Biology subjects

Takizawa, K.

Publications and source records attributed to Takizawa, K..

8 recordsLinked to original sources

bioRxiv2026

The gut-liver axis and the role of bacteria in severe dengue virus infection in mice

Patients with severe dengue virus (DENV) infection can experience hemorrhage, shock and organ damage that coincides with defervescence and declining viremia. In addition to vascular leak, published work has shown that gut barrier permeability and elevated serum lipopolysaccharide (LPS) levels correlate with DENV disease severity. We previously described profound gut pathology in a mouse model of infection. This led to the hypothesis that a loss of gut epithelial barrier integrity and the influx of microbial products contribute to exacerbated inflammation and severe dengue disease. Consistent with this, here we demonstrated that DENV2 infection of AG129 mice compromised the gut epithelial barrier, promoted bacterial translocation, and induced microbial changes indicative of dysbiosis, including a reduced abundance of putatively beneficial microbial taxa and disrupted microbial circadian oscillations. Depleting gut bacteria with antibiotics from 1-day post-infection sharply reduced gut pathology as well as viral RNA in the proximal colon and liver, and the number of infected Kupffer cells in the liver. There was no evidence for systemic suppression of viral replication. We propose that viral infection of intestinal macrophages leads to inflammatory damage and mucosal barrier breakdown, dysbiosis and gut leak, with gut bacteria-dependent products promoting the susceptibility of Kupffer cells to DENV infection. Given the importance of liver damage in severe and fatal dengue disease, therapies that protect the gut barrier may help reduce disease severity.

microbiology↗

bioRxiv2025

Self-organized fingering instabilities drive the emergence of tissue morphogenesis in digit organoids.

The emergence of complex anatomical structures -such as the hands- from unstructured tissues remains a fundamental question in developmental biology. Turing-type reaction-diffusion models have provided a molecular explanation for the periodic pre-patterning of digits; however, the physical principles driving 3D morphogenesis remain incompletely understood. To identify the biophysical design principles leading to digit formation, we develop a limb-mesenchymal organoid system that spontaneously forms elongated, digit-like protrusions. Iterations between experiments and agent-based models at the cellular level identify sufficient microscopic mechanisms leading to morphogenesis of digit-like structures: symmetry-breaking and the elongation of digits result from a combination of differential cell adhesion and morphogen-induced chemotaxis and convergent-extension. Lastly, to describe tissue-scale deformations, we perform a coarse-graining analysis of the agent-based model and derive a continuum model that reveals a structural analogy to Cahn-Hilliard-type equations. These equations are typically used to describe fluid phase separation and so-called ''fingering instabilities'' in fluid physics. Here, we show that they also accurately describe organoid morphogenesis. These findings suggest that ''finger'' formation is driven by a mechanical fingering instability acting in concert with chemical patterning, shedding a new light on vertebrate limb morphogenesis.

developmental biology↗

bioRxiv2025

A copper-dependent, redox-based hydrogen peroxide perception in plants

Redox-related molecules, such as quinones and reactive oxygen species (ROS), are important signaling molecules for all living organisms. A plant-specific leucine rich-repeat receptor-like kinase (LRR-RLK) CANNOT RESPOND TO DMBQ 1 (CARD1), also known as HYDROGEN-PEROXIDE-INDUCED Ca2+ INCREASES (HPCA1), perceives both quinones and ROS, but knowledge on key structural features is unknown. Here, we determine the structure of the CARD1 ectodomain and uncover its unique features. Structural studies, coupled with genetics and biochemical analysis, demonstrated that previously identified unique cysteine residues are not essential for signal perception in CARD1. Interestingly, CARD1 harbors a copper ion on the surface of the ectodomain via histidine-coordination that is crucial for hydrogen peroxide signaling. Our work reports the first copper-dependent redox receptor and highlights a unique perspective between a receptor and non-peptide stimuli during their perception.

plant biology↗

bioRxiv2025

Enhanced delivery of lipid nanoparticle-based immunotherapy by modulating the tumor tissue stiffness using ultrasound-activated nanobubbles

Tumors often exhibit an extracellular matrix with elevated stiffness due to excessive accumulation and crosslinking of proteins, particularly collagen. This elevated stiffness acts as a physical barrier, impeding the infiltration of immune cells and the effective delivery of various immunotherapeutic agents, such as lipid nanoparticle-based RNA therapeutics. Here, we investigate the ability of ultrasound-activated nanobubbles (US-NBs) to increase the permeability and immunogenicity of tumors. Our results show that US-NBs physically remodel the tumor tissue by decreasing its stiffness by 60% five days after a single treatment. US-NB-treated tumors display randomly oriented collagen with a 5.47-fold lower deposition compared to untreated tumors. This leads to the effective delivery and widespread distribution of lipid nanoparticles (LNPs) in the tumor. When LNPs are assisted by US-NB, they have higher gene-transfection across pan-immune cells relative to LNPs alone. Notably, US-NB enables LNPs to genetically modify T cells directly in vivo. By effectively engaging both arms of the immune system, US-NB-assisted LNPs enhance the tumor immunogenicity and infiltration of cytotoxic cells by 4-fold when compared to LNPs alone. These results indicate that gentle mechanical stimulation of the tumor using US-NB offers a promising strategy to augment the delivery and efficacy of existing immunotherapies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/648512v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@da7fborg.highwire.dtl.DTLVardef@8f5f27org.highwire.dtl.DTLVardef@b002f6org.highwire.dtl.DTLVardef@19265da_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Remote Detection of Red-Edge Spectral Characteristics in Floating Aquatic Vegetation

