellular water and energetics, damage to DNA and proteins, oxidative stress, and disruption of the cell envelope. However, for chassis strains used in or being considered for gas-phase bioprocesses, their desiccation tolerance and responses to desiccation stress remain incompletely defined. ResultsHere, we evaluated the viability, energy status, and gas-phase toluene degradation of Acinetobacter sp. Tol 5 as a chassis for gas-phase processes after controlled desiccation (8%, 52%, and >95% RH), in comparison with Acinetobacter baylyi ADP1, Pseudomonas putida, and Escherichia coli. To minimize adhesion-related bias in post-desiccation measurements, we used an ataA-deficient Tol 5 mutant (Tol 5 {Delta}ataA) for the assays. Acinetobacter strains maintained high viability during desiccation for 16 days, whereas P. putida and E. coli showed significant loss of viability at 8% RH and 52% RH. Intracellular ATP measurements further indicated that desiccation reduced intracellular ATP in all strains, but E. coli rapidly exhausted ATP at 8% and 52% RH, whereas Acinetobacter strains and P. putida retained intracellular ATP. In a gas-phase toluene degradation assay, immobilized Tol 5 retained higher toluene-degrading activity after desiccation than P. putida mt-2. Transcriptome profiling revealed a multilayered Tol 5 response involving DNA and RNA maintenance, cell envelope trafficking and remodeling, redox-responsive functions, and broad repression of growth-associated metabolism. ConclusionsOur results highlight Acinetobacter, particularly Tol 5, as a promising chassis strain for gas-phase bioprocesses and suggest potential mechanistic targets for stabilizing bacterial cells under low-water-activity conditions.

microbiology↗

bioRxiv2025

Expression dynamics and functional characterization of the pigmented and non-diapausing egg gene (pnd) and pnd-2, responsible for the initiation of embryonic diapause in the silkworm, Bombyx mori

Diapause in insects is a developmental arrest that serves as an adaptation to severe environmental conditions. In the silkworm Bombyx mori, embryonic diapause in the next generation is maternally induced by the diapause hormone (DH). However, the downstream factors responsible for initiating diapause have remained unidentified. The pnd and pnd-2 mutants produce pigmented and non-diapausing eggs despite intact DH signaling, indicating that the pnd and pnd-2 genes act downstream as potential initiators of diapause. Here, we analyzed their expression dynamics and functions. Expression analyses showed that pnd was strongly upregulated in diapause-destined eggs in a DH-signal-dependent manner and was suppressed by HCl treatment that prevents diapause initiation. In contrast, pnd-2 exhibited a transient expression peak independent of DH-signal and was unaffected by HCl treatment. RNAi-mediated knockdown of either gene inhibited the diapause initiation, and injection of pnd mRNA into non-diapause-destined eggs induced a diapause-like state in embryos. These findings demonstrate that pnd and pnd-2 are required downstream of the DH-signal to initiate diapause, providing key insights into the molecular mechanism underlying embryonic diapause induction in B. mori. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/667111v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@7e9516org.highwire.dtl.DTLVardef@6dddc2org.highwire.dtl.DTLVardef@fa11baorg.highwire.dtl.DTLVardef@1a2054e_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Sustained visual signals in the primate cerebellar dentate nucleus drive associative learning

A number of studies have suggested that the cerebellum has cognitive functions; however, the underlying neuronal mechanisms remain unclear. In this study, we demonstrated that sustained visual signals in the cerebellar dentate nucleus represent the visuomotor associative information. We recorded neural activity from the dentate nucleus when monkeys performed a learning task involving the association between visual objects and saccade directions. We found that sustained visual activity was greater in the region during learning than during memory retrieval. This enhancement disappeared under the uncertain reward condition, wherein the monkey did not perform the heuristic learning strategy. Furthermore, sustained visual signals changed the response to visual objects depending on the associated saccade direction. This direction selectivity was positively correlated with modulation during learning. These results suggest that sustained visual signals in the dentate nucleus reflect learning motivation and drive learning by increasing the strength of discrimination among visual objects.

