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*** Endocytic Adaptor Protein Numb Functions in Müller Glia to Maintain Retinal Polarity and Photoreceptor Survival through the Polarity Determinant Crumbs

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Annals of Eye Science 2019年第1期 221-221页

作者： Maude Vinette Marie-Claude Bélanger Christine Jolicoeur Mina Gabraie Pierre Lachapelle Michel Cayouette Cellular neurobiology research Unit Institut de recherches cliniques de Montréal(IRCM)MontrealQCCanada Integrated Program in Neuroscience McGill UniversityMontrealQCCanada Division of Experimental Medicine McGill UniversityMontrealQCCanada Department of Ophthalmology Research Institute of the McGill University Health CentreMontrealQCCanada Department of Neurology and Neurosurgery McGill UniversityMontrealQCCanada Department of Medicine Universitéde MontréalMontrealQCCanada

Background:The loss of cell polarity plays a key part in retinal dystrophies such as retinitis pigmentosa(RP)and Leber congenital amaurosis(LCA),resulting in photoreceptor(PR)degeneration and vision *** not knowing the direct genotype-to-phenotype correlation,many disease-causing mutations in the polarity determinant Crumbs(Crb1),have been ***,the loss of Crb1 in mice was shown to cause PR death,due to the loss of adhesions between PR and Müller cells at the apical surface of the ***,although the role of Crb1 in neuron polarity and survival is well established,little is known about how its intracellular trafficking is *** future treatments for retinal degenerative diseases in mind,the goal of this project is to understand the mechanism by which Crb1 is regulated and how it maintains retinal *** work in our laboratory showed that Numb,an endocytic adaptor protein,is an important regulator of protein trafficking in retinal *** therefore hypothesized that Numb might function as regulator of Crb1 in Müller ***:To study Numb function in Müller cells,we generated a conditional knockout(cKO)mouse line to inactivate Numb specifically in Müller cells by crossing a Glast-CreERT2 mouse line with a Numb-floxed *** 30 days,mice were administered tamoxifen to trigger inactivation of Numb and retinas were then collected at time points varying from 2 weeks to 17 months for ***,we studied the retinal morphology and outer limiting membrane integrity by histology and *** electron microscopy(EM),adhesions between Müller glia and photoreceptors were analysed and retinal function was assayed in live mice by electroretinography(ERG).To detect protein expression levels,protein extracts were prepared from cKO and control retinas for *** test for the presence of a biochemical interaction,Hek-293 cells were transfected with Numb and Crb1 vectors,and protein ext

关键词： Degeneration retinal polarity Crumbs-related dystrophies(Crb1-related dystrophies)

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一株在监狱系统持续蔓延的结核分枝杆菌

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结核与肺部疾病杂志 2005年第3期8卷 85-89页

作者： K. Ijaz G. Templeton W. W. Stead J. H. Bates M. D. Cave 张宗德 Division of Tuberculosis Elimination Centers for Disease Control and Prevention Atlanta Georgia Arkansas Department of Health Little Rock Department of Epidemiology University of Arkansas for Medical Sciences Little Rock Arkansas Department of Medicine University of Arkansas for Medical Sciences Little Rock Medical Research Service Central Arkansas Veterans Healthcare Services Little Rock Arkansas Department of Health Little Rock Department of Medicine University of Arkansas for Medical Sciences Little Rock Medical Research Service Central Arkansas Veterans Healthcare Services Little Rock Arkansas Department of Health Little Rock Department of Epidemiology University of Arkansas for Medical Sciences Little Rock Arkansas Department of Medicine University of Arkansas for Medical Sciences Little Rock Medical Research Service Central Arkansas Veterans Healthcare Services Little Rock Medical research Service Central Arkansas Veterans Healthcare Services Little Rock Departments of Anatomy and Neurobiology University of Arkansas for Medical Sciences Little Rock Arkansas USA

地点:某年末平均人口为9084 名囚犯的监狱系统。目的:确定在一个较长时期内的结核病传播动力学;确定该结核杆菌株是否为监狱系统中结核病流行的主要原因;确定社区病例分离株的成簇性是否和监狱系统有联系。设计:对过去9 年中监狱系统报... 详细信息

