Biology subjects

Takagi, D.

Publications and source records attributed to Takagi, D..

6 recordsLinked to original sources

bioRxiv2026

HNRNPC-mediated RNA processing promotes VHL-associated excessive vasculogenesis in von Hippel-Lindau syndrome revealed from patient-derived blood vessel models

Von Hippel-Lindau Syndrome (VHLS) is an inherited disorder characterized by excessive vascularization, which contributes to the development of hemangioblastomas and benign or malignant tumors, as well as renal cell carcinoma (RCC) and cysts in multiple organs. VHLS is caused by mutations in VHL tumor suppressor gene, which encodes a component of an E3 ubiquitin ligase complex. Although therapeutic agents targeting hypoxia-inducible factor 2 alpha (HIF2A), which is stabilized by VHL loss and promotes tumor angiogenesis, have been approved for clinical use, their therapeutic response remains limited in RCC patients associated with VHLS. Therefore, there is an unmet need for the development of alternative therapeutic approaches independent of HIF2A. Here, we establish a human iPSCs-based model of VHLS-associated excessive vasculogenesis using induced pluripotent stem cells (iPSCs) derived from VHLS patients and VHL-edited isogenic iPSC lines. Vascular cells (VCs) differentiated from these VHLS-specific iPSCs exhibited excessive blood vessel formation compared to healthy donor-derived VCs, leading to vascular lesion formation characterized by abundant blood vessels and abnormal cellular growth in vivo. Mechanistically, RNA-binding proteins (RBPs) were preferentially stabilized in the patient-VCs. Among these RBPs, the stabilization of heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC), which is a substrate for pVHL-mediated protein degradation independent of HIF2A expression, was critical for the dysregulated vascularization caused by VHL inactivation in this model. These findings provide an iPSCs-derived vascular platform to elucidate VHLS mechanisms and identify HNRNPC as a potential therapeutic target for VHL-driven vascular lesion formations through an HIF2A-independent mechanism.

cell biology↗

bioRxiv2025

Promotion of seed germination in Echinochloa crus-galli with atmospheric air plasma

Plasma technology has attracted increasing attention for potential agricultural applications, and it has been investigated for decades particularly for its ability to promote seed germination. However, most studies have focused on crop species, and little is known about its potential use for weed management. In this study, we examined whether air plasma influences the germination of Echinochloa crus-galli, a major paddy field weed. When seeds were cultivated without stratification, direct irradiation with air plasma did not enhance germination. In contrast, once dormancy was partially released by cold stratification, plasma treatment significantly promoted germination. Interestingly, the effect disappeared after prolonged chilling, when dormancy was completely released. These results suggest that plasma promotes germination by acting on the dormancy-breaking process. In addition, plasma-activated water (PAW) also stimulated germination, although its effect was weaker than that of gaseous plasma. Overall, this study demonstrates that air plasma can promote the germination of grass weed seeds, providing a potential strategy for weed control by inducing germination prior to crop seeding.

plant biology↗

bioRxiv2024

Antimycin A induces light hypersensitivity of photosystem II in the presence of QB-site binding herbicides

Photosynthetic electron transport consists of linear electron flow and two cyclic electron flow (CEF) pathways around photosystem I (PSI). PGR5-dependent CEF-PSI is thought to be the major CEF-PSI pathway and an important regulator of photosynthetic electron transfer. Antimycin A (AA) is commonly recognized as an inhibitor of PGR5-dependent CEF-PSI in photosynthesis. Although previous findings imply that AA may also affect photosystem II (PSII), which does not participate in CEF-PSI, these "secondary effects" tend to be neglected, and AA is often used for inhibition of PGR5-dependent CEF-PSI as if it were a specific inhibitor. Here, we investigated the direct effects of AA on PSII using isolated spinach PSII membranes, and spinach and Chlamydomonas thylakoid membranes. Measurements of QA- reoxidation kinetics showed that AA affects the acceptor side of PSII and inhibits electron transport within PSII. Furthermore, repetitive Fv/Fm measurements revealed that, in the presence of QB-site binding inhibitors, AA treatment results in severe photoinhibition even from a single-turnover flash. The direct effects of AA on PSII are non-negligible and caution is required when using AA as an inhibitor of PGR5-dependent CEF-PSI. Meanwhile, we found that the commercially available compound AA3, which is a component of the AA complex, inhibits PGR5-dependent CEF-PSI without having notable effects on PSII. Thus, we propose that AA3 should be used for the physiological study of the PGR5-dependent CEF-PSI.

plant biology↗

bioRxiv2023

Blind cavefish evolved food-searching behavior without changing sensory modality compared with sighted conspecies in the dark

