Biology subjects

Yamamoto, N.

Publications and source records attributed to Yamamoto, N..

At least 19 recordsLinked to original sources

bioRxiv2026

HMGA2 Expression in Pancreatic Ductal Adenocarcinoma Controls Tumor Microenvironment and Immunosuppression via IL1α

The basal-like subtype of pancreatic ductal adenocarcinoma (PDAC) is associated with poor outcomes and increased chemoresistance. Expression of high mobility group AT-hook 2 (HMGA2), a chromatin architectural protein, marks basal PDAC cells and associates with specific features of the tumor microenvironment (TME), including more immunosuppressive cancer associated fibroblasts (CAFs) and fewer cytotoxic CD8+ T cells. Expression of HMGA2 by tumor cells leads to upregulation of the immunosuppressive markers interleukin 6 (IL6) and leucine-rich repeat containing protein 15 (LRRC15) in associated fibroblasts. Mechanistically, HMGA2 in the tumor cell binds the interleukin 1 alpha (IL1) promoter and upregulates transcription, increasing IL1 in the TME, in turn inducing immunosuppressive fibroblast polarization, increasing regulatory T cells, and decreasing CD8+ T cells. Blockade of the IL1 signaling axis disrupts this tumor-driven microenvironment phenotype and combines with inhibitors of oncogenic KRAS to improve tumor control.

cancer biology↗

bioRxiv2026

Right-lateralized prefrontal signature with successful Stroop-like interference control in early childhood

The Stroop effect is a canonical measure of executive control, yet its neural architecture has been defined largely in literate children and adults, where left frontal mechanisms have long been implicated in resolving verbal conflict. How the developing brain supports Stroop-like interference control before literacy and stable verbal responding are established remains unknown. Here we show that successful interference control in early childhood is associated with the selective engagement of right lateral prefrontal regions. We used multichannel functional near-infrared spectroscopy to measure prefrontal hemodynamics in 94 children aged 35-79 months during a color-pointing Stroop-like task, in which children pointed to colors in response to spoken color names. Stroop-like conflict elicited broad activation across bilateral lateral prefrontal regions, a conflict response already present from around 3 years of age and did not show a detectable age-related increase. By contrast, individual differences in accuracy under conflict were selectively associated with greater activation in the right dorsolateral and right rostrolateral prefrontal cortices, independent of age. These findings suggest that right lateral prefrontal regions play an important role in successful interference control in early childhood, indicating that preschool Stroop-like control is not merely a weaker form of the adult left-lateralized system.

neuroscience↗

bioRxiv2026

Glycolipid MPIase is essential for the TAT (Twin-Arginine Translocation) pathway

TAT (Twin-Arginine Translocation) is a preprotein translocation system dedicated to membrane translocation of prefolded proteins in plants and bacteria. The TAT translocon, consisting of the TatABC subunits, drives translocation using proton motive force. However, there have been no reports on the successful reconstitution of the TAT system. In this report, we show that MPIase, a glycolipid that has been known to catalyze membrane protein integration, is essential for the TAT system. Our findings in recombinant Escherichia coli demonstrate that overproducing TatABC increases MPIase levels and that depleting MPIase results in TAT precursor accumulation in the cytosol. Furthermore, co-reconstitution of MPIase with TatABC revealed the translocation activities of TAT substrates in a proton motive force-dependent manner. This is the first successful reconstitution of the TAT system and will be advantageous for understanding its mechanisms.

biochemistry↗

bioRxiv2026

Tumor-associated tissue-resident macrophages drive pancreatic cancer progression through IGF1-IGF1R signaling

