Synthesis and photochemical reactivity of caged glutamates with a π-​extended coumarin chromophore as a photolabile protecting group

International audience'Caging' and 'uncaging' bioactive substrates are key techniques in studying a wide variety of biological processes. In the present study, two-types of novel caged glutamates with a two-photon absorption (TPA) core, that is, π-extended coumarin, were synthesized and their photochemical release of glutamate was analyzed. The high yields of glutamate (>92%) were observed in the photolysis of compounds 1 and 10, respectively

On-Orbit Demonstration of Innovative Multifunctional Membrane Structure for Ultra-Lightweight Solar Arrays and Array Antennas by 3U CubeSat OrigamiSat-1

The 3U CubeSat OrigamiSat-1’s deployable membrane structure is 1m-by-1m in size after deployment and is stowed in less than 1U CubeSat (10cm-by-10cm-by-8cm), including a hold-and-release mechanism. The major significance of the structural concept is that it allows the attachment of thin-film devices, such as thin-film solar cells or flexible substrates for antennas throughout the membrane. This was achieved by two features: (i) use of textile and (ii) invention of hybrid boom made of tubular carbon composite and metal convex tape. In addition, a visual membrane measurement system consisting of stereo cameras was developed. This paper describes the new technologies developed for this CubeSat

ADAMTS13 gene deletion enhances plasma high-mobility group box1 elevation and neuroinflammation in brain ischemia-reperfusion injury

Highly adhesive glycoprotein von Willebrand factor (VWF) multimer induces platelet aggregation and leukocyte tethering or extravasation on the injured vascular wall, contributing to microvascular plugging and inflammation in brain ischemia-reperfusion. A disintegrin and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) cleaves the VWF multimer strand and reduces its prothrombotic and proinflammatory functions. Although ADAMTS13 deficiency is known to amplify post-ischemic cerebral hypoperfusion, there is no report available on the effect of ADAMTS13 on inflammation after brain ischemia. We investigated if ADAMTS13 deficiency intensifies the increase of extracellular HMGB1, a hallmark of post-stroke inflammation, and exacerbates brain injury after ischemia-reperfusion. ADAMTS13 gene knockout (KO) and wild-type (WT) mice were subjected to 30-min middle cerebral artery occlusion (MCAO) and 23.5-h reperfusion under continuous monitoring of regional cerebral blood flow (rCBF). The infarct volume, plasma high-mobility group box1 (HMGB1) level, and immunoreactivity of the ischemic cerebral cortical tissue (double immunofluorescent labeling) against HMGB1/NeuN (neuron-specific nuclear protein) or HMGB1/MPO (myeloperoxidase) were estimated 24h after MCAO. ADAMTS13KO mice had larger brain infarcts compared with WT 24h after MCAO (p<0.05). The rCBF during reperfusion decreased more in ADAMTS13KO mice. The plasma HMGB1 increased more in ADAMTS13KO mice than in WT after ischemia-reperfusion (p<0.05). Brain ischemia induced more prominent activation of inflammatory cells co-expressing HMGB1 and MPO and more marked neuronal death in the cortical ischemic penumbra of ADAMTS13KO mice. ADAMTS13 deficiency may enhance systemic and brain inflammation associated with HMGB1 neurotoxicity, and aggravate brain damage in mice after brief focal ischemia. We hypothesize that ADAMTS13 protects brain from ischemia-reperfusion injury by regulating VWF-dependent inflammation as well as microvascular pluggin

ｶｴﾙ心臓八木式灌流法の定量的実験への改良 ―心拍出量測定から心電図同時記録まで―

伝統的な生理学実習項目の一つであるｶｴﾙ心臓の八木式灌流実験法に改良を加え､心室拍動をより定量的に観察記録できるようにした｡すなわち､収縮･拡張ｻｲｸﾙ中の心室の容積変化を気圧変化に変換して捉える簡便な装置(連通標本槽)を考案し､圧変化を拍出量の指標として連続描記できるようにした｡連通標本槽は心室を浸す槽と圧変化を発生する気密な槽とを連結したものである｡この方法により､前負荷の増減に適応する心拍出量の増減､すなわちﾌﾗﾝｸ･ｽﾀｰﾘﾝｸﾞ機構を明確に示すことができる｡また､大動脈内静水圧を増加させる装置を考案した｡これを用いることにより､後負荷増加に対応する心室拍動動態のﾕﾆｰｸな変化を観察できる｡さらに､この実験系における心電図の安定した記録法を考案した｡これにより心臓の機械的活動と電気的活動とを同時に対応させることができる｡われわれの新しい実験方法は､学生実習において学生に心臓の生理学･薬理学的性質を学ばせるために大変有用であろう｡The Yagi\u27s perfusion system has widely been used to study the beats of excised frog heart. Here, we describe a new method to obtain a measure of cardiac output of the frog heart perfused with the Yagi\u27s system. In the new method, the changes in ventricular volume during systole and diastole are converted to the changes in air pressure by using the communicating vessel chamber in which the tissue chamber bathing the ventricle is connected via a communicating tube to the air-tight chamber for pressure detection. With this method, the Frank-Starling mechanism associated with the changes in preload is clearly demonstrable. With an additional apparatus to increase the hydrostatic pressure within the aorta, it is possible to show the unique changes in ventricular dynamics accompanying the increases in afterload. In addition, a method to stably record the ECG simultaneously with the above measurement is described. Our new methods may be useful for the student practice in which students should learn the physiological as well as pharmacological properties of heart

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

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

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (–OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss

Development of miscibility improved oil for R32

R32 has been widely applied as an air-conditioner refrigerant. It is known that R32 is inferior to other refrigerants such as HFC and HFO in the miscibility with refrigeration oils. In addition, when R32　dissolves in refrigeration oils, the kinematic viscosity of the oils reduces remarkably. So it is difficult to improve the miscibility of refrigeration oil while suppressing the kinematic viscosity decrease of the oil when R32 dissolves in. Various investigations have revealed that the formulation of a new base material in POE improves the miscibility with R32 without decreasing the kinematic viscosity of the oil when R32 dissolves in. By using this technology, we have developed new refrigerating oils whose phase separation temperatures were -20 degree C or less under R32 atmosphere. In addition, the kinematic viscosities of the new oils when R32 dissolves in were equal to or greater than those of POE currently used for R410A.These new refrigerating oils are expected to be developed in a large model in which oil returnability is important in a refrigeration system. In this study, we will report the method and various characteristics under HFOs