Biology subjects

Taki, Y.

Publications and source records attributed to Taki, Y..

8 recordsLinked to original sources

bioRxiv2026

Organ-resolved endothelial regulatory programs link aging and metabolic overload to vascular immune remodeling

Systemic aging and metabolic overload remodel the vasculature; however, how endothelial cells integrate these stresses across organs remains unclear. Using multi-organ single-cell and spatial transcriptomics with functional validation, we mapped endothelial and hematopoietic responses in adipose tissue, skeletal muscle, liver, and heart. Organ-specific endothelial transcriptional features were relatively preserved, whereas chronic stress selectively reconfigured regulatory programs: aging induced a conserved Irf/Stat-centered endothelial program, while high-fat diet engaged organ-biased lipid and remodeling programs. Spatial analysis revealed perivascular niches centered on aging-associated interferon-stimulated endothelial activation, with neighboring immune and stromal cells expressing C3 and LRP1-associated signals. Rather than simply amplifying inflammation, these niches contained mechanisms that restrained IFN activation, as C3 depletion upregulated vascular IRF7 expression. In parallel, the IFN downstream effector BST2 promoted anti-inflammatory macrophage differentiation and suppressed atherosclerosis. These findings define vascular inflammaging as an organ-resolved niche process in which endothelial IFN activation is coupled to local inflammatory restraint. HighlightsO_LIAging induces a shared endothelial type I IFN program across organs. C_LIO_LIA high-fat diet triggers organ-biased endothelial remodeling programs. C_LIO_LIPerivascular interferon niches couple inflammation with local restraint. C_LIO_LIIFN-induced endothelial BST2 promotes CD200R-associated macrophage regulatory features. C_LI

cell biology↗

bioRxiv2025

Intergenerational effects of maternal and paternal childhood maltreatment on offspring cortical gyrification are sex-specific: the Transmit Radiant Individuality to Offspring (TRIO) study

The effects of parental childhood maltreatment (CM) can be transmitted across generations; however, the underlying sex-specific biological mechanisms are poorly understood. To better understand how parental adversity is passed on to offspring, we investigated the impact of maternal and paternal CM on the local gyrification index (LGI) of offspring using parent-offspring trio data. The LGI was selected as a key neurodevelopmental metric because it is thought to reflect the fetal environment and remain relatively stable postnatally, making it less susceptible to later life experiences. Using multiple regression, we analyzed sex- stratified associations between parental CM subtypes and the offspring LGI and tested for mediation by parental psychosocial functioning. The results revealed a distinct parent-of-origin, sex-specific pattern: maternal emotional abuse was associated with a lower LGI in male offspring, whereas paternal physical neglect was associated with a lower LGI in female offspring. These associations were not mediated by the current mental health or marital relationships of the parents. Collectively, these findings provide compelling evidence that the neurodevelopmental consequences of parental CM can be biologically embedded in the next generation even before birth.

neuroscience↗

bioRxiv2025

Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis

Metabolic dysfunction-associated steatohepatitis (MASH) represents a progressive form of steatotic liver disease which increases the risk for fibrosis and advanced liver disease. The accumulation of discrete species of bioactive lipids has been postulated to activate signaling pathways that promote inflammation and fibrosis. However, the key pathogenic lipid species is a matter of debate. We explored candidates using various dietary, molecular, and genetic models. Mice fed a choline-deficient L-amino acid-defined high-fat diet (CDAHFD) developed steatohepatitis and manifested early markers of liver fibrosis associated with increased cholesterol content in liver lipid droplets within 5 days without any changes in total liver cholesterol content. Treating mice with antisense oligonucleotides (ASOs) against Coenzyme A synthase (Cosay) or treatment with bempedoic acid or atorvastatin decreased liver lipid droplet cholesterol content and prevented CDAHFD-induced MASH and the fibrotic response. All these salutary effects were abrogated with dietary cholesterol supplementation. Analysis of human liver samples demonstrated that cholesterol in liver lipid droplets was increased in humans with MASH and liver fibrosis and was higher in PNPLA3 I148M (variants rs738409) than in HSD17B13 variants (rs72613567). Together, these data identify cholesterol in liver lipid droplets as a critical mediator of MASH and demonstrate that COASY knockdown and bempedoic acid are novel therapeutic approaches to reduce liver lipid droplet cholesterol content and thereby prevent the development of MASH and liver fibrosis. Significance StatementMetabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to fibrosis. The role of specific lipid species in its pathogenesis remains debated. Using dietary, molecular, and genetic models, we found that mice on a choline-deficient, high-fat diet (CDAHFD) developed steatohepatitis and early fibrosis, marked by increased cholesterol in liver lipid droplets within five days. Targeting COASY with antisense oligonucleotides or treating with bempedoic acid or atorvastatin reduced lipid droplet cholesterol and prevented MASH. However, dietary cholesterol supplementation negated these effects. Human liver samples confirmed elevated lipid droplet cholesterol in MASH and fibrosis, especially in PNPLA3 I148M carriers. These findings highlight cholesterol reduction as a potential MASH therapy.