physiology↗

bioRxiv2025

Fast-spiking neurons in monkey orbitofrontal cortex underlie economic value computation

Inhibitory interneurons are fundamental constituents of cortical circuits that process information to shape economic behaviors. However, the role of inhibitory interneurons in this process in the core cortical reward region, the orbitofrontal cortex (OFC), remains elusive. Here, we show that presumed parvalbumin-containing GABAergic interneurons (fast-spiking neurons, FSNs) differ from regular-spiking pyramidal neurons (RSNs) in computing economic value. While monkeys perceived a visual lottery for probability and magnitude of rewards, identified FSNs constituted 12% of OFC neurons and showed high-frequency firing rates and wide dynamic ranges, which are both key intrinsic cellular characteristics regulating cortical computation. We found that FSNs showed stronger neural modulation compared to RSNs in signaling probability and magnitude information. Unambiguously, both neural populations signaled the expected values, but FSNs processed the reward information more strongly under the influence of dynamic range. Thus, stronger FSN signals may appear with wider dynamic range for expected value computation.

neuroscience↗

bioRxiv2024

Inhibition of p38-MK2 pathway enhances the efficacy of microtubule inhibitors in breast cancer cells

Microtubule-targeting agents (MTAs) have been successfully translated from basic research into clinical therapies and have been widely used as first- and second-line chemotherapy drugs for various cancers. However, current MTAs exhibit positive responses only in subsets of patients and are often accompanied by side effects due to their impact on normal cells. This underscores an urgent need to develop novel therapeutic strategies that enhance MTA efficacy while minimizing toxicity to normal tissues. In this study, we demonstrate that inhibition of the p38-MK2 (MAP kinase-activated protein kinase 2) pathway sensitizes cancer cells to MTA treatment. We utilize CMPD1, a dual-target inhibitor, to concurrently suppress the p38-MK2 pathway and microtubule dynamicity. In addition to its established role as an MK2 inhibitor, we find that CMPD1 rapidly induces microtubule depolymerization, preferentially at the microtubule plus-end, leading to the inhibition of tumor growth and cancer cell invasion in both in vitro and in vivo models. Notably, 10 nM CMPD1 is sufficient to induce irreversible mitotic defects in cancer cells, but not in non-transformed normal cells, highlighting its high specificity to cancer cells. We further validate that a specific p38-MK2 inhibitor significantly potentiates the efficacy of sub-clinical concentrations of MTA. In summary, our findings suggest that the p38-MK2 pathway presents a promising therapeutic target in combination with MTAs in cancer treatment.

cancer biology↗

bioRxiv2024

Basic fibroblast growth factor helps protect facial nerve cells in a freeze-induced paralysis model

Severe axonal damage in the peripheral nerves results in retrograde degeneration towards the central side, leading to neuronal cell death, eventually resulting in incomplete axonal regeneration and functional recovery. Therefore, it is necessary to evaluate the facial nerve nucleus in models of facial paralysis and investigate the efficacy of treatments, to identify treatment options for severe paralysis. Consequently, we aimed to examine the percentage of facial nerve cell reduction and the extent to which intratympanic administration of a basic fibroblast growth factor (bFGF) inhibits neuronal cell death in a model of severe facial paralysis. A severe facial paralysis model was induced in Hartley guinea pigs by freezing the facial canal. Animals were divided into two groups: one group was treated with gelatin hydrogel impregnated with bFGF and the other was treated with saline. Facial movement scoring, electrophysiological testing, and histological assessment of facial neurons were performed at different postoperative time points. The freezing-induced facial paralysis model showed a facial neuronal cell death rate of 29.0%; however, bFGF administration reduced neuronal cell death to 15.8%. Facial movement scores also demonstrated improvement in the bFGF group compared with those in the control group. Intratympanic bFGF administration has a protective effect on facial neurons in a model of severe facial paralysis. These findings suggest a potential therapeutic approach for treating patients with refractory facial paralysis. Further studies are required to explore the clinical applicability of this treatment.

