Biology subjects

Maeda, H.

Publications and source records attributed to Maeda, H..

13 recordsLinked to original sources

bioRxiv2026

Establishment of the grass lignin metabolic network during monocot evolution

Plants produce a vast diversity of chemical compounds, yet the evolutionary history of the underlying complex metabolic networks remains poorly understood. Grasses (Poaceae family) possess a unique lignin metabolic network that can utilize both phenylalanine and tyrosine as precursors to synthesize canonical lignin as well as non-canonical acylated and tricin-conjugated lignin subunits. This study traces the evolutionary remodeling and establishment of the grass lignin metabolic network by combining phylogenomics with biochemical and chemical analyses across Poaceae, Poales, and other monocot species. These multidisciplinary comparative analyses reveal that the acylated lignin evolved in commelinids, followed by tyrosine-derived lignin biosynthesis in non-grass graminids through fine-tuning of pathway enzymes and transcriptional factors. Later, biosynthesis and incorporation of the flavonoid tricin into the cell wall took place within the core grasses via the evolution of chrysoeriol 5'-hydroxylase (C5'H) activity within the CYP75B enzyme family. These findings illustrate the emergence of different network modules at distinct times during monocot evolution that became integrated into the complex yet coherent metabolic network underlying the unique lignin chemical diversity of grasses.

plant biology↗

bioRxiv2026

Nitrogen metabolic map of Escherichia coli mediated by multi-functional aminotransferases

Nitrogen is a key element of organic molecules essential to all life. Unlike extensively characterized carbon metabolic maps, it remains elusive how assimilated nitrogen flows through metabolic networks. Here we determined the nitrogen metabolic map of Escherichia coli and used it to construct an enzyme-constrained metabolic model that includes multi-functionality of aminotransferase enzymes responsible for nitrogen transfer reactions. We characterized substrate specificities of sixteen E. coli aminotransferase enzymes by evaluating 2,528 reactions, uncovering 56 previously unrecognized activities. The cellular concentrations of these aminotransferase enzymes were quantified and used to estimate their catalytic rates across all enzyme-substrate pairs, leading to improved predictions of nitrogen flows in E. coli. This work advances our fundamental understanding of the nitrogen metabolic map critical for metabolism and growth.

biochemistry↗

bioRxiv2026

Dual reinforcement-learning network modules for modeling decision-making with multiple strategies

Animals and humans use multiple behavioral strategies to perform tasks. However, neural implementations of multiple strategies remain elusive, as some studies propose distinct pathways, while others observe overlapping brain regions associated with strategies. We propose a hybrid deep reinforcement learning (H-DRL) method, in which one network model implements model-free and inference-based behaviors through synaptic plasticity and recurrent activity. H-DRL uses a single updating rule and switches the strategy according to task demands without an explicit arbitrator. H-DRL reproduced mixed strategies of humans in a two-step task. In the mouse perceptual decision-making task, H-DRL adapted the recurrent dynamics with rich learning when the task condition required inference-based behavior, while adopting model-free behavior with lazy learning for a simple condition. The activity of H-DRL units showed condition-dependent maintenance of previous events, consistent with orbitofrontal cortical activity in mice. Our model provides a unified view that one cortical network automatically determines strategies in use depending on task conditions.

neuroscience↗

bioRxiv2024

Soybean Cyst Nematode-Resistant Protein AATRhg1 Affects Amino Acid Homeostasis and Betalain Accumulation

