Biology subjects

Nakata, K.

Publications and source records attributed to Nakata, K..

5 recordsLinked to original sources

bioRxiv2026

From introduction to eradication: reconstructing population size and removal history of an invasive species

O_LIUnderstanding the processes underlying successful eradication of invasive species is essential for achieving global island conservation goals. Despite the widespread availability of capture records from eradication programs, modeling frameworks that utilize these datasets to elucidate spatio-temporal population dynamics remain underdeveloped. C_LIO_LIIn this study, we reconstructed the spatio-temporal population dynamics of the small Indian mongoose on Amami-Oshima Island (712 km{superscript 2}), Japan, where the species was introduced in 1979 and officially declared eradicated in 2024 after more than 30 years of systematic removal. We integrated introduction records, capture data, and monitoring data using a hierarchical harvest-based model (HBM). To evaluate the models capacity to support management decisions and assess eradication success, we conducted retrospective analyses and compared estimated eradication probabilities with those obtained from a rapid eradication assessment (REA; Samaniego-Herrera et al., 2013). C_LIO_LIThe estimated population size (before reproduction) peaked at 5,449 individuals (95% CI: 4,703, 6,175) in 2000 and subsequently declined almost monotonically. The maximum invaded area was 547.78 km{superscript 2} (posterior median, 95% CI: 496.47, 566.04) in 2009, indicating that the removal program successfully prevented island-wide expansion. Retrospective analyses showed that population estimates remained within the 95% credible intervals of the full dataset estimates, demonstrating temporal consistency. Eradication probabilities estimated by the HBM were substantially higher than those from the REA, highlighting the sensitivity of estimates to fine-scale heterogeneity in detection processes. C_LIO_LISynthesis and applications: Hierarchical HBMs provide a powerful framework for reconstructing, predicting, and evaluating invasive species eradication dynamics. Being aware of the limitations for application to eradication evaluations, HBMs can support adaptive management in long-term eradication programs and improve our understanding of the mechanisms underlying successful eradication. C_LI

ecology↗

bioRxiv2026

Active Nuclear Shuttling Enables Efficient Virus-Free CAR Gene Integration Using Ready-to-Use Lipid Nanoparticles

Non-viral engineering of chimeric antigen receptor T (CAR-T) cells is highly desirable to overcome the cost, safety, and scalability limitations associated with viral vectors and electroporation. However, efficient nuclear delivery and stable genomic integration of DNA in primary human T cells remain major challenges. Here, we established a virus-free CAR-T manufacturing platform using lipid nanoparticles (LNPs) combined with a nuclear localization signal (NLS) shuttle strategy. We developed proprietary ready-to-use LNPs that enable on-demand encapsulation of nucleic acids. To overcome nuclear transport barriers, NLS-fused transposase or genome-editing nuclease was used to bind donor DNA in the cytoplasm and promote active nuclear import. This approach enabled highly efficient and low-toxicity delivery of mRNA and plasmid DNA into primary human T cells. NLS-assisted transposase delivery markedly enhanced genomic integration of the CAR gene, resulting in high expression levels and improved cell viability compared with electroporation-based methods. In addition, TRAC locus-specific targeted integration was achieved more efficiently through end-joining-based repair pathways than through homology-directed repair following LNP delivery. The resulting engineered CAR-T cells exhibited potent and antigen-specific cytotoxic activity. Together, these results demonstrate that NLS-assisted LNP delivery overcomes a key bottleneck in non-viral gene integration and provides a robust strategy for the generation of functional CAR-T cells.

bioengineering↗

bioRxiv2025

Knockout of tusA facilitates flagella formation and cationic antimicrobial resistance by disrupting Fur transcriptional regulation in Escherichia coli

