The movements of cytoplasmic dynein on microtubule (MT) tracks is achieved by two-way communication between the microtubule-binding domain (MTBD) and the ATPase domain via a coiled-coil stalk, but the structural basis of this communication remains elusive. Here, we regulate MTBD either in high-affinity or low-affinity states by introducing a disulfide bond to the stalk and analyze the resulting structures by NMR and cryo-EM. In the MT-unbound state, the affinity changes of MTBD are achieved by sliding of the stalk α-helix by a half-turn, which suggests that structural changes propagate from the ATPase-domain to MTBD. In addition, MT binding induces further sliding of the stalk α-helix even without the disulfide bond, suggesting how the MT-induced conformational changes propagate toward the ATPase domain. Based on differences in the MT-binding surface between the high-and lowaffinity states, we propose a potential mechanism for the directional bias of dynein movement on MT tracks.

The movements of cytoplasmic dynein on microtubule (MT) tracks is achieved by two-way communication between the microtubule-binding domain (MTBD) and the ATPase domain of dynein via an a-helical coiled-coil stalk, but the structural basis of this communication remains elusive. Here, we regulated MTBD either in high-affinity or low-affinity states by introducing a disulfide bond between the coiled-coils and analyzed the resulting structures by NMRand cryo-EM.In the MT-unbound state, the affinity changes of MTBD were achieved by sliding of the N-terminal α-helix by one half-turn, which suggests that structural changes propagate from the ATPase-domain to MTBD. In addition, cryo-EM analysis showed that MT binding induced further sliding of the N-terminal α-helix even without the disulfide bond, which suggests the MT-induced conformational changes propagate toward the ATPase domain. Based on differences in the MT-binding surface between the high-and low-affinity states, we propose a potential mechanism for the directional bias of dynein movement on MT tracks. Nishida et al.

Separation of the dispensing function and the prescribing function, Iyaku Bungyo, has been progressing in Japan. We are now witnessing the advent of a new society where patients select pharmacists and their satisfaction is recognized as one of the healthcare outcome indicators. It is necessary to clarify which factors aŠect patients' satisfaction with the services provided at community pharmacies and how they do so. A survey was conducted among 104 community pharmacies and their patients around the Tokyo metropolitan area in Japan. The questionnaire comprised 11 items (observed variables), each with aˆve-grade scale. With the transformed data-oriented pharmacy, the percentage of being not unsatisfactory was examined in two multivariate analyses of the relation and structure of patient satisfaction with a community pharmacy. Structural equation modeling (SEM) with factor analysis (FA) was performed using the observed variables and latent factors. Multiple regression analysis was performed with comprehensive satisfaction as an independent variable, examining the factors that aŠect comprehensive satisfaction with the pharmacy. The result of the FA indicated three latent factors of instruction on the use of drugs, quality of staŠ, and environment, based on which SEM model was constructed with a relatively high goodness ofˆt index. The result of multiple regression analyses indicated almost all variables such as satisfaction with reception by the pharmacist aŠected the comprehensive satisfaction, but privacy did not show a signiˆcant eŠect. These results, notably the relationship between each variables and latent factors, suggested the importance of higher skills of pharmacists, service qualities at pharmacies, and their functions adjusted to the community.

In an asbestos qualitative analysis, the major methods are X-ray diffraction analysis and visual observation by operators using a microscope. In particular, a major method of visual evaluation is dispersion staining. In the usual visual observation process, the operators check the asbestos fibers in the view of the microscope and count the number of asbestos fibers. The method presented here attempts to detect asbestos fibers in the images taken by a microscope. The dispersion staining method identifies asbestos fibers with color dispersion from an immersion liquid combined with polarization. The presented method employs color changes of asbestos fibers associated with polarization. Specifically, candidate asbestos fibers are identified using the changes of dispersion colors and also position-matching between two images. The performance of the method has been evaluated by comparing its results with the results obtained by a human expert.

We propose a boron–rhodamine-containing carboxylic acid (BRhoC) substance as a new sugar chemosensor. BRhoC was obtained by the Friedel–Crafts reaction of 4-formylbenzoic acid and N,N-dimethylphenylboronic acid, followed by chloranil oxidation. In an aqueous buffer solution at pH 7.4, BRhoC exhibited an absorption maximum (Absmax) at 621 nm. Its molar absorption coefficient at Absmax was calculated to be 1.4 × 105 M−1 cm−1, and it exhibited an emission maximum (Emmax) at 644 nm for the excitation at 621 nm. The quantum yield of BRhoC in CH3OH was calculated to be 0.16. The borinate group of BRhoC reacted with a diol moiety of sugar to form a cyclic ester, which induced a change in the absorbance and fluorescence spectra. An increase in the D-fructose (Fru) concentration resulted in the red shift of the Absmax (621 nm without sugar and 637 nm with 100 mM Fru) and Emmax (644 nm without sugar and 658 nm with 100 mM Fru) peaks. From the curve fitting of the plots of the fluorescence intensity ratio at 644 nm and 658 nm, the binding constants (K) were determined to be 2.3 × 102 M−1 and 3.1 M−1 for Fru and D-glucose, respectively. The sugar-binding ability and presence of a carboxyl group render BRhoC a suitable building block for the fabrication of highly advanced chemosensors.