The specific contribution of tissue-resident macrophages (TRMs) to pancreatic ductal adenocarcinoma (PDAC) progression remains unclear. Here, we found that a high abundance of TRM-derived tumor-associated macrophages (TRM-TAMs) is an independent indicator of poor prognosis in patients with PDAC. To elucidate the underlying mechanism, we established an advanced organoid platform (iMac-FPCO), which incorporates macrophages derived from human induced pluripotent stem cells to reflect the differentiation process of TRMs. Single-cell transcriptomic analysis revealed this model recapitulates the transcriptional identity of TRM-TAMs in patient tissue. We demonstrated that TRM-TAMs drive cancer cell proliferation, while maintaining chemoresistance, and identified TRM-derived insulin-like growth factor 1 (IGF1) as the critical mediator. This result provides a rationale for why previous trials targeting IGF1 receptor (IGF1R) failed to improve survival in unselected patient populations. We hypothesize that stratifying patients by TRM-TAM abundance could help identify a responsive subgroup, thereby reviving IGF1R-targeted therapy as a viable treatment for PDAC.

cancer biology↗

bioRxiv2026

Dissociable pupil-linked arousal during overt and inner speech

Inner (covert) speech, the silent production of language in ones mind, plays a central role in human cognition and is known to activate speech-related cortical regions while also requiring executive and attentional resources. However, the conventional focus on cortical similarity or dissimilarity between inner and overt speech leaves unaddressed the question of whether arousal systems sustain cortical language processing. Here, using pupillometry across three controlled counting experiments, we show a dissociation between inner and overt speech. Overt speech consistently led to pupil dilation across all conditions. Inner speech, by contrast, produced a strikingly different profile: pupil constriction during simple counting, no deviation from baseline during noun-phrase counting, and clear dilation only under a high cognitive load, but with dilation remaining significantly less than that for overt speech in every condition. Covert verbal production thus proceeds at a reduced arousal cost, yet this cost scales flexibly with task demands rather than being fixed. This pupillometric dissociation reveals that inner and overt speech occupy fundamentally distinct arousal states, even when their cortical substrates partially overlap. These findings open a non-invasive window for tracking inner speech physiology across development, individual differences, and clinical populations in whom inner speech is altered.

neuroscience↗

bioRxiv2026

Emergent blink rate in early childhood is associated with neural origins of executive function

Executive function develops rapidly in early childhood and predicts later success in life, yet its neurobiological correlates during this period remain poorly understood. In adults, executive function is supported by prefrontal-striatal circuits under neuromodulatory control, including dopamine. Here, we show that spontaneous eye-blink rate (sEBR), a physiological output influenced by neuromodulatory systems, is associated with the developmental trajectory of executive function and prefrontal functional differentiation. We used fNIRS to monitor prefrontal cortex (PFC) activation in 113 children (35-80 months) during a cognitive flexibility task. With increasing age, the childrens task performance improved, and their PFC activation showed greater right-hemisphere and dorsal bias, reflecting functional differentiation. Importantly, higher sEBR was also associated with this right-dorsal PFC activation and with better task performance. The current findings demonstrate that emergent sEBR is associated with the neural origins of executive function development in young children. This highlights the potential of sEBR to serve as a unique and previously unrecognised indicator of this critical developmental neural mechanism.

neuroscience↗

bioRxiv2026

Building neuroanatomical resources for three-spined sticklebacks: Brain areas important for social behavior

IntroductionThree-spined stickleback fish are famous for their diversity and charismatic social behavior. However, there are few neuroanatomical resources for studying the neural and brain mechanisms underlying their fascinating behavior. Methods and ResultsWe identify 11 brain areas important for social behavior by referencing brain atlases for six other teleost fishes. Brain regions were identified via neuroanatomical landmarks and we characterized the presence / absence of tyrosine hydroxylase (TH), a key gene product of the dopaminergic system, in those regions. Comparing the neuroanatomical location of these regions in the stickleback brain and the expression of TH therein to that of other fish species highlights similarities and differences and the need for a brain atlas specific to sticklebacks. This resource serves as a map of the location of regions important for social behavior in the stickleback brain. ConclusionThis resource will help guide future studies connecting gene function to social behavior through the brain and will enable future work to understand the evolution of neural mechanisms that contribute to the diversity of social behavior in this emerging model organism.

