The importance of threonine-301 from cytochromes P-450 (laurate (ω-1)-hydroxylase and testosterone 16α-hydroxylase) in substrate binding as demonstrated by site-directed mutagenesis

AbstractThreonine-301 from rabbit liver cytochromes P-450 (laurate (ω-1)-hydroxylase and testosterone 16α-hydroxylase) has been replaced by histidine via site-directed mutagenesis. In the oxidized state the mutant P-450s exhibited typical low-spin type absorption spectra of P-450 and their reduced CO complexes showed a Soret peak at 450 nm. However, no spectral change was induced on addition of substrates for their wild-type counterparts. The mutant P-450s were also completely devoid of the hydroxylase activity. These findings suggest that threonine-301, which is highly conserved in P-450s and located at the distal heme surface, plays an important role in substrate binding

Roles of Foundation for Riverfront Improvement and Restoration to Promote Nature-Oriented River Management

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Bayesian Inference of Self-intention Attributed by Observer

Most of agents that learn policy for tasks with reinforcement learning (RL) lack the ability to communicate with people, which makes human-agent collaboration challenging. We believe that, in order for RL agents to comprehend utterances from human colleagues, RL agents must infer the mental states that people attribute to them because people sometimes infer an interlocutor's mental states and communicate on the basis of this mental inference. This paper proposes PublicSelf model, which is a model of a person who infers how the person's own behavior appears to their colleagues. We implemented the PublicSelf model for an RL agent in a simulated environment and examined the inference of the model by comparing it with people's judgment. The results showed that the agent's intention that people attributed to the agent's movement was correctly inferred by the model in scenes where people could find certain intentionality from the agent's behavior

Human RAD18 is involved in S phase-specific single-strand break repair without PCNA monoubiquitination

Switching from a replicative to a translesion polymerase is an important step to further continue on replication at the site of DNA lesion. Recently, RAD18 (a ubiquitin ligase) was shown to monoubiquitinate proliferating cell nuclear antigen (PCNA) in cooperation with RAD6 (a ubiquitin-conjugating enzyme) at the replication-stalled sites, causing the polymerase switch. Analyzing RAD18-knockout (RAD18−/−) cells generated from human HCT116 cells, in addition to the polymerase switch, we found a new function of RAD18 for S phase-specific DNA single-strand break repair (SSBR). Unlike the case with polymerase switching, PCNA monoubiquitination was not necessary for the SSBR. When compared with wild-type HCT116 cells, RAD18−/− cells, defective in the repair of X-ray-induced chromosomal aberrations, were significantly hypersensitive to X-ray-irradiation and also to the topoisomerase I inhibitor camptothecin (CPT) capable of inducing single-strand breaks but were not so sensitive to the topoisomerase II inhibitor etoposide capable of inducing double-strand breaks. However, such hypersensitivity to CPT observed with RAD18−/− cells was limited to only the S phase due to the absence of the RAD18 S phase-specific function. Furthermore, the defective SSBR observed in S phase of RAD18−/− cells was also demonstrated by alkaline comet assay

Three-dimensional analysis of trabecular bone structure of human vertebra in vivo using multi-detector row computed tomography -cross sectional and longitudinal studies-

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 2002～2005課題番号: 14570852研究代表者: 高田 政彦（滋賀医科大学・医学部・講師）研究分担者: 今井 晋二（滋賀医科大学・医学部・助教授

Extended x-ray absorption fine structure study on the cerium(IV)-induced DNA hydrolysis: Implication to the roles of 4f orbitals in the catalysis

At various Ce(IV)/DPP (DPP: diphenyl phosphate) molar ratios, the structure of Ce clusters in aqueous solutions was studied by extended x-ray absorption fine structure measurements. Although the Ce–Ce bond was strong in the absence of DPP, the corresponding signal was significantly reduced when the Ce(IV)/DPP molar ratio was 1. The result indicates the existence of a strong interaction between Ce(IV) ions and DPP, and suggests the formation of a Ce–DPP structure in solution. With an increase in the molar ratio, the signal of Ce–Ce bonds increased again, and exceeded that observed in the absence of DPP, suggesting the formation of a Ce–Ce–DPP structure. Ce(IV) ions in the complexes were found to have ~ 0.67 4f electrons. On the other hand, no measurable charge transfer was observed in the case of Ce(III) ions. These results demonstrate the role of the 4f orbital of Ce(IV) ions for its enormous activity for DNA hydrolysis