地点:某年末平均人口为9084 名囚犯的监狱系统。目的:确定在一个较长时期内的结核病传播动力学;确定该结核杆菌株是否为监狱系统中结核病流行的主要原因;确定社区病例分离株的成簇性是否和监狱系统有联系。设计:对过去9 年中监狱系统报告的结核病例进行回顾性流行病学分析。另外,将囚犯结核杆菌分离株的IS6110-RFLP 图谱与其它病例进行总体比较。将RFLP 分析结果与流行病学调查结果进行对照。结果:监狱系统中约80%的病例分离株成簇。在过去的9 年中50%以上病例属同一结核杆菌株。社区内由同一株结核杆菌引起的病例与监狱系统存在明显关联。结论:虽然已实行了强有力的结核病控制措施,但是某结核杆菌株仍在监狱系统持续流行。在被诊断和治疗之前,其持留性可使潜伏感染复燃,并感染其他患者,从而使传播链持续下去。

关键词：结核病流行病学监狱 IS6110 RFLP 结核分枝杆菌监狱系统流行病学分析结核病例蔓延结核杆菌潜伏感染传播动力学

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Programmed death ligand-1 regulates angiogenesis and metastasis by participating in the c-JUN/VEGFR2 signaling axis in ovarian cancer

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Cancer Communications 2021年第6期41卷 511-527页

作者： Yufei Yang Lingfang Xia Yong Wu Hongyu Zhou Xin Chen Haoran Li Midie Xu Zihao Qi Ziliang Wang Huizhen Sun Xi Cheng Department of Gynecological Oncology and Cancer research Institute Fudan University Shanghai Cancer CenterShanghai 200032P.R.China Department of Gynecology and Obstetrics Xinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200092P.R.China Clinical research Unit of Shanghai Municipal Hospital of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Shanghai 200071P.R.China Department of Pathology and Tissue Bank Fudan University Shanghai Cancer CenterShanghai 200032P.R.China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032P.R.China Department of General Surgery Huadong Hospital Affiliated to Fudan UniversityShanghai 200040P.R.China

Background:Although programmed cell death-ligand 1(PD-L1)plays a wellknown function in immune checkpoint response by interacting with programmed cell death-1(PD-1),the cell-intrinsic role of PD-L1 in tumors is still ***,we explored the molecular regulatory mechanism of PD-L1 in the progression and metastasis of ovarian ***:Immunohistochemistry of benign tissues and ovarian cancer samples was performed,followed by migration,invasion,and angiogenesis assays in PDL1-knockdown ovarian cancer ***,mass spectrometry,and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD-L1 in ovarian ***:Our results showed that PD-L1 induced angiogenesis,which further promoted cell migration and invasion in vitro and in vivo of ovarian ***,PD-L1 was identified to directly interact with vascular endothelial growth factor receptor-2(VEGFR2)and then activated the FAK/AKT pathway,which further induced angiogenesis and tumor progression,leading to poor prognosis of ovarian cancer ***,PD-L1 was found to be regulated by the oncogenic transcription factor c-JUN at the transcriptional level,which enhanced the expression of PD-L1 in ovarian ***,we demonstrated that PD-L1 inhibitor durvalumab,combined with the antiangiogenic drug,apatinib,could enhance the effect of anti-angiogenesis and the inhibition of cell migration and ***:Our results demonstrated that PD-L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c-JUN/VEGFR2 signaling axis,suggesting that the combination of PD-L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients.

关键词： Angiogenesis Apatinib c-JUN Metastasis Ovarian Cancer PD-L1 VEGFR2 zebrafish

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Chip-based multimodal super-resolution microscopy for histological investigations of cryopreserved tissue sections

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Light(Science & Applications) 2022年第3期11卷 35-51页

作者： Luis E.Villegas-Hernández Vishesh Dubey Mona Nystad Jean-Claude Tinguely David A.Coucheron Firehun T.Dullo Anish Priyadarshi Sebastian Acuña Azeem Ahmad JoséM.Mateos Gery Barmettler Urs Ziegler Åsa Birna Birgisdottir Aud-Malin Karlsson Hovd Kristin Andreassen Fenton Ganesh Acharya Krishna Agarwal Balpreet Singh Ahluwalia Department of Physics and Technology UiT The Arctic University of NorwayKlokkargårdsbakken N-9019TromsøNorway Department of Clinical Medicine Women’s Health and Perinatology Research GroupUiT The Arctic University of NorwayTromsøNorway Department of Obstetrics and Gynecology University Hospital of North NorwayTromsøNorway Center for Microscopy and Image Analysis University of ZurichZürichSwitzerland Division of Cardiothoracic and Respiratory Medicine University Hospital of North NorwayTromsøNorway Department of Clinical Medicine Clinical Cardiovascular Research GroupUiT The Arctic University of NorwayTromsøNorway Department of Medical Biology RNA and Molecular Pathology Research GroupUiT The Arctic University of NorwayTromsøNorway Division of Obstetrics and Gynecology Department of Clinical ScienceIntervention and TechnologyKarolinska InstituteStockholmSweden

