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Nature:科学家鉴别出调节机体睡眠的两个关键基因

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现代生物医学进展 2017年第6期17卷 I0002-I0002页

作者： Hiromasa Funato, Chika Miyoshi, Tomoyuki Fujiyama, Takeshi Kanda, Makito Sato, Zhiqiang Wang, Jing Ma, Aya Ikkyu, Miyo Kakizaki, Noriko Hotta-Hirashima, Satomi Kanno, Haruna Komiya, Fuyuki Asano, Takato Honda, Staci J. Kim, Kanako Harano, Hiroki Muramoto, Toshiya Yonezawa, Shinichi Miyazaki, Linzi Connor, Yu Hayashi, Qinghua Liu, Joseph S. Takahashi Masashi Yanagisawa Hiromasa Funato Makito Sato Masashi Yanagisawa Shin Nakane, Jun Tomita Kazuhiko Kume Seiya Mizuno, Fumihiro Sugiyama Satoru Takahashi Vivek Kumar Joseph S. Takahashi Vivek Kumar Ikuo Miura, Tomohiro Suzuki Shigeharu Wakana Atsushi Watanabe Manabu Abe Kenji Sakimura Yu Hayashi Qinghua Liu Joseph S. Takahashi Masashi Yanagisawa Masashi Yanagisawa International Institute for Integrative Sleep Medicine (WPI-IIIS) University of Tsukuba Tsukuba Ibaraki 305-8575 Japan Department of Anatomy Faculty of Medicine Toho University Ota-ku Tokyo 143-8540 Japan Department of Molecular Genetics University of Texas Southwestern Medical Center Dallas Texas 75390 USA Department of Neuropharmacology Graduate School of Pharmaceutical Sciences Nagoya City University Nagoya Aichi 467-8603 Japan laboratory Animal Resource Center University of Tsukuba Tsukuba Ibaraki 305-8575 Japan Department of Neuroscience University of Texas Southwestern Medical Center Dallas Texas 75390 USA The Jackson laboratory Bar Harbor Maine 04609 USA Technology and Development Team for Mouse Phenotype Analysis RIKEN Bioresource Center Tsukuba Ibaraki 305-0074 Japan laboratory of research Advancement National Center for Geriatrics and Gerontology Obu Aichi 474-8511 Japan Department of Cellular neurobiology Brain Research Institute Niigata University Niigata 951-8585 Japan PRESTO Japan Science and Technology Agency Kawaguchi Saitama 332-0012 Japan Department of Biochemistry University of Texas Southwestern Medical Center Dallas Texas 75390 USA Howard Hughes Medical Institute University of Texas Southwestern Medical Center Dallas Texas 75390 USA Life Science Center Tsukuba Advanced Research Alliance University of Tsukuba Tsukuba Ibaraki 305-8575 Japan

近日，刊登在国际杂志Nature上的一项研究报告中，来自西南医学中心等机构的研究人员通过研究鉴别出了两个关键的核心基因，这两个基因能够帮助调节机体深度睡眠和做梦的水平，相关研究或为阐明相关的基因控制睡眠的网络提供新的线索。... 详细信息

近日，刊登在国际杂志Nature上的一项研究报告中，来自西南医学中心等机构的研究人员通过研究鉴别出了两个关键的核心基因，这两个基因能够帮助调节机体深度睡眠和做梦的水平，相关研究或为阐明相关的基因控制睡眠的网络提供新的线索。此前研究者通过对小鼠进行研究发现了能够控制机体快速眼动睡眠的基因，同时该基因还能够诱导深度睡眠。而第二个基因能够控制机体对快速眼动睡眠的需求量，相关研究为科学家们提供了一个关键的切入点来帮助解释睡眠工作的机制，同时研究者还鉴别出了治疗睡眠障碍的潜在靶点。

关键词：睡眠障碍核心基因科学家机体鉴别基因控制研究人员需求量

Identification of noncoding RNA-encoded proteins on lipid droplets

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Science Bulletin 2021年第4期66卷 314-318,M0003页

