293 research outputs found

    Leucine-Rich Repeat Containing Protein LRRC8A Is Essential for Swelling-Activated Cl\u3csup\u3e−\u3c/sup\u3e Currents and Embryonic Development in Zebrafish

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    Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. A volume-regulated anion channel (VRAC) has been electrophysiologically characterized in innumerable mammalian cell types. VRAC is activated by cell swelling and mediates the volume regulatory efflux of Cl− and small organic solutes from cells. Two groups recently identified the mammalian leucine-rich repeat containing protein LRRC8A as an essential VRAC component. LRRC8A must be coexpressed with at least one of the other four members of this gene family, LRRC8B-E, to reconstitute VRAC activity in LRRC8−/− cells. LRRC8 genes likely arose with the origin of chordates. We identified LRRC8A and LRRC8C-E orthologs in the zebrafish genome and demonstrate that zebrafish embryo cells and differentiated adult cell types express a swelling-activated Cl− current indistinguishable from mammalian VRAC currents. Embryo cell VRAC currents are virtually eliminated by morpholino knockdown of the zebrafish LRRC8A ortholog lrrc8aa. VRAC activity is fully reconstituted in LRRC8−/− human cells by coexpression of zebrafish lrrc8aa and human LRRC8C cDNAs. lrrc8aa expression varies during zebrafish embryogenesis and lrrc8aa knockdown causes pericardial edema and defects in trunk elongation and somatogenesis. Our studies provide confirmation of the importance of LRRC8A in VRAC activity and establish the zebrafish as a model system for characterizing the molecular regulation and physiological roles of VRAC and LRRC8 proteins

    High-speed metasurface modulator using critically coupled bimodal plasmonic resonance

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    Free-space electro-optic (EO) modulators operating at gigahertz and beyond are attractive for a wide range of emerging applications, including high-speed imaging, free-space optical communication, microwave photonics, and diffractive computing. Here we experimentally demonstrate a high-speed plasmonic metasurface EO modulator operating at a near-infrared wavelength range with a gigahertz modulation bandwidth. To achieve efficient intensity modulation of reflected light from an ultrathin metasurface layer, we utilize the bimodal plasmonic resonance inside a subwavelength metal-insulator-metal grating, which is precisely tuned to satisfy the critical coupling condition. As a result, perfect absorption of -27 dB (99.8%) and a high quality (Q) factor of 113 are obtained at a resonant wavelength of 1650 nm. By incorporating an EO polymer inside the grating, we achieve a modulation depth of up to 9.5 dB under an applied voltage of ±\pm30 V. The 3-dB modulation bandwidth is confirmed to be 1.25 GHz, which is primarily limited by the undesired contact resistance. Owing to the high electrical conductivity of metallic gratings and a compact device structure with a minimal parasitic capacitance, the demonstrated device can potentially operate at several tens of gigahertz, which opens up exciting opportunities for ultrahigh-speed active metasurface devices in various applications.Comment: Main text: 18 pages, 3 figures, 39 references Supplementary material: 3 pages, 2 figures

    New coronary aneurysm formation and malapposition after zotarolimus-eluting stent implantation in Kawasaki disease

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    AbstractCoronary artery involvement is the most important complication of Kawasaki disease. Coronary artery bypass surgery has been performed for ischemic heart disease caused by Kawasaki disease, however, long-term coronary graft patency is not satisfactory. Therefore, percutaneous coronary intervention (PCI) has its role in Kawasaki disease-related coronary artery disease. The incidence of new aneurysm is lower following stent implantation than balloon dilatation alone, even if a higher balloon pressure is applied. However, there are few reports about the efficacy of drug-eluting stent implantation for Kawasaki disease with coronary artery disease. Here, we describe a case of new coronary aneurysm formation and malapposition after zotarolimus-eluting stent implantation in Kawasaki disease.<Learning objective: New aneurysm formation after balloon angioplasty for coronary artery lesions in Kawasaki disease is a relatively well-known phenomenon, however there have been no reports about the influence of drug-eluting stents for coronary artery disease with Kawasaki disease. This report is useful when we consider strategies of revascularization for coronary artery disease with Kawasaki disease.

    Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-κB activation

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    BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL). HTLV-1 encoded Tax1 oncoprotein activates the transcription of genes involved in cell growth and anti-apoptosis through the NF-κB pathway, and is thought to play a critical role in the pathogenesis of ATL. While Tax1 expression is usually lost or minimal in ATL cells, these cells still show high constitutive NF-κB activity, indicating that genetic or epigenetic changes in ATL cells induce activation independent of Tax1. The aim of this study was to identify the molecules responsible for the constitutive activation of NF-κB in ATL cells using a retroviral functional cloning strategy. RESULTS: Using enhanced green fluorescent protein (EGFP) expression and blasticidin-resistance as selection markers, several retroviral cDNA clones exhibiting constitutive NF-κB activity in Rat-1 cells, including full-length CD30, were obtained from an ATL cell line. Exogenous stable expression of CD30 in Rat-1 cells constitutively activated NF-κB. Elevated expression of CD30 was identified in all ATL lines examined, and primary ATL cells from a small number of patients (8 out of 66 cases). CONCLUSION: Elevated CD30 expression is considered one of the causes of constitutive NF-κB activation in ATL cells, and may be involved in ATL development

    Trained innate lymphoid cells in allergic diseases

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    Group 2 innate lymphoid cells (ILC2s) reside in peripheral tissues such as the lungs, skin, nasal cavity, and gut and provoke innate type 2 immunity against allergen exposure, parasitic worm infection, and respiratory virus infection by producing TH2 cytokines. Recent advances in understanding ILC2 biology revealed that ILC2s can be trained by IL-33 or allergic inflammation, are long-lived, and mount memorylike type 2 immune responses to any other allergens afterwards. In contrast, IL-33, together with retinoic acid, induces IL-10-producing immunosuppressive ILC2s. In this review, we discuss how the allergic cytokine milieu and other immune cells direct the generation of trained ILC2s with immunostimulatory or immunosuppressive recall capability in allergic diseases and infections associated with type 2 immunity. The molecular mechanisms of trained immunity by ILCs and the physiological relevance of trained ILC2s are also discussed

    High Human T Cell Leukemia Virus Type-1(HTLV-1) Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders

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    <p>Abstract</p> <p>Background</p> <p>To address the clinical and virological significance of a high HTLV-1 proviral load (VL) in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR) quantification (infected cell % of peripheral mononuclear cells) and Southern blotting hybridization (SBH) methods.</p> <p>Results</p> <p>The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2%) of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells). In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL.</p> <p>Conclusion</p> <p>The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by step.</p

    Carbon(sp2)-carbon(sp3) Bond-forming Cross-coupling Reactions Using Sulfur-Modified Au-Supported Nickel Nanoparticle Catalyst

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    We report a carbon(sp2)-carbon(sp3) bond-forming cross-coupling reactions by employing a nano-size nickel catalyst supported on sulfur-modified gold (SANi). This transformation demonstrates an efficient synthesis of functionalized aryl compounds, including heterocycles. Notably, the reactions proceeded in good yields with significantly low leaching of nickel from SANi. Moreover, SANi could be recycled several times without significant loss of catalytic activity.This is the peer reviewed version of the following article: Ohta R., Shio Y., Akiyama T., et al. Carbon(sp2)-carbon(sp3) Bond-forming Cross-coupling Reactions Using Sulfur-Modified Au-Supported Nickel Nanoparticle Catalyst. Asian Journal of Organic Chemistry, which has been published in final form at https://doi.org/10.1002/ajoc.202200229. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited
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