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Kawano, S.

Publications and source records attributed to Kawano, S..

11 recordsLinked to original sources

High-fat diet-induced obesity differentially alters circadian gene expression across peripheral tissues

Circadian rhythms regulate diverse physiological processes, including metabolism, and their disruption has been implicated in metabolic disorders such as obesity. However, the tissue-specific effects of obesity on peripheral circadian clocks remain incompletely understood. Here, we investigated the impact of high-fat diet (HFD)-induced obesity on circadian gene expression in skeletal muscle, liver, and white adipose tissue (WAT). Mice were fed either a regular diet (RD) or HFD for 6 weeks, followed by tissue collection at 4-hour intervals over a 24-hour period. Under RD conditions, key circadian regulators and their downstream targets exhibited robust 24-hour oscillations across all tissues. In contrast, HFD feeding induced distinct, tissue-specific alterations. In the liver, Per2, Dbp, and Rev-erb showed phase-advanced expression patterns, whereas in WAT, rhythmic expression was markedly attenuated. Notably, skeletal muscle largely preserved circadian gene expression patterns, indicating relative resistance to HFD-induced circadian disruption. In addition, HFD feeding altered metabolic gene expression in adipose tissue, characterized by reduced Pgc1 expression and increased Leptin expression. Together, these findings demonstrate that HFD-induced obesity differentially disrupts peripheral circadian clocks in a tissue-specific manner and highlight skeletal muscle as a relatively resilient tissue. These results provide insight into how circadian dysregulation contributes to metabolic abnormalities in obesity.

physiology↗

Network-based integration of cross-dataset proteomic profiles using fold-change directionality

MotivationThe rapid expansion of proteomic data has created new opportunities for large-scale integrative analyses. However, substantial variability across platforms, experimental designs, and processing pipelines limits direct quantitative comparisons among studies. Differential proteomic changes between conditions are often considered to be more reproducible than absolute abundances and may therefore provide a robust basis for cross-dataset integration. However, the systematic ability of differential change-based approaches to capture biologically meaningful relationships across heterogeneous datasets remains unclear. ResultsWe developed a differential-change framework and applied it to public proteomic datasets. Pairwise contrasts were defined as differential proteomic profiles, and the concordance of up- and down-regulated proteins was quantified using odds ratios. Significant profile pairs were visualized as an integrative network. The treatment of anti-cancer drug doxorubicin vs control (MCF-7) comparison emerged as a central hub, with breast cancer proteome profiles clustering around it and associating with tumor stage (p = 0.03). Enrichment analysis revealed overrepresentation of lipid- and cholesterol-related pathways. Availability and implementationThe source code for proteome network integration is available at https://github.com/manakanishizaki/proteome-network-integration.git.

bioinformatics↗

Identification of novel hepaciviruses in rock pigeon (Columba livia )

Recent advances in sequencing technology and transcriptome mining have revealed highly divergent hepaciviruses in birds. However, only a limited number of avian hepaciviruses have been identified to date, leaving their diversity and evolutionary history poorly understood. Moreover, deep phylogenetic gaps among known avian hepaciviruses suggest that additional lineages remain undiscovered. Here, we screened publicly available RNA-seq data and identified three previously undescribed hepaciviruses from rock pigeon (Columba livia), rusty-margined flycatcher (Myiozetetes cayanensis), and Hispaniolan amazon (Amazona ventralis), named rock pigeon hepacivirus (RpHV), rusty-margined flycatcher hepacivirus (RfHV), and Hispaniolan amazon hepacivirus (HaHV). Although these three viruses meet the ICTV species demarcation criteria relative to their closest known relatives, the NS5B-based criterion was not satisfied between RfHV and HaHV. Notably, however, their genome sequence identity is low at 43.2%, and their hosts differ at the order level, suggesting that their classification warrants further consideration. Our phylogenetic analysis showed that avian hepaciviruses, including those found in this study, are monophyletic, but phylogenetic incongruence was observed between avian hepaciviruses and their hosts, suggesting past cross-species transmission among avian hepaciviruses. Overall, this study provides novel insights into the diversity and evolution of hepaciviruses.

microbiology↗

Identification of a novel nidovirus in the common chameleon (Chamaeleo chamaeleon recticrista )

