Biology subjects

Matsumoto, R.

Publications and source records attributed to Matsumoto, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Multidimensional semantic representations emerge from multi-frequency representational similarity learning

Current theories of semantic representation are agnostic about how fine-grained neurophysiological activity corresponds to representation of multidimensional semantic information. By applying an innovative multivariate technique (representational similarity learning; RSL), we adjudicated three hypotheses: (1) that multidimensional semantic structure is represented within a single frequency range (e.g., gamma/high gamma); (2) that each semantic dimension is independently represented within a different frequency range; and (3) that multidimensional semantic information is "transfrequency" (at least some information emerges only when multiple frequencies are considered together). RSL was applied to time-frequency power and phase data extracted from electrocorticography (ECoG) grid electrodes on the surface of human ventral anterior temporal lobe (vATL). We found significant decoding of graded, multidimensional semantic information from a wide range of frequencies (4 - 200 Hz), but not from individual frequency bands, providing clear evidence that multidimensional semantic information is coded in a transfrequency fashion.

neuroscience↗

bioRxiv2026

Evolution of an unstable sex determination system in white Guinea yam (Dioscorea rotundata)

Plants often produce unstable sex phenotypes; however, the underlying evolutionary and molecular mechanisms are unclear. In white Guinea yam (Dioscorea rotundata), the most economically important tuber crop, genetic improvement is critical for food security but remains constrained by dioecy and complex sex phenotypes. White Guinea yam has a ZZ/ZW sex determination system in which ZZ individuals are consistently male, whereas ZW individuals can be female, male, or monoecious. Here we show that chromosome 11 is the sex chromosome, featuring a 1.2-Mb inversion between the Z and W chromosomes. A 170-kb W-specific region carries the microRNA gene dro-MIR432, likely involved in sex switching. The recent emergence of this miRNA-mediated ZZ/ZW system, distinct from the XY/XX system within Dioscorea, underscores the dynamic evolution of plant sex determination.

plant biology↗

bioRxiv2026

Acute inflammation-mediated attenuation of behavioural sensitization in methamphetamine-sensitized mice via distinct COX-2 and TNF-α pathways

Background and PurposeWhile inflammation has been generally considered to exacerbate symptoms of schizophrenia, some clinical observations suggest that acute inflammation may alleviate positive symptoms. However, animal models often use excessive inflammatory stimuli, and the effects of acute inflammation--comparable to levels observed in patients--remain unknown. Experimental ApproachTo address this, we examined whether acute inflammation induced under relatively mild, clinically relevant conditions suppresses behavioural sensitization in methamphetamine (METH)-sensitized mice, a model of psychostimulant-induced psychosis with relevance to certain aspects of positive symptoms of schizophrenia. We used a repeated METH (1 mg/kg) sensitized model to evaluate the effects of acute inflammation on behavioural sensitization. Acute inflammation was induced via two methods using either lipopolysaccharides (LPS; 1 g/kg) to mimic peripheral immune activation or restraint stress (RS; single 2-h exposure) to model the neuroinflammation induced by psychological stress. LPS doses were adjusted with reference to the magnitude of peripheral cytokine elevation reported in patients, and RS was applied in short single sessions to avoid excessive inflammation. Key ResultsBoth LPS and RS significantly suppressed behavioural sensitization, without inducing other behavioural abnormalities. This suppression was dependent on toll-like receptor-4 activation. LPS-mediated suppression involved cyclooxygenase-2, whereas RS-mediated suppression was linked to the microglia-derived tumour necrosis factor-. LPS did not alter, whereas RS significantly reduced the striatal extracellular dopamine levels. Conclusion and ImplicationsThese findings suggest that acute inflammation suppresses behavioural sensitization through distinct mechanisms depending on the inflammatory trigger, providing a framework for understanding how inflammation may influence psychosis-related processes, with potential relevance to schizophrenia.

pharmacology and toxicology↗

bioRxiv2026

Human frontal eye field and eyelid motor area revisited with electrical cortical stimulation and electrode co-registration