pathology↗

bioRxiv2025

Association of human gut microbiota with Alzheimers disease pathogenesis: An exploratory clinical study

The relationship between Alzheimers disease (AD) onset and the brain-gut axis has garnered increasing attention. This study aimed to investigate the potential role of the brain-gut axis in AD pathogenesis, with a specific focus on microbiota composition. This exploratory study enrolled 10 patients with AD and 13 healthy adults, grouped by age ([≤]30 years, 31-40 years, and [≥]41 years). Fecal samples were collected, and 16S rRNA gene sequencing was employed to analyze differences in fecal microbiota composition at the bacterial species level. Certain bacterial species appeared more abundant in the AD group (e.g., Ruminococcus inulinivorans and Ruminococcus torques), while others were relatively more abundant in healthy adults (e.g., Prevotella vulgatus 1, Bacteroides wexlerae, Clostridium butyricum, and Alistipes rectalis). However, these differences were not statistically significant, likely because of the limited sample size. These findings suggest that fecal microbiota composition may differ between patients with AD and healthy individuals, with a potential intermediate group at risk of AD development. Larger-scale clinical studies are necessary to further elucidate the bacterial species associated with AD pathogenesis, potentially enabling the use of microbiota composition as a screening tool to distinguish between healthy individuals, patients with AD, and those with preclinical AD.

neuroscience↗

bioRxiv2024

Parent-offspring brain similarity: Specificities and commonalities across gender combinations - the Transmit Radiant Individuality to Offspring (TRIO) study

Research suggests that parent-offspring brain similarities may underlie intergenerational transmission of psychopathology. However, most studies have focused on mothers and offspring, with few including fathers. This study aimed to extend understanding of parent-offspring neural similarities by examining parent-offspring trios. The study included 152 Japanese biological parent-offspring trios who participated in the Transmit Radiant Individuality to Offspring (TRIO) study. We analyzed the parent-offspring similarities in brain structural features (cortical thickness, surface area, local gyrification index, and subcortical volume) across different parent-offspring gender combinations (father-son, father-daughter, mother-son, and mother-daughter). Additionally, we investigated the relationship between brain similarities and similarities in intelligence and personality traits in parents and offspring. Our findings confirmed that correlations in brain structural features between father-offspring or mother-offspring dyads were significantly stronger than those between unrelated individuals. Notably, both sons and daughters exhibited brain regions similar to their fathers only, mothers only, both parents, or neither parent. Furthermore, a significant association was observed between similarities in general intelligence and the surface area of auditory regions in both father-offspring and mother-offspring dyads. These results provide valuable insights into the genetic and environmental factors influencing brain development and aging across generations. This study is expected to contribute to future research elucidating the mechanisms underlying the intergenerational transmission of psychiatric disorders.