Nidoviruses (the order Nidovirales) are positive strand RNA viruses, and the order currently contains 14 families, 48 genera, and 130 species. Novel nidoviruses have been identified in a variety of animal hosts, but many phylogenetic gaps remain, suggesting the presence of yet-to-be-identified viruses. In this study, we identified a novel nidovirus from publicly available RNA-seq data obtained from the blood of the common chameleon (Chamaeleo chamaeleon recticrista [Boettger, 1880]), and tentatively named it common chameleon nidovirus 1 (CCNV-1). Phylogenetic analysis showed that CCNV-1 is clustered with a member of the family Nanhypoviridae and some unclassified viruses designated as arteriviruses. Further, CCNV-1 genetically distinct from known viruses, exhibiting 50.9% amino acid identity in the RdRp sequence to its closest relative, Jingmen rodent arterivirus 1. Thus, this study provides novel insights into the diversity of nidoviruses.

microbiology↗

Drosophila learn about properties of objects through physical interaction

Animals interact with unfamiliar objects to learn about their properties and guide future behavior, but the underlying neurobiological mechanism is not well understood. Here, we developed a behavioral paradigm in which freely walking Drosophila melanogaster are repeatedly guided to spherical objects using a visual cue. Flies exhibited diverse and structured object interaction motifs, including "ball pulling", and "ball walking", that evolved over time. Notably, flies developed a strong preference for immobile over mobile spherical objects, despite their near identical appearance, suggesting they learn about the objects stability through physical interaction. This preference was impaired by silencing specific h{Delta} neurons in the fan-shaped body, previously implicated in spatial navigation but not known to contribute to object interactions. Our results show that h{Delta} neurons also modulate object interaction motifs and fidelity of following visual guidance cues, pointing to a role in balancing goal-directed and exploratory behaviors. These findings establish Drosophila as a model for investigating how internal representations and multimodal feedback contribute to adaptive object interaction.

neuroscience↗

Cold-induced suppression of myogenesis in skeletal muscle stem cells contributes to delayed muscle regeneration during hibernation

Mammalian hibernators experience profound cold stress and prolonged physical inactivity during torpor periods; however, it is unclear how skeletal muscle stem cells (satellite cells; SCs) respond to these challenges. In this study, we demonstrate that SCs from a mammalian hibernator, Syrian hamster exhibit remarkable resistance to cold-induced cell death, which is associated with intrinsically higher expression of the antioxidant enzyme GPX4, which likely contributes to the suppression of ferroptosis. RNA-seq analysis revealed widespread downregulation of myogenesis-related genes following cold exposure, which suggests suppression of the myogenic program. Consistently, SCs exposed to cold stress exhibited reduced activation and differentiation capacities upon subsequent rewarming, with an increased number of quiescent Pax7-positive/MyoD-negative cells. Muscle regeneration was markedly delayed during hibernation, accompanied by decreased SC activation and macrophage infiltration, suggesting that cold-induced suppression of SC function underlies limited regenerative capacity in hibernating hamsters. Our results provide insight into the unique physiology of mammalian hibernators: SC viability is preserved, whereas regenerative activity is selectively suppressed during hibernation.

physiology↗

Compositional Flexibility of the ER-Mitochondria Encounter Structure

Yeast mitochondria receive the majority of their lipids from the endoplasmic reticulum (ER) via the heterotetrameric ERMES lipid transport complex. This complex is thought to establish a lipid transporting tube of fixed composition spanning the space between both organelles. Intriguingly, however, some of the lipid-transporting components of the complex can be replaced by an artificial ER-mitochondria tether without lipid transport activity, indicating that ERMES subunits are not all of equal importance for lipid transport. Here, we propose a model whereby lipid transfer by the ERMES complex can occur with various sub-ensembles of ERMES, and minimally with only one of the four members, namely Mmm1. Our results imply flexibility in the composition of the ERMES complex, which might help it accommodate various interorganelle distances.

cell biology↗

Role of the Topoisomerase IIα Chromatin Tether domain in Nucleosome Binding & Chromosome Segregation

Due to the intrinsic nature of DNA replication, replicated genomes retain catenated genomic loci that must be resolved to ensure faithful segregation of sister chromatids in mitosis. Type II DNA Topoisomerase (TopoII) decatenates the catenated genomic DNA through its unique Strand Passage Reaction (SPR). Loss of SPR activity results in anaphase chromosome bridges and formation of Polo-like Kinase Interacting Checkpoint Helicase (PICH)-coated ultra-fine DNA bridges (UFBs) whose timely resolution is required to prevent micronuclei formation. Vertebrates have two TopoII isoforms- TopoII and TopoII{beta}, that share a conserved catalytic core. However, the essential mitotic function of TopoII cannot be compensated by TopoII{beta}, due to differences in their catalytically inert C-terminal domains (CTDs). Using genome-edited human cells, we show that specific binding of TopoII to methylated histone, tri-methylated H3K27 (H3K27me3), via its Chromatin Tether (ChT) domain within the CTD contributes critically to avoid anaphase UFB formation. Reducing H3K27 methylation prior to mitosis increases UFBs, revealing a requirement for proper establishment of H3K27me3 after DNA replication to facilitate TopoII-ChT dependent UFB prevention. We propose that interaction of the TopoII-ChT with H3K27me3 is a key factor that ensures the complete resolution of catenated loci to permit faithful chromosome segregation in human cells. Summary StatementGenomic catenations originating from the DNA replication process must be resolved by DNA Topoisomerase II (TopoII) to permit sister chromatid disjunction. The results show that specific recognition of methylated histone containing chromatin by TopoII is critical for complete resolution of the genome.