We investigated the anatomical localization of the frontal eye field (FEF) and its relationship to the eyelid motor area (EMA) and precentral motor cortex. We performed functional mapping using electrical cortical stimulation (ECS) and correlated electrode position by non-linear co-registration techniques using postoperative MRI. We studied 22 patients who underwent chronic implantation of subdural electrodes for epilepsy surgery. Eye movements were elicited at 52 electrodes overall. The majority of the movements were conjugated, saccadic eye deviation contralateral to the side of ECS. Head turning and non-saccadic eye deviation more frequently occurred in the vicinity of the precentral sulcus. Anatomically, FEF was located at Brodmanns area 6 in the most-caudal region of the middle frontal gyrus and in the adjacent part of the superior frontal sulcus and precentral sulcus. Functionally, FEF was situated at the level of the hand motor area, more dorsal than was described in Penfields motor homunculus. The FEF is situated anteriorly from the precentral motor cortex. The EMA was situated within the precentral motor cortex, partially overlapping with but distinctly ventral and caudal to FEF, and dorsal to the lower face motor area. A standardized map of the FEF and precentral motor homunculus is provided as a reference for human system neuroscience research.

neuroscience↗

bioRxiv2025

Infraslow histaminergic dynamics govern priming states to gate moment-to-moment memory accessibility

Memory expression fluctuates even in response to identical cues, suggesting that ongoing brain states bias memory accessibility. However, the cellular and circuit principles governing these state-dependent fluctuations remain unclear. Here, we show that spontaneous pre-cue activity of histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) modulates the expression of reward-associative memory in mice. TMN histaminergic activity exhibited infraslow dynamics (0.05-0.1 Hz) that closely tracked an integrated brain-body state. Closed-loop cue delivery during high histaminergic states enhanced memory expression. Brief optogenetic activation or inhibition of these neurons before the cue bidirectionally modulated memory expression, and direct activation of histaminergic terminals in the basolateral amygdala (BLA) was sufficient to enhance memory expression. Furthermore, histaminergic inhibition before the cue impaired the cue-evoked BLA population response. Thus, ongoing histaminergic activity exerts an infraslow, state-setting influence that primes BLA circuits for robust cue responses, and in turn, modulates moment-to-moment memory accessibility.

neuroscience↗

bioRxiv2025

Cellular fitness is determined by ribosomal protein S12-mediated release of a truncated Xrp1

Multicellular tissues require continuous optimization to maintain their structure and function by actively eliminating viable, yet unfit cells via a mechanism known as cell competition. During this process, unfit loser cells commonly upregulate the C/EBP family transcription factor Xrp1, which causes their elimination, indicating that intracellular Xrp1 levels determine cellular fitness. However, despite its central role, the mechanism by which Xrp1 is upregulated in unfit cells remains unknown. Here, we show that Xrp1 is upregulated through a previously unrecognized post-transcriptional regulatory mechanism mediated by the ribosomal protein S12 (RpS12). Surprisingly, Xrp1 mRNA is abundantly expressed even in wild-type cells, yet it is not translated. This is due to an upstream open reading frame (uORF) located in the 5UTR of the initial coding exon of Xrp1 mRNA, which inhibits the translation of the main Xrp1 ORF. Intriguingly, in unfit cells, RpS12 causes splicing-mediated skipping of this initial exon, leading to the use of an alternate start codon that generates a short isoform of Xrp1 protein, causing cell death. Notably, protein structural analysis reveals that RpS12 is highly homologous to that of a spliceosomal component SNU13, suggesting the role of RpS12 in directly regulating alternative splicing of Xrp1 mRNA. Our findings thus provide not only a mechanistic insights into how cellular fitness is determined but also how tissue optimization is achieved.

cell biology↗

bioRxiv2025

Improved genome assembly of whale shark, the world's biggest fish: revealing "chromocline" in intragenomic heterogeneity

High-quality chromosome-level assemblies are essential for understanding genome evolution but remain difficult to obtain for large and complex genomes. Here we present a near gap-free genome assembly of the whale shark (Rhincodon typus) generated with long-read sequencing and Hi-C scaffolding, markedly improving contiguity and completeness. In particular, the X chromosome was extended to nearly twice its previous length, and putative pseudoautosomal regions were identified. Moreover, we report the first Y-linked scaffolds for this species. Comparative analyses with the zebra shark revealed exceptionally low substitution rates across the genome. We further detected a negative correlation between chromosome length and synonymous substitution rate (dS), explained by a positional gradient, designated as "chromocline", in which substitution rates gradually decrease from chromosomal ends toward central regions. Notably, the X chromosome exhibited low dS compared with autosomes of similar size, consistent with male-driven evolution. Our results highlight positional and sex-chromosome effects as key determinants of molecular evolutionary rates. The improved assembly will enable broad application to population-genetic and conservation genomic analyses in the whale shark.

evolutionary biology↗

bioRxiv2025

All spectral frequencies of neural activity reveal semantic representation in the human anterior ventral temporal cortex

