Biology subjects

Takemoto, S.

Publications and source records attributed to Takemoto, S..

4 recordsLinked to original sources

bioRxiv2026

In vivo brain temperature measurement using quantum dot imaging temperature sensors

Temperature regulation in the brain is essential for maintaining neuronal function and preventing thermally induced damage. Here, we report the development and in vivo application of quantum dots (QDs) to high-resolution thermometry in the mouse brain using two-photon excitation microscopy. These QDs, via the red-to-green photoluminescence (PL) intensity ratios, enabled stable temperature measurements in both normal and chronically hypo-perfused cerebral tissue. Our findings show that localized neuronal activity leads to transient heat generation, which is rapidly dissipated by cerebrovascular responses. In a chronic hypoperfusion model, impaired vascular function resulted in exaggerated and prolonged brain temperature elevations. This thermometry system provides unprecedented insight into the mechanisms of cerebral thermoregulation and highlights the importance of vascular cooling in protecting the brain from heat-induced stress, particularly in pathological conditions such as stroke.

bioengineering↗

bioRxiv2023

Different Physical Parameters in the Bonds between Platelet Glycoprotein Ibalpha with von Willebrand factor and with Coagulant Factor XI -Results from the Molecular Dynamic Simulation-

BackgroundBoth von Willebrand factor (VWF) and coagulation factor XI (FXI) bind with platelet membrane glycoprotein (GP) Ib. However, the differences in the physical parameters in the bonds between VWF-GPIb and FXI-GPIb mediating different biological functions are unclear. MethodsThe FXI molecule was arranged in 9 different initial positions around the structure of GPIb bound to VWF. The position coordinate and velocity vectors of all atoms constructing VWF, GPIb, and FXI were calculated in each 2 femto (10-15) second using the Chemistry at HARvard Macromolecular Mechanics (CHARMM) force field. The physical parameters of VWF-GPIb and FXI-GPIb bonds were calculated by molecular dynamic (MD) simulations. ResultsMD calculation revealed 2.8 to 11.3 times greater positional fluctuations in atoms constructing FXI-GPIb as compared to those constructing VWF-GPIb (RMSDs: 5.9{+/-}1.5 to 18.1{+/-}7.9 [A] for FXI-GPIb vs 1.6{+/-}0.1 to 2.1{+/-}0.3 [A] for VWF-GPIb). The absolute value of non-covalent binding energy generated in FXI-GPIb (65.5{+/-}79.7 to 517.6{+/-}54.2 kcal/mol) was smaller than that generated in VWF-GPIb (678.5{+/-}58.3 to 1000.4{+/-}75.1 kcal/mol). The binding structure of VWF-GPIb was stable and was only minimally influenced by the presence of FXI-GPIb binding. ConclusionsOur MD calculation results revealed that atoms constructing the VWF-GPIb bond are physically more stable and produce more non-covalent binding energy than the bond of FXI-GPIb. The physical parameters in the VWF-GPIb bond were not largely influenced by FXI binding with GPIb.

bioengineering↗

bioRxiv2023

ncBAF, a chromatin remodeler, enhances PXR-mediated transcriptional activation in the human and mouse liver

Pregnane X receptor (PXR) is one of the key regulators of drug metabolism, gluconeogenesis, and lipid synthesis in the human liver. Activation of PXR by drugs such as rifampicin, simvastatin, and efavirenz causes adverse reactions such as drug{square}drug interaction, hyperglycemia, and dyslipidemia. The inhibition of PXR activation has merit in preventing such adverse events. Here, we demonstrated that bromodomain containing protein 9 (BRD9), a component of non-canonical brahma-related gene 1-associated factor (ncBAF), one of the chromatin remodelers, interacts with PXR. Rifampicin-mediated induction of CYP3A4 expression was attenuated by iBRD9, an inhibitor of BRD9, in human primary hepatocytes and CYP3A/PXR-humanized mice, indicating that BRD9 enhances the transcriptional activation of PXR in vitro and in vivo. Chromatin immunoprecipitation assay reveled that iBRD9 treatment resulted in attenuation of the rifampicin-mediated binding of PXR to the CYP3A4 promoter region, suggesting that ncBAF functions to facilitate the binding of PXR to its response elements. Efavirenz-induced hepatic lipid accumulation was attenuated by iBRD9 in C57BL/6J mice, suggesting that the inhibition of BRD9 would be useful to reduce the risk of efavirenz-induced hepatic steatosis. Collectively, we found that inhibitors of BRD9, a component of ncBAF that plays a role in assisting transactivation by PXR, would be useful to reduce the risk of PXR-mediated adverse reactions.

pharmacology and toxicology↗

bioRxiv2020

Receptor-linked environment-sensitive probe monitors the local membrane environment surrounding the insulin receptor

Functional membrane proteins in the plasma membrane are suggested to have specific membrane environments that play important roles to maintain and regulate the function of proteins. However, the local membrane environments of membrane proteins remain largely unexplored due to the lack of techniques allowing to monitor them in living cells. We have developed a method to probe the local membrane environment surrounding a membrane protein in the plasma membrane by covalently tethering a solvatochromic, environment-sensitive dye, Nile red, to a membrane protein via a flexible linker. Our direct imaging reported on the spatio-temporal properties of membrane fluidity of the local environment surrounding the insulin receptor. The local environment was distinct from the average plasma membrane fluidity and was quite dynamic and heterogeneous. Upon addition of insulin, the local membrane environment surrounding the receptor increased in fluidity in an insulin receptor-kinase dependent manner. This new technology should allow researchers to examine changes in membrane properties caused by receptor activation and devise ways to address the role of these changes in physiological processes.

cell biology↗