作者： Ting Huang Adekunle T.Bamigbade Shimeng Xu Yaqin Deng Kang Xie Ololade O.Ogunsade Ahmed Hammad Mirza Jifeng Wang Pingsheng Liu Shuyan Zhang School of Basic Medical Sciences Southwest Medical UniversityLuzhou 646000China National laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

With the rapid development of high-throughput sequencing technologies,it has recently become evident that the eukaryotic genome is extensively transcribed[1,2].Large-scale projects for the systematic annotation and functional characterization of genes,such as GENCODE and FANTOM,have demonstrated that at least 80%of mammalian genomic DNA is actively *** has become increasingly clear that many genomic regions classified as noncoding actually harbor short open reading frames(sORFs)with fewer than 300 nucleotides,encoding small,functional proteins or *** small proteins have evaded detection due to their small size,low abundance,instability,and loss during sample preparation[3].However,emerging experimental techniques,including ribosome profiling and mass spectrometry,along with computational advances have enabled their discovery and analysis[3,4).Most have been identified in prokaryotic organisms[4],but a growing number have also been discovered in eukaryotic organisms,including plants,zebrafish,insects,mice,and humans[2-4].These proteins have been found to play important roles in many fundamental biological processes[3]and have been reported to localize to cellular compartments such as mitochondria[5],late endosomes/lysosomes[6],and endoplasmic reticulum[7].However,given the large number of putative proteins encoded by noncoding RNAs,there is a need for much more *** particular,there is a need for more information on the subcellular localization of these proteins,which may provide insight into their biological functions.

关键词：代谢疾病非编码RNA 中性脂质谱学骨骼肌细胞脂质代谢磷脂膜细胞脂质

Developmental toxicity of TCBPA on the nervous and cardiovascular systems of zebrafish (Danio rerio): A combination of transcriptomic and metabolomics

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Journal of Environmental Sciences 2023年第5期127卷 197-209页

作者： Wentao Liu Yifan Pan Lu Yang Yun Xie Xuanyue Chen Jing Chang Weiyu Hao Lifei Zhu Bin Wan research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China Agricultural Information Institute Chinese Academy of Agricultural SciencesBeijing 100081China Institute of Food Safety Chinese Academy of Inspection and QuarantineBeijing 100176China Beijing Academy of Agriculture and Forestry Sciences Beijing 100097China

Tetrachlorobisphenol A(TCBPA),a widely used halogenated flame retardant,is frequently detected in environmental compartments and human ***,unknown developmental toxicity and mechanisms limit the entire understanding of its *** this study,zebrafish(Danio rerio)embryos were exposed to various concentrations of TCBPA while a combination of transcriptomics,behavioral and biochemical analyzes as well as metabolomics were applied to decipher its toxic effects and the potential *** found that TCBPA could interfere with nervous and cardiovascular development through focal adhesion and extracellular matrix-receptor(ECM-receptor)interaction pathways through transcriptomic *** and biochemical analysis results indicated abnormal swimming behavior of zebrafish *** observations revealed that TCBPA could cause the loss of head blood *** analysis showed that arginine-related metabolic pathways were one of the main pathways leading to TCBPA developmental *** study demonstrated that by using omics,TCBPA was shown to have neurological and cardiovascular developmental toxicity and the underlying mechanisms were uncovered and major pathways identified.

关键词： Tetrachlorobisphenol A(TCBPA) zebrafish Developmental toxicity Transcriptomics Metabolomics

CXCR5^(+)PD-1^(++)CD4^(+)T cells colonize infant intestines early in life and promote B cell maturation

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Cellular & Molecular Immunology 2023年第2期20卷 201-213页

