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The autophagy protein Atg9 functions in glia and contributes to parkinsonian symptoms in a Drosophila model of Parkinson’s disease

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Neural Regeneration Research 2024年第5期19卷 1150-1155页

作者： Shuanglong Yi Linfang Wang Margaret S.Ho Shiping Zhang School of life Science and technology ShanghaiTech UniversityShanghaiChina College of life sciences University of Chinese Academy of SciencesBeijingChina

Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy *** in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s ***,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the *** the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult *** from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in ***9 is persistently in contact with these *** glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate *** suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic ***,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial *** findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s *** results may provide new insights on the underlying mechanism of Parkinson’s disease.

关键词： Atg9 autophagy glia Parkinson’s disease

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

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National Science Review 2024年第1期11卷 161-173页

作者： Feng Xue Fei Li Ke-ming Zhang Lufeng Ding Yang Wang Xingtao Zhao Fang Xu Danke Zhang Mingzhai Sun Pak-Ming Lau Qingyuan Zhu Pengcheng Zhou Guo-Qiang Bi Department of Precision Machinery and Precision Instruments University of Science and Technology of China Hefei National Laboratory for Physical sciences at the Microscale University of Science and Technology of China Interdisciplinary Center for Brain Information the Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Faculty of life and Health sciences Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences School of life sciences University of Science and Technology of China Institute of Semiconductors Chinese Academy of Sciences Department of Modern life sciences and Biotecnology Xiongan Institute of Innovation Xiongan New Area Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions Suzhou Institute for Advanced Research University of Science and Technology of China Institute of Artiflcial Intelligence Hefei Comprehensive National Science Center

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the ***, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in ***-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

关键词： miniature microscope multiple sites calcium imaging multimodal integration hippocampus

Single-cell network analysis reveals gene expression programs for Arabidopsis root development and metabolism

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Plant Communications 2024年第8期5卷 32-49页

作者： Ershang Han Zhenxing Geng Yue Qin Yuewei Wang Shisong Ma MOE Key Laboratory for Cellular Dynamics School of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaInnovation Academy for Seed DesignChinese Academy of SciencesHefei 230027China School of Data Science University of Science and Technology of ChinaHefei 230027China

Single-cell RNA-sequencing datasets of Arabidopsis roots have been generated,but related comprehensive gene co-expression network analyses are *** conducted a single-cell gene co-expression network analysis with publicly available scRNA-seq datasets of Arabidopsis roots using a SingleCellGGM *** analysis identified 149 gene co-expression modules,which we considered to be gene expression programs(GEPs).By examining their spatiotemporal expression,we identified GEPs specifically expressed in major root cell types along their developmental *** GEPs define gene programs regulating root cell development at different stages and are enriched with relevant developmental *** examples,a GEP specific for the quiescent center(QC)contains 20 genes regulating QC and stem cell niche homeostasis,and four GEPs are expressed in sieve elements(SEs)from early to late developmental stages,with the early-stage GEP containing 17 known SE developmental *** also identified GEPs for metabolic pathways with cell-type-specific expression,suggesting the existence of cell-type-specific metabolism in *** the GEPs,we discovered and verified a columellaspecific gene,NRL27,as a regulator of the auxin-related root gravitropism *** analysis thus systematically reveals GEPs that regulate Arabidopsis root development and metabolism and provides ample resources for root biology studies.

关键词： single-cell RNA sequencing single-cell gene co-expression network analysis gene expression program Arabidopsis root development NRL27 gravitropism

TIP60 acetylation of Bub1 regulates centromeric H2AT120 phosphorylation for faithful chromosome segregation

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Science China(life sciences) 2024年第9期67卷 1957-1969页

作者： Mengjie Sun Biying Yang Guangwei Xin Yao Wang Jia Luo Qing Jiang Chuanmao Zhang The Academy for Cell and life Health Faculty of Life Science and TechnologyKunming University of Science and TechnologyKunming 650500China The Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life SciencesPeking UniversityBeijing 100871China