neuroscience↗

bioRxiv2020

Genetic Diversity and Population Structure in the Yaeyama flying fox

The Ryukyu flying fox (Pteropus dasymallus) is distributed throughout the island chain spanning across southern Japan, Taiwan, and possibly the Philippines. Although P. dasymallus is listed as VU (vulnerable) in the IUCN Red List, only few genetic works have been conducted to support its conservation. In this study we analyzed 19 markers (mtDNA haplotypes and 18 microsatellite markers) to evaluate genetic diversity and investigate the genetic structure of this species. mtDNA analysis was conducted with 142 DNA remote samples, mostly from feces, and wing tissues collected on eight islands (Miyako, Ishigaki, Kohama, Kuroshima, Hateruma, Taketomi, Iriomote, Yonaguni). 39 haplotypes were identified in 526bp of the control region, and haplotype network showed no clear genetic structure. Microsatellite analysis was also conducted with 155 samples collected on six islands (Miyako, Ishigaki, Kohama, Taketomi, Iriomote, Yonaguni). It showed that the Yonaguni population exhibits low genetic diversity, high inbreeding, and clear genetic differentiation from other populations. Gene flow between Ishigaki and Miyako through small stepstone islands might be preventing inbreeding of the Miyako population. We provide for the first time indirect proof of long-distance inter-island dispersal in the Ryukyu flying fox and revealed genetic diversity, gene flow and genetic differentiation among populations of the archipelago. These results will be useful for delineating conservation units and designing specific conservation policies for each island based on metapopulation genetic structure.

genetics↗

bioRxiv2019

Development of CRISPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria

Emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. We established a series of CRISPR-Cas13a-based antibacterial nucleocapsid, termed CapsidCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus through promiscuous RNA cleavage after recognizing corresponding antimicrobial resistance genes. CapsidCas13a constructs were generated by packaging CRISPR-Cas13a into a bacteriophage capsid to target antimicrobial resistance genes. Contrary to Cas9-based antimicrobials that lack bacterial killing capacity when the target genes are located on a plasmid, the CapsidCas13a(s) exhibited strong bacterial killing activities upon recognizing target genes regardless of their location. The antimicrobials treatment efficacy was confirmed using a Galleria mellonella larvae model. Further, we demonstrated that the CapsidCas13a(s) can assist in bacterial gene detection without employing nucleic acid amplification and optical devices.

microbiology↗

bioRxiv2019

Composition and Diversity of CRISPR-Cas13a systems in the genus Leptotrichia

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13a, previously known as CRISPR-C2c2, is the most recently identified RNA-guided RNA-targeting CRISPR-Cas system and has the unique characteristics of both targeted and collateral single-stranded RNA (ssRNA) cleavage activities, which was first identified in Leptotrichia shahii CRISPR-Cas13a. Here, the complete whole genome sequences of 11 Leptotrichia strains were determined and compared with 18 publicly available Leptotrichia genomes in regard to the composition, occurrence and diversity of the CRISPR-Cas13a and other CRISPR-Cas systems. Various types of CRISPR-Cas systems, I-B, II-C, III-A, III-D, III-like and VI-A, were unevenly distributed among the Leptotrichia genomes, accounting for 10 (34.4%), 1 (2.6%), 6 (15.4%), 6 (15.4%), 3 (7.7%) and 11 (37.9%) of the 29 strains, respectively, while 8 (20.5%) strains had no CRISPR-Cas system. The Cas13a effectors were highly divergent with amino acid sequence similarities ranging from 61% to 90% to that of L. shahii and their collateral ssRNA cleavage activities, resulting in cytotoxicity to host cell, were found to be maintained. CRISPR-Cas spacers represent a sequential achievement of former intruder encounters, and the retained spacers reflect the evolutionary phylogeny or relatedness of strains. Analysis of spacer contents and numbers among Leptotrichia species showed considerable diversity with only 2 (0.5%) of 400 spacers through CRIPSR-Cas I-VI were shared by two strains. The organisation and distribution of CRISPR-Cas systems (type I-VI) encoded by all registered Leptotrichia species revealed that effector or spacer sequences of the CRISPR-Cas systems were very divergent, and the prevalence of types I, III and VI was almost equal. There was only one strain carrying type II, while none carried type IV or V. These results provide new insights into the characteristics and divergences of CRISPR-Cas systems among Leptotrichia species.

microbiology↗