An Enantioselective Synthesis of 2-Imidazolidinones through Bifunctional Thiourea-Catalyzed Tandem Mannich/Cyclization of Isocyanatomalonate Diester

A chiral bifunctional thiourea-catalyzed Mannich reaction of diethyl 2-isocyanatomalonate with N-sulfonylimines was described. The tandem cyclization proceeded smoothly after Mannch reaction, directly furnishing chiral 2-imidazolidinones in 72‒99% yields with 83‒98% ees. Sterically demanding sulfonyl group was crucial for aliphatic imines to afford the corresponding product in high enantioselectivity

Identification of the basic amino acid residues on the PsbP protein involved in the electrostatic interaction with photosystem II

AbstractThe PsbP protein is an extrinsic subunit of photosystem II (PSII) that is essential for photoautotrophic growth in higher plants. Several crystal structures of PsbP have been reported, but the binding topology of PsbP in PSII has not yet been clarified. In this study, we report that the basic pocket of PsbP, which consists of conserved Arg48, Lys143, and Lys160, is important for the electrostatic interaction with the PSII complex. Our release-reconstitution experiment showed that the binding affinities of PsbP-R48A, -K143A, and -K160A mutated proteins to PSII were lower than that of PsbP-WT, and triple mutations of these residues greatly diminished the binding affinity to PSII. Even when maximum possible binding had occurred, the R48A, K143A, and K160A proteins showed a reduced ability to restore the rate of oxygen evolution at low chloride concentrations. Fourier transform infrared resonance (FTIR) difference spectroscopy results were consistent with the above finding, and suggested that these mutated proteins were not able to induce the normal conformational change around the Mn cluster during S1 to S2 transition. Finally, chemical cross-linking experiments suggested that the interaction between the N-terminus of PsbP with PsbE was inhibited by these mutations. These data suggest that the basic pocket of PsbP is important for proper association and interaction with PSII. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: Keys to Produce Clean Energy

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Liming and Phosphate Application Influence Soil Carbon and Nitrogen Mineralization Differently in Response to Temperature Regimes in Allophanic Andosols

Andosols are characterized by high organic matter content and play a significant role in carbon storage. However, they have low phosphorus fertility because of the high phosphate-fixing capacity of active aluminum. For agricultural use of Andosols, it is necessary to ameliorate its poor phosphorus fertility by applying lime and high doses of phosphate fertilizers. The objective of the present study was to clarify how such soil amendments affect the mineralization of soil organic carbon (C) and nitrogen (N) in allophanic Andosols under different temperature regimes. The soil was treated using combinations of liming and heavy phosphate application, followed by incubation under different temperature conditions. The N mineralization and the soil CO2 evolution rate were measured periodically. The patterns of N mineralization were analyzed by fitting them to first-order kinetics. Liming increased C and N mineralization irrespective of temperature, and the increase was further enhanced by phosphate application. Kinetic analysis of the N mineralization curve indicated lowering of the activation energy of N mineralization reactions with phosphate application, suggesting that P application may accelerate N mineralization at lower temperatures. These findings provide a basis for developing soil management strategies to reduce the loss of soil organic matter

Liming and Phosphate Application Influence Soil Carbon and Nitrogen Mineralization Differently in Response to Temperature Regimes in Allophanic Andosols

Andosols are characterized by high organic matter content and play a significant role in carbon storage. However, they have low phosphorus fertility because of the high phosphate-fixing capacity of active aluminum. For agricultural use of Andosols, it is necessary to ameliorate its poor phosphorus fertility by applying lime and high doses of phosphate fertilizers. The objective of the present study was to clarify how such soil amendments affect the mineralization of soil organic carbon (C) and nitrogen (N) in allophanic Andosols under different temperature regimes. The soil was treated using combinations of liming and heavy phosphate application, followed by incubation under different temperature conditions. The N mineralization and the soil CO2 evolution rate were measured periodically. The patterns of N mineralization were analyzed by fitting them to first-order kinetics. Liming increased C and N mineralization irrespective of temperature, and the increase was further enhanced by phosphate application. Kinetic analysis of the N mineralization curve indicated lowering of the activation energy of N mineralization reactions with phosphate application, suggesting that P application may accelerate N mineralization at lower temperatures. These findings provide a basis for developing soil management strategies to reduce the loss of soil organic matter

Excavation Report Chōja-Sukumozuka Kofun No. 1, Higashi-Hiroshima City, Hiroshima Prefecture (5th Campaign)

The Chōja-Sukumozuka mounded tomb group (kofun gun) is located in Saijō-chō (Saijō Basin), Higashi-Hiroshima City, Hiroshima Prefecture, Japan. It consists of three burial mounds, but one (No. 3) has disappeared. After the initial survey, the Laboratory of Archaeology at the Hiroshima University conducted an excavation of mounded tomb No. 1 in 2020 to determine the composition of ceramic funerary sculptures (haniwa) placed on the mounded tomb, the setup location and the date of the mound construction. The survey revealed cylindrical haniwa (entō haniwa) and pebbles at the burial mound no. 1. In addition, due to the date of the excavated cylindrical haniwa, it may be assumed that the mounded tomb was built in the middle to last third of 4th century AD. Considering the method of construction of the mounded tombs in the Saijō Basin, we can find that even chiefly mounded tombs, which had box-shaped stone coffins (hakogata sekkan) in 4th century AD, were the “mound last” type of mounded tombs (mound construction is carried out at the end) or the “concurrent progression” type of mounded tombs (construction as a result of repeated burial and backfill operations). The unearthed haniwa exhibit differences concerning size, clay, and the shape of protruding clay bands, and it is possible that this reflects the aesthetic and/or ideological differences among the manufacturer's groups. In addition, it is thought that this mounded tomb could easily attract people's attention owing to its location and panoramic views. From this point on one might infer ancient roads.本研究報告は『古墳時代の首長墓系列に関する地域研究』と題する科学研究費補助金（基盤研究（Ｃ）、課題番号19K01096〈研究代表者：野島 永〉）による調査研究成果の一部である