neuroscience↗

bioRxiv2024

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↗

bioRxiv2024

The effects of parasitism on sex allocation of a hermaphroditic acorn barnacle

Sex allocation theory predicts the adaptive allocation of resources to male versus female reproduction in simultaneous hermaphrodites in response to individual characteristics or environmental factors. Because parasites uptake resources from their hosts, their presence could affect the sex allocation of the hosts. We investigated the effects of infestation status and infestation intensity by the rhizocephalan barnacle Boschmaella japonica on reproduction, including sex allocation, of the host intertidal barnacle Chthamalus challengeri. Feeding activity was also examined as a factor related to resource intake. Both male and female reproductive investment decreased with increasing parasite infestation, and the sex allocation of large infested hosts was more male-biased than that of large uninfested hosts. Moreover, in contrast to the model prediction that male investment does not change under resource limitation, male investment decreased in infested hosts whose resources were taken by parasites. This reduction in male investment could be explained by changes in mating group size, since infested hosts have shorter penises and consequently are able to access fewer mating partners.

evolutionary biology↗

bioRxiv2023

A method for evaluating hunger and thirst in monkeys by measuring blood ghrelin and osmolality levels

Hunger and thirst drive animals consumption behavior and regulate their decision-making regarding rewards. We previously assessed the thirst states of monkeys by measuring blood osmolality under controlled water access and related the thirst states to risky decisions for fluid rewards. However, hunger assessments in monkeys have been poorly performed. Moreover, the lack of precise measures for hunger states leads to another issue regarding how hunger and thirst states interact with each other in each individual. Thus, when controlling food access to motivate subject performances, how these two physiological needs are satisfied in captive monkeys remains unclear. Here, we measured blood ghrelin levels and osmolality for hunger and thirst, respectively, in four captive macaques. Using enzyme-linked immunosorbent assay, we found that the levels of blood ghrelin, a widely measured hunger-related peptide hormone in humans, were high after 20 h of no food access (with ad libitum water), which is a typical controlled food access condition. One hour after consuming the regular dry meal, the value decreased in three out of four monkeys to within the range of individual blood ghrelin levels. Additionally, blood osmolality measured from the same blood sample, the standard hematological index of hydration status, increased after consuming regular dry meals with no water access. Thus, ghrelin and osmolality may provide a precise reflection of the physiological states of individual monkeys for hunger and thirst, suggesting that these indices can be used as a tool for monitoring hunger and thirst levels that mediate the animals decision-making for consuming rewards.

neuroscience↗

bioRxiv2023

Distinct roles of the orbitofrontal cortex, ventral striatum, and dopamine neurons in counterfactual thinking of decision outcomes

Individuals often assess past decisions by comparing what was gained with what would have been gained had they acted differently. Thoughts of past alternatives that counter what actually happened are called "counterfactuals". Recent theories emphasize the role of the prefrontal cortex in processing counterfactual outcomes in decision-making, although how subcortical regions contribute to this process remains to be elucidated. Here we report a clear distinction among the roles of the orbitofrontal cortex, ventral striatum and midbrain dopamine neurons in processing counterfactual outcomes in monkeys. Our findings suggest that actually-gained and counterfactual outcome signals are both processed in the cortico-subcortical network constituted by these regions but in distinct manners, and integrated only in the orbitofrontal cortex in a way to compare these outcomes. This study extends the prefrontal theory of counterfactual thinking and provides key insights regarding how the prefrontal cortex cooperates with subcortical regions to make decisions using counterfactual information. TeaserCortical and subcortical systems both contribute to counterfactual thinking of decision outcomes but in distinct manners.

