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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

Impact of tourism on the vigilance behavior of the Cyprus rock agama(Laudakia cypriaca)

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Integrative Zoology 2024年第3期19卷 577-583页

作者： Artur GOLAWSKI Iris CHARALAMBIDOU Sylwia GOLAWSKA Faculty of sciences Siedlce University of Natural Sciences and HumanitiesSiedlcePolandand department of life sciences School of Life and Health SciencesUniversity of NicosiaNicosiaCyprus

Escape behavior is a common antipredator strategy among wild ***,we investigated the effect of four factors on the vigilance behavior of the endemic Cyprus rock agama(Laudakia cypriaca).Flight initiation distance(FID,the minimum distance to which an observer can approach a lizard before it flees)was measured in relation to the type of location(tourist *** area),the observer’s starting distance,air temperature,and substrate *** collected data for 39 agamas in tourist areas and 34 of these lizards in nontourist *** a whole,the mean starting distance was 10.5 m and the FID was 3.6 *** average substrate temperature was 34.0℃ and the average air temperature 29.6℃.Only the type of area affected the agamas’escape decisions with FID being 1.8 m shorter in tourist areas than in nontourist areas(2.7 m vs.4.5 m).This is probably due to the habituation of lizards to the presence of humans in the former *** study shows that tourism strongly affects the behavior of lizards,which may have consequences for the functioning of the *** can increase the safety of lizards by creating a human shield to deter *** the tourist season is over,lizards may become more vulnerable to predators.

关键词： anthropogenic disturbance flight initiation distance lizards tourism vigilance behavior

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

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

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

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

Light-stabilized GIL1 suppresses PIN3 activity to inhibit hypocotyl gravitropism

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Journal of Integrative Plant Biology 2024年第9期66卷 1886-1897页

作者： Xiaolian Wang Yanfang Yuan Laurence Charrier Zhaoguo Deng Markus Geisler Xing Wang Deng Haodong Chen Center for Plant Biology School of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua‐Peking Center for life sciences Beijing 100084China School of Advanced Agricultural sciences and School of life sciences Peking‐Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China department of Biology University of FribourgFribourg 1700Switzerland

Light and gravity coordinately regulate the directional growth of *** Gravitropic in the Light 1(GIL1)inhibits the negative gravitropism of hypocotyls in red and far-red light,but the underlying molecular mechanisms remain *** study found that GIL1 is a plasma membrane-localized *** endodermal cells of the upper part of hypocotyls,GIL1 controls the negative gravitropism of ***1 directly interacts with PIN3 and inhibits the auxin transport activity of *** of PIN3 suppresses the abnormal gravitropic response of gil1 *** GIL1 protein is unstable in darkness but it is stabilized by red and far-red ***,our data suggest that light-stabilized GIL1 inhibits the negative gravitropism of hypocotyls by suppressing the activity of the auxin transporter PIN3,thereby enhancing the emergence of young seedlings from the soil.

关键词： GIL1 gravitropism hypocotyls light PIN3

How variable progenitor clones construct a largely invariant neocortex

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National Science Review 2024年第1期11卷 129-144页

作者： Zhongfu Shen Jiajun Yang Qiangqiang Zhang Kuiyu Wang Xiaohui Lv Xiaolin Hu Jian Ma Song-Hai Shi New Cornerstone Science Laboratory IDG/McG overn Institute for Brain Research Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University department of Computer sciences Tsinghua University College of life sciences Nankai University Chinese Institute for Brain Research

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors(RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

关键词： neocortex radial glial progenitor intermediate progenitor neurogenesis clonal variability layer formation

Structural insights into AtABCG25,an angiosperm-specific abscisic acid exporter

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Plant Communications 2024年第1期5卷 284-295页

作者： Jian Xin Yeling Zhou Yichun Qiu He Geng Yuzhu Wang Yi Song Jiansheng Liang Kaige Yan department of Chemical Biology School of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China Institute of Plant and Food Science Department of BiologySchool of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China Max Planck Institute of Molecular Plant Physiology Potsdam-GolmGermany Institute for Biological Electron Microscopy Southern University of Science and TechnologyShenzhenGuangdongChina

Cellular hormone homeostasis is essential for precise spatial and temporal signaling responses and *** acid(ABA)plays pivotal roles in orchestrating various developmental and stress re-sponses and confersfitness benefits over ecological and evolutionary timescales in terrestrial *** ABA level is regulated by complex processes,including biosynthesis,catabolism,and ***25 is thefirst ABA exporter identified through genetic screening and affects diverse ABA *** the structural basis of ABA export by ABCG25 is critical for further manipulations of ABA homeostasis and *** used cryo-electron microscopy to elucidate the structural dynamics of AtABCG25 and successfully characterized different states,including apo AtABCG25,ABA-bound AtABCG25,and ATP-bound AtABCG25(E232Q).Notably,AtABCG25 forms a homodimer that fea-tures a deep,slit-like cavity in the transmembrane domain,and we precisely characterized the critical residues in the cavity where ABA *** binding triggers closure of the nucleotide-binding domains and conformational transitions in the transmembrane *** show that AtABCG25 belongs to a conserved ABCG subfamily that originated during the evolution of *** subfamily neofunctionalized to regulate seed germination via the endosperm,in concert with the evolution of this angio-sperm-specific,embryo-nourishing ***,thesefindings provide valuable insights into the intricate substrate recognition and transport mechanisms of the ABA exporter AtABCG25,paving the way for genetic manipulation of ABA homeostasis and plantfitness.

关键词： AtABCG25 abscisic acid ABC transporters cryo-EM structure