Biology subjects

Goto, Y.

Publications and source records attributed to Goto, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Putrescine-responsive post-transcriptional feedback regulation of Arabidopsis ADC2 mediated by 5'-UTR elements

Putrescine (Put) is a bioactive polyamine that contributes to plant growth, development, and stress responses, whereas excessive Put accumulation impairs growth. However, how plants maintain Put levels within an appropriate range remains poorly understood. In Arabidopsis thaliana, expression of the arginine decarboxylase 2 (ADC2) gene is a major determinant of Put abundance. Here, we show that the 5' untranslated region (5'-UTR) of ADC2 mediates Put-responsive feedback regulation and contributes to Put homeostasis in Arabidopsis. In transient expression assays using an emerald luciferase (Eluc) gene placed downstream of the ADC2 5'-UTR (ADC2 5'-UTR:Eluc), Eluc activity was reduced by exogenously applied Put but increased when endogenous Put biosynthesis was impaired by adc2 mutations or treatment with an arginine decarboxylase inhibitor. In transgenic plants carrying ADC2 5'-UTR:Eluc, Put treatment modestly decreased Eluc mRNA abundance but substantially reduced Eluc activity and translation efficiency, suggesting that this Put-responsive repression occurs mainly at the translational level. Among the cis-regulatory elements in the ADC2 5'-UTR, mutations affecting either the conserved AUU/CUG-initiated upstream ORF or the predicted RNA secondary structure in the ADC-box, a conserved GC-rich motif, abolished Put-responsive repression, indicating that these elements are required for this regulation. Two genome-edited lines carrying deletions spanning these elements exhibited delayed germination and impaired growth, and the more severely affected line showed increased Put accumulation. Together, these findings reveal a feedback mechanism that regulates ADC2 expression through its 5'-UTR and support a role for this mechanism in Put homeostasis in Arabidopsis.

plant biology↗

bioRxiv2026

Impaired Reinforcement Learning Underlying Explore-Exploit Decision Making in Theft Recidivists

Larceny imposes profound societal and economic burdens; however, punitive judicial measures frequently fail to deter recidivism. The neurobehavioral mechanisms driving habitual offending, whether instrumental or kleptomanic, in theft recidivists remain poorly understood. In this study, we investigated explore-exploit decision-making and underlying reinforcement learning architectures in theft recidivists with a 4-arm bandit task while prefrontal cortex (PFC) hemodynamics were continuously monitored using functional near-infrared spectroscopy (fNIRS). Model-free behavioral analyses revealed that non-kleptomanic (TR-K) but not kleptomanic (TR+K) theft recidivists accumulated significantly higher cumulative regret and made fewer optimal choices compared to control individuals without criminal records (CT). Model-based analyses through Variational Bayesian Analysis identified Q-learning with decay model as the optimal computational fit. Parameter extraction using the model demonstrated that the TR-K group exhibited a lower learning rate than CT and TR+K groups, indicating a learning deficit in updating action values following environmental feedback. fNIRS tracking of trial-by-trial latent reinforcement variables revealed that while PFC activity was modulated by these variables, group differences were characterized by static baseline hemodynamic shifts rather than rewirings of value-tracking neural circuits. These findings suggest that non-kleptomanic recurrent thefts may be associated with impaired reinforcement learning mechanisms, challenging current punitive deterrence models.

neuroscience↗

bioRxiv2026

Altered Social Cognition Associated with Kleptomanic and Instrumental Thefts

Theft, including shoplifting, extorts a pervasive societal and economic burden. However, the neurobehavioral mechanisms underlying recurrent theft remain sparsely understood. In this study, we investigated social cognition deficits in theft recidivists with kleptomania (TR+K) and instrumental theft recidivists without kleptomania (TR-K) compared to control subjects without criminal records (CT), for which the Social Norms Questionnaire (SNQ-22) to assess explicit moral knowledge, alongside the Dictator Game (DG) and Hawk-Dove Game (HDG) to evaluate discretionary and competitive resource allocation with others, respectively, were administered. Bayesian statistical analyses revealed that all groups demonstrated comparable social norm recognition in SNQ-22 and prosociality in the DG. However, distinct behavioral profiles emerged in specific contexts, such that TR+K exhibited more unfairness than CT and TR-K at discretionary resource allocations in the DG, whereas in the HDG, TR-K demonstrated more aggressive, resource-monopolizing responses, particularly when against an aggressive opponent, than CT and TR+K. These results suggest that theft recidivism may stem from contextual failures rather than general deficits in moral knowledge, which are distinct between TR+K rooted in the internal factor, such as heightened loss aversion, and TR-K characterized by impulsivity over the external factor, such as social conflicts with others.