Histology involves the observation of structural features in tissues using a *** diffraction-limited optical microscopes are commonly used in histological investigations,their resolving capabilities are insufficient to visualize details at subcellular *** a novel set of super-resolution optical microscopy techniques can fulfill the resolution demands in such cases,the system complexity,high operating cost,lack of multi-modality,and low-throughput imaging of these methods limit their wide adoption for histological *** this study,we introduce the photonic chip as a feasible high-throughput microscopy platform for super-resolution imaging of histological *** cryopreserved ultrathin tissue sections of human placenta,mouse kidney,pig heart,and zebrafish eye retina prepared by the Tokuyasu method,we demonstrate diverse imaging capabilities of the photonic chip including total internal reflection fluorescence microscopy,intensity fluctuation-based optical nanoscopy,single-molecule localization microscopy,and correlative light-electron *** results validate the photonic chip as a feasible imaging platform for tissue sections and pave the way for the adoption of super-resolution high-throughput multimodal analysis of cryopreserved tissue samples both in research and clinical settings.

关键词： resolution modal feasible

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Animal models of T-cell acute lymphoblastic leukemia: mimicking the human disease

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Journal of Bio-X research 2018年第1期1卷 32-40页

作者： Qin You Hexiu Su Jingchao Wang Jue Jiang Guoliang Qing Hudan Liu Medical research Institute Wuhan University Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

T-cell acute lymphoblastic leukemia(T-ALL)is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic *** the past decade,large-scale genomic analysis has shed new light on providing potentially important oncogenic or tumor suppressive candidates involved in the disease *** in silico analysis,functional studies are usually performed to vigorously investigate the biological roles of candidate *** this purpose,animal models faithfully recapitulating the human disease are widely applied to decipher the mechanism underlying T-cell ***,an increased understanding of T-ALL biology,including identification of oncogene NOTCH1,TAL1 and MYC as well as tumor suppressor phosphatase and tensin homolog(PTEN),has significantly improved the development of T-ALL animal *** progresses have opened opportunities for development of new therapeutic strategy to benefit T-ALL *** this review,we particularly summarize the mouse and zebrafish models used in T-ALL research and also the most recent advances from these in vivo studies.

关键词： hematopoietic stem cell transplant T-cell acute lymphoblastic leukemia transgenetic mice transgenic zebrafish xenograft

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Chlorpyrifos-Oxon Disrupts Motor behavior and Axonal Growth in Embryonic zebrafish

Chlorpyrifos-Oxon Disrupts Motor Behavior and Axonal Growth ...

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中国毒理学会生化与分子毒理专业委员会第六届全国学术会议、中国毒理学会遗传毒理专业委员会第五届全国学术会议、广东省预防医学会卫生毒理专业委员会学术会议、广东省环境诱变剂学会学术会议

作者： Dongren Yang Jane Ladu Kalmia Buels Holly Lauridsen Robert Tanguay Pamela Lein Center for research on Occupational and Environmental Toxicology Oregon Health & Science University Environmental & Molecular Toxicology Oregon State University

Axonal morphology is a critical determinant of neuronal connectivity,and perturbation of the rate or extent of axonal growth during development has been linked to behavioral deficits in animal models and in *** previously demonstrated that organophosphorus pesticides (OPs) inhibit axonal growth in primary mammalian neuronal cell cultures,but data confirming that OPs similarly disrupt axonal growth in vivo is *** this study,we utilized transgenic zebrafish that express green fluorescent protein in dorsal root ganglia (DRG) sensory neurons,primary motoneurons or secondary motoneurons to determine whether chlorpyrifos (CPF) or its oxon metabolite (CPFO) alter normal spatiotemporal patterns of axonal growth in *** studies of zebrafish embryos exposed from 24-72 hour post fertilization to these OPs in the water at concentrations ranging from 0.004 to 1μM,indicated that CPFO,but not CPF, inhibited acetylcholinesterase activity,suggesting that zebrafish embryos lack the metabolic enzymes necessary to activate CPF during this life *** to CPF also had no effect on axonal growth and motor ***,CPFO significantly inhibited axonal growth of primary motoneurons,secondary motoneurons and DRG sensory *** effects of CPFO on axonal growth correlated with altered swimming behavior,suggesting that these structural changes had functional consequences.