Intracranial electrophysiology offers a unique insight into the nature of information representation in the brain - it can be used to disentangle information encoded in local neuronal activity (gamma and high gamma frequencies) from information encoded via long-range interactions (lower frequencies). We used regularised logistic regression to decode animacy from time-frequency power and phase extracted from electrocorticography (ECoG) grid electrode data recorded on the surface of human vATL. Power in gamma (30 - 60 Hz) and high gamma (60 - 200 Hz) produced reliable decoding, indicating that semantic information is indeed expressed by local populations in vATL. However, power from a wide range of frequencies (4 - 200 Hz) produced significantly higher decoding accuracy and also exhibited the same rapidly-changing dynamic code previously observed when decoding voltage. These findings support the theory that semantic information is encoded by a local vATL "hub" that interacts with distributed cortical "spokes".

neuroscience↗

bioRxiv2025

A universal polyphosphate kinase powers in vitro transcription

Polyphosphate kinases (PPKs) catalyze phosphoryl transfer between polyphosphates and nucleotides. Polyphosphates are a cost-effective source of phosphorylating power, making polyphosphate kinases an attractive enzyme for nucleotide production and regeneration. However, at present, applications that require the simultaneous utilization of diverse nucleotides, such as RNA transcription, remain out of reach due to the restricted substrate profiles of known PPK enzymes. Here, we present the discovery and characterization of a universal PPK capable of efficiently phosphorylating all eight common ribonucleotides: purines and pyrimidines, monophosphates and diphosphates to triphosphates. Under optimal reaction conditions, approximately 70% triphosphate conversion was observed for all common ribonucleotides, with only limited over-phosphorylation. At elevated temperatures, however, production of adenine-capped polyphosphates up to a 30-mer was achieved. An analysis of mutant and chimeric enzymes revealed a rugged functional landscape, particularly for non-adenine nucleotides. Finally, we demonstrated the biotechnological potential of a universal PPK enzyme with a one-pot assay for PPK-powered in vitro transcription.

synthetic biology↗

bioRxiv2025

Transcriptional control of T cell tissue adaptation and effector function in infants and adults

The first years of life are essential for the development of memory T cells, which rapidly populate the bodys diverse tissue sites during infancy. However, the degree to which tissue memory T cell responses in early life reflect those during adulthood is unclear. Here, we use single cell RNA-sequencing of resting and ex vivo activated T cells from lymphoid and mucosal tissues of infant (aged 2-9 months) and adult (aged 40-65 years) human organ donors to dissect the transcriptional programming of memory T cells over age. Infant memory T cells demonstrate a unique stem-like transcriptional profile and tissue adaptation program, yet exhibit reduced activation capacity and effector function relative to adults. Using CRISPR-Cas9 knockdown, we define Helios (IKZF2) as a critical transcriptional regulator of the infant-specific tissue adaptation program and restricted effector state. Our findings reveal key transcriptional mechanisms that control tissue T cell fate and function in early life.

immunology↗

bioRxiv2024

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

The immune system comprises multiple cell lineages and heterogeneous subsets found in blood and tissues throughout the body. While human immune responses differ between sites and over age, the underlying sources of variation remain unclear as most studies are limited to peripheral blood. Here, we took a systems approach to comprehensively profile RNA and surface protein expression of over 1.25 million immune cells isolated from blood, lymphoid organs, and mucosal tissues of 24 organ donors aged 20-75 years. We applied a multimodal classifier to annotate the major immune cell lineages (T cells, B cells, innate lymphoid cells, and myeloid cells) and their corresponding subsets across the body, leveraging probabilistic modeling to define bases for immune variations across donors, tissue, and age. We identified dominant tissue-specific effects on immune cell composition and function across lineages for lymphoid sites, intestines, and blood-rich tissues. Age-associated effects were intrinsic to both lineage and site as manifested by macrophages in mucosal sites, B cells in lymphoid organs, and T and NK cells in blood-rich sites. Our results reveal tissue-specific signatures of immune homeostasis throughout the body and across different ages. This information provides a basis for defining the transcriptional underpinnings of immune variation and potential associations with disease-associated immune pathologies across the human lifespan.

immunology↗

bioRxiv2024

Long-Term Monolayer Cultivation Captures Homeostatic and Regenerative Features of Human Colonic Epithelial Cells