Amino acid transporters play crucial roles in plant nitrogen metabolism but also defense responses. AATRhg1, an apparent amino acid transporter encoded by Glyma.18g022400 (Rhg1-GmAAT) at the soybean Rhg1 locus, contributes to resistance to soybean cyst nematode (SCN), although the in planta function of AATRhg1 remains elusive. In this study we discovered that overexpression of Rhg1-GmAAT in soybean roots enhances the betalain pigment synthesis driven by a RUBY transgene cassette, potentially through its transporter activity affecting tyrosine level and amino acid homeostasis. Silencing Rhg1-GmAAT also moderately increased betalain accumulation while co-overexpression of Rhg1-GmAAT and GmRBOHG (encoding an AATRhg1-interacting NADPH oxidase) blocked the betalain phenotype, indicating a complex role of AATRhg1 in regulating cellular metabolism. Soybean AATRhg1 did not show a betalain accumulation phenotype when co-overexpressed with RUBY in Nicotiana benthamiana leaves, suggesting that soybean AATRhg1 functions differently in N. benthamiana. In soybean, the expression of AATRhg1 proteins mutated at conserved residues D122A or Y268L mitigated or enhanced the betalain phenotypes, respectively, suggesting that these residues are important for AATRhg1 function. This study advances our understanding of AATRhg1 while presenting a novel strategy for enhancing betalain biosynthesis by modulating transport and homeostasis of amino acids.

plant biology↗

bioRxiv2024

Real-cyber hybrid neural network for predicting neural circuits in mouse decision-making

A major challenge in neuroscience is to elucidate how the brain processes sensory input to generate behavior, especially given the difficulty to measure neural activity across the whole brain. To address this limitation, previous studies have used artificial neural networks (ANNs) and modeled decision-making circuits in the brain. Here, we developed a real-cyber hybrid neural network (HNN) that directly input the activity of real neurons to an ANN, imposing biological constraints on the model. Using spike inputs from cortical or subcortical regions, the HNN predicted body movements of head-fixed mice during a task better than the ANN did. This improvement arose not only from the added mouse neuronal activity, but from the activity generated within the HNN. The generated activity potentially included unrecorded neuronal activity from mice, which was difficult for the ANN. We propose that HNNs develop brain-like activity to predict animal movements and compensate for unrecorded neural activity.

neuroscience↗

bioRxiv2024

Blastocoel expansion and AMOT degradation cooperatively promote YAP nuclear localization during epiblast formation

The epiblast is a pluripotent cell population formed in the late blastocyst stage of preimplantation embryos. During the process of epiblast formation from the inner cell mass (ICM) of the early blastocyst, activation of the Hippo pathway transcription factor TEAD by the nuclear translocation of the coactivator protein YAP is required for the robust expression of pluripotency factors. However, the mechanisms that alter YAP localization during epiblast formation remain unknown. Here, we reveal two such mechanisms. Expansion of the blastocoel promotes nuclear YAP localization by increasing cytoplasmic F-actin and reducing YAP phosphorylation. Additionally, cell differentiation regulates YAP. Expression of the junctional Hippo component, AMOT, gradually decreases during epiblast formation through a tankyrase-mediated degradation. SOX2 expression in the ICM is necessary for the reduction of AMOT and YAP phosphorylation. These two mechanisms function in parallel. Thus, the blastocoel-F-actin and SOX2-AMOT axes cooperatively suppress YAP phosphorylation and promote YAP nuclear localization during epiblast formation. The cooperation of these two distinct mechanisms likely contributes to the robustness of epiblast cell differentiation.

developmental biology↗

bioRxiv2024

Fate specification triggers a positive feedback loop of TEAD-YAP and NANOG to promote epiblast formation in preimplantation embryos

In preimplantation embryos, epiblast (EPI) fate specification from the inner cell mass is controlled by the segregation of NANOG and GATA6 expression. TEAD-YAP interaction is activated during EPI formation, and is required for pluripotency factor expression. These events occur asynchronously with similar timing during EPI formation, and their relationship remains elusive. Here, we examined the relationship between NANOG-GATA6 and TEAD-YAP. The nuclear accumulation of YAP takes place only in EPI-specified cells, and a positive feedback loop operates between NANOG and TEAD-YAP. The effects of TEAD-YAP on SOX2 upregulation in EPI-specified cells are likely indirect. EPI fate specification also alters the response of Nanog, Sox2 and Cdx2 to TEAD-YAP. These results suggest that EPI-fate specification alters the transcriptional network from the morula-like to the EPI-specified state and activates TEAD-YAP to trigger a positive feedback loop with NANOG, which stabilizes the EPI fate. The coordinated occurrence of these processes in individual cells likely supports proper EPI formation under the condition of asynchronous EPI-fate specification. Summary statementEpiblast fate specification by segregation of NANOG from GATA6 alters the transcriptional network and activates TEAD-YAP, triggering a positive feedback loop with NANOG to promote epiblast formation.