Proper function of the centromeres ensures correct attachment of kinetochores to spindle microtubules and faithful chromosome segregation in *** in the integrity and function of centromeres can result in chromosome missegregation and genomic ***1 is essential for the mitotic centromere dynamics,yet the underlying molecular mechanisms remain largely ***,we demonstrate that TIP60 acetylates Bub1 at K424 and K431 on kinetochores in early *** acetylation increases the kinase activity of Bub1 to phosphorylate centromeric histone H2A at T120(H2Ap T120),which recruits Aurora B and Shugoshin 1(Sgo1)to regulate centromere integrity,protect centromeric cohesion,and ensure the subsequent faithful chromosome *** of the nonacetylated Bub1 mutant reduces its kinase activity,decreases the level of H2Ap T120,and disrupts the recruitment of centromere proteins and chromosome congression,leading to genomic instability of daughter *** cells exit mitosis,HDAC1-regulated deacetylation of Bub1 decreases H2Ap T120 levels and thereby promotes the departure of centromeric CPC and Sgo1,ensuring timely centromeres ***,our results reveal a molecular mechanism by which the acetylation and deacetylation cycle of Bub1 modulates the phosphorylation of H2A at T120 for recruitment of Aurora B and Sgo1 to the centromeres,ensuring faithful chromosome segregation during mitosis.

关键词： acetylation Bub1 TIP60 H2ApT120 chromosome segregation

ATM Activation is Key in Vasculogenic Mimicry Formation by Glioma Stem-like Cells

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Biomedical and Environmental sciences 2024年第8期37卷 834-849页

作者： Jing Xie Jiaxin Tang Yuan Li Xue Kong Wei Wang Haibo Wu Department of Pathology the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina Intelligent Pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina

Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains *** We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM *** stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional *** the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were *** VM and high pATM expression occurred in 38.5% and 41.8% of tumors,respectively,and were significantly associated with reduced progression-free and overall *** with VM-positive GBMs exhibited higher pATM levels(r_(s)=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in *** inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin *** VM may predict a poor GBM prognosis and is associated with pATM *** propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

关键词： Glioblastoma Vasculogenic mimicry Ataxia-telangiectasia mutated(ATM) Glioma stem-like cell

Density functional theory study of B- and Si-doped carbons and their adsorption interactions with sulfur compounds

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Carbon Energy 2024年第2期6卷 195-208页

作者： Peng Guo Hong Zhang Shuliang Dong Libao An College of Mechanical Engineering North China University of Science and TechnologyTangshanHebeiChina College of life sciences North China University of Science and TechnologyTangshanHebeiChina

Understanding the adsorption interactions between carbon materials and sulfur compounds has far-reaching impacts,in addition to their well-known important role in energy storage and conversion,such as lithium-ion *** this paper,properties of intrinsic B or Si single-atom doped,and B-Si codoped graphene(GR)and graphdiyne(GDY)were investigated by using density functional theory-based calculations,in which the optimal doping configurations were explored for potential applications in adsorbing sulfur *** showed that both B or Si single-atom doping and B-Si codoping could substantially enhance the electron transport properties of GR and GDY,improving their surface ***,B and Si atoms displayed synergistic effects for the codoped configurations,where B-Si codoped GR/GDY exhibited much better performance in the adsorption of sulfurcontaining chemicals than single-atom doped *** addition,results demonstrated that,after B-Si codoping,the adsorption energy and charge transfer amounts of GDY with sulfur compounds were much larger than those of GR,indicating that B-Si codoped GDY might be a favorable material for more effectively interacting with sulfur reagents.

关键词： adsorption density functional theory doping graphdiyne graphene sulfur compounds

A repertoire of intronic lariat RNAs reveals tissue-specific regulation and target mimicry potential in plants

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Science China(life sciences) 2024年第6期67卷 1280-1291页

作者： Yong Zhang Xiaotuo Zhang Qi Tang Lei Li Ting Jiang Yixiao Fang Hong Zhang Jixian Zhai Guodong Ren Binglian Zheng State Key Laboratory of Genetic Engineering Institute of Plant BiologySchool of Life SciencesFudan UniversityShanghai 200438China Department of Biology School of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China

Lariat RNA is concomitantly produced by excised intron during RNA splicing,which is usually debranched by DBR1,an RNA debranching ***,increasing evidence showed that some lariat RNA could escape *** is known about how and why these lariat RNAs could be *** comparing the atlas of lariat RNAs between the non-dividing cell(mature pollen)and three actively dividing tissues(young shoot apex,young seeds,and young roots),we identified hundreds to thousands of lariat RNA naturally retained in each tissue,and the incidence of lariat RNA retention is much less in shoot apex while much more in *** lariat RNAs derived from the same intron or different lariat RNAs from the same pre-m RNA could be retained in one tissue while degraded in the other *** deciphering lariat RNA sequences,we identified an AG-rich(RAAAAVAAAR)motif and a UC-rich(UCUCUYUCUC)motif for pollen-specific and the other three tissues-retained lariat RNAs,*** of the pollen-specific AG-rich motif indeed enhanced lariat RNA retention in ***,hundreds of lariat RNAs harbored mi RNA binding sites,and dual-luciferase reporter assay showed that these natural lariat RNAs had the potential to protect expression of mi RNA target ***,our results uncover that selective retention of lariat RNA is an actively regulatory process,and provide new insights into understanding how lariat RNA metabolism may impact mi RNA activity.

