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Satoh, A.

Publications and source records attributed to Satoh, A..

13 recordsLinked to original sources

Secretory ferritins mediate iron delivery during magnetite tooth formation in chitons

Iron is essential to most organisms, yet unbound iron is toxic, necessitating tight regulation of its storage and transport. Chitons concentrate extraordinary amounts of iron in radular tissue to form magnetite-mineralized teeth, but how iron is supplied to developing teeth remains unclear. Here, synchrotron radiation X-ray fluorescence mapping resolved the spatiotemporal redistribution of iron from the radular epithelium toward developing teeth. Integrated transcriptomic and proteomic analyses identified secretory ferritin subunits in radular tissue whose genes were highly expressed in the midgut gland and whose proteins were also present in the hemolymph. In vivo fluorescence tracking showed that circulating ferritin was selectively taken up by the radular epithelium, and following injection of Ag-loaded hemolymph ferritin, Ag was detected in developing teeth. Together, these findings support a model in which secretory ferritins produced in the midgut gland transport iron through the hemolymph to the radula, enabling the pronounced iron accumulation required for tooth mineralization.

molecular biology↗

The vagus nerve drives cognitive function through the default mode network

The afferent vagus nerve transmits interoceptive signals to the brain but a systematic understanding of how vagal signals affect brain-wide neuronal dynamics remains elusive. Here, comprehensive spatiotemporal analyses across the entire mouse brain revealed that vagus nerve stimulation activated neuronal ensembles within the default mode network (DMN). In contrast, vagal-independent mechanisms predominantly affected the salience network. The vagal-DMN association was mediated by locus coeruleus neuronal subpopulations. Selective activation or silencing of vagal-responsive DMN neuronal ensembles replicated or abolished VNS-induced enhancement of cognitive behaviors and progressive problem-solving behaviors. These findings establish a unifying framework for how the vagus nerve drives cognitive functions by engaging the DMN.

neuroscience↗

TALE-independent transcriptional activation of the rice executor gene Xa23 is regulated via histone acetylation during zygote development

Transcription activator-like effectors (TALEs) from Xanthomonas activate transcription of executor (E) genes in host plants, leading to cell death and thereby restricting proliferation of biotrophic pathogens. Because E gene transcripts had only been detected upon activation by cognate Xanthomonas TALEs, E genes were thought to function exclusively in plant immunity. Here, we detect TALE-independent transcription of the rice E gene Xa23 in zygotes 4-6 hours after gamete fusion. Histone deacetylase inhibition induces Xa23 transcription in unfertilized egg cells, implicating histone acetylation in Xa23 regulation. We identified potential cis-regulatory elements and transcription start sites associated with native Xa23 transcription during zygote development. Together, our findings suggest that Xa23 is a developmentally regulated gene with a native role during early zygote development. This supports a previously proposed model in which E genes have native functions in development, while fortuitous upstream polymorphisms can create TALE-binding sites that convert them into immune executors.

plant biology↗

Systematic overexpression reveals a conserved spectrum of harmful and beneficial amino acid homorepeats shaped by evolution

Proteins are composed of combinations of 20 amino acids, yet the principles governing their sequence compatibility within living cells remain poorly understood. Here, we evaluated the "neutrality"--an integrated measure of harmful versus beneficial properties--of amino acid homorepeats (PolyX) in Saccharomyces cerevisiae. Using the genetic tug-of-war (gTOW) method to quantify maximum expression limits, we found that neutrality is highly amino-acid-specific and intrinsically linked to physicochemical properties. Hydrophobic repeats (I, V, W, F, Y) were universally harmful and aggregation-prone, while hydrophilic repeats (E, S, N, Q) not only exhibited high neutrality but also actively suppressed the proteotoxic stress and aggregation of host proteins. These experimental neutrality values show a striking correlation with the occurrence and length of homorepeats across diverse eukaryotic proteomes. Our findings suggest that PolyX neutrality defines the "compatible sequence space" of proteins, where certain sequences like Poly10E act as evolutionary buffers to maintain proteostasis. This study provides a quantitative framework for understanding how physical constraints on protein solubility shape the evolution of proteomes and offers a new metric for rational protein design.

systems biology↗

The integration mechanism of the four positional cues--anterior, posterior, dorsal, and ventral--in axolotl limb regeneration

Axolotls (Ambystoma mexicanum) exhibit a remarkable ability to regenerate limbs after amputation. Classical experiments have suggested that contact between cells derived from distinct orientations--dorsal, ventral, anterior, and posterior--within the regenerating blastema is necessary for accurate limb pattern formation. However, the molecular basis for this requirement has remained largely unknown. Here, we demonstrate that both dorsal and ventral tissues are required for limb formation via induction of Shh expression, which plays a crucial role in limb patterning. Using the accessory limb model (ALM), we induced position-specific blastemas lacking cells derived from a single orientation (anterior, posterior, dorsal, or ventral). Patterned limb formation occurred only in blastemas containing both dorsal- and ventral-derived cells. We further observed that Shh expression requires dorsoventral contact within a blastema, highlighting the necessity of dorsoventral contact for inducing Shh expression. In addition, we identified WNT10B and FGF2 as dorsal- and ventral-mediated signals, respectively, that create the inductive environment for Shh expression. Our findings clarify the role of dorsal and ventral cells in inducing Shh, a mechanism that has rarely been studied in the context of limb regeneration and pattern formation. This model provides new insights into how cells with different positional identities drive the regeneration process.