developmental biology↗

bioRxiv2024

Host-encoded DNA methyltransferases modify the epigenome and host tropism of invading phages

Restriction modification (RM) systems are ubiquitous bacterial defense systems; however, some phages evade RM system and adapt to their bacterial hosts. In such cases, phages are thought to stochastically acquire DNA methylation from host-encoded DNA methyltransferases (MTases), facilitating host adaptation. However, no studies have directly compared the methylomes of host bacteria and their infecting phages. Here, we demonstrate the epigenetic landscape of adapted phages with diverse infection histories, focusing on the broad host-range phage KHP30T as its adapts to three Helicobacter pylori strains. Using a multistage infection system, we observed that the adapted phages displayed significantly high titers against the last infected H. pylori strain, suggesting an attendant change in host tropism. Single-molecule real-time sequencing revealed that methylated motifs were predominantly shared between the adapted phages and their most recent host. Our findings enhance our understanding of epigenetic phage-host interactions, which have significant implications for microbial ecology.

microbiology↗

bioRxiv2024

Phylochemical mapping of natural products onto the plant tree of life using text mining and large language models.

Plants produce a staggering array of chemicals that are the basis for organismal function and diversity and also provide essential human nutrients and medicine. However, it is poorly defined how these compounds have evolved and are distributed across the diverse lineages of the plant kingdom, hindering a systematic view and understanding of plant chemical diversity. Recent advances in plant genome/transcriptome sequencing have provided a well-defined molecular phylogeny of plants, on which the presence of diverse natural products can be mapped to systematically determine their phylogenetic distribution. Here, we built a proof-of-concept workflow via which previously reported diverse tyrosine-derived plant natural products were mapped on to the plant tree of life. Plant chemical-species associations were mined from literature, filtered, evaluated through manual inspection of over 2,500 scientific articles, and mapped onto the plant phylogeny. The resulting phylochemical map confirmed several highly lineage-specific compound class distributions, such as betalain pigments and Amaryllidaceae alkaloids. The map also highlighted several lineages enriched in dopamine-derived compounds, including the orders Caryophyllales, Liliales, and Fabales. Additionally, the application of large language models using our manually curated data as a ground truth set showed that post-mining manual processing steps can largely be automated with a low false positive rate. Our study demonstrates that a workflow combining text mining with language model-based processing can generate broader phylochemical maps, which will serve as a critical community resource to uncover key evolutionary events that underlie plant chemical diversity and enable system-level views of natures millions of years of chemical experimentation. Significance StatementThis study introduces a novel workflow to map the distribution of natural products onto a phylogeny. It also demonstrates the effectiveness of combining text mining of the literature with large language model evaluation for constructing a phylochemical database that can organize vast portions of the chemical diversity present across the plant tree of life.

plant biology↗

bioRxiv2024

Synthetic spider silk forming highly-aligned nanoarchitectures on 2D-material surfaces

The synergy between silk proteins and nanomaterials can lead to novel materials with improved mechanical and electrical properties. Designed peptides have been previously utilised in the functionalisation of two-dimensional material surfaces in a self-assembly manner, including graphite, to develop highly sensitive electrical biosensors. These studies have predominantly focused on functionalising the surfaces with peptides of less than several kDa in size. In this work, we assessed the capability of a [~]35 kDa synthetic spider silk protein to serve as a candidate biomolecular scaffold on a range of two-dimensional materials: graphite, molybdenum disulphide and boron nitride. The structural properties of the synthetic spider silk protein at the 2D material surface were characterised at the nanoscale for the first time using a multi-analysis approach incorporating atomic force microscopy and fluorescence microscopy, in addition to polarised Raman and tip-enhanced Raman spectroscopy. The synthetic spider silk protein was revealed to self-assemble into stable nanowire structures of monolayer thickness. Our findings have demonstrated the feasibility of functionalising 2D materials with spider silk-based proteins and will unlock new possibilities in the development of next-generation high-performance biosensing devices.

