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Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses

Cellular & Molecular Immunology 2021年第6期18卷 1463-1475页

作者： Ryan AAdams Cátia Fernandes-Cerqueira Antonella Notarnicola Elisabeth Mertsching Zhiwen Xu Wing-Sze Lo Kathleen Ogilvie Kyle PChiang Jeanette Ampudia Sanna Rosengren Andrea Cubitt david jking John DMendlein Xiang-Lei Yang Leslie ANangle Ingrid ELundberg Per-Johan Jakobsson Paul Schimmel aTyr Pharma 3545 John Hopkins CourtSuite 250San DiegoCA92121USA Division of Rheumatology Department of MedicineSolnaKarolinska InstitutetKarolinska University HospitalSE-17176StockholmSweden IAS HKUST-Scripps R&D Laboratory Institute for Advanced StudyHong Kong University of Science and Technologyand Pangu BiopharmaHong KongChina The Scripps Laboratories for tRNA Synthetase Research 10650 North Torrey Pines RoadLa JollaCA92037USA The Scripps Laboratories for tRNA Synthetase Research Scripps Florida130 Scripps WayJupiterFL33458USA

His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4+ and CD8+ T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome.

关键词： Immunology Autoimmunity Synthetase tRNA HARS

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Developing multifunctional crops by engineering Brassicaceae glucosinolate pathways

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Plant Communications 2023年第4期4卷 30-57页

作者： Han Qin Graham jking Priyakshee Borpatragohain Jun Zou National Key Laboratory of Crop Genetic Improvement College of Plant Science and TechnologyHuazhong Agricultural UniversityWuhanChina Southern Cross Plant Science Southern Cross UniversityLismoreNSWAustralia

Glucosinolates(GSLs),found mainly in species of the Brassicaceae family,are one of the most well-studied classes of secondary *** by the action of myrosinase on GSLs,GSL-derived hydrolysis products(GHPs)primarily defend against biotic stress in *** also significantly affect the quality of crop products,with a subset of GHPs contributing unique food flavors and multiple therapeutic benefits or causing disagreeable food odors and health ***,we explore the potential of these bioactive functions,which could be exploited for future sustainable *** first summarize our accumulated understanding of GSL diversity and distribution across representative Brassicaceae *** then systematically discuss and evaluate the potential of exploited and unutilized genes involved in GSL biosynthesis,transport,and hydrolysis as candidate GSL engineering *** from available information on GSL and GHP functions,we explore options for multifunctional Brassicaceae crop ideotypes to meet future demand for food diversification and sustainable crop *** integrated roadmap is subsequently proposed to guide ideotype development,in which maximization of beneficial effects and minimization of detrimental effects of GHPs could be combined and associated with various end *** on several use-case examples,we discuss advantages and limitations of available biotechnological approaches that may contribute to effective deployment and could provide novel insights for optimization of future GSL engineering.

关键词： glucosinolate glucosinolate hydrolysis product metabolic engineering Brassicaceae multifunctional crop ideotype

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Exmouth海底高原(澳大利亚西北大陆架)由热源桂泄漏形成的天然气水合物系统

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海洋地质 2019年第2期35卷 1-29页

作者： Matteo Paganoni James jking Martino Foschi 蔡庆芳(翻译) 王显莹(校对) 不详广州海洋地质调查局

沉积盆地天然气水合物和浅层游离气的识别对于理解浅层岩石圈中的有机碳循环动力学机制,以及与研究商业油气田开发相关的地质灾害研究至关重要。在这项研究中,我们首次报告了在澳大利亚大陆边缘Exmouth海底高原(澳大利亚西北大陆架)可... 详细信息

沉积盆地天然气水合物和浅层游离气的识别对于理解浅层岩石圈中的有机碳循环动力学机制,以及与研究商业油气田开发相关的地质灾害研究至关重要。在这项研究中,我们首次报告了在澳大利亚大陆边缘Exmouth海底高原(澳大利亚西北大陆架)可能存在天然气水合物系统的证据。通过ODP和工业钻井标定的高品质三维地震数据,我们发现了一系列浅部强振幅异常现象,包括似海底反射(BSR),并将其解释为在天然气水合物稳定底界之下的游离气体富集以及上覆高饱和水合物或自生碳酸盐层的地震学表示。天然气水合物储层是由新近纪和第四纪的细粒钙质超微化石和有孔虫软泥构成,浅层游离气和水合物的斑片状分布,是深层储层热成因气泄漏的结果,并反映了深层断块的几何结构。水合物气源自热成因的证据如下:(1)在研究区域晚三叠世储层中已发现多个热成因气藏;(2)表土之下,地震资料显示存在跨层和沿层的气体迁移现象;(3)深层储层与浅层天然气水合物体系之间存在游离气体富集;(4)地球化学和岩性证据表明,该区不存在有利于浅层微生物气生成的条件。为了验证本文提出的解释和假设,有必要通过在地震观测到的振幅异常区中获取井下测井资料和样本数据。

关键词：天然气水合物游离气体热成因气天然气储层 BSR 振幅异常流体活动

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