作者： Ana Jordan-Paiz Glòria Martrus Fenja L.Steinert Max Kaufmann Adrian F.Sagebiel Renée R.C.E.Schreurs Anne Rechtien Martin E.Baumdick Johannes M.Jung Kimberly J.Möller Lucy Wegner Cordula Grüttner Laura Richert Roland Thünauer Jennifer Schroeder-Schwarz Johannes Bvan Goudoever Teunis B.H.Geijtenbeek Marcus Altfeld Steven T.Pals Daniel Perez Paul L.Klarenbeek Christian Tomuschat Guido Sauter Ingo Königs Udo Schumacher Manuel A.Friese Nathaniel Melling Konrad Reinshagen Madeleine J.Bunders Department of Virus Immunology Leibniz Institute of VirologyHamburg20251Germany University Medical Center Hamburg-Eppendorf Hamburg20246Germany Institute of Neuroimmunology and Multiple Sclerosis Center for Molecular Neurobiology HamburgUniversity Medical Center Hamburg-EppendorfHamburg20251Germany Department of General Visceral and Thoracic SurgeryUniversity Medical Center Hamburg-EppendorfHamburg20246Germany Department of Experimental Immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatrics Emma Children’s HospitalAmsterdam University Medical CenterUniversity of Amsterdam and Vrije Universiteit AmsterdamAmsterdam1105 AZThe Netherlands I.Department of Medicine University Medical Center Hamburg-EppendorfHamburg20246Germany Partner Site Hamburg-Lübeck-Borstel-Riems German Center for Infection Research(DZIF)Hamburg20246Germany University of Bordeaux Institut National de la Santéet de la Recherche MédicaleBordeaux Population Health Research Center UMR1219 and INRIA SISTM TeamBordeaux33000France Institute of Anatomy and Experimental Morphology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pathology Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Rheumatology and Clinical Immunology and Department of Experimental Immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1007 MBThe Netherlands Amsterdam Rheumatology&Immunology Center Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatric Surgery University Medical Center Hamburg-EppendorfHamburg20246Germany Institute of Pathology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pediatric Surgery Altona Children’s HospitalHamburg22763Germany III.Department of Medicine University M

Gastrointestinal infections are a major cause for serious clinical complications in *** induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human *** CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to *** findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to ***-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B *** together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.

关键词： TFH cells B cells Antibodies Intestine Pediatrics

zebrafish Foxc1a controls ventricular chamber maturation by directly regulating wwtr1 and nkx2.5 expression

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Journal of Genetics and Genomics 2022年第6期49卷 559-568页

作者： Luqingqing He Qinxin Zhang Dongya Jiang Yunfeng Zhang Yuxuan Wei Yuxi Yang Nan Li Shuang Wang Yunyun Yue Qingshun Zhao Model Animal research Center Medical SchoolNanjing UniversityNanjingJiangsu 210061China Department of Prenatal Diagnosis Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu 210004China School of Traditional Chinese Pharmacy China Pharmaceutical UniversityNanjingJiangsu 210009China

Chamber maturation is a significant process in cardiac development. Disorders of this crucial process lead to a range of congenital heart defects. Foxc1a is a critical transcription factor reported to regulate the specification of cardiac progenitor cells. However, little is known about the role of Foxc1a in modulating chamber maturation. Previously, we reported that foxc1a-null zebrafish embryos exhibit disrupted heart structures and functions. In this study, we observe that ventricle structure and cardiomyocyte proliferation are abolished during chamber maturation in foxc1a-null zebrafish embryos. To observe the endogenous localization of Foxc1a in the hearts of living embryos, we insert eyfp at the foxc1a genomic locus using TALEN. Analysis of the knockin zebrafish show that foxc1a is widely expressed in ventricular cardiomyocytes during chamber development. Cardiac RNA sequencing analysis reveals the downregulated expression of the Hippo signaling effector wwtr1. Dual-luciferase and chromatin immunoprecipitation assays reveal that Foxc1a can bind directly to three sites in the wwtr1 promoter region. Furthermore, wwtr1m RNA overexpression is sufficient to reverse the ventricle defects during chamber maturation. Conditional overexpression of nkx2.5 also partially rescues the ventricular defects during chamber development. These findings demonstrate that wwtr1 and nkx2.5 are direct targets of Foxc1a during ventricular chamber maturation.