neuroscience↗

bioRxiv2026

Mapping the sequence preference of the generalist class II lanthipeptide synthetase ProcM by mRNA display

The biosynthetic machineries of ribosomally synthesized and post-translationally modified peptides (RiPPs) are often substrate tolerant. A remarkable example is the class II lanthipeptide synthetase ProcM, which naturally functions as a generalist enzyme that has not evolved to use a specific substrate during its evolutionary history. Although ProcM has been studied extensively, the sequence features associated with productive modification remain underexplored. In this study, we use the ultrahigh-throughput mRNA display technique to map the sequence compatibility of ProcM across a focused library. This approach expands the landscape of ProcM reactivity beyond native substrates and individually characterized variants. Machine learning (ML) is used as a tool to demonstrate that the selected dataset contains learnable signatures and classification architectures revealed a balanced accuracy of 0.73. This performance contrasts sharply with the near-perfect accuracy of specialized enzyme models as the sequence-fitness landscape of the generalist enzymes are characterized by class imbalance and limited by intrinsic dataset features. Our results provide a high-throughput view of ProcM reactivity and highlight differences with previous high-throughput studies on substrate selectivity of RiPP modification enzymes. Future studies will need to assess whether these differences are common when comparing generalist with specialist enzymes.

biochemistry↗

bioRxiv2026

Nationwide multi-omics profiling of Japanese jack mackerel reveals geographic gut microbiome structuring despite host panmixia

Host genetic markers often fail to resolve regional origins in highly connected or panmictic marine species. The Japanese jack mackerel, Trachurus japonicus, is a commercially important fishery species around Japan that shows little or no detectable population structure. Here, we used nationwide multi-omics profiling to compare host genomic variation and gut microbiome composition in wild T. japonicus collected from coastal regions across Japan. We generated MIG-seq data for 43 individuals and 16S rRNA gene profiles for 24 individuals; after quality filtering, 19 individuals remained for matched host-microbiome comparison. Genome-wide host SNP analyses showed weak or absent geographic population structure, consistent with previous evidence of panmixia in Japanese waters. In contrast, gut microbiome composition showed geographic structuring based on Bray-Curtis dissimilarity and PERMANOVA, and this pattern was not explained by proximity to river mouths or host-related variables. Locality- or individual-associated bacterial lineages contributed to the observed differences in the microbiome, while chloroplast-associated and Cyanobacteria-assigned ASVs suggested recent dietary or environmental input. These results indicate that gut microbiome can show regional biological variation not apparent from host genetic markers alone. Our study provides a proof-of-concept example of integrating host genomics and gut microbiome profiling to evaluate regional characteristics and origins in highly connected marine animals.

microbiology↗

bioRxiv2026

Higher Impulsivity in the Heterogeneous Structure of Theft Recidivists with and without Kleptomania

Impulsivity is associated with various maladaptive behaviors, although its specific role in criminology has remained largely unexplored. We investigated impulsivity in theft recidivists (TR) with and without a diagnosis of kleptomania (KA) compared to control (CT) subjects with no criminal record in this study. Impulsivity was measured using a 5-trial adjusting delay discounting task, and prefrontal cortical (PFC) hemodynamics were assessed using functional near-infrared spectroscopy. Self-report questionnaires were also administered to further evaluate the relationships between impulsivity, negative affect, and reward and punishment sensitivity. TR demonstrated significantly higher impulsivity than CT, along with altered dorsomedial PFC hemodynamic responses. In addition, negative affect was significantly higher in the TR than in the CT participants. Path analysis revealed that the moderation of negative affect on reward, but not punishment, sensitivity, mediated impulsivity in TR. Notably, heightened impulsivity was observed across the TR participants regardless of KA diagnosis, whereas severe depression specifically distinguished KA from TR without it. These findings suggest that while trait impulsivity associated with PFC alterations may be a universal feature of TR, recurrent theft may be a heterogeneous condition, with specific affective dysregulations contributing differently to TR. SIGNIFICANCE STATEMENTRecurrent thefts, such as shoplifting, are a devastating social problem, posing massive financial losses. Nonetheless, surprisingly nothing is known about the neurobehavioral mechanisms that drive people stealing. In fact, kleptomania is a psychiatric disorder that had been identified over 200 years ago, yet exceptionally few studies have investigated this psychiatric condition, and its mechanism remains essentially unknown to date. This study demonstrates that impulsivity is elevated among incarcerated individuals with recurrent thefts with and without a diagnosis of kleptomania, which is associated with the activity of the left dorsomedial prefrontal cortex. Conversely, heightened depression among negative affect is a unique characteristic to kleptomania, providing evidence of heterogeneity among theft recidivists.