neuroscience↗

bioRxiv2025

The Latency of a Domain-General Visual Surprise Signal is Attribute Dependent

Predictions concerning upcoming visual input play a key role in resolving percepts. Sometimes input is surprising, under which circumstances the brain must calibrate erroneous predictions so that perception is veridical. Despite the extensive literature investigating the nature of prediction error signalling, it is still unclear how this process interacts with the functionally segregated nature of the visual cortex, particularly within the temporal domain. Here, we recorded electroencephalography (EEG) from humans whilst they viewed static image trajectories containing a bound object that sequentially changed along different visual attribute dimensions (shape and colour). Crucially, the context of this change was designed to appear random (and unsurprising) or violate the established trajectory (and cause a surprise). Event-related potential analysis found no effects of surprise after controlling for cortical adaptation. However, multivariate pattern analyses found whole-brain neural representations of visual surprise that overlapped between attributes, albeit at distinct, attribute-specific latencies. These findings suggest that visual surprise results in whole-brain, generalised (i.e., attribute-agnostic) prediction error responses that conform to an attribute-dependent temporal hierarchy.

neuroscience↗

bioRxiv2025

Human fibrosarcoma cells selected for very-high doxorubicin resistance, acquire trabectedin and eribulin cross-resistance, remain sensitive to recombinant methioninase, and have increased c-MYC expression

Doxorubicin is first-line chemotherapy for soft tissue sarcoma; however, the development of drug resistance limits its efficacy. The purpose of the present study was to select very-high doxorubicin-resistant (VHDR) HT1080 fibrosarcoma cells, determine cross-resistance to second-line chemotherapy drugs, determine maintenance of sensitivity to recombinant methioninase (r-METase) alone and in combination with doxorubicin, and measure the level of c-MYC expression. VHDR-HT1080 cells were generated by cultivating HT-1080 cells in a series of step-wise progressively higher concentrations of doxorubicin, ranging from 8 nM to 15 {micro}M, an 1875-fold increase, over a five-month period. The WST-8 reagent was used to assess cell viability. Four groups of in vitro drug-sensitivity tests were conducted, which involved both parental HT1080 and VHDR-HT1080 cells: 1) doxorubicin alone; 2) rMETase alone; 3) a combination of doxorubicin and rMETase; and 4) untreated control. The cross-resistance of VHDR-HT1080 cells to eribulin, trabectedin, gemcitabine and docetaxel was determined. The c-MYC levels in HT1080 and VHDR-HT1080 cells were measured using Western blotting. Doxorubicin had an IC50 of 3.3 {micro}M against HT1080 cells and 38.2 {micro}M against VHDR-HT1080 cells an 11.6-fold increase. The rMETase IC50 value for HT1080 was 0.75 U/ml and 0.59 U/ml for VHDR-HT1080. rMETase sensitized VHDR-HT1080 cells to doxorubicin. VHDR-HT1080 cells were cross-resistant to trabectedin 8.9-fold and cross-resistant to eribulin 1.87-fold compared to parental HT1080 cells. c-MYC expression was 8.4 times higher in VHDR-HT1080 cells compared to HT-1080 cells. The present results suggest rMETase may be used as a future clinical strategy to overcome super-doxorubicin resistance in soft tissue sarcoma.

cancer biology↗

bioRxiv2025

Developing terrestrial environmental DNA sampling methods for detecting arboreal invasive reptiles: a case study of the green anole in the Ogasawara Island, Japan

Early detection of invasive alien species is essential for preventing establishment and mitigating ecological impacts, particularly in island ecosystems harbouring evolutionarily isolated endemic species. Recently, despite increasing reptile introductions and their suggested widespread impacts, methods for monitoring arboreal invasive reptiles remain limited. This study addressed the need for practical detection tools by developing terrestrial environmental DNA (eDNA) sampling methods that collect DNA from leaf surfaces to detect the arboreal invasive green anole (Anolis carolinensis) in the Ogasawara Islands, Japan. Two methods, wiping leaf surfaces with gauze and rinsing with sprayed water, were tested. At an invaded site, green anoles were successfully detected in eight out of 10 samples in both methods. Although no significant difference in eDNA concentration was observed, the wiping method was selected for its greater simplicity. Subsequently, the relationship between green anole population density and eDNA concentrations detected using the wiping method was investigated, suggesting a significant positive relationship. This is the first report demonstrating that terrestrial eDNA concentrations can reflect arboreal reptile population density, suggesting potential applications in quantitative terrestrial biodiversity assessments. Furthermore, the successful detection of eDNA even in the extremely low-density habitat of the green anole demonstrates the usefulness of eDNA-based surveys for early detection of invasions. The method developed here may be broadly applicable to terrestrial biodiversity monitoring, especially in tree-dwelling taxa. Given accelerating biological invasions and biodiversity loss, this approach is expected to benefit managers, conservationists, and researchers concerned with terrestrial ecosystems.

