Analysis of intranuclear binding process of glucocorticoid receptor using fluorescence correlation spectroscopy

AbstractThe diffusion properties of EGFP-hGRα and mutants C421G, A458T and I566 in living cells were analyzed. The wild type and mutants C421G and A458T translocated from the cytoplasm to the nucleus after addition of Dex; however, the Brownian motions of the proteins were different. The diffusion constant of wild-type GRα after addition of Dex slowed to 15.6% of that in the absence of Dex, whereas those of A458T and C421G slowed to 34.8% and 61.7%, respectively. This is the first report that dimer formation is less important than the binding activity of GRα to GRE in the living cell

Pioneers in biomedical optics: special section honoring professor Frans F. Jobsis of Duke University.

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Self-Organized Rotating Filament Structure in Plasma in the Large Helical Device After Tracer Encapsulated Solid Pellet Injection

A small tungsten grain encapsulated in a polystyrene pellet was injected into plasmas in the large helical device. The ionized tungsten was transported and accumulated in the plasma center to drastically drop the central electron temperature. A tangentially viewing fast framing camera observed a bubble-like structure expanding from the plasma center after the pellet injection. After that, a self-organized filament appeared on the surface of the bubble, and the filament began to rotate around the plasma center, which was stably sustained for ∼0.22 s

99mTc generator using molybdenum nanoparticles

The version of record of this article, first published in Journal of Radioanalytical and Nuclear Chemistry, is available online at Publisher’s website: https://doi.org/10.1007/s10967-023-09173-

Typical atrial flutter with atypical flutter wave morphology due to abnormal interatrial conduction

We report a case of typical counterclockwise atrial flutter (AFL) with conduction block from right to left atrium along the coronary sinus (CS) musculature, confirmed by discontinuous CS activation sequence during pacing near the ostium and differential right atrial pacing. AFL was associated with an atypical flutter wave morphology, due to the detour of the activation wavefront from right to left atrium via alternate interatrial electrical connections, such as Bachmann’s bundle, the interatrial septum, or both. (Cardiol J 2011; 18, 4: 450–453

A new multi-tracer pellet injection for a simultaneous study of low- and mid/high-Z impurities in high-temperature plasmas

A new multi-tracer technique in the Tracer-Encapsulated Solid Pellet (TESPEL) method has been developed in order to acquire simultaneously the information about the behaviors of various impurities, i.e., to study concurrently the behaviors of low- and mid/high-Z impurities in magnetically confined high-temperature plasmas. In this new technique, an inorganic compound (for example, lithium titanate, Li2TiO3) is proposed to be used as a tracer embedded in the core of the TESPEL, instead of pure elements. The results of the proof-of-principle experiment clearly demonstrate the applicability of the new multi-tracer technique in the TESPEL method for the simultaneous study of behaviors of low- and mid/high-Z impurities in high-temperature plasmas

Revisiting PFA-mediated tissue fixation chemistry: FixEL enables trapping of small molecules in the brain to visualize their distribution changes

ホルマリン漬けから着想した小分子可視化法 --医薬品開発効率化につながる新たな戦略--. 京都大学プレスリリース. 2022-12-05.Various small molecules have been used as functional probes for tissue imaging in medical diagnosis and pharmaceutical drugs for disease treatment. The spatial distribution, target selectivity, and diffusion/excretion kinetics of small molecules in structurally complicated specimens are critical for function. However, robust methods for precisely evaluating these parameters in the brain have been limited. Herein, we report a new method termed “fixation-driven chemical cross-linking of exogenous ligands (FixEL), ” which traps and images exogenously administered molecules of interest (MOIs) in complex tissues. This method relies on protein-MOI interactions and chemical cross-linking of amine-tethered MOI with paraformaldehyde used for perfusion fixation. FixEL is used to obtain images of the distribution of the small molecules, which addresses selective/nonselective binding to proteins, time-dependent localization changes, and diffusion/retention kinetics of MOIs such as the scaffold of PET tracer derivatives or drug-like small molecules

Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains

生きた動物脳内で発現する神経伝達物質受容体に目印を付ける新手法を開発 --遺伝子操作を伴わず、生体内でたんぱく質の機能解析が可能に--. 京都大学プレスリリース. 2024-02-05.Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because the spatiotemporal expression profiles and dynamics of neurotransmitter receptors involved in many functions are delicately governed in the brain, in vivo research tools with high spatiotemporal resolution for receptors in intact brains are highly desirable. Covalent labeling by chemical reaction (chemical labeling) of proteins without genetic manipulation is now a powerful method for analyzing receptors in vitro. However, selective target receptor labeling in the brain has not yet been achieved. This study shows that ligand-directed alkoxyacylimidazole (LDAI) chemistry can be used to selectively tether synthetic probes to target endogenous receptors in living mouse brains. The reactive LDAI reagents with negative charges were found to diffuse well over the whole brain and could selectively label target endogenous receptors, including AMPAR, NMDAR, mGlu1, and GABAAR. This simple and robust labeling protocol was then used for various applications: three-dimensional spatial mapping of endogenous receptors in the brains of healthy and disease-model mice; multi-color receptor imaging; and pulse–chase analysis of the receptor dynamics in postnatal mouse brains. Here, results demonstrated that bioorthogonal receptor modification in living animal brains may provide innovative molecular tools that contribute to the in-depth understanding of complicated brain functions