Derivation of the small-angle scattering profile of a target biomacromolecule from a profile deteriorated by aggregates. AUC–SAS

Aggregates cause a fatal problem in the structural analysis of a biomacromolecule in solution using small-angle X-ray or neutron scattering (SAS): they deteriorate the scattering profile of the target molecule and lead to an incorrect structure. Recently, an integrated method of analytical ultracentrifugation (AUC) and SAS, abbreviated AUC–SAS, was developed as a new approach to overcome this problem. However, the original version of AUC–SAS does not offer a correct scattering profile of the target molecule when the weight fraction of aggregates is higher than ca 10%. In this study, the obstacle point in the original AUC–SAS approach is identified. The improved AUC–SAS method is then applicable to a solution with a relatively larger weight fraction of aggregates (≤20%)

Solution structure of multi-domain protein ER-60 studied by aggregation-free SAXS and coarse-grained-MD simulation

Multi-domain proteins (MDPs) show a variety of domain conformations under physiological conditions, regulating their functions through such conformational changes. One of the typical MDPs, ER-60 which is a protein folding enzyme, has a U-shape with four domains and is thought to have different domain conformations in solution depending on the redox state at the active centres of the edge domains. In this work, an aggregation-free small-angle X-ray scattering revealed that the structures of oxidized and reduced ER-60 in solution are different from each other and are also different from those in the crystal. Furthermore, structural modelling with coarse-grained molecular dynamics simulation indicated that the distance between the two edge domains of oxidized ER-60 is longer than that of reduced ER-60. In addition, one of the edge domains has a more flexible conformation than the other

元代蒙漢合璧命令文の研究(二)

「内陸アジア言語の研究」第6号 (Studies on the Inner Asian Languages

元代蒙漢合璧命令文の研究(一)

「内陸アジア言語の研究」第5号 (Studies on the Inner Asian Languages

Histone variant H2A.B-H2B dimers are spontaneously exchanged with canonical H2A-H2B in the nucleosome

精子形成に重要なヒストンによるDNAの新たな折りたたみを解明. 京都大学プレスリリース. 2021-02-22.H2A.B is an evolutionarily distant histone H2A variant that accumulates on DNA repair sites, DNA replication sites, and actively transcribing regions in genomes. In cells, H2A.B exchanges rapidly in chromatin, but the mechanism has remained enigmatic. In the present study, we found that the H2A.B-H2B dimer incorporated within the nucleosome exchanges with the canonical H2A-H2B dimer without assistance from additional factors, such as histone chaperones and nucleosome remodelers. High-speed atomic force microscopy revealed that the H2A.B nucleosome, but not the canonical H2A nucleosome, transiently forms an intermediate “open conformation”, in which two H2A.B-H2B dimers may be detached from the H3-H4 tetramer and bind to the DNA regions near the entry/exit sites. Mutational analyses revealed that the H2A.B C-terminal region is responsible for the adoption of the open conformation and the H2A.B-H2B exchange in the nucleosome. These findings provide mechanistic insights into the histone exchange of the H2A.B nucleosome

Application of Compound Action Potential of Facial Muscles Evoked by Transcranial Stimulation as a Reference Waveform of Motor-evoked Potential in Spinal Surgery

Transcranial electrical stimulation motor-evoked potential (TES-MEP) has been widely used to monitor major motor pathways in cranial and spinal surgeries. However, the results of TES-MEP might be strongly influenced by anesthetic agents and muscle relaxants. To compensate for this effect, a technique using compound muscle action potentials of the abductor pollicis brevis (APB-CMAP) evoked by median nerve stimulation has recently been reported. In this article, we adopted the transcranial electrical stimulation motor-evoked potential of facial muscles (TES-FMEP) instead of APB-CMAP as a reference waveform for compensation. Intraoperative monitoring in spinal surgeries using TES-MEP, TES-FMEP and APB-CMAP was performed in 64 patients. We compared with and without compensation methods using TES-FMEP and APB-CMAP to evaluate TES-MEP. The cases which demonstrated postoperative motor disturbance, including transient symptoms, were judged to be positive cases. Postoperative transient paraplegia was shown in one intramedullary tumor case among those 64 cases. Compensation by TES-FMEP exhibited t he highest specificity (90.5%) and lowest false-positive rate (9.5%) among the three compensation modalities when evaluated at 80% amplitude decrease. TES-FMEP, being derived from motor cortex stimulation, is not influenced by the original spinal lesion or surgical manipulation of the spine. Therefore, compensation using TES-FMEP is suitable for intraoperative monitoring during spinal surgery. The authors advocate TES-FMEP as a reference waveform for the compensation of intraoperative TES-MEP

Eosinophilic myocarditis without hypereosinophilia accompanied by giant cell infiltration

AbstractA 53-year-old woman with a history of allergic disease was admitted to our hospital because of syncope induced by sustained ventricular tachycardia. The clinical course and the laboratory data did not correspond to those of acute myocarditis. Although eosinophils in the peripheral blood count were not increased, the diagnosis of eosinophilic myocarditis was made following a right ventricular endomyocardial biopsy that showed a remarkable infiltration of eosinophils. While giant cells were another histopathological feature of this case, they were considered to be an expression of the disease severity. This is a rare case of eosinophilic myocarditis, without peripheral eosinophilia.<Learning objective: Eosinophils in the peripheral blood usually increase in eosinophilic myocarditis. We describe a case of eosinophilic myocarditis without hypereosinophilia. Even in the absence of hypereosinophilia, endomyocardial biopsy should be performed during the investigation of unexplained myocardial disease.