neuroscience↗

bioRxiv2026

From introduction to eradication: reconstructing population size and removal history of an invasive species

O_LIUnderstanding the processes underlying successful eradication of invasive species is essential for achieving global island conservation goals. Despite the widespread availability of capture records from eradication programs, modeling frameworks that utilize these datasets to elucidate spatio-temporal population dynamics remain underdeveloped. C_LIO_LIIn this study, we reconstructed the spatio-temporal population dynamics of the small Indian mongoose on Amami-Oshima Island (712 km{superscript 2}), Japan, where the species was introduced in 1979 and officially declared eradicated in 2024 after more than 30 years of systematic removal. We integrated introduction records, capture data, and monitoring data using a hierarchical harvest-based model (HBM). To evaluate the models capacity to support management decisions and assess eradication success, we conducted retrospective analyses and compared estimated eradication probabilities with those obtained from a rapid eradication assessment (REA; Samaniego-Herrera et al., 2013). C_LIO_LIThe estimated population size (before reproduction) peaked at 5,449 individuals (95% CI: 4,703, 6,175) in 2000 and subsequently declined almost monotonically. The maximum invaded area was 547.78 km{superscript 2} (posterior median, 95% CI: 496.47, 566.04) in 2009, indicating that the removal program successfully prevented island-wide expansion. Retrospective analyses showed that population estimates remained within the 95% credible intervals of the full dataset estimates, demonstrating temporal consistency. Eradication probabilities estimated by the HBM were substantially higher than those from the REA, highlighting the sensitivity of estimates to fine-scale heterogeneity in detection processes. C_LIO_LISynthesis and applications: Hierarchical HBMs provide a powerful framework for reconstructing, predicting, and evaluating invasive species eradication dynamics. Being aware of the limitations for application to eradication evaluations, HBMs can support adaptive management in long-term eradication programs and improve our understanding of the mechanisms underlying successful eradication. C_LI

ecology↗

bioRxiv2026

Behavioral Economic Profiles in Theft Recidivists with and without Kleptomania

Recurrent theft, such as shoplifting, is a devastating social problem that poses a significant economic burden on society. However, the neurobehavioral mechanisms underlying such criminal offenses remain barely understood. Here we investigated the behavioral economic profiles of theft recidivists (TR) with and without kleptomania. To identify the decision-making processes underlying stealing behaviors, the hypothetical purchase task and the balloon analogue risk task (BART) structured with gain and loss frames were administered, along with concurrent measurement of prefrontal cortex (PFC) activity during the BART using functional near-infrared spectroscopy. TR with kleptomania demonstrated heightened loss aversion and price sensitivity (elasticity) compared to TR without kleptomania and control subjects with no criminal records, with a significant correlation between these factors, suggesting that heightened loss aversion may contribute to higher elasticity. Moreover, the relative loss-to-risk aversion ratio was found to be positively and negatively associated with the right and left PFC, respectively, suggesting that an imbalance between left and right PFC activity may be involved in the altered behavioral economic profiles. These findings challenge the conventional view of theft as a reward-seeking behavior, revealing that an abnormally inflated fear of monetary loss may play a role in recurrent stealing in kleptomania.

neuroscience↗

bioRxiv2026

EC1 body controls sperm cell reception via gamete pit formation.

