18 research outputs found

    Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition

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    Ishikawa, T., Kitaura, Y., Kadota, Y. et al. Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition. Sci Rep 7, 39825 (2017). https://doi.org/10.1038/srep3982

    The Plasma Wave Experiment (PWE) on board the Arase (ERG) satellite

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    The Exploration of energization and Radiation in Geospace (ERG) project aims to study acceleration and loss mechanisms of relativistic electrons around the Earth. The Arase (ERG) satellite was launched on December 20, 2016, to explore in the heart of the Earth’s radiation belt. In the present paper, we introduce the specifications of the Plasma Wave Experiment (PWE) on board the Arase satellite. In the inner magnetosphere, plasma waves, such as the whistler-mode chorus, electromagnetic ion cyclotron wave, and magnetosonic wave, are expected to interact with particles over a wide energy range and contribute to high-energy particle loss and/or acceleration processes. Thermal plasma density is another key parameter because it controls the dispersion relation of plasma waves, which affects wave–particle interaction conditions and wave propagation characteristics. The DC electric field also plays an important role in controlling the global dynamics of the inner magnetosphere. The PWE, which consists of an orthogonal electric field sensor (WPT; wire probe antenna), a triaxial magnetic sensor (MSC; magnetic search coil), and receivers named electric field detector (EFD), waveform capture and onboard frequency analyzer (WFC/OFA), and high-frequency analyzer (HFA), was developed to measure the DC electric field and plasma waves in the inner magnetosphere. Using these sensors and receivers, the PWE covers a wide frequency range from DC to 10 MHz for electric fields and from a few Hz to 100 kHz for magnetic fields. We produce continuous ELF/VLF/HF range wave spectra and ELF range waveforms for 24 h each day. We also produce spectral matrices as continuous data for wave direction finding. In addition, we intermittently produce two types of waveform burst data, “chorus burst” and “EMIC burst.” We also input raw waveform data into the software-type wave–particle interaction analyzer (S-WPIA), which derives direct correlation between waves and particles. Finally, we introduce our PWE observation strategy and provide some initial results

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

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    「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

    Factors Associated with Reclosure of Posterior Capsule Aperture by Flat Opacifications with Pearls after Nd:YAG Laser Posterior Capsulotomy

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    In this retrospective case series, we investigated factors associated with posterior capsule aperture (PCA) reclosure following neodymium-yttrium aluminum garnet (Nd:YAG) laser posterior capsulotomy. The study encompassed patients who underwent cataract surgery with intraocular lens (IOL) implantation or a combined vitrectomy, cataract surgery, and IOL implantation between 2009 and 2022. PCA reclosure was observed in 22 eyes of 17 patients: 45% (10 eyes) underwent the triple procedure, and 55% (12 eyes) received cataract surgery with IOL implantation. In our clinic, 14% of patients were given IOLs with a 4% water content, while 73% (13 eyes) of those experiencing PCA reclosure had IOLs with a 4% water content. The mean interval between Nd:YAG capsulotomies was notably shorter than that between the initial cataract surgery and the first Nd:YAG laser capsulotomy. We also identified five stages of PCA reclosure progression. In conclusion, IOL water content may be linked to PCA reclosure, and the time to recurrence is shorter with each successive reclosure. Further research is needed to verify these findings and uncover additional contributing factors

    Design strategy for serine hydroxymethyltransferase probes based on retro-aldol-type reaction

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    Serine hydroxymethyltransferase (SHMT) is an enzyme that catalyzes the reaction that converts serine to glycine. It plays an important role in one-carbon metabolism. Recently, SHMT has been shown to be associated with various diseases. Therefore, SHMT has attracted attention as a biomarker and drug target. However, the development of molecular probes responsive to SHMT has not yet been realized. This is because SHMT catalyzes an essential yet simple reaction; thus, the substrates that can be accepted into the active site of SHMT are limited. Here, we focus on the SHMT-catalyzed retro-aldol reaction rather than the canonical serine–glycine conversion and succeed in developing fluorescent and 19F NMR molecular probes. Taking advantage of the facile and direct detection of SHMT, the devel- oped fluorescent probe is used in the high-throughput screening for human SHMT inhibitors, and two hit compounds are obtained
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