Primary intestinal epithelial stem cell culture methods have significantly advanced understanding of mammalian intestinal development and disease. However, progress has been hampered by inconsistent methodological reporting and challenges comparing in vitro systems with in vivo observations. We previously established a unique method for long-term 2{-}dimensional (2D) cultivation of mouse lECs using an air-liquid interface (ALI) technique which appears to faithfully recapitulate homeostatic and regenerative features in vitro. Here, we further refined these methods and optimized protocols for long-term, self-organizing 2D cultivation of human lECs. During the culture, we observed that epithelial cells undergo a dynamic morphological transition from squamous to columnar shape. Using single cell transcriptomics, we identified both major lineages and minor populations, including enteroendocrine cells, tuft cells, and BEST4/CA7+ cells. Leveraging the power and scalability of a biomedical foundation model (BMFM) trained on single cell RNA sequencing data, we performed classification tasks to identify cell types across sample sources and to quantitatively benchmark our in vitro differentiated cells against cells collected from patient biopsies. We observed a striking degree of similarity between our in vitro differentiated cells and the corresponding cell types in vivo for multiple differentiated lineages. This novel approach using BMFM holds promise to expand our understanding of the regulatory mechanisms including gene-gene regulation underlying homeostasis and regeneration as well as the functions of rare and poorly understood lineages within the human intestinal epithelia. Moreover, these methods are generalizable to other organs and can be used to assess the correspondence of cells across experimental modalities. SignificanceThis manuscript addresses challenges in quantitative comparisons of cell types grown in vitro vs their in vivo counterparts. Here we use the intestinal epithelium as a model system to address this challenge. We devised an in vitro culture platform that supports multipotent intestinal epithelial stem cells and their numerous differentiated progeny. This system gives rise to all known rare and abundant lineages in correct proportions. Novel use of biomedical foundation models pre-trained on publicly available data and then fine-tuned to data from this platform enabled demonstration of high concordance of multiple in vitro differentiated lineages with the corresponding cells in vivo.

cell biology↗

bioRxiv2022

Representational similarity learning reveals a graded multi-dimensional semantic space in the human anterior temporal cortex

Neurocognitive models of semantic memory have proposed that the ventral anterior temporal lobes (vATLs) encode a graded and multidimensional semantic space--yet neuroimaging studies seeking brain regions that encode semantic structure rarely identify these areas. In simulations we show that this discrepancy may arise from a crucial mismatch between theory and analysis approach. Utilizing an analysis recently formulated to investigate graded multidimensional representations, representational similarity learning (RSL), we decoded semantic structure from ECoG data collected from the vATL cortical surface while participants named line drawings of common items. The results reveal a graded, multidimensional semantic space encoded in neural activity across the vATL, which evolves over time and simultaneously expresses both broad and finer-grained semantic structure amongst animate and inanimate concepts. The work resolves the apparent discrepancy within the semantic cognition literature and, more importantly, suggests a new approach to discovering representational structure in neural data more generally. Conflict of interestThe Department of Epilepsy, Movement Disorders, and Physiology, Kyoto University Graduate School of Medicine conducts Industry-Academia Collaboration Courses, supported by Eisai Co., Ltd, Nihon Kohden Corporation, Otsuka Pharmaceutical Co., and UCB Japan Co., Ltd.

neuroscience↗

bioRxiv2022

Elasmobranch genome sequencing reveals evolutionary trends of vertebrate karyotypic organization

Genomic studies of vertebrate chromosome evolution have long been hindered by the scarcity of chromosome-scale DNA sequences of some key taxa. One of those limiting taxa has been the elasmobranchs (sharks and rays), which harbor species often with numerous chromosomes and enlarged genomes. Here, we report the chromosome-scale genome assembly for the zebra shark Stegostoma tigrinum, an endangered species that has the smallest genome sequenced to date among sharks (3.71 Gb), as well as for the whale shark Rhincodon typus. Our analysis employing a male-female comparison identified an X chromosome, the first genomically characterized shark sex chromosome. The X chromosome harbors a Hox C cluster whose intact linkage has not been shown for an elasmobranch fish. The sequenced shark genomes exhibit a gradualism of chromosome length with remarkable length-dependent characteristics--shorter chromosomes tend to have higher GC content, gene density, synonymous substitution rate, and simple tandem repeat content as well as smaller gene length, which resemble the edges of longer chromosomes. This pattern of intragenomic heterogeneity, previously recognized as peculiar to species with so-called microchromosomes, occurs in more vertebrates including elasmobranchs. We challenge the traditional binary classification of karyotypes as with and without microchromosomes, as even without microchromosomes, shorter chromosomes tend to have higher contents of GC and simple tandem repeats and harbor shorter and more rapid-evolving genes. Such characteristics also appear on the edges of longer chromosomes. Our investigation of elasmobranch karyotypes underpins their unique characteristics and provides clues for understanding how vertebrate karyotypes accommodate intragenomic heterogeneity to realize a complex readout.