In nature, animals must navigate to forage according to their sensory inputs. Different species use different sensory modalities to locate food efficiently. For teleosts, food emits visual, mechanical, chemical, and/or possibly weak-electrical signals, which can be detected by optic, auditory/lateral line, and olfactory/taste buds sensory systems. However, how fish respond to and use different sensory inputs when locating food, as well as the evolution of these sensory modalities, remain unclear. We examined the Mexican tetra, Astyanax mexicanus, which is composed of two different morphs: a sighted riverine (surface fish) and a blind cave morph (cavefish). Compared with surface fish, cavefish have enhanced non-visual sensory systems, including the mechanosensory lateral line system, chemical sensors comprising the olfactory system and taste buds, and the auditory system to help navigate toward food sources. We tested how visual, chemical, and mechanical stimuli evoke food-seeking behavior. In contrast to our expectations, both surface fish and cavefish did not follow a gradient of chemical stimulus (food extract) but used it as a cue for the ambient existence of food. Surface fish followed visual cues (red plastic beads and food pellets), but, in the dark, were likely to rely on mechanosensors--the lateral line and/or tactile sensor--as cavefish did. Our results indicate cavefish used similar sensory modality to surface fish in the dark, while adherence levels to stimuli were higher in cavefish. In addition, cavefish evolved an extended circling strategy to capture food, which may yield a higher chance to capture food by swimming-by the food multiple times instead of once through zigzag motion. In summary, we propose ancestors of cavefish similar to surface fish may have needed little modification in food-seeking strategy to adapt to the dark.

ecology↗

bioRxiv2021

Transitioning to confined spaces impacts bacterial swimming and escape response

Symbiotic bacteria often navigate complex environments before colonizing privileged sites in their host organism. Chemical gradients are known to facilitate directional taxis of these bacteria, guiding them towards their eventual destination. However, less is known about the role of physical features in shaping the path the bacteria take and defining how they traverse a given space. The flagellated marine bacterium Vibrio fischeri,which forms a binary symbiosis with the Hawaiian bobtail squid, Euprymna scolopes, must navigate tight physical confinement, squeezing through a bottleneck constricting to ~2 m in width on the way to its eventual home. Using microfluidic in vitro experiments, we discovered that V. fischeri cells alter their behavior upon entry into confined space, straightening their swimming paths and promoting escape from confinement. Using a computational model, we attributed this escape response to two factors: reduced directional fluctuation and a refractory period between reversals. Additional experiments in asymmetric capillary tubes confirmed that V. fischeri quickly escape from tapered ends, even when drawn into the ends by chemoattraction. This avoidance was apparent down to a limit of confinement approaching the diameter of the cell itself, resulting in a balance between chemoattraction and evasion of physical confinement. Our findings demonstrate that non-trivial distributions of swimming bacteria can emerge from simple physical gradients in the level of confinement. Tight spaces may serve as an additional, crucial cue for bacteria while they navigate complex environments to enter specific habitats. Significance StatementSymbiotic bacteria that navigate to and through specific host tissues often face tight physical confinement. This work reveals that confinement-associated changes in swimming can dramatically alter taxis, shaping bacterial localization in conjuncture with other motility-directing cues. This work helps explain how bacteria can avoid getting stuck in confined areas while transiting to privileged spaces, adding confinement as an environmental cue that symbiotic bacteria use to shape their motility behavior.

biophysics↗

bioRxiv2021

Manganese toxicity disrupts indole acetic acid homeostasis and suppresses CO2 assimilation reaction in rice plants

Despite the essentiality of Mn in terrestrial plants, its excessive accumulation in plant tissues causes growth defects, known as Mn toxicity. Mn toxicity can be divided into apoplastic and symplastic types depending on its onset. For growth defects, symplastic rather than apoplastic Mn toxicity is hypothesised to be more critical. However, details of the relationship between growth defects and symplastic Mn toxicity remains elusive. In this study, we aimed to elucidate the molecular mechanisms of symplastic Mn toxicity in rice plants. We found that under excess Mn conditions, CO2 assimilation was inhibited by stomatal closure, and both carbon anabolic and catabolic activities were decreased. In addition to stomatal dysfunction, stomatal and leaf anatomical development were also altered by excess Mn accumulation. Furthermore, the indole acetic acid (IAA) concentration was decreased, and auxin-responsive gene expression analyses showed IAA-deficient symptoms in leaves due to excess Mn accumulation. These results suggest that excessive Mn accumulation causes IAA deficiency, and low IAA concentrations suppress plant growth by suppressing stomatal opening and leaf anatomical development for efficient CO2 assimilation in leaves. HIGHLIGHTIncreased Mn concentration lowers auxin concentrations in rice leaves, which suppresses photosynthesis by changing stomatal function and development.

plant biology↗