The remarkable efficiency of double fertilization in flowering plants depends on the precise delivery of immotile sperm cells to two female gametes1. Although sperm cells are rapidly released from the pollen tube, how they are accurately directed to their fertilization site has remained unknown. Here we identify a transient extracellular structure, termed the gamete pit, that forms at the egg cell-central cell (EC-CC) interface immediately after pollen tube discharge and serves as the landing site for sperm cells. Gamete pit formation is enabled by localized dissociation of the EC-CC interface, mediated by extracellular protein assemblies designated EC1 bodies. These structures contain extracellular deposits enriched in EGG CELL 1 (EC1) peptides2, including amyloid-like assemblies. Loss of EC1 bodies prevented gamete pit formation, causing sperm-cell backflow or catastrophic over-penetration of pollen tube contents into the central cell. Surprisingly, ectopic deposition of a heterologous amyloidogenic protein alleviated over-penetration and partially restored fertility. Our findings reveal a mechanism by which extracellular protein assemblies remodel the gamete interface for sperm-cell reception, uncover an unexpected structural role for the conserved gamete-activating peptide EC1, and establish protein-mediated cell-interface remodeling as a fundamental principle underlying double fertilization in flowering plants.

plant biology↗

bioRxiv2026

Use of anodal transcranial direct current stimulation for improving motor performance in healthy adults: A systematic review and meta-analysis

PurposeTranscranial direct current stimulation (tDCS) can noninvasively modulate activity in targeted brain regions. It is well established that the excitability of motor-related regions can increase when the target region is located beneath the anode (anodal tDCS), suggesting its potential to increase motor performance. Although such attempts have been widely examined, the results remain inconclusive. The purpose of this study was to assess the conditions under which anodal tDCS may improve motor performance in healthy adults. MethodsWe conducted a systematic review of studies on the use of anodal tDCS for improving motor performance in healthy adults. A computerized search was performed using the Web of Science, Scopus, PubMed, JDreamIII, and Ichushi-Web to identify relevant studies published between January 1, 1990 and May 25, 2022. ResultsTwenty-five studies were included in the qualitative synthesis. For the meta-analysis, 25 trials (N=885) were extracted from 23 studies. There were significant effects of anodal tDCS on motor performance improvement, but with evidence of publication bias and substantial heterogeneity among the trials. Post-hoc analysis revealed that motor performance 24 hours after the application of anodal tDCS may benefit from stimulation. There was no marked effect related to stimulation intensity, duration, or whether stimulation was provided during motor performance. ConclusionsOur study clarified the current state of anodal tDCS use for motor performance enhancement and indicates that there is currently no reliable evidence to support its effectiveness. Further studies, particularly randomized controlled trials, are necessary to establish the reliability of these effects for future applications.

neuroscience↗

bioRxiv2026

Opto-MDMi: a dual-lock optogenetic system for robust activation of endogenous p53

Optogenetics has emerged as a powerful technology for manipulating biological functions with high spatiotemporal resolution, yet the precise control of endogenous molecules remains a significant challenge. In this study, we developed Opto-MDMi, a dual-lock optogenetic platform designed to control the activity of endogenous p53, a master regulator of cell cycle and apoptosis. The p53 pathway is strictly governed by its negative regulators, MDM2 and MDMX, which inhibit p53 through direct binding and ubiquitination. Our system integrates two distinct light-responsive modules: Opto-MDMi (LOVTRAP), which regulates the nuclear translocation of p53-activating peptides, and Opto-MDMi (LOV2-PMI), which controls the binding activity of these peptides by photocaging them within the AsLOV2 domain. Through extensive in vitro screening and live-cell assays, we discovered that truncating the J helix of LOV2 effectively restricts the movement of fused inhibitory peptides, thereby masking their interaction with MDM2/MDMX under dark conditions. By combining these two regulatory layers into a dual-lock system, we achieved robust light-dependent activation of endogenous p53 while significantly suppressing basal activity in the dark. Our findings not only provide a potent tool for p53 research but also establish a general design principle for optogenetically regulating functional peptides with the LOV2 domain, offering a versatile framework for the future development of optogenetic actuators.

systems biology↗

bioRxiv2026

Efficient generation of hematopoietic progenitor cells from human pluripotent stem cells by robotic automation