关键词： Chlorpyrifos-Oxon Disrupts Motor behavior and Axonal Growth in Embryonic zebrafish

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***2f1/2 are required for the specification of cone photoreceptors in the developing retina

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Annals of Eye Science 2018年第1期 446-446页

作者： Awais Javed Pierre Mattar Michel Cayouette Cellular neurobiology research Unit Institut de Recherches Cliniques de Montreal(IRCM)MontrealQCCanada Molecular Biology Program Universitéde MontréalMontrealQCCanada Department of Medicine Universitéde MontréalMontrealQCCanada Division of Experimental Medicine Department of Anatomy and Cell BiologyMcGill UniversityMontrealQCCanada

Background:Rods and cones are critical for light *** there has been considerable work done in elucidating the molecular mechanisms involved in rod development,not much is known about how the cone cell fate decision is made by the multipotent retinal progenitor cells during *** of the promoter regions of Nrl and trβ2,rod and cone differentiation factors respectively,revealed DNA binding motifs of two POU-domain containing transcription factors,Pou2f1 and *** experiments showed that Pou2f1/2 are expressed during the peak of cone genesis in the embryonic ***,we hypothesize that Pou2f1/2 specify cone cell fate in the developing ***:We used immunofluorescence and in situ hybridization to establish the spatiotemporal expression of Pou2f1/2 during *** performed in vivo electroporation in post-natal mice to misexpress Pou2f1/2 and used antibodies specific to proteins expressed in cones such as Rxrγand S-opsin to count *** ex vivo electroporation of embryonic retinal explants,we knocked out Pou2f1 and Pou2f2 using CRISPR/Cas9 gRNAs at the peak of cone production ***,we transfected post-natal retinal explants with a combination of regulatory elements of Nrl or thrb with control backbone vector,Pou2f1 or Pou2f2 using ***:We found that Pou2f1/2 are expressed in retinal progenitor cells in the developing retina and subsequently in the differentiated ***2f1/2 misexpression outside the cone genesis window led to an increase in cones at the expense of ***2f1/2 indel knockouts generated by CRISPR/Cas9 gRNAs led to a decrease in cones and a converse increase in ***,we found that Pou2f1/2 activate the cis-regulatory module(CRM)of the thrb gene and repress the activity of the CRM of ***:These results uncover novel players that establish the complex gene regulatory network for cone photoreceptor fate specification in the retinal proge

关键词： Cones rods cell biology molecular biology retinogenesis

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m^(6)A reader Igf2bp3 enables germ plasm assembly by mA-dependent regulation of gene expression in zebrafish

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Science Bulletin 2021年第11期66卷 1119-1128,M0004页

作者： Fan Ren Ran Miao Rui Xiao Jie Mei College of Fisheries Huazhong Agricultural UniversityWuhan 430070China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430071China Department of Hematology Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China

Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown *** present study demonstrates that an m^(6)A reader Igf2bp3 interacts and colocalizes with Buc in the *** to the loss of Buc,the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification,which can be partially restored by the injection of igf2 bp3 ***2bp3 binds to m^(6)A-modified GPorganizer and GP mRNAs in an m^(6)A-dependent manner and prevents their *** findings indicate that the functions of Igf2bp3,a direct effector protein of Buc,in GP mRNA expression and GP assembly involve m^(6)A-dependent regulation;these results emphasize a critical role of m^(6)A modification in the process of GP assembly.

关键词： Igf2bp3 m^(6)A reader Bucky ball Germ plasm assembly m^(6)A-dependent regulation Germ cell specification

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Toxicity assessment of β-diketone antibiotic mixtures using zebrafish(Danio rerio)

Toxicity assessment of β-diketone antibiotic mixtures using...

