Biology subjects

Araki, H.

Publications and source records attributed to Araki, H..

9 recordsLinked to original sources

bioRxiv2026

Optimising passive eDNA sampling: A theoretical framework for time-dependent eDNA accumulation

O_LIEnvironmental DNA (eDNA) methods are developing rapidly for ecological surveys, and passive eDNA sampling has emerged as a promising approach for integrating DNA signals over deployment time. However, how deployment duration affects the amount of detectable DNA retained by a sampler remains poorly understood. C_LIO_LIHere, an analytical model was developed to examine how DNA input, degradation, finite substrate capacity and residual retention of degraded DNA shape passive eDNA accumulation. The model distinguishes detectable adsorbed DNA from degraded, non-detectable DNA that may remain on the substrate and continue to occupy capacity. The residual-retention parameter,{theta} , represents the fraction of degraded DNA that remains capacity-occupying, with{theta} = 0 corresponding to complete replacement and{theta} = 1 to complete non-replacement. C_LIO_LIThe model predicts three key behaviours. First, when degraded DNA does not occupy substrate capacity ({theta} = 0), detectable eDNA accumulates monotonically towards equilibrium, but equilibrium recovery increases less than proportionally with DNA input. Thus, passive-sampler measurements can compress quantitative differences in environmental DNA supply. Second, when degraded DNA remains capacity-occupying ({theta} > 0), detectable eDNA can reach a finite peak and subsequently decline. Higher DNA input increases peak yield but shifts the peak earlier, whereas greater substrate capacity increases peak yield and delays the peak. Third, under prolonged deployment with{theta} > 0, a higher-input condition can yield less detectable eDNA than a lower-input condition, reversing the expected input-rate ranking. C_LIO_LIThese results show that passive eDNA recovery can follow saturating, unimodal or intermediate dynamics depending on substrate capacity and post-adsorption DNA fate. Thus, retrieval time cannot be optimised by adjusting deployment duration alone. Although investigators can choose deployment duration and sampler design, including substrate capacity, optimisation also requires calibration or explicit assumptions about ambient DNA supply, DNA degradation rate and residual retention of degraded DNA. C_LI

ecology↗

bioRxiv2026

TET2-mutant clonal hematopoiesis prevents T-cell exhaustion and suppresses cancer metastasis

Clonal hematopoiesis (CH) is widely regarded as a risk factor for age-associated disease, yet its influence on solid tumor progression remains poorly understood. Here, we uncover an unexpected tumor-suppressive role for TET2-mutant CH in solid tumors. Through an analysis of over 16,000 cancer patients, we demonstrate that TET2 mutations are associated with a significant reduction in metastatic burden. Mechanistically, we show that Tet2 deficiency prevents terminal exhaustion in CD8+ tumor-infiltrating lymphocytes (CD8+ TILs). This resistance is driven by DNA hypermethylation at regulatory elements of the transcription factor Tox, which prevents the induction of the terminal exhaustion program. Consequently, Tet2-deficient CD8+ TILs maintain stem-like, effector-competent states that mediate durable anti-tumor immunity and suppress metastatic outgrowth. Our findings establish TET2-mutant CH as a natural epigenetic constraint on T-cell exhaustion and uncover a mechanistically defined pathway with translational potential for enhancing anti-tumor immune responses.

immunology↗

bioRxiv2024

Structural and functional insights into Cdc45 recruitment by Sld7-Sld3 for CMG complex formation

DNA replication requires recruitment of Cdc45 and GINS into the MCM double hexamer by initiation factors to form an active helicase, the Cdc45-MCM-GINS (CMG) complex, at the replication origins. The initiation factor Sld3 is a central regulator of Cdc45 and GINS recruitment, working with Sld7 together. However, the mechanism through which Sld3 regulates CMG complex formation remains unclear. Here, we present the structure of the Sld3 Cdc45-binding domain in complex with Cdc45 (Sld3CBD-Cdc45), showing detailed interactions and conformational changes required for binding to each other. The mutant analysis indicated that the binding between Sld3CBD and Cdc45 could be broken easily. We also revealed that Sld3CBD, GINS, and MCM bind to different sites on Cdc45 in the Sld3CBD-CMG model, indicating that after recruitment of Cdc45, Sld7-Sld3 could remain in Cdc45-MCM until CMG formation. The consistency between the particle size of Sld7-Sld3-Cdc45 and the distance between Sld3CBDs in the Cdc45-MCM dimer indicated the binding manner of the Cdc45-Sld3-[Sld7]2-Sld3-Cdc45 off/on MCM double hexamer. A DNA-binding assay of Sld3 and its complexes with single-stranded ARS1 fragments revealed a relationship between the dissociation of Sld7-Sld3 from CMG and the unwound single-stranded DNA. These findings help to further our understanding of the molecular basis of the regulation of CMG complex formation by Sld3.