Differentiation of human pluripotent stem cells (hPSCs) into therapeutic cell types requires stringent control of developmental signals, but conventional manual operations introduce substantial intra- and inter-operator variability. While automation can reduce such variability, fixed systems often lack compatibility with the dynamic, stage-specific, and format-diverse manipulations required for hPSC culture and differentiation. Here, we establish a flexible robotic platform to standardize a stroma- and xeno-free embryoid body (EB)-based hematopoietic progenitor cell (HPC) differentiation process and integrate machine learning (ML) to optimize key process parameters including the concentrations of multiple signaling molecules. Despite intrinsic biological stochasticity and technical complexity associated with EB formation, the robotic platform substantially reduced experimental variation. ML-guided, unbiased exploration not only identified combinations of signaling inputs that markedly improved the efficiency and reproducibility of HPC differentiation and subsequent natural killer cell generation, but also illuminated key signaling logic underlying early human hematopoietic development. Together, these results demonstrate that data-driven robotic automation can uncover optimal culture conditions that are difficult to identify through conventional human-driven experimentation.

developmental biology↗

bioRxiv2026

UFD1 Recognition of Initiator and Proximal Ubiquitin Drives p97-Mediated Substrate Unfolding enhanced by FAF1, FAF2, and UBXD7

The AAA-ATPase p97 and its primary adaptor UFD1-NPL4 (UN) unfold ubiquitinated substrates for their proteasomal degradation. Although cryo-EM has shown that substrate processing begins with unfolding of the initiator ubiquitin and its capture by NPL4, the specific contribution of UFD1 to K48-linked ubiquitin chain engagement has not been fully defined. Here we report a 1.31 [A] crystal structure of the human UFD1-UT3 bound to a K48-linked di-ubiquitin mimic, revealing that UFD1-UT3 engages the unfolded initiator ubiquitin via its Nc subdomain and the proximal ubiquitin via its Nn subdomain. AlphaFold3-guided analyses further demonstrate that accessory adaptors FAF1, FAF2, and UBXD7 enhance p97-UN activity through divergent strategies. FAF1 and FAF2 scaffold UFD1-UT3 near the NPL4-tower, whereas UBXD7 stabilizes transient interactions between UFD1 and the ubiquitin chain. Our results provide a comprehensive molecular model for the initiation of p97-mediated substrate unfolding.

biochemistry↗

bioRxiv2026

Integration of UAS-based spatial surveys and bio-logging tracking enhances precision in population size estimation

Accurately estimating wildlife population sizes, essential for ecological theory and conservation management, yet remains challenging. Although unmanned aerial systems (UASs) combined with machine learning, have revolutionized population estimation, they face limitations in addressing the hierarchical population processes from individual behavior to colony-and population-level dynamics. To overcome this limitation, we developed a data integration framework that jointly analyzes multiple datasets, representing different scales of the same underlying process, were jointly analyzed. Using a seabird colony as a model system, we integrated UAS-based count data in the colony with bio-logging-based tracking data to estimate population size by quantifying both the number of individuals present and the proportion absent from the surveyed area. These complementary datasets were linked using state-space models allowing accurate population estimates with explicit uncertainty quantification. Furthermore, we evaluated the robustness of the estimations with respect to sample size. Sub-sampling simulations revealed that estimation uncertainty was more sensitive to sample size in bio-logging-based tracking data than in UAS-based count data. This finding highlights the importance of understanding dataset-specific properties when designing effective investigations. Overall, our resource-efficient framework is broadly applicable across species and populations and demonstrates how integrating complementary observation methods can improve population estimates and inform conservation practice.

ecology↗

bioRxiv2025

Individual bounded rationality destabilizes cooperative dynamics in human-AI groups

Cooperative dynamics arise from interactions among individuals, including humans and artificial agents, yet it remains unclear how individual-level cognition and motion shape collective dynamics in such human-AI groups. We combined a dynamic cooperative task, in which one attacker was controlled by a human and two by heuristic artificial agents facing a deep reinforcement learning defender, with counterfactual simulations of artificial groups. Across nine task conditions, groups including a human consistently underperformed relative to groups composed solely of artificial agents. Humans exhibited restricted movement options and probabilistic rather than deterministic action choices, which shifted coordination dynamics towards less symmetric, less organized patterns and reduced performance for both individuals and groups. Embedding these boundedly rational movement and decision parameters into artificial agents reproduced human-like behavior and performance declines. These results demonstrate how limitations of a single individual can destabilize cooperative dynamics and provide insights into the design of robust human-AI systems.