developmental biology↗

Radular teeth matrix protein 1 directs iron oxide deposition in chiton teeth

Chitons deposit magnetite, a type of iron oxide, on the cusps of their radular teeth. The molecules that control the deposition of iron oxide on chiton teeth have not been identified. Using immunofluorescence staining, we found that chiton-specific radular teeth matrix protein 1 (RTMP1) is highly expressed in tooth epithelial cells prior to iron oxide deposition and preexists in the cusp at the site of iron oxide deposition. RTMP1 was found to be secreted from the elongated epithelial cells covering teeth and transported into teeth through microvilli. Moreover, recombinant RTMP1 exhibited the ability to form iron oxide. These results indicate that RTMP1 is a key molecule for iron oxide deposition in chiton teeth.

molecular biology↗

Effects of psychogenic stress on oxidative stress and antioxidant capacity at different growth stages.

This study examined the psychogenic stress (PS) effects on changes in oxidative stress and the antioxidant capacity of an organism at different growth stages. The experimental animals were male Wistar rats of five different ages from growth periods (GPs) to old age. The growth stages were randomly classified into control (C) and experimental (PS) groups. PS was performed using restraint and water immersion once daily for 3 h for 4 weeks. Reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) were measured before and after the experiment. In addition, the liver and adrenal glands were removed, and the wet weight was measured. The d-ROM and BAP of all growth stages given PS increased significantly. The d-ROM in the C group without PS increased significantly in GPs while decreased significantly in old-aged. In addition, the BAP of the C group in GP and early adulthood were all significantly elevated. There were significant differences in organ weights between the C and PS groups at all growth stages. Oxidative stress and antioxidant capacity differed depending on the organisms developmental status and growth stage, and PS also showed different effects. In particular, the variability in oxidative stress was remarkable, suggesting that the effect of PS was more significant in the organisms immature organs.

developmental biology↗

Age-associated sleep-wake patterns are altered with Prdm13 signaling in the dorsomedial hypothalamus and dietary restriction in mice

Old animals display significant alterations in sleep-wake patterns such as increases in sleep fragmentation and sleep propensity. Here we demonstrated that dorsomedial hypothalamus-specific PR-domain containing protein 13-knockout (DMH-Prdm13-KO) mice recapitulated age-associated sleep alterations such as sleep fragmentation and increased sleep attempts during sleep deprivation (SD). These phenotypes were further exacerbated during aging, with increased adiposity and decreased physical activity, resulting in shortened lifespan. Dietary restriction (DR), a well-known anti-aging intervention in diverse organisms, ameliorated age-associated sleep alterations, whereas these effects of DR were abrogated in DMH-Prdm13-KO mice. Moreover, overexpression of Prdm13 in the DMH ameliorated sleep fragmentation and excessive sleepiness during SD in old mice. Therefore, maintaining Prdm13 signaling in the DMH might play an important role to control sleep-wake patterns during aging.

physiology↗

Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress response

GlycoMaple is a new tool to predict glycan structures based on the expression levels of 950 genes encoding glycan biosynthesis-related enzymes and proteins using RNA-seq data. The antioxidant response, protecting cells from oxidative stress, has been focused on because its activation may relieve pathological conditions, such as neurodegenerative diseases. Genes involved in the antioxidant response are defined within the GO:0006979 category, including 441 human genes. Fifteen genes overlap between the glycan biosynthesis-related genes defined by GlycoMaple and the antioxidative response genes defined by GO:0006979, one of which is FUT8. 5-Hydroxy-4-phenyl-butenolide (5H4PB) extracted from Chinese aromatic vinegar induces the expression of a series of antioxidant response genes that protect cells from oxidative stress via activation of the nuclear factor erythroid 2-related factor 2-antioxidative response element pathway. Here, we show that FUT8 is upregulated in both our RNA-seq data set of 5H4PB-treated cells and publicly available RNA-seq data set of cells treated with another antioxidant, sulforaphane. Applying our RNA-seq data set to GlycoMaple led to a prediction of an increase in the core fucose of N-glycan that was confirmed by flow cytometry using a fucose-binding lectin. These results suggest that FUT8 and core fucose expression may increase upon the antioxidant response.

pharmacology and toxicology↗

Spatially unique Shh-Fgf8 distribution in regenerating limb guarantees consistent limb morphogenesis in different limb sizes and contributes to axolotl specific digit patterning.