molecular biology↗

bioRxiv2024

Robust and accurate method for measuring tumor volume using optical 3D scanning for nonclinical in vivo efficacy study

In a nonclinical in vivo efficacy test for anticancer drugs, immunodeficient mice subcutaneously transplanted with human cancer cells were quantified and evaluated with regard to the manner in which the skin bulges where locally proliferated cancer cells regress after drug administration. A caliper is conventionally used to measure the tumor bulge. However, its volume is an estimated value and results in high variability. Alternatively, cancer cell lines that express genetically encoded marker genes have been used in recent years for optical and nondestructive measurements. However, estimations using calipers exhibit large errors, and biological tissues have low light transparency. This hinders quantitative optical measurements. In addition, variations in measurements owing to subjective and human operations are likely. From the chemistry, manufacturing, and control (CMC) perspective, precise measurement is required to evaluate drug efficacy and quality. Therefore, we aimed to eliminate errors caused by the use of estimated values, subjectivity, and human manipulation by precisely quantifying the volume of the tumor bulge using a 3D scanner. This study demonstrated that optical 3D scanner measurements were accurate, had low variability, and was highly correlated with tumor weight. The tumor bulge was observed to vary to a flattened oval dome shape rather than a semicircle. This caused high variability in measurements of tumor volume. However, the proposed 3D scanner was more sensitive to volumetric regression than the caliper. Additionally, it exhibited drug efficacies with higher resolution than the caliper. Furthermore, the high linearity of the scanner provided more accurate measurements over a wider range of tumor sizes than luminescence imaging. The accurate and sensitive properties of such 3D scanners are also likely to make these exceptionally effective analytical tools for ensuring product equivalency when modifying raw materials or manufacturing processes in the development of cell therapy products. As described above, robust and accurate drug efficacy measurements using nondestructive and noninvasive 3D scanners that require no training and are convenient to operate provide many analytical improvements and advantages. This is likely to play an important role in 1) the efficacy evaluation of cell therapy products that have large variations originating from the raw materials and large differences between manufacturing lots and 2) the quality evaluation, property analysis of the characteristics of variations in the shape of tumor bulges over time, and comparability testing of the products in the CMC section of pharmaceutical companies.

cancer biology↗

bioRxiv2023

Transcription factor-mediated direct cellular reprogramming yields cell-type specific DNA methylation signature

Direct reprogramming is a technique for inducing the conversion of one type of somatic cell into another by the forced expression of defined transcription factors. Cell differentiation is generally determined by specific gene expression profiles based on distinct genome-wide epigenetic signatures. Although the CpG methylation of genomic DNA is an essential epigenetic factor that affects the transcriptional state of genes, little is known about how DNA methylation changes and what roles it plays in direct reprogramming. Here, we performed comparative genome-wide DNA methylation analyses of mouse embryonic fibroblasts (MEFs) and cells composing organoids formed by intestinal stem cells (ISCs) or induced ISCs (iISCs) that were directly induced from MEFs to investigate the impact of DNA methylation dynamics on direct reprogramming. We found that the methylation state of CpG was similar between cells forming ISC organoids and iISC organoids, while they differed widely from those in MEFs. Moreover, genomic regions that were differentially methylated between ISC organoid- and iISC organoid-forming cells did not significantly affect gene expression. These results demonstrate the accuracy and safety of iISC induction, as they show that the DNA methylation state transitions to a state close to that of ISCs during direct reprogramming from MEFs to iISCs.

cell biology↗

bioRxiv2022

LSD1 acts as an epigenetic barrier against glucocorticoid-induced atrophy and exercise-induced hypertrophy in skeletal muscle