animal behavior and cognition↗

bioRxiv2025

High-Resolution Imaging of the Rhizosphere Using Resin-Embedded Cross-Sectional Polishing and Scanning Electron Microscopy for Biological Samples (bioCP-SEM)

Understanding microbial colonization in plant-associated environments requires high-resolution imaging of intact plant-microbe interfaces under natural soil conditions. However, conventional electron microscopy is limited by sample distortion and poor compatibility with heterogeneous substrates. Here, we present bioCP-SEM, a cross-sectional polishing scanning electron microscopy technique optimized for biological specimens inhabiting unsterilized soil. This method integrates resin embedding, diamond band saw sectioning, and mechanical polishing to enable high-quality imaging across large, complex samples. Using bioCP-SEM, we visualized bacterial clusters in a model plant root, and multilayered biofilm-like structures and fungal structures, including arbuscule-like forms, in a wild weed species. We further applied this method to intact moss collected from an urban environment, capturing spatially resolved interactions among biofilms, spores, protozoa, and annelids. Notably, microbial cells and subcellular structures, such as cilia, were preserved in situ. These results demonstrate the versatility of bioCP-SEM for mapping microbial architecture across diverse biological and environmental contexts.

microbiology↗

bioRxiv2025

Regulation of cell proliferation by a novel feedback system on Cdk function

The proliferation of eukaryotic cells is regulated by a complex network of regulatory systems that promotes efficient cell cycle progression and ensures proper responses to the environment. Despite this complexity, the core inputs that are necessary and sufficient for robust alternation of DNA replication and mitosis are surprisingly simpler than anticipated. Indeed, fission yeast cells operating with an engineered minimal cell cycle network that lacks the highly conserved Wee1+Cdc25 feedback loops on Cdk1 function are viable, although slow growing. This provides a unique entry for evaluating how such simplified cells can evolve and improve their proliferation potential while exploring unknown mechanisms modulating cell cycle progression. Taking advantage of this model, we applied laboratory evolution assays to minimal fission yeast backgrounds and selected for the emergence of faster growing populations. We found that loss of the small disordered protein Spo12 brings about enhanced population growth in cells lacking the Wee1+Cdc25 mitotic switch. Importantly, we demonstrate that Spo12 defines a new and conserved family of inhibitors of the Cdk-counteracting phosphatase PP2A that are directly regulated by Cdk-dependent phosphorylation. Our results also reveal a trade-off associated with Spo12-dependent regulation, which may have implications for our understanding of the principles underlying the evolution of cell cycle control. Finally, our study highlights how combining simplified circuits with experimental evolution allows for uncovering regulatory elements that may be obscured by network complexity.

cell biology↗

bioRxiv2025

Aminoacyl-tRNA specificity of a ligase catalyzing non-ribosomal peptide extension

Peptide aminoacyl-transfer ribonucleic acid ligases (PEARLs) are amide bond-forming enzymes that extend the main chain of peptides using aminoacyl-tRNA (aa-tRNA) as a substrate. In this study, we investigated the substrate specificity of the PEARL BhaBCAla from Bacillus halodurans, which utilizes Ala-tRNAAla. By leveraging flexizyme, a ribozyme capable of charging diverse acids onto a desired tRNA, we generated an array of aa-tRNAs in which we varied both the amino acid and the tRNA to dissect the substrate scope of BhaBCAla. We demonstrate that BhaBCAla catalyzes peptide extension with non-cognate proteinogenic and non-canonical amino acids, hydroxy acids, and mercaptocarboxylic acids when attached to tRNAAla. For most of these, the efficiency was considerably reduced compared to Ala, indicating the enzyme recognizes the amino acid. By varying the different parts of the tRNA, enzyme specificity was shown to also depend on the acceptor stem and the anticodon arm of the tRNA. These findings establish the molecular determinants of PEARL specificity and provide a foundation for engineering these enzymes for broader applications in peptide synthesis.

biochemistry↗