Limb regeneration in Ambystoma mexicanum occurs in various size fields and can recreate consistent limb morphology. The mechanism that supports such stable limb morphogenesis regardless of size is unknown. Sonic hedgehog (SHH) and fibroblasts growth factor 8 (FGF8) play important roles in anteroposterior limb patterning, similar to other tetrapods. Focusing on these two factors, we investigated the detailed expression pattern and function of Shh and Fgf8 in various blastema sizes in axolotl limb regeneration. We measured and functionally analyzed the expression domains of Shh and Fgf8 in regenerating limb blastema of various sizes, and found that, although the position and size of the Shh+ and Fgf8+ domains varied depending on the size of the blastema, the secretion of SHH was maintained at a relatively fixed working distance, regardless of blastema size. This stable secretory distance of SHH resulted in the formation of an active proliferative zone (aPZ) in the vicinity of SHH, regardless of blastema size. The aPZ was under the mitogenic influence of SHH and FGF8, resulting in high cell density in the aPZ. We also examined the impact of the aPZ on digit formation. We found that the first digit formation occurs in the aPZ. Next, the aPZ gradually shifts posteriorly as digits develop, which contributes to new digit formation at the site of the shifted aPZ. We also found that the exogenously formed aPZ caused extra digit formation even after the completion of autopod morphogenesis. Our findings suggest that the variable Shh-Fgf8 positioning in various blastema sizes causes various positioning of the aPZ, and that the aPZ leads to digit formation. The mechanism we propose here accounts for stable digit morphogenesis regardless of blastema sizes and urodele-specific digit formation. One-Sentence SummaryA unique SHH-FGF8 spatial interaction compensates for robust limb morphogenesis in various limb sizes.

developmental biology↗

Fluctuation of cellular differentiation in limb regeneration is regulated by Pde4b in urodele amphibians

Urodele amphibians, Pleurodeles waltl and Ambystoma mexicanum, have organ-level regeneration capability, such as limb regeneration. Multipotent cells are induced by an endogenous mechanism in amphibian limb regeneration. It is well known that dermal fibroblasts receive regenerative signals and turn into multipotent cells, called blastema cells. However, the induction mechanism of the blastema cells from matured dermal cells was unknown. We previously found that BMP2, FGF2, and FGF8 (B2FF) could play sufficient roles in blastema induction in urodele amphibians. Here, we show that B2FF treatment can induce dermis-derived cells that can participate in multiple cell lineage in limb regeneration. We first established a newt dermis-derived cell line and confirmed that B2FF treatment on the newt cells provided plasticity in cellular differentiation in limb regeneration. Interspecies comparative analysis clarified that Pde4b upregulation by B2FF specifically took place in the newt cells. Blocking PDE4B signaling by Rolipram suppressed dermis-to-cartilage transformation and the mosaic knockout animals showed consistent results. Our results are a valuable insight into how dermal fibroblasts acquire multipotency during the early phase of limb regeneration via an endogenous program in amphibian limb regeneration.

developmental biology↗

MS-DIAL 4: accelerating lipidomics using an MS/MS, CCS, and retention time atlas

To the EditorWe formulated mass spectral fragmentations of lipids across 117 lipid subclasses and included ion mobility tandem mass spectrometry (MS/MS) to provide a comprehensive lipidome atlas with retention time, collision cross section, and MS/MS information. The all-in-one solution from import of raw MS data to export of a common output format (mztab-M) was packaged in MS-DIAL 4 (http://prime.psc.riken.jp/) providing an enhanced standardized untargeted lipidomics procedure following lipidomics standards initiative (LSI) semi-quantitative definitions and shorthand notation system of lipid structures with a 1-2% estimated false discovery rate, which will contribute to harmonizing lipidomics data across laboratories to accelerate lipids research.

bioinformatics↗

Highly reliable, targeted photothermal cancer therapy combined with thermal dosimetry using indocyanine green lactosome

Indocyanine green (ICG) is a near-infrared light-absorbing substance. Thus, when a tumor in which ICG has accumulated is irradiated with a near-infrared (NIR) laser, only the tumor can be heated by a photothermal reaction. We developed ICG lactosome, a novel drug delivery system (DDS) composed of polymeric micelles and ICG that shows selective accumulation in tumor based on an enhanced permeability and retention (EPR) effect. We showed that ICG lactosome accumulated in a tumor by using an intradermal tumor mouse model of a murine colon cancer cell line (Colon26) transfected with Nano lantern luminescent protein (NLC26). Two days after the administration of ICG lactosome, the tumor was irradiated with an 808-nm diode-laser while monitoring tumor temperature. The results showed that the treated tumors were cured when the peak of tumor temperature during NIR irradiation reached 43{degrees}C or higher. To verify these results, photothermal therapy (PTT) using ICG lactosome was carried out using a newly developed system that can control the temperature at the NIR irradiation site at a constant level. All of the tumors that had been kept at 43{degrees}C during irradiation were cured, while 2 of 5 tumors that had been kept at 42{degrees}C were not cured, and none of tumors that had been kept at a temperature below 41{degrees}C were cured. ICG lactosome-assisted PTT combined with thermal dosimetry is a highly reliable method for cancer treatment and may afford further clinical opportunities for PTT.

bioengineering↗