molecular biology↗

bioRxiv2024

YibN, a bona fide interactor of YidC with implications in membrane protein insertion and membrane lipid production

YidC, a prominent member of the Oxa1 superfamily, is essential for the biogenesis of the bacterial inner membrane, significantly influencing its protein composition and lipid organization. It interacts with the Sec translocon, aiding the proper folding of multi-pass membrane proteins. It also functions independently, serving as an insertase and lipid scramblase, augmenting the insertion of smaller membrane proteins while contributing to the organization of the bilayer. Despite the wealth of structural and biochemical data available, how YidC operates remains unclear. To investigate this, we employed proximity-dependent biotin labeling (BioID), leading to the identification of YibN as a crucial component within the YidC protein environment. We then demonstrated the association between YidC and YibN by affinity purification-mass spectrometry assays conducted on native membranes, with further confirmation using on-gel binding assays with purified proteins. Co-expression studies and in vitro assays indicated that YibN enhances the production and membrane insertion of YidC substrates, such as M13 and Pf3 phage coat proteins, ATP synthase subunit c, and various small membrane proteins like SecG. Additionally, the overproduction of YibN was found to stimulate membrane lipid production and promote inner membrane proliferation, perhaps by interfering with YidC lipid scramblase activity. Consequently, YibN emerges as a significant physical and functional interactor of YidC, influencing membrane protein insertion and lipid organization.

biochemistry↗

bioRxiv2024

Evolutionary conserved cis-trans regulation machinery for diterpenoid phytoalexin production in Poaceae

O_LIMomilactones and phytocassanes are diterpenoid phytoalexins involved in plant chemical defense. These metabolites, along with biosynthetic gene clusters (BGCs), are conserved in wild rice. However, the mechanisms by which phytoalexins are regulated in wild rice are unclear. Thus, we aimed to investigate the regulatory mechanisms for biosynthetic genes within the BGCs of diterpenoid phytoalexins. C_LIO_LIWe conducted a transcriptome analysis of five wild rice species, Oryza rufipogon, Oryza punctata, Oryza officinalis, Oryza brachyantha, and Leersia perrieri, after CuCl2 treatment. C_LIO_LIAmong the CuCl2-responsive transcription factors, diterpenoid phytoalexin factor (DPF), which regulates phytoalexin production in cultivated rice (Oryza sativa), was broadly conserved in wild rice and showed phytoalexin-inducing activity when introduced into cultivated rice. Highly conserved genomic regions containing N-boxes (5'-CACGAG-3'), the potential binding motif of DPF, were found. CRISPR/Cas9 genome editing to remove these regions showed that biosynthetic gene expression and phytoalexin production were significantly attenuated after CuCl2 treatment in the leaves of the edited plants. Thus, the cis-trans factor combination of DPF and N-boxes is a key determinant of regulation. C_LIO_LIDPF has evolved as a strong cis-trans regulatory system for diterpenoid phytoalexin production, with N-boxes generated within the cluster region during the evolution from wild rice to cultivated rice. C_LI

