Biology subjects

Kan, T.

Publications and source records attributed to Kan, T..

4 recordsLinked to original sources

bioRxiv2025

Bacteria break through one-micrometer-square passages by flagellar wrapping

Confined spaces are omnipresent in the micro-environments, including soil aggregates and intestinal crypts, yet little is known about how bacteria behave under such conditions where movement is challenging due to limited diffusion. Stinkbug symbiont Caballeronia insecticola navigates a narrow gut passage about one micrometer in diameter to reach the stinkbugs symbiotic organ. Here, we developed a microfluidic device mimicking the hosts sorting organ, wherein bacterial cells are confined in a quasi-one-dimensional fashion, and revealed that this bacterium wraps flagellar filaments around its cell body like a screw thread to control fluid flow and generate propulsion for smooth and directional movement in narrow passages. Physical simulations and genetic experiments revealed that hook flexibility is essential for this wrapping; increasing hook rigidity impaired both wrapping motility and infectivity. Thus, flagellar wrapping likely represents an evolutionary innovation, enabling bacteria to break through confined environments using their motility machinery.

microbiology↗

bioRxiv2024

Continual integration of single-cell multimodal data with MIRACLE

Single-cell sequencing technologies have revolutionized our understanding of cellular heterogeneity and facilitated the construction of multi-omics cell atlases via data integration. However, updating these atlases with new data conventionally requires reintegration of all data and is computationally intensive, hindering timely updates and dynamic adjustments in biological and medical research. To address this challenge, we present Multimodal Integration with Continual Learning (MIRACLE), a novel online learning framework for the adaptive and efficient integration of single-cell multimodal data. MIRACLE employs dynamic architectures and data rehearsal strategies to support continual learning, allowing diverse data to be integrated while minimizing information loss over time. Our evaluations demonstrate that MIRACLE achieves accurate online integration with reduced computational requirements, effectively updating and expanding atlases with new cross-tissue and cross-modal data, and precisely identifying novel cell types and transferring labels across datasets. MIRACLE provides an efficient and flexible tool for single-cell community to integrate, share and explore biological knowledge from single-cell multimodal data.

bioinformatics↗

bioRxiv2024

Nobiletin, a Polymethoxyflavonoid, Activates the Desuccinylase Activity of SIRT5 and Prevents the Development of Heart Failure

Nobiletin is a natural compound useful for the prevention and treatment of several diseases. However, the precise role of nobiletin in heart failure is unclear. Nobiletin treatment prevents pressure overload- and myocardial infarction-induced heart failure. Using affinity purification of biotinylated nobiletin from rat heart cell lysates, we identified sirtuin 5 (SIRT5) as a novel nobiletin-binding protein. Nobiletin enhanced the desuccinylase activity of SIRT5 in vitro. Compared to wild-type mice, SIRT5-overexpressing transgenic mice resisted pressure overload-induced systolic dysfunction. Conversely, SIRT5 knockout disrupted the nobiletin-mediated therapeutic effects on heart failure in mice. SIRT5 desuccinylated p300 at lysine 1568 and reduced the histone acetyltransferase (HAT) activity of p300. The desuccinylated p300 mutant suppressed the phenylephrine-induced cardiomyocyte hypertrophic responses. These findings suggest that nobiletin prevents heart failure development through SIRT5-dependent inhibition of p300-HAT activity. Nobiletin, a nontoxic dietary compound, is a potential therapeutic agent for heart failure in humans.

molecular biology↗

bioRxiv2022

Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Osteoclasts are cells which are primarily involved in bone remodeling and osteolytic bone diseases. Hyperactive osteoclastogenesis leads to pathological bone loss and microarchitectural deterioration, particularly in postmenopausal osteoporosis. However, given the limitations of current first-line osteoclast inhibitors, there is an urgent need for a novel antiresorptive agent with higher efficiency and fewer side effects. Cell-free fat extract (CEFFE) is the liquid fraction obtained from human adipose tissues, which are enriched with a variety of cytokines and growth factors. This study aims to explore its pharmaceutical effect on hyperactive osteoclast formation in vivo and in vitro. CEFFE exhibits excellent potentials to attenuate osteoclast-associated bone loss in an ovariectomy (OVX) mouse model and to inhibit RANKL-induced osteoclastogenesis in primary bone marrow-derived monocytes. Furthermore, the cationic protein fraction of CEFFE (CEFFE-Cation) is identified as the main inhibitory component in osteoclast formation assay. Excessive reactive oxygen species (ROS) production is the main cause of osteoclast overactivation. According to LC-MS/MS analysis, the CEFFE-Cation fraction mainly consists of various antioxidant enzymes, extracellular matrix, and secreted cytokines, which endow it with a superior antioxidant capacity. Ca2+ signaling contributes to osteoclast maturation. In addition to scavenging ROS, CEFFE-Cation is also capable of mitigating Ca2+ oscillation, calcineurin activation, and subsequent NFATc1 nuclear translocation during osteoclastogenesis. Overall, this study elucidates the promising translational potential of CEFFE as a next-generation personalized antiresorptive agent for osteolytic bone disease treatment.

pathology↗