Direct Addition of Amides to Glycals Enabled by Solvation-Insusceptible 2-Haloazolium Salt Catalysis

The direct 2‐deoxyglycosylation of nucleophiles with glycals leads to biologically and pharmacologically important 2‐deoxysugar compounds. Although the direct addition of hydroxyl and sulfonamide groups have been well developed, the direct 2‐deoxyglycosylation of amide groups has not been reported to date. Herein, we show the first direct 2‐deoxyglycosylation of amide groups using a newly designed Brønsted acid catalyst under mild conditions. Through mechanistic investigations, we discovered that the amide group can inhibit acid catalysts, and the inhibition has made the 2‐deoxyglycosylation reaction difficult. Diffusion‐ordered two‐dimensional NMR spectroscopy analysis implied that the 2‐chloroazolium salt catalyst was less likely to form aggregates with amides in comparison to other acid catalysts. The chlorine atom and the extended π‐scaffold of the catalyst played a crucial role for this phenomenon. This relative insusceptibility to inhibition by amides is more responsible for the catalytic activity than the strength of the acidity

Improved Electrochemical Performance of a GexS1-x Alloy Negative Electrode for Lithium-Ion Batteries

A GexSi1−x alloy electrode is useful for addressing the shortcomings of a Si negative electrode for lithium-ion batteries. To further improve the electrochemical performance of a GexSi1−x negative electrode, a film-forming additive and the formation of a composite with LaSi2 were applied. A Ge0.1Si0.9 electrode exhibited better cyclability in the additive-containing electrolyte with a discharge capacity of 1240 mA h g−1 at the 400th cycle. In addition, a Ge0.1Si0.9/LaSi2 composite electrode showed better cycle performance than a Ge0.1Si0.9 electrode

Influence of mechanical grinding on lithium insertion and extraction properties of iron silicide/silicon composites

We prepared composite electrodes of iron silicide/Si by using mechanical grinding for mixtures of ferrosilicon and Si followed by gas-deposition, and investigated their electrochemical properties as Li-ion battery anode. With increasing the mechanical grinding time, the phase transformation from FeSi to FeSi2 took place more significantly, and the composite electrode showed better cycle stabilities. There was no remarkable difference in mechanical properties and electronic conductivity between FeSi and FeSi2. On the other hand, the FeSi2 exhibited about three times larger capacities in comparison with the FeSi electrode. In addition, a result of our first principle calculation indicates that Li ion can diffuse more easily in FeSi2 lattice than in FeSi lattice. It is suggested that the better cyclability of the composite electrodes was attributed to the moderate reactivity of FeSi2 with Li and the smooth Li-ion diffusion in it

Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans

Removal of the fucose residue from the N-glycans of the Fc portion of immunoglobulin G (IgG) results in a dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC) through improved affinity for Fcγ receptor IIIa (FcγRIIIa). Here, we present the 2.2-Å structure of the complex formed between nonfucosylated IgG1-Fc and a soluble form of FcγRIIIa (sFcγRIIIa) with two N-glycosylation sites. The crystal structure shows that one of the two N-glycans of sFcγRIIIa mediates the interaction with nonfucosylated Fc, thereby stabilizing the complex. However, fucosylation of the Fc N-glycans inhibits this interaction, because of steric hindrance, and furthermore, negatively affects the dynamics of the receptor binding site. Our results offer a structural basis for improvement in ADCC of therapeutic antibodies by defucosylation

Neutrophil S100A9 supports M2 macrophage niche formation in granulomas

慢性炎症「肉芽腫」における好中球の新しい炎症制御系の解明 --M2マクロファージの新たな誘導メカニズム解明--. 京都大学プレスリリース. 2023-02-17.In search of inflammatory Achilles heel. 京都大学プレスリリース. 2023-03-10.Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPβ, which cooperatively activates the Cox-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Because the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 inhibitor, we propose the S100A9/Cox-2 axis as a major pathway driving M2 niche formation in granulomas

Speech organ contour extraction using real-time MRI and machine learning method

Chiba Institute of TechnologyChiba Institute of TechnologyChiba Institute of TechnologyChiba Institute of TechnologyKonan UniversityNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsReal-time MRI can be used to obtain videos that describe articulatory movements during running speech. For detailed analysis based on a large number of video frames, it is necessary to extract the contours of speech organs, such as the tongue, semi-automatically. The present study attempted to extract the contours of speech organs from videos using a machine learning method. First, an expert operator manually extracted the contours from the frames of a video to build training data sets. The learning operators, or learners, then extracted the contours from each frame of the video. Finally, the errors representing the geometrical distance between the extracted contours and the ground truth, which were the contours excluded from the training data sets, were examined. The results showed that the contours extracted using machine learning were closer to the ground truth than the contours traced by other expert and non-expert operators. In addition, using the same learners, the contours were extracted from other naive videos obtained during different speech tasks of the same subject. As a result, the errors in those videos were similar to those in the video in which the learners were trained

Hardware-Oriented Algorithm for Human Detection using GMM-MRCoHOG Features

In this research, we focus on Gaussian mixture model-multiresolution co-occurrence histograms of oriented gradients (GMM-MRCoHOG) features using luminance gradients in images and propose a hardware-oriented algorithm of GMM-MRCoHOG to implement it on a field programmable gate array (FPGA). The proposed method simplifies the calculation of luminance gradients, which is a high-cost operation in the conventional algorithm, by using lookup tables to reduce the circuit size. We also designed a human-detection digital architecture of the proposed algorithm for FPGA implementation using high-level synthesis. The verification results showed that the processing speed of the proposed architecture was approximately 123 times faster than that of the FPGA implementation of VGG-16.17th International Joint Conference on Computer Vision Theory and Applications (VISAPP 2022), February 6-8, 2022, Online Streamin

An Angiotensin II Type 1 Receptor Blocker Prevents Renal Injury via Inhibition of the Notch Pathway in Ins2 Akita Diabetic Mice

Recently, it has been reported that the Notch pathway is involved in the pathogenesis of diabetic nephropathy. In this study, we investigated the activation of the Notch pathway in Ins2 Akita diabetic mouse (Akita mouse) and the effects of telmisartan, an angiotensin II type1 receptor blocker, on the Notch pathway. The intracellular domain of Notch1 (ICN1) is proteolytically cleaved from the cell plasma membrane in the course of Notch activation. The expression of ICN1 and its ligand, Jagged1, were increased in the glomeruli of Akita mice, especially in the podocytes. Administration of telmisartan significantly ameliorated the expression of ICN1 and Jagged1. Telmisartan inhibited the angiotensin II-induced increased expression of transforming growth factor β and vascular endothelial growth factor A which could directly activate the Notch signaling pathway in cultured podocytes. Our results indicate that the telmisartan prevents diabetic nephropathy through the inhibition of the Notch pathway

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