plant biology↗

bioRxiv2024

Alteration of long and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis

Myeloid-biased hematopoiesis is a well-known age-related alteration. Several possibilities, including myeloid-biased hematopoietic stem cell (HSC) clones, may explain this. However, the precise mechanisms remain controversial. Utilizing the Hoxb5 reporter system to prospectively isolate long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs), we found that young and aged LT-HSCs co-transplanted into the same recipients demonstrated nearly equivalent myeloid lineage output, contrary to the theory of myeloid-biased HSC clones. Transcriptomics indicated no significant myeloid gene enrichment in aged LT-HSCs compared to their young counterparts. Instead, transplanting reconstituted young HSCs with the ratio of LT/ST-HSCs seen in aged mice can significantly skew the lineage output to myeloid cells. In addition, while the niche environment in the bone marrow minimally affects myeloid-biased hematopoiesis, aged thymi and spleens substantially hinder lymphoid hematopoiesis, resulting in further myeloid-domination. Thus, we demonstrate that myeloid-biased hematopoiesis in aged organisms originates due to alteration of the ratio between LT-HSCs and ST-HSCs rather than in heterogeneous HSC clones with various cell fates.

developmental biology↗

bioRxiv2023

Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice

Entorhinal cortical (EC)-hippocampal (HPC) circuits are crucial for learning and memory. Although it was traditionally believed that superficial layers (II/III) of the EC mainly project to the HPC and deep layers (V/VI) receive input from the HPC, recent studies have highlighted the significant projections from layers Va and VI of the EC into the HPC. However, it still remains unknown whether Vb neurons in the EC provide projections to the hippocampus. In this study, using a molecular marker for Vb and retrograde tracers, we identified that the outer layer of Vb in the medial EC (MEC) neurons directly project to both dorsal and ventral hippocampal DG, with a significant preference for the ventral DG. In contrast to the distribution of DG-projecting Vb cells, anterior thalamus-projecting Vb cells are distributed through the outer to the inner layer of Vb. Furthermore, dual tracer injections revealed that DG-projecting Vb cells and anterior thalamus-projecting Vb cells are distinct populations. These results suggest that the roles of MEC Vb neurons are not merely limited to the formation of EC-HPC loop circuits, but rather contribute to multiple neural processes for learning and memory.

neuroscience↗

bioRxiv2023

Reduction in myocardial fibrosis in MDX mice on oral consumption of Aureobasidium Pullulans produced Neu REFIX Beta-glucans; holds potential as an adjuvant in managing post-transplantation organ fibrosis

Organ fibrosis is one of the major causes of morbidity and mortality globally. Though fibrosis in genetic diseases such as Duchenne muscular dystrophy (DMD) may be attributed to the genetic defect, chronic microinflammation remains a key mechanism underlying such fibrosis, which also precedes both other organ fibrosis and post-organ transplant fibrosis. Having proven the anti-inflammatory, anti-fibrotic effects of Beta-1,3-1,6-glucan (Neu-REFIX) produced by N-163 strain of Aureobasidium Pullulans in earlier clinical and pre-clinical studies, we performed the current study to evaluate its effects on myocardial fibrosis. N-163 beta-glucan was administered to 45 mice in three groups, each fifteen animals, Gr. 1, normal mice, Gr.2, mdx mice as vehicle, Gr.3, mdx mice which were administered Neu REFIX beta-glucan orally. Evaluation of Collagen Type I (Col-I) in myocardium was performed by immunohistochemistry. Percentage of myocardium Col-I positive area of 6.42 {+/-} 2.67 significantly decreased in the Neu-REFIX group (4.32 {+/-} 1.78) (p-value < 0.01). As myocardial fibrosis has been shown to be reduced following treatment with N-163 beta glucan in a genetic, muscle structure anomaly disease such as DMD, in addition to adding value to DMD patients, in whom myocardial failure occurs in the advanced stages leading to pre-mature death, Neu-REFIX beta-glucan adjuvant treatment in the setting of solid organ transplantation may be of value to reduce the incidence of fibrosis which is a known feature of chronic allograft rejection leading to graft loss.

genetics↗

bioRxiv2023

Enhanced muscle regeneration in mdx mice, Duchenne muscular dystrophy animal model, proven by CD44 & MYH3 expression, on oral feeding of N-163 strain of Aureobasidium Pullulans produced B-Glucan

