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National Science Review 2022年第1期9卷 47-55页

作者： Xiaopeng Wan Jiqing Li Yupeng Wang Xiaofei Yu Xijun He Jianzhong Shi Guohua Deng Xianying Zeng Guobin Tian Yanbing Li Yongping Jiang Yuntao Guan Chengjun Li Feng Shao Hualan Chen State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences National Institute of Biological Sciences

The H7 N9 influenza virus emerged in China in 2013,causing more than 1560 human infections,39% of which were fatal.A ’cytokine storm’ in the lungs of H7 N9 patients has been linked to a poor prognosis and death;however,the underlying mechanism that triggers the cytokine storm is unknown.Here,we found that efficient replication of the H7 N9 virus in mouse lungs activates gasdermin E(GSDME)-mediated pyroptosis in alveolar epithelial cells,and that the released cytosolic contents then trigger a cytokine storm.Knockout of Gsdme switched the manner of death of A549 and human primary alveolar epithelial cells from pyroptosis to apoptosis upon H7 N9 virus infection,and Gsdme knockout mice survived H7 N9 virus lethal infection.Our findings reveal that GSDME activation is a key and unique mechanism for the pulmonary cytokine storm and lethal outcome of H7 N9 virus infection and thus opens a new door for the development of antivirals against the H7 N9 virus.

关键词： H7N9 virus cytokine storm gasdermin E pyroptosis

Animal models in the study of Alzheimer's disease and Parkinson's disease:A historical perspective

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Animal Models and Experimental Medicine 2022年第1期5卷 27-37页

作者： Rajashree Banerjee Arushi Rai Shreyas M.Iyer Sonia Narwal Meghana Tare Department of biological sciences Birla Institute of Technology and SciencePilaniIndia

Alzheimer's disease and Parkinson's disease are two of the most prevalent and disabling neurodegenerative diseases globally.Both are proteinopathic conditions and while occasionally inherited,are largely sporadic in nature.Although the advances in our understanding of the two have been significant,they are far from complete and neither diagnosis nor the current practices in treatment and rehabilitation is adequately helpful.Animal models have historically found application as testing beds for novel therapeutics and continue to be valuable aids in pharmacological research.This review chronicles the development of those models in the context of Alzheimer's and Parkinson's disease,and highlights the shifting paradigms in studying two humanspecific conditions in non-human organisms.

关键词： Alzheimer's disease animal models neurodegeneration Parkinson's disease

The diversity of adult lung epithelial stem cells and their niche in homeostasis and regeneration

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Science China(Life sciences) 2021年第12期64卷 2045-2059页

作者： Yanxiao Wang Nan Tang National Institute of Biological Sciences Beijing 102206China

The adult lung,a workhorse for gas exchange,is continually subjected to a barrage of assaults from the inhaled particles and pathogens.Hence,homeostatic maintenance is of paramount importance.Epithelial stem cells interact with their particular niche in the adult lung to orchestrate both natural tissue rejuvenation and robust post-injury regeneration.Advances in single-cell sequencing,lineage tracing,and living tissue imaging have deepened our understanding about stem cell heterogeneities,transition states,and specific cell lineage markers.In this review,we provided an overview of the known stem/progenitor cells and their subpopulations in different regions of the adult lung,and explored the regulatory networks in stem cells and their respective niche which collectively coordinated stem cell quiescence and regeneration states.We finally discussed relationships between dysregulated stem cell function and lung disease.

关键词： lung stem cell regeneration niche

Lantana camara——an Ecological Bioindicator Plant for Decontamination of Pb-Impaired Soil Under Organic Waste-Supplemented Scenarios

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Pedosphere 2019年第2期29卷 248-258页

作者： Frank Ogenna ALARIBE Pariatamby AGAMUTHU Institute of Biological Sciences University of Malaya

Heavy metal extraction and processing from ores releases elements into the environment. Soil, being an "unfortunate" sink, has its bionomics impaired and affected by metal pollution. Metals sneak into the food chain and pose risk to humans and other edaphicdependent organisms. For decontamination, the use of an ecosystem-friendly approach involving plants is known as phytoremediation.In this study, different lead(Pb) concentrations(80, 40, 20, and 10 mg kg^(-1)) were used to contaminate a well-characterized soil,(un)supplemented with organic waste empty fruit bunch(EFB) or spent mushroom compost(SMC), with non-edible plant—Lantana camara. Lead removal by L. camara ranged from 45.51% to 88.03% for supplemented soil, and from 23.7% to 57.8% for unsupplemented soil(P < 0.05). The EFB-supplemented and L. camara-remediated soil showed the highest counts of heavy metal-resistant bacteria(HMRB)(79.67 × 10~6–56.0 × 10~6 colony forming units(CFU) g^(-1) soil), followed by SMC-supplemented and L. camara-remediated soil(63.33 × 10~6–39.0 × 10~6 CFU g^(-1) soil). Aerial metal uptake ranged from 32.08 ± 0.8 to 5.03 ± 0.08 mg kg^(-1) dry weight, and the bioaccumulation factor ranged from 0.401 to 0.643(P < 0.05). Half-lives(t_(1/2)) of Pb were 7.24–2.26 d in supplemented soil,18.39–11.83 d in unsupplemented soil, and 123.75–38.72 d in the soil without plants and organic waste. Freundlich isotherms showed that the intensity of metal absorption(n) ranged from 2.44 to 2.51 for supplemented soil, with regression coefficients of determination(R^2) between 0.901 2 and 0.984 0. The computed free-energy change(?G) for Pb absorption ranged from -5.01 to 0.49 kJ mol^(-1) K^(-1) for EFB-supplemented soil and -3.93 to 0.49 k J mol^(-1) K^(-1) for SMC-supplemented soil.