tRNA 2-thiouridine synthesizing protein A (TusA), a sulfur-carrier protein, plays a crucial role in tRNA sulfur modification. Recent studies have reported that tusA deficiency affects iron-sulfur (Fe-S) homeostasis and cluster formation in Escherichia coli; however, its association with this phenotype remains unclear. In this study, we analyzed the phenotype of tusA-deficient E. coli ({Delta}tusA) and its underlying mechanisms using RNA sequencing. We observed that tusA deletion disrupted the expression of genes regulated by the ferric uptake regulator Fur or Fur-regulated transcription factors (flagellar transcriptional regulators D and C [FlhDC] and fumarate and nitrate reduction regulator [Fnr]). Increased expression of flhDC, which is the master regulator of flagellar genes facilitated flagella formation even under conditions in which the wild-type formed few flagella. Additionally, {Delta}tusA was resistant to cationic antibacterial agents, such as cetyltrimethylammonium bromide, cetylpyridinium chloride, and protamine sulfate. This resistance is associated with the increased expression of ompX or ompF, regulated by Fur and Fnr, respectively. Notably, both enhanced flagella formation and resistance to cationic antibacterial agents caused by tusA deletion were abolished in the fur-deficient background. These findings indicate that impaired expression of the fur regulon, possibly because of impaired Fe-S cluster formation, induces multiple phenotypic alterations in {Delta}tusA. IMPORTANCETusA is a sulfur carrier protein involved in tRNA sulfur modification, and its effect on translation has been studied. Recent studies have reported that tusA deficiency affects Fe-S homeostasis and cluster formation in Escherichia coli; however, its association with the phenotype remains unclear. Based on RNA sequencing, we indicated that the altered gene expression in {Delta}tusA resulted from the disruption of fur regulation that is controlled by Fe-S clusters. We further demonstrated that enhanced flagella formation and resistance to cationic drugs were mediated by Fur-dependent gene expression alterations. Our data indicate that the regulation of sulfur allocation for tRNA modification by TusA affects the global gene expression in bacteria.

microbiology↗

bioRxiv2024

Cholesterol sulfate prevents maternal-fetal conflict by locally modulating immune reactivity

Although placental mammals are at high risk of maternal-fetal immune conflict, it is unclear how the semi-allogeneic fetus avoids rejection. Cholesterol sulfate (CS) is a bioactive metabolite that inhibits leukocyte migration and activation. This study investigated the roles and cells associated with CS in pregnant mice and humans. CS was sequentially produced by maternal-derived endometrial cells and fetal-derived placental trophoblasts before and after placentation. When mated with allogeneic males, CS-deficient mice showed increased fetal resorption rates under induced placental inflammation. This phenotype disappeared when the activity of the CS-producing enzyme was restored in the placenta. Placental CS levels were reduced in patients with "villitis of unknown etiology." Thus, we uncovered the spatiotemporal control of CS production and its relevance to local immunosuppression during pregnancy.

immunology↗

bioRxiv2024

Amyloid-β-induced Alteration of Fast and Localized Calcium Elevations in Cultured Astrocytes

Alzheimers disease (AD) is a progressive neurodegenerative disorder that causes cognitive decline. Uncovering the mechanisms of neurodegeneration in the early stages is essential to establish a treatment for AD. Recent research has proposed the hypothesis that amyloid-{beta} (A{beta}) oligomers elicit an excessive glutamate release from astrocytes toward synapses through intracellular free Ca2+ ([Ca2+]i) elevations in astrocytes, finally resulting in neuronal dendritic spine loss. Under physiological conditions, astrocytic [Ca2+]i elevations range spatially from microdomains to network-wide propagation and temporally from milliseconds to tens of seconds. Astrocytic localized and fast [Ca2+]i elevations might correlate with glutamate release; however, the A{beta}-induced alteration of localized, fast astrocytic [Ca2+]i elevations remains unexplored. In this study, we quantitatively investigated the A{beta} dimers-induced changes in the spatial and temporal patterns of [Ca2+]i in a primary culture of astrocytes by two-photon excitation spinning-disk confocal microscopy. The frequency of fast [Ca2+]i elevations occurring locally in astrocytes ([≤]0.5 s, [≤]35 {micro}m2) and [Ca2+]i event occupancy relative to cell area significantly increased after exposure to A{beta} dimers. The effect of A{beta} dimers appeared dose-dependently above 500 nM, and these A{beta} dimers-induced [Ca2+]i elevations were primarily mediated by a metabotropic purinergic receptor (P2Y1 receptor) and Ca2+ release from the endoplasmic reticulum. Our findings suggest that the A{beta} dimers-induced alterations and hyperactivation of astrocytic [Ca2+]i is a candidate cellular mechanism in the early stages of AD.

neuroscience↗