cell biology↗

Universal Spectrum Identifier for mass spectra

Mass spectra provide the ultimate evidence for supporting the findings of mass spectrometry (MS) proteomics studies in publications, and it is therefore crucial to be able to trace the conclusions back to the spectra. The Universal Spectrum Identifier (USI) provides a standardized mechanism for encoding a virtual path to any mass spectrum contained in datasets deposited to public proteomics repositories. USIs enable greater transparency for providing spectral evidence in support of key findings in publications, with more than 1 billion USI identifications from over 3 billion spectra already available through ProteomeXchange repositories.

bioinformatics↗

Shikonin induces odontoblastic differentiation of dental pulp stem cells via AKT-mTOR signaling in the presence of CD44

In our previous study, we demonstrated that hyaluronan induces odontoblastic differentiation of dental pulp stem cells via interactions with CD44. However, it remains unclear whether CD44 expression by dental pulp stem cells is required for odontoblastic differentiation. Therefore, we searched for a compound that induces odontoblastic differentiation of dental pulp stem cells, regardless of the chemical structure and function of hyaluronan, and examined whether CD44 is involved in the induction of odontoblastic differentiation by the compound. Because vitamin K analogues can promote bone formation and tissue calcification, we focused on derivatives of naphthoquinone, the skeleton of vitamin K; we verified whether those compounds could induce odontoblastic differentiation of dental pulp stem cells. We found that dentin sialophosphoprotein, a marker of odontoblasts, was expressed in dental pulp stem cells after treatment with shikonin. The shikonin-induced expression of dentin sialophosphoprotein was inhibited by PI3K, AKT, and mTOR inhibitors. In addition, in dental pulp stem cells transfected with siRNA against CD44, the shikonin-induced expression of dentin sialophosphoprotein was inhibited. Thus, shikonin can stimulate dental pulp stem cells to undergo odontoblastic differentiation through a mechanism involving the AKT-mTOR signaling pathway and CD44. Hyaluronan stimulated dental pulp stem cells to undergo CD44-mediated odontoblastic differentiation in our previous study; the present study indicated that CD44 is necessary for dental pulp stem cells to undergo odontoblastic differentiation. Although expression of CD44 is important for inducing odontoblastic differentiation of dental pulp stem cells, the relationship between the AKT-mTOR signaling pathway and CD44 expression, in the context of shikonin stimulation, has not yet been elucidated. This study suggested that shikonin may be useful for inducing odontoblastic differentiation of dental pulp stem cells, and that it may have clinical applications, including protection of dental pulp.

cell biology↗

An asexual flower of Silene latifolia and Microbotryum lychnidis-dioicae promoting its sexual-organ development

Silene latifolia is a dioecious flowering plant with sex chromosomes in the family Caryophyllaceae. Development of a gynoecium and stamens are suppressed in the male and female flowers of S. latifolia, respectively. Microbtryum lychnidis-dioicae promotes stamen development when it infects the female flower. If suppression of the stamen and gynoecium development is regulated by the same mechanism, suppression of gynoecium and stamen development is released simultaneously with the infection by M. lychnidis-dioicae. To assess this hypothesis, an asexual mutant, without gynoecium or stamen, was infected with M. lychnidis-dioicae. A filament of the stamen in the infected asexual mutant was elongated at stages 11 and 12 of the flower bud development as well as the male, but the gynoecium did not form. Instead of the gynoecium, a filamentous structure was suppressed as in the male flower. Developmental suppression of the stamen was released by M. lychnidis-dioicae, but that of gynoecium development was not released. It is thought, therefore, that the suppression of gynoecium development was not released by the infection of M. lychnidis-dioicae. M. lychnidis-dioicae would have a function similar to SPF since the elongation of the stamen that is not observed in the healthy asexual mutant was observed after stage 8 of flower bud development. Such an infection experiment also that the Y chromosome of the asexual mutant has genes related to the differentiation of archesporial cells, but none related to maturation of the tapetal cells.

plant biology↗