关键词： bioaccumulation factor empty fruit bunch first-order kinetics heavy metal metal pollution phytoremediation spent mushroom compost

Arabidopsis Trithorax histone methyltransferases are redundant in regulating development and DNA methylation

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Journal of Integrative Plant Biology 2022年第12期64卷 2438-2454页

作者： Ji-Yun Shang Xue-Wei Cai Yin-Na Su Zhao-Chen Zhang Xin Wang Nan Zhao Xin-Jian He National Institute of Biological Sciences Beijing 102206China Tsinghua institute of Multidisciplinary Biomedical Research Tsinghua UniversityBeijing 100084China

Although the Trithorax histone methyltransferases ATX1-5 are known to regulate development and stress responses by catalyzing histone H3 K4 methylation in Arabidopsis thaliana,it is unknown whether and how these histone methyltransferases affect DNA methylation.Here,we found that the redundant ATX1-5 proteins are not only required for plant development and viability but also for the regulation of DNA methylation.The expression and H3 K4 me3 levels of both RNAdirected DNA methylation(RdDM)genes(NRPE1,DCL3,IDN2,and IDP2)and active DNA demethylation genes(ROS1,DML2,and DML3)were downregulated in the atx1/2/4/5 mutant.Consistent with the facts that the active DNA demethylation pathway mediates DNA demethylation mainly at CG and CHG sites,and that the RdDM pathway mediates DNA methylation mainly at CHH sites,whole-genome DNA methylation analyses showed that hyper-CG and CHG DMRs in atx1/2/4/5 significantly overlapped with those in the DNA demethylation pathway mutant ros1 dml2 dml3(rdd),and that hypo-CHH DMRs in atx1/2/4/5 significantly overlapped with those in the RdDM mutant nrpe1,suggesting that the ATX paralogues function redundantly to regulate DNA methylation by promoting H3 K4 me3 levels and expression levels of both RdDM genes and active DNA demethylation genes.Given that the ATX proteins function as catalytic subunits of COMPASS histone methyltransferase complexes,we also demonstrated that the COMPASS complex components function as a whole to regulate DNA methylation.This study reveals a previously uncharacterized mechanism underlying the regulation of DNA methylation.

关键词： development DNA demethylation DNA methylation histone methylation NRPE1 ROS1

Chromatin-remodeling complexes:Conserved and plant-specific subunits in Arabidopsis

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Journal of Integrative Plant Biology 2022年第2期64卷 499-515页

作者： Ji-Yun Shang Xin-Jian He National Institute of Biological Sciences Beijing102206 China Tsinghua institute of Multidisciplinary Biomedical Research Tsinghua UniversityBeijing100084 China

Adenosine triphosphate-dependent chromatin remodeling complexes are important for the regulation of transcription,DNA replication,and genome stability in eukaryotes.Although genetic studies have illustrated various biological functions of core and accessory subunits of chromatin-remodeling complexes in plants,the identification and characterization of chromatin-remodeling complexes in plants is lagging behind that in yeast and animals.Recent studies determined whether and how the Arabidopsis SWI/SNF,ISWI,INO80,SWR1,and CHD chromatin remodelers function in multi-subunit complexes in Arabidopsis.Both conserved and plant-specific subunits of chromatin-remodeling complexes have been identified and characterized.These findings provide a basis for further studies of the molecular mechanisms by which the chromatinremodeling complexes function in plants.