neuroscience↗

bioRxiv2023

Functional Trajectories after Zebrafish Spinal Cord Transection

Adult zebrafish are capable of anatomical and functional recovery following severe spinal cord injury. Axon growth, glial bridging and adult neurogenesis are hallmarks of cellular regeneration during spinal cord repair. However, the correlation between these cellular regenerative processes and functional recovery remains to be elucidated. Whereas the majority of established functional regeneration metrics measure swim capacity, we hypothesize that gait quality is more directly related to neurological health. Here, we performed a longitudinal swim tracking study for sixty individual zebrafish spanning eight weeks of spinal cord regeneration. Multiple swim parameters as well as axonal and glial bridging were integrated. We established rostral compensation as a new gait quality metric that highly correlates with functional recovery. Tensor component analysis of longitudinal data supports a correspondence between functional recovery trajectories and neurological outcomes. Moreover, our studies predicted and validated that a subset of functional regeneration parameters measured 1 to 2 weeks post-injury is sufficient to predict the regenerative outcomes of individual animals at 8 weeks post-injury. Our findings established new functional regeneration parameters and generated a comprehensive correlative database between various functional and cellular regeneration outputs.

neuroscience↗

bioRxiv2022

Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells

Cell migration is essential for both physiological and pathological processes such as embryonic morphogenesis, wound repair and metastasis of cancer cells. Collective cell migration is the coordinated movement of multiple cells connected with cadherin-based adherence junctions. Cadherins undergo dynamic intracellular trafficking and their surface level is determined by a balance between endocytosis, recycling and degradation. However, regulatory mechanisms of cadherin turnover in the collective cell migration remain to be elucidated. In this study, we show that a BAR domain protein pacsin 2 plays an essential role in collective cell migration by regulating the internalization of N-cadherin in human bladder cancer cells T24. Pacsin 2 and its associating GTPase dynamin 2 colocalized with N-cadherin at the cell periphery in T24 cells. Depletion of either pacsin 2 or dynamin 2 induced interdigitating cell-cell contacts enriched with N-cadherin. Imaging analyses of the wound healing assay showed that pacsin 2-depleted T24 cells migrated in a collective and directed manner in contrast with randomly migrating control cells. Furthermore, cell-surface biotinylation assay showed that internalization of N-cadherin is attenuated in pacsin 2-depleted cells. Interestingly, the GST-pulldown assay demonstrated that the SH3 domain of pacsin 2 binds to the cytoplasmic domain of N-cadherin, suggesting that surface levels of N-cadherin are regulated by pacsin 2-mediated endocytosis. These data support new insights into a novel endocytic route of N-cadherin in collective cell migration providing pacsin 2 as a possible therapeutic target for cancer metastasis.

cell biology↗

bioRxiv2022

Identification of a novel chalcone reductase gene for isoliquiritigenin biosynthesis in dahlia (Dahlia variabilis)

Butein is one of flavonoids conferring bright yellow flower color and is a precursor of aurone in some species. Butein is synthesized by two steps, 3-malonyl CoA and 4-coumaloyl CoA are converted to isoliquiritigenin in the first step, and then isoliquiritigenin is converted to butein in the second step. In the first step, chalcone synthase (CHS) and chalcone reductase (CHR) catalyze this reaction, however, CHR has been reported for the isoflavone biosynthesis pathway in legumes, and CHR for butein biosynthesis has not yet been isolated. In this study, we report CHR that is evolutionally different gene from legume species is involved in isoliquiritigenin biosynthesis in dahlia. To isolate CHR gene, we conducted comparative RNA-seq analysis between Shukuhai and its butein-loss lateral mutant Rinka. We found DvCHR showed significant difference in expression levels that encodes an aldo-keto reductase (AKR) 13 family protein, which was phylogenetically different from legume CHRs belonging to AKR4A family. Gene expression levels and genotype of DvCHR were correlated with butein accumulation among various dahlia cultivars. Though single over expression of DvCHR was not able to accumulate isoliquiritigenin in tobacco, co-overexpression of DvCHR with a chalcone glucosyltransferase Am4'CGT and a MYB transcription factor CaMYBA successfully induced isoliquiritigenin accumulation. In addition, DvCHR homologous gene expression was detected from butein or aurone accumulating Coreopsideae species but not from non-butein or non-aurone accumulating Asteraceae species. These results indicated DvCHR functions as chalcone reductase for butein biosynthesis in dahlia, and isoliquiritigenin biosynthesis in Coreopsideae species has been developed independently from legume species.