evolutionary biology↗

bioRxiv2022

Lung evolution in vertebrates and the water-to-land transition

A crucial evolutionary change in vertebrate history was the Palaeozoic (Devonian ~400 million years ago) water-to-land transition, allowed by key morphological and physiological modifications including the acquisition of lungs. Nonetheless, the origin and early evolution of vertebrate lungs remain highly controversial, particularly whether the ancestral state was paired or unpaired. Due to the rarity of fossil soft tissue preservation, lung evolution can only be traced based on the extant phylogenetic bracket. Here we investigate, for the first time, lung morphology in extensive developmental series of key living lunged osteichthyans using synchrotron X-ray microtomography and histology. Our results shed light on the primitive state of vertebrate lungs as unpaired, evolving to be truly paired in the lineage towards the tetrapods. The water-to-land transition confronted profound physiological challenges and paired lungs were decisive for increasing the surface area and the pulmonary compliance and volume, especially during the air-breathing on land.

evolutionary biology↗

bioRxiv2021

Molecular programs of fibrotic change in aging human lung

Aging is associated with both overt and subclinical lung fibrosis, which increases risk for mortality from viruses and other respiratory pathogens. The molecular programs that induce fibrosis in the aging lung are not well understood. To overcome this knowledge gap, we undertook multimodal profiling of distal lung samples from healthy human donors across the lifespan. Telomere shortening, a cause of cell senescence and fibrosis, was progressive with age in a sample of 86 lungs and was associated with foci of DNA damage. Bulk RNA sequencing confirmed activation of cellular senescence and pro-fibrotic pathways as well as genes necessary for collagen processing with increasing age. These findings were validated in independent datasets for lung and sun-exposed skin, but not other organs including heart, liver and kidney. Cell type deconvolution analysis revealed a progressive loss of lung epithelial cells and an increasing proportion of fibroblasts. Consistent with the observed pro-fibrotic transcriptional profile, second harmonic imaging demonstrated increased density of interstitial collagen in aged human lungs. Furthermore, regions of parenchymal fibrosis were associated with decreased alveolar expansion and surfactant secretion. These findings reveal the transcriptional and structural features of fibrosis and associated physiologic impairments in normal lung aging.

genomics↗

bioRxiv2020

Genome analyses reveal the hybrid origin of the staple food crop white Guinea yam

White Guinea yam (Dioscorea rotundata) is an important staple tuber crop of West Africa. However, its origin remains unclear. In this study, we re-sequenced 336 accessions of white Guinea yam and compared them with the sequences of the wild Dioscorea species using an improved reference genome sequence of D. rotundata. Our results suggest a hybrid origin of white Guinea yam from crosses between the rainforest wild species D. praehensilis and the savannah-adapted D. abyssinica. We identified a higher genomic contribution from D. abyssinica in the sex chromosome of Guinea yam and an extensive introgression around the SWEETIE gene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improvement of this crop through molecular breeding.

evolutionary biology↗

bioRxiv2019

Connectivity Gradient in the Human Left Inferior Frontal Gyrus: Intraoperative Cortico-Cortical Evoked Potential Study

In the dual-stream model of language processing, the exact connectivity of the ventral stream to the anterior temporal lobe remains elusive. To investigate the connectivity among the inferior frontal gyrus (IFG) and the lateral part of the temporal and parietal lobes, we integrated spatiotemporal profiles of cortico-cortical evoked potentials (CCEPs) recorded intraoperatively from 14 patients who had had resective surgeries for brain tumor or epileptic focus. The 4D visualization of the combined CCEP data showed that the pars opercularis (Brocas area) connected to the posterior temporal cortices and the supramarginal gyrus, while the pars orbitalis connected to the anterior lateral temporal cortices and the angular gyrus. Quantitative topographical analysis of CCEP connectivity confirmed an anterior-posterior gradient of connectivity from IFG stimulus sites to the temporal response sites. Reciprocality analysis indicated that the anterior part of the IFG is bi-directionally connected to the temporal or parietal area. The present study revealed that each IFG subdivision has a different connectivity to the temporal lobe with an anterior-posterior gradient and supports the classical connectivity concept of Dejerine that the frontal lobe is connected to the temporal lobe through the arcuate fasciculus and also a double-fan-shaped structure, anchored at the limen insulae.

neuroscience↗