关键词： intron turnover lariat RNA miRNA RNA splicing DBR1

microRNA-2184 orchestrates Mauthner-cell axon regeneration in zebrafish via syt3 modulation

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Journal of Genetics and Genomics 2024年第9期51卷 911-921页

作者： Xinghan Chen Yueru Shen Zheng Song Xinliang Wang Huaitong Yao Yuan Cai Zi-Ang Zhao Bing Hu Hefei National Research Center for Physical sciences at the Microscale University of Science and Technology of ChinaHefeiAnhui 230026China The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230026China Center for Advanced Interdisciplinary Science and Biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230026China

MicroRNAs(miRNAs)play a significant role in axon regeneration following spinal cord ***,the functions of numerous miRNAs in axon regeneration within the central nervous system(CNS)remain largely ***,we elucidate the positive role of microRNA-2184(miR-2184)in axon regeneration within zebrafish Mauthner cells(M-cells).The upregulation of miR-2184 in a single M-cell can facilitate axon regeneration,while the specific sponge-induced silencing of miR-2184 leads to impeded *** show that syt3,a downstream target of miR-2184,negatively regulates axon regeneration,and the regeneration suppression modulated by syt3 depends on its binding to Ca2+.Furthermore,pharmacological stimulation of the cAMP/PKA pathway suggests that changes in the readily releasable pool may affect axon *** data indicate that miR-2184 promotes axon regeneration of M-cells within the CNS by modulating the downstream target syt3,providing valuable insights into potential therapeutic strategies.

关键词： Axon regeneration Axon ablation miR-2184 syt3 Readily releasable pool

STING mediates microglial pyroptosis via interaction with NLRP3 in cerebral ischaemic stroke

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Stroke & Vascular Neurology 2024年第2期9卷 153-164页

作者： Wenyu Li Nan Shen Lingqi Kong Hongmei Huang Xinyue Wang Yan Zhang Guoping Wang Pengfei Xu Wei Hu Department of Neurology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina

background Ischaemia-evoked neuroinflammation is a critical pathogenic event following ischaemic *** D(GSDMD)-associated pyroptosis represents a type of inflammation-associated programmed cell death,which can exacerbate neuroinflammatory responses and brain *** of interferon genes(STING)was recently described as a vital innate immune adaptor protein associated with ***,the regulatory effects of STING on microglial pyroptosis post-stroke have not been well *** STING-knockout and wild-type(WT)mice were subjected to middle cerebral artery occlusion(MCAO).STING small interfering RNA(siRNA)was transfected into BV2 cells before oxygen-glucose deprivation/reoxygenation(OGD/R).STING-overexpressing adeno-associated virus(AAV)and NOD-like receptor family pyrin domain containing 3(NLRP3)siRNA were administered by stereotaxic injection.2,3,5-Triphenyl tetrazolium chloride(TTC)staining,TdT-mediated dUTP nick end labeling(TUNEL)staining,Fluoro-Jade C(FJC)staining,neurobehavioural tests,immunohistochemistry,cytokine antibody array assay,transmission electron microscopy,immunoblot,Enzyme-linked immunosorbent assay(ELISA)and quantitative real-time polymerase chain reaction(qRT-PCR)were carried ***-immunoprecipitation assays were used to investigate the interplay between STING and *** STING expression was increased after MCAO and mainly detected on *** deletion alleviated brain infarction,neuronal damage and neurobehavioural impairment in mice subjected to *** knockout suppressed microglial activation and the secretion of inflammatory chemokines,accompanied by mitigation of microglial *** upregulation of microglial STING by AAV-F4/80-STING aggravated brain injury and microglial ***,co-immunoprecipitation showed that STING bound to NLRP3 in *** of NLRP3 siRNA reversed AAV-F4/80-STING-induced deterioration of microglial pyropt

关键词： NLRP3 cerebral inflammation