biophysics↗

bioRxiv2020

Generation of Somatic Mitochondrial DNA-Replaced Cells for Mitochondrial Dysfunction Treatment

Mitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed over the long term, even inducing the production of pluripotent stem cells from the mitochondrial DNA-replaced cells to maintain the genotype without a reversion to the original. Both mitochondrial disease patient-derived and aged fibroblasts could regain respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. The mitochondrial DNA-replaced cells could be a resource for transplantation to treat not only mitochondrial diseases, but also senescence-related diseases.

cell biology↗

bioRxiv2020

Analyzing cannabinoid-induced abnormal behavior in a zebrafish model

This study investigated the locomotor activity and responses under stressful conditions to assess marijuana-induced abnormal behavior in zebrafish larvae (Danio rerio), as an alternative to the standard rodent model. To induce the desired symptoms, cannabidiol and WIN55,212-2, two chemical components derived from marijuana plants, were used. A repeated light and dark test was used to assess how drug exposure influenced locomotive responses. Subjects were examined after moderate cannabidiol and WIN55,212-2 exposure and 24 h after relocation into untreated water. Cannabidiol did not produce a dose-dependent inhibitory effect on locomotor activity; 0.5 and 10 g/mL cannabidiol decreased total distance and velocity, and 10 g/mL cannabidiol attenuated responses in the darkness. No differences between the control and cannabidiol-treated groups were apparent after 24 h in fresh water. WIN55,212-2 at 0.5 and 1 g/mL almost completely stopped fish activity even in darkness and at 10 g/mL induced mortality. Spending 24 h in fresh water almost reversed drug-induced immobilization, even in WIN55,212-2-treated groups. Subjects were evaluated for responses to additional cannabidiol after WIN55,212-2 exposure. Cannabidiol attenuated WIN55,212-2-induced abnormal immobilization, whereas commensurate doses of cannabidiol and WIN55,212-2 produced a mixed response. In conclusion, the behavioral effects of marijuana depend on the ratio of the two different cannabinoid properties. The repeated light and dark test might be a suitable method for drug-induced behavioral assay.

pharmacology and toxicology↗

bioRxiv2019

Safety assessment of a novel C-type natriuretic peptide derivative and the mechanism of bone- and cartilage-specific toxicity

ASB20123, a C-type natriuretic peptide/ghrelin chimeric peptide, was designed as a novel peptide and demonstrated full agonistic activity for natriuretic-peptide receptor B and a significantly longer half-life in plasma compared with the native peptide. We researched the toxicological profile of ASB20123, the correlation between the morphological change of the epiphyseal plate and bone and cartilage toxicity, and biomarkers to detect the toxicity. ASB20123 was systemically administered to male and female rats at daily dose levels of 0.5, 1.5, and 5.0 mg/kg/day for 4 weeks. In this study, toxicity was observed as changes related to bone and cartilage tissues, and no other toxicological changes were observed in all animals. Next, ASB20123 was administered to 12-month-old rats with a little epiphyseal plate. The toxic changes related to bone and cartilage tissues were not observed in any animal with a closed epiphyseal plate, indicating that the toxic changes were triggered by the growth-accelerating effect on the bone and cartilage. Furthermore, we searched for the biomarker related to the bone and cartilage toxicity using rats treated with ASB20123 at doses of 0.005, 0.05, 0.5, and 5.0 mg/kg/day for 4 weeks. A close correlation between necrosis/fibrosis in the epiphysis and metaphysis and thickness of the epiphyseal plate in the femur was confirmed in this study. A decrease in the bone mineral density (BMD) of the femur also was associated with the appearance of bone toxicity. These results indicated that the toxicity of ASB20123 was limited to bone- and cartilage-specific changes, and these changes were triggered by an excessive growth accelerating effect. Furthermore, our data suggested that the thickness of the epiphyseal plate and BMD could be reliable biomarkers to predict bone toxicity.

pharmacology and toxicology↗