The vegetation red-edge of terrestrial plants is a key biosignature for detecting Earth-like habitable exoplanets. Although water is essential for plants, an excess of water can limit the distribution of terrestrial vegetation. On planets with extensive water coverage and limited land, floating vegetation on the waters surface could serve as a crucial indicator of life. This study examined the spectral reflectance of floating plants across various scales, from individual leaves to lake-wide vegetation coverage. Our comparisons between individual leaves revealed that the red-edge of floating plants was equivalent to or even more pronounced than that of terrestrial plants. Although water can reduce plant reflectance, the naturally low reflectance of water enhances the detection sensitivity for floating vegetation. Seasonal changes, such as the proliferation of floating plants in summer and their decline in winter, lead to significant variations in lake reflectance. By analyzing satellite images of lakes and marshes over a five-year period, we confirmed that these seasonal variations in reflectance reliably indicate the presence of floating vegetation. The seasonal signal showed robustness to the effects of clouds, which pose another challenge on water-rich planets. We propose that floating vegetation be considered alongside, or even in place of, terrestrial vegetation in the search for extraterrestrial life.

plant biology↗

bioRxiv2023

SART1 localizes to spindle poles forming a SART1 cap and promotes spindle pole assembly

The nuclear protein SART1 has been associated with pre-mRNA splicing but SART1 RNAi knockdown results also in defects in mitotic progression, centrosome biogenesis and chromosome cohesion. The mitotic roles of SART1 have not been characterized in detail and it remains unclear whether SART1 functions in mitosis directly or indirectly via pre-mRNA splicing. Here, we identify SART1 as a direct, mitosis-specific microtubule-associated protein. SART1 downregulation in human cells leads to spindle assembly defects with reduced microtubule dynamics, lack of end-on attachment, and checkpoint activation, while microtubule dynamics remain unaffected in interphase. SART1 uniquely localizes to the distal surface of mitotic centrosomes along the spindle axis, forming a previously not described structure we refer to as SART1 cap. Immunoprecipitation of SART1 consistently identifies centrosomal proteins as interaction partners. Immunostaining of these shows that SART1 downregulation does not affect centriole duplication and centrosome-accumulation of {gamma}-tubulin but reduces the accumulation of selective pericentriolar material (PCM) proteins like Ninein. Depletion of SART1 from frog egg extracts disrupts spindle pole assembly around sperm nuclei and DNA-coated beads. Spindles formed around DNA-coated beads do not contain centrosomes but still recruits PCM proteins for spindle pole assembly. We finally show that the N-terminus of SART1 is its microtubule-binding region and essential for spindle assembly. Our data unravel a unique localization of SART1 and a novel function to recruit selective PCM proteins for spindle pole assembly in centrosomal and acentrosomal spindle assembly.

cell biology↗

bioRxiv2021

Structural basis of LhcbM5-mediated state transitions in green algae

In green algae and plants, state transitions serve as a short-term light acclimation process to regulate light harvesting capacity of photosystems I and II (PSI and PSII). During the process, a portion of the light-harvesting complexes II (LHCII) are phosphorylated, dissociate from PSII and bind PSI to form PSI-LHCI-LHCII supercomplex. Here we report high-resolution structures of PSI-LHCI-LHCII supercomplex from Chlamydomonas reinhardtii, revealing the mechanism of assembly between PSI-LHCI complex and two phosphorylated LHCII trimers containing all four types of LhcbM proteins. Two specific LhcbM isoforms, namely LhcbM1 and LhcbM5, directly interact with the PSI core through their phosphorylated amino-terminal regions. Furthermore, biochemical and functional studies on mutant strains lacking either LhcbM1 or LhcbM5 indicate that only LhcbM5 is indispensable in the supercomplex formation. The results unraveled the specific interactions and potential excitation energy transfer routes between green algal PSI and two phosphorylated LHCIIs.

plant biology↗

bioRxiv2020

Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway

Salicylic acid (SA) and its structural analogs are nonsteroidal anti-inflammatory drugs (NSAIDs) that target mammalian cyclooxygenases. In plants, SA acts as a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identified a number of NSAIDs that enhance bacterial effector-induced cell death. Among them, the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent immune responses in plants. TNX treatment reduces NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. Surprisingly, however, cysteine modification associated with NPR1 oligomerization via intermolecular disulfide bonds is not affected by either SA or TNX. Therefore, oxicam-type NSAIDs highlight importance of SA effects on the cytosolic redox status, but not on cysteine modification or oligomerization of NPR1.

plant biology↗