plant biology↗

bioRxiv2022

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↗

bioRxiv2021

A neuronal prospect theory model in the brain reward circuitry

Prospect theory, arguably the most prominent theory of choice, is an obvious candidate for neural valuation models. How the activity of individual neurons, a possible computational unit, reflects prospect theory remains unknown. Here, we show with theoretical accuracy equivalent to that of human neuroimaging studies that single-neuron activity in four core reward-related cortical and subcortical regions represents the subjective valuation of risky gambles in monkeys. The activity of individual neurons in monkeys passively viewing a lottery reflects the desirability of probabilistic rewards, parameterized as a multiplicative combination of a utility and probability weighting functions in the prospect theory framework. The diverse patterns of valuation signals were not localized but distributed throughout most parts of the reward circuitry. A network model aggregating these signals reliably reconstructed risk preferences and subjective probability perceptions revealed by the animals choices. Thus, distributed neural coding explains the computation of subjective valuations under risk.

neuroscience↗

bioRxiv2021

Bovine serum albumin as a resuscitation promoting factor for viable but non-culturable Mycobacterium tuberculosis via the activation of protein kinase A-dependent cellular processes

We investigated the mechanisms underlying the fetal bovine serum (FBS)-induced reactivation of the viable but non-culturable (VBNC) state of Mycobacterium tuberculosis (Mtb) using the H37Rv strain. We found that bovine serum albumin (BSA), a major component of FBS, could reactivate the VBNC state of Mtb cells without other reactivation-promoting agents. Human serum albumin also had a restorative effect similar to BSA, but mouse serum albumin and egg-white albumin (ovalbumin) did not, suggesting that a common protein structure between bovine and human serum albumin is essential for reactivation. In addition, antioxidative agents, such as N-acetyl-L-cysteine, showed no restorative effect, suggesting that the restoration of culturability might not be due to the antioxidative property of BSA. BSA-mediated reactivation is inhibited by H89 and staurosporine. These inhibitors are known to inhibit multiple protein kinases, including serine/threonine protein kinases, in Mtb, suggesting the involvement of mycobacterial protein kinases in cell division during reactivation. These findings provide new insights into the mechanisms of Mtb reactivation, and may contribute to the development of novel strategies for the treatment of latent tuberculosis. ImportanceReactivation of dormant, including viable but non-culturable (VBNC) Mycobacterium tuberculosis (Mtb) cells, represents a critical step in the progression from latent infection to active tuberculosis. However, the molecular mechanisms that trigger this transition are not yet fully understood. We herein report that bovine serum albumin (BSA), a major component of fetal bovine serum, can restore the culturability of VBNC Mtb cells. Human serum albumin showed a similar effect, whereas mouse and egg-white albumins did not, suggesting that the specific structural features shared between bovine and human albumins are essential for reactivation. The lack of reactivation by the antioxidant N-acetyl-L-cysteine indicates that the mechanism is not related to redox balance. Inhibition of BSA-induced reactivation by H89 and staurosporine implicates mycobacterial serine/threonine protein kinases in this process. These findings highlight the previously unrecognized role of albumin-kinase signaling in Mtb reactivation and suggest new molecular targets for preventing tuberculosis relapse.

microbiology↗