Skeletal muscle exhibits remarkable plasticity in response to environmental cues, with stress-dependent effects on the fast-twitch and slow-twitch fibers. Although stress-induced gene expression underlies environmental adaptation, it is unclear how transcriptional and epigenetic factors regulate fiber type-specific responses in the muscle. Here, we show that flavin-dependent lysine-specific demethylase 1 (LSD1) differentially controls responses to glucocorticoid and exercise in postnatal skeletal muscle. Using skeletal muscle-specific LSD1 knockout mice and in vitro approaches, we found that LSD1 loss exacerbated glucocorticoid-induced atrophy in the fast fiber-dominant muscles, with reduced nuclear retention of Foxk1, an anti-autophagic transcription factor. Furthermore, LSD1 depletion enhanced endurance exercise-induced hypertrophy in the slow fiber-dominant muscles, by induced expression of ERR{gamma}, a transcription factor that promotes oxidative metabolism genes. Thus, LSD1 serves as an "epigenetic barrier" that optimizes fiber type-specific responses and muscle mass under the stress conditions. Our results uncover that LSD1 modulators provide emerging therapeutic and preventive strategies against stress-induced myopathies such as sarcopenia, cachexia, and disuse atrophy. Graphical abstract. LSD1 serves as an "epigenetic barrier" that defines stress sensitivities in the skeletal muscleLSD1 attenuates glucocorticoid (GC)-induced atrophy in the fast fiber-dominant muscles, in collaboration with Foxk1, an anti-autophagic transcription factor. On the other hand, LSD1 attenuates endurance exercise-induced hypertrophy in the slow fiber-dominant muscles, by inhibiting ERR{gamma}, a transcription factor that promotes oxidative metabolism genes. The loss of LSD1 remarkably sensitized the muscles to GC and endurance exercise.

cell biology↗

bioRxiv2020

Effects of species traits and ecosystem characteristics on species detection by eDNA metabarcoding in lake fish communities

Although environmental DNA (eDNA) metabarcoding is acknowledged to be an exceptionally useful and powerful tool for monitoring surveys, it has limited applicability, particularly for nationwide surveys. To evaluate the performance of eDNA metabarcoding in broad-scale monitoring, we examined the effects of species ecological/biological traits and ecosystem characteristics on species detection rates and the consequences for community analysis. We conducted eDNA metabarcoding on fish communities in 18 Japanese lakes on a country-wide scale. By comparing species records, we found that certain species traits, including body size, body shape, saltwater tolerance, and habitat preferences, influenced eDNA detection. We also found that the proportion of species detected decreased significantly with an increase in lake surface area, owing to an ecosystem-size effect on species detection. We conclude that species traits, including habitat preferences and body size, and ecosystem size should be taken into consideration when assessing the performance of eDNA metabarcoding in broad-scale monitoring.

ecology↗

bioRxiv2020

Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle

Skeletal muscle stem cells (satellite cells) are distributed throughout the body with heterogeneous properties that corresponds to region-specific pathophysiology. However, topographical genes that have functions remain unidentified in satellite cells of adult muscle. Here, we showed that expression of Homeobox (Hox)-A cluster genes, key regulators of the embryonic body plan, was robustly maintained in both muscles and satellite cells in adult mice and humans, which recapitulates their embryonic origin. We observed that regionally specific expressed Hox genes were linked to hypermethylation of the Hox-A locus. We examined Hoxa10 inactivation in satellite cells and found it led to genomic instability and mitotic catastrophe, which resulted in a decline in the regionally specific regenerative ability of muscles in adult mice. Thus, our results showed that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating the region-specificity in adult skeletal muscles.

developmental biology↗

bioRxiv2017

Predation Of Stocked Masu Salmon (Oncorhynchus masou) By Riparian Wildlife

Predation after release is one of the major concerns of hatchery fish conservation and propagation. However, the relationship among the size of hatchery fish, the predator species, and their behaviors in natural environments is largely unknown. To understand the relationship, we conducted predation experiments in outdoor tanks and a semi-natural stream with exposure to local predators. Two different ranges of fork lengths of masu salmon (Oncorhynchus masou) were examined as prey sizes. Camera trap data showed that grey herons (Ardea cinerea) were the primary predator animal in the system, and that most herons utilized shallow areas in the morning or evening. Increasing the density of stocked salmon brought in more grey herons. More importantly, predation by grey herons resulted in the survival rate of larger salmon being significantly lower than that of the smaller salmon. Our results suggest that it is important to understand local predators, adjust the optimum body size of hatchery fish at release, and choose the appropriate stocking site and time of day for maximizing the effectiveness of fish stocking.

ecology↗