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华东六省一市生物化学与分子生物学学会2014年学术交流大会暨浙江省第十一届学会会员代表大会

作者： Yuna Zhang Xiaohan Yin Ming Gao Xuedong Wang Huili Wang Wenzhou Applied Technology& Environmental research Institute Wenzhou Medical University School of Life Sciences Wenzhou Medical University

P-Diketone antibiotics(DKAs)are a"pseudo-persistent"environmental pollutant,however,currently,there are limited data concerning sublethal physiological effects of DKAs on adult fishes,and the consequences of DKA exposure to reproductive systems are also *** study examined the effects of mixed DKA acute exposure on mortality,hatching and malformation rates,and long-term exposure on sperm motility,four biomarkers,and transcriptional levels of three *** analysis of hver and skeletal musclewasperformed for evidence of tissue damage.A positive dose-dependence was observed in DKA-exposed groups with a 72-hpf EC50 of 130.3 mg/L for hatching rate,120-hpf LCof 149.8 mg/L for mortality rate,and 120-hpf EC50 of 135.1 mg/L for malformation *** embryos subjected to DKA exposure showed yolk sac edema and *** DKA exposure concentration(90 mg/L)resulted in yolk sac edema,uninflated swim bladder and pericardial *** motility has the potential to affect the reproductive ability of male *** affected the reproductive ability of male zebrafish withtotal sperm motility decreased by ca.30%due to DKA *** kinase activityincreased in allDKA treatments compared to the control group at 14 and 21DAE(days after exposure).A reduction in creatinine concentration occurred at 21 DAE,with an average reduction of 35-44%in the 60 and 90 mg/L treatments compared tothe control *** compared with the control,acetylcholine esterase activity increased by ca.2-fold at7,14 and 21 *** significant elevation in the intracellular malondialdehyde(MDA)levels revealed that DKA exposure induces intracellular MDA and abduct oxidative stress during the 7-14 DAE period.7-14 *** exposureincreased mRNA levelsfor AHRRa and CKma,andremarkable down-regulation *** exposure resulted in severetissue damage includingmitochondria swelling,reduction of mitochondrial cristae and deepening of mitochondrialcristae ***

关键词： Mixed DKA exposure Histopathological analysis Gene transcriptional level Biomarker Hepatotoxicity Sperm motility Aquatic environments

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Prospects for sociogenomics in avian cooperative breeding and parental care

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Current Zoology 2020年第3期66卷 293-306页

作者： Flavia TERMIGNONI-GARCIA Matthew I.M.LOUDER Christopher N.BALAKRISHNAN Lauren O’CONNELL Scott V.EDWARDS Department of Organismic and Evolutionary Biology Harvard UniversityCambridgeMA 02138USA Museum of Comparative Zoology Harvard UniversityCambridgeMA 02138USA International research Center for Neurointelligence The University of TokyoHongoBunkyo-kuTokyo 113-0033Japan Department of Biology East Carolina UniversityGreenvilleNC 27858USA Department of Biology Stanford UniversityStanfordCA 94305USA

For the last 40 years,the study of cooperative breeding(CB)in birds has proceeded primarily in the context of discovering the ecological,geographical,and behavioral drivers of *** advent of molecular tools in the early 1990s assisted in clarifying the relatedness of helpers to those helped,in some cases,confirming predictions of kin selection *** for genome-wide analysis of sequence variation,gene expression,and epigenetics promise to add new dimensions to our understanding of avian CB,primarily in the area of molecular and developmental correlates of delayed breeding and dispersal,as well as the ontogeny of achieving parental status in ***,we outline key ways in which modern-omics approaches,in particular genome sequencing,transcriptomics,and epigenetic profiling such as ATAC-seq,can be used to add a new level of ana-lysis of avian *** on recent and ongoing studies of avian social behavior and sociogenom-ics,we review how high-throughput sequencing of a focal species or clade can provide a robust foundation for downstream,context-dependent destructive and non-destructive sampling of spe-cific tissues or physiological states in the field for analysis of gene expression and epigenetics.-Omics approaches have the potential to inform not only studies of the diversification of CB over evolutionary time,but real-time analyses of behavioral interactions in the field or *** of birds represents a new branch in the network of methods used to study CB,and can help clarify ways in which the different levels of analysis of CB ultimately interact in novel and unexpected ways.

关键词： ATAC-seq behavior convergent evolution epigenetics neurobiology phylogeny

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