关键词： ATPase chromatin remodeling complex INO80 ISWI SWI/SNF SWR1 transcription

MeCP2:multifaceted roles in gene regulation and neural development

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Neuroscience Bulletin 2014年第4期30卷 601-609页

作者： Tian-Lin Cheng Zilong Qiu institute of Neuroscience Shanghai Institutes for Biological SciencesChinese Academy of Sciences

Methyl-CpG-binding protein 2 （MeCP2） is a classic methylated-DNA-binding protein, dysfunctions of which lead to various neurodevelopmental disorders such as Rett syndrome and autism spectrum disorder. Initially recognized as a transcriptional repressor, MeCP2 has been studied extensively and its functions have been expanded dramatically in the past two decades. Recently, it was found to be involved in gene regulation at the post-transcriptional level. MeCP2 represses nuclear microRNA processing by interacting directly with the Drosha/DGCR8 complex. In addition to its multifaceted functions, MeCP2 is remarkably modulated by post- translational modifications such as phosphorylation, SUMOylation, and acetylation, providing more regulatory dimensions to its functions. The role of MeCP2 in the central nervous system has been studied extensively, from neurons to glia. Future investigations combining molecular, cellular, and physiological methods are necessary for defining the roles of MeCP2 in the brain and developing efficient treatments for MeCP2-related brain disorders.

关键词： MeCP2 Rett syndrome central nervous system gene expression regulation post-translationalmodification post-transcriptional regulation glia

A mouse model of vitiligo based on endogenous auto-reactive CD8+T cell targeting skin melanocyte

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Cell Regeneration 2022年第1期11卷 316-332页

作者： Daoming Chen Zijian Xu Jun Cui Ting Chen National Institute of Biological Sciences BeijingChina Tsinghua institute of Multidisciplinary Biomedical Research Tsinghua UniversityBeijingChina

Vitiligo is the most common human skin depigmenting disorder.It is mediated by endogenous autoreactive CD8+T cells that destruct skin melanocytes.This disease has an estimated prevalence of 1%of the global population and cur-rently has no cure.Animal models are indispensable tools for understanding vitiligo pathogenesis and for developing new therapies.Here,we describe a vitiligo mouse model which recapitulates key clinical features of vitiligo,including epidermis depigmentation,CD8+T cell infiltration in skin,and melanocyte loss.To activate endogenous autoreactive cytotoxic CD8+T cells targeting melanocytes,this model relies on transient inoculation of B16F10 melanoma cells and depletion of CD4+regulatory T cells.At cellular level,epidermal CD8+T cell infiltration and melanocyte loss start as early as Day 19 after treatment.Visually apparent epidermis depigmentation occurs 2 months later.This protocol can efficiently induce vitiligo in any C57BL/6 background mouse strain,using only commercially available reagents.This enables researchers to carry out in-depth in vivo vitiligo studies utilizing mouse genetics tools,and provides a powerful platform for drug discovery.

关键词： Vitiligo Mouse model Activation Endogenous autoreactive cytotoxic CD8+T cells

Sensing bacterial infections by NAIP receptors in NLRC4 inflammasome activation

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Protein & Cell 2012年第2期3卷 98-105页

作者： Yi-Nan Gong Feng Shao National Institute of Biological Sciences Beijing 102206China Howard Hughes Medical institute National Institute of Biological SciencesBeijing 102206China

The inflammasome is an emerging new pathway in innate immune defense against microbial infection or endogenous danger signals.The inflammasome stimulates activation of inflammatory caspases,mainly caspase-1.Caspase-1 activation is responsible for processing and secretion of IL-1βand IL-18 as well as for inducing macrophage pyroptotic death.Assembly of the large cytoplasmic inflammasome complex is thought to be mediated by members of NOD-like receptor(NLR)family.While functions of most of the NLR proteins remain to be defined,several NLR proteins including NLRC4 have been shown to assemble distinct inflammasome complexes.These inflammasome pathways,particularly the NLRC4 inflammasome,play a critical role in sensing and restricting diverse types of bacterial infections.Here we review recent advances in defining the exact bacterial ligands and the ligand-binding receptors involved in NLRC4 inflammasome activation.Implications of the discovery of the NAIP family of inflammasome receptors for bacterial flagellin and type III secretion apparatus on future inflammasome and bacterial infection studies are also discussed.

关键词： inflammasome NOD-like receptors NLRC4 caspase-1 NAIP type III secretion system flagellin Salmonella Legionella enteropathogenic E.coli Burkholderia

TransitID通过串联邻近标记和富集无偏鉴定蛋白质移位

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科学通报:英文版 2023年第19期68卷 2139-2141,M0003页

作者：曹勇董梦秋 National Institute of Biological Sciences BeijingBeijing 102206China Tsinghua institute of Multidisciplinary Biomedical Research Tsinghua UniversityBeijing 102206China

Every eukaryotic cell is a busy microcosm filled with organelles,and the proper functioning of a protein is contingent upon its arrival at the correct location.As such,transportation of proteins takes place constantly within and between cells,some of which is constitutive and some regulated.For example,fibroblasts secrete collagens constitutively,which involves transportation of newly synthesized collagen proteins from the endoplasmic reticulum to the Golgi apparatus,and finally across the plasma membrane via secretory vesicles[1].In contrast,only under stressful conditions does the transcription factor forkhead box O(FOXO)translocate from the cytoplasm to the nucleus to launch a transcriptional response consisting of hundreds of genes[2–4].

关键词： constitutive hundreds filled