IntroductionDuchenne muscular dystrophy (DMD) is a rare genetic disease, causing muscle degeneration due to lack of dystrophin with inadequate muscle regeneration culminating in muscle dysfunction. The N-163 strain of Aureobasidium Pullulans produced Beta-1,3-1,6-glucan (Neu REFIX) reported to be safe with anti-inflammatory and anti-fibrotic efficacy earlier, herein we evaluated its effects on muscle regeneration in mdx mice. MethodsForty-five mice in three groups (n=15 each): Group 1 (normal), Group 2 (mdx control), and Group 3 (mdx fed Neu REFIX) were evaluated for 45 days. IGF-1, Dystrophin, CD44 and MYH3 in diaphragm, plasma and skeletal muscle were evaluated by ELISA and immunohistochemistry. ResultsMean IGF-1 expression was 20.32% and 16.27% higher in plasma (p = 0.03) and diaphragm respectively in Neu-REFIX group. Mean dystrophin was higher in Neu-REFIX group by 70.3% and 4.7% in diaphragm and plasma respectively than control. H-score intensity of CD44+ was >2.0 with an MYH3-positivity 20% higher in Neu-REFIX than control. ConclusionOral administration of Neu REFIX was safe. Significantly enhanced plasma IGF-1 beside increased Dystrophin, MYH3 and CD44, proving a restoration of muscle regeneration and differentiation, especially in diaphragm, makes us recommend it as a disease modifying adjuvant in both early and advanced stages of DMD.

genetics↗

bioRxiv2023

EBF1 limits the numbers of cochlear hair and supporting cells and forms the scala tympani and spiral limbus during the development of the inner ear

Early B-cell factor 1 (EBF1) is a basic helix-loop-helix transcription factor essential for the differentiation of various tissues. Our single-cell RNA sequencing data suggest that Ebf1 is expressed in the sensory epithelium of the inner ear. Here, we found that the Ebf1 gene and its protein are expressed in the prosensory domain of the inner ear, medial region of the cochlear floor, inner ear mesenchyme, and cochleo-vestibular ganglion. Ebf1 deletion results in incomplete formation of the spiral limbus and scala tympani, increased number of cells in the organ of Corti and Kollikers organ, and aberrant course of the spiral ganglion axons. The inner ear-specific deletion of Ebf1 revealed that scala tympani formation depended on Ebf1 expressed in the otic mesenchyme. Ebf1 deletion in the cochlear epithelia caused the proliferation of SOX2-positive cochlear cells at E13.5, indicating that EBF1 suppresses the proliferation of the prosensory domain and cells of Kollikers organ to facilitate the development of appropriate numbers of hair and supporting cells. Furthermore, mice with deletion of cochlear epithelium-specific Ebf1 showed poor postnatal hearing function. Our results suggest that Ebf1 is essential for normal auditory function in mammals.

developmental biology↗

bioRxiv2023

In vivo Stability and Biodistribution of Liposome Coated with SlpB from Levilactobacillus brevis

SlpB from Levilactobacillus brevis offers a solution to stabilise liposome in gastrointestinal tract, and to target intestinal APCs in Peyers patches, rendering it a powerful tool for oral delivery of drugs, and to yield the benefits provided by oral delivery. However, the stability of SlpB-coated liposome (SlpB-LP) and its distribution in tissues were not characterized. In this study, we have demonstrated that SlpB-coating could improve the stability of liposome in gastrointestinal tract, and facilitate specific uptake of liposome into Peyers patches, but not intestinal, nor intestinal mucosa. Furthermore, we have shown that uptake of SlpB-LP into Peyers patches enhanced bioavailability of drugs, which have resulted in 427.65-fold increase in bioavailability and at least 2.41-fold decrease in retention of fluorophore in liver where drug metabolism takes places, to a degree which approximate control group. In conclusion, this study shows that SlpB could increase stability of liposome in gastrointestinal tract, increase specific uptake of liposome into Peyers patches, and improve bioavailability. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/533723v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@ed508aorg.highwire.dtl.DTLVardef@42cef8org.highwire.dtl.DTLVardef@2219a9org.highwire.dtl.DTLVardef@c2e3dd_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