关键词： zebrafish Foxc1a Cardiac ventricular development wwtr1 nkx2.5

ORIGINAL ARTICLES APPLICATION OF SILVER ACETATE AUTOMETALLOGRAPHY AND GOLD-SILVER STAINING METHODS FOR IN SITU DNA HYBRIDIZATION

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中华医学杂志(英文版) 1993年第2期106卷 83-92页

作者： GW Hacker AH Graf C Hauser-Kronberger G Wirnsberger A Schiechl G Bernatzky U Wittauer 苏慧慈 H Adam J Thurner G Danscher L Grimelius Landeskrankenanstalten Salzburg Institute of Pathological AnatomyImmunohistochemistry and Biochemistry UnitSalzburgAustria University of Graz Institute of PatholOgical AnatomyGraz.Austria University of Salzburg Institute of ZoologySalzburgAuatria University of Salzburg Institute of ZoologySalzburgAustria Department of Histology and Embryology Fourth Military Medical UniversityXi'anShaanxiPR China University of Salzburg Institute of ZoologySalzburgAuStria Landeskrankenanstalten Salzburg Institute Of Pathological AnatomyyImmunohistochemistry and Biochemistry UnitSalzburgAustria University of Aarhus Institute of AnatomyDepartment of NeurobiologyAarhusDenmark Uppsala University Hospital Institute of PathologyUppsalaSweden

In situ hybridization using biotinylated DNA probes hasbecome an important tool in *** is well knownthat the sensitivity of the methods used to demonstrate viralDNA in formalin-fixed and paraffin-embedded specimen de-pends strongly on the detection system *** the presentstudy,an optimized in situ DNA hybridization protocol wascombined with four different approaches of gold-silver *** silver enhancement,the recently described meth-od of silver acetate autometallography,a technique allowinghighly efficient development without the necessity of dark roomillumination has been *** most efficient detection methodfound in our experiments was the use of gold-adsorbedanti-biotin antibodies with subsequent silver *** procedure can be completed in 5 hours includinghybridization and is a highly sensitive alternative to peroxidaseand alkaline phosphatase detection systems.

关键词： MESSENGER-RNA ELECTRON-MICROSCOPY PARAFFIN SECTIONS DETECTION SYSTEMS GENE-EXPRESSION CDNA PROBE VIRUS-DNA IMMUNOGOLD TISSUE IMMUNOCYTOCHEMISTRY

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通过MRI识别BRAF基因突变型颅咽管瘤

中国现代神经疾病杂志 2020年第3期20卷 185-185页

作者： Yue Q Yu Y Shi Z Wang Y Zhu W Du Z Yao Z Chen L Mao Y 吴向宸(编译) Departments of Neurosurgery School of Basic Medical Sciences and Institutes of Brain ScienceFudan UniversityShanghaiChina Radiology School of Basic Medical Sciences and Institutes of Brain ScienceFudan UniversityShanghaiChina Pathology Huashan HospitalFudan UniversitySchool of Basic Medical Sciences and Institutes of Brain ScienceFudan UniversityShanghaiChina State Key laboratory of Medical neurobiology School of Basic Medical Sciences and Institutes of Brain ScienceFudan UniversityShanghaiChina 天津市环湖医院神经外科

研究背景BRAF基因突变抑制剂对部分难治性颅咽管瘤具有缩小肿瘤体积的作用,是一种具有临床应用前景的治疗方法,可用于颅咽管瘤的术前治疗,有助于切除肿瘤。本研究探讨基于MRI特征的BRAF基因突变型颅咽管瘤的非侵袭性诊断技术。方法共纳... 详细信息

研究背景BRAF基因突变抑制剂对部分难治性颅咽管瘤具有缩小肿瘤体积的作用,是一种具有临床应用前景的治疗方法,可用于颅咽管瘤的术前治疗,有助于切除肿瘤。本研究探讨基于MRI特征的BRAF基因突变型颅咽管瘤的非侵袭性诊断技术。方法共纳入52例经术后病理确诊的颅咽管瘤患者,采用聚合酶链反应(PCR)检测肿瘤标本BRAF和CTNNB1基因突变。由两位不知晓患者身份和BRAF基因突变等临床信息的神经影像学专家对颅咽管瘤患者的MRI表现(包括肿瘤部位、大小、形状和成分,囊肿信号强度和强化特征,垂体柄形态,颈内动脉毗邻关系)以及临床特征(包括BRAF基因突变)进行分析。比较BRAF基因突变型与野生型颅咽管瘤的MRI表现。BRAF基因突变型颅咽管瘤中具有明显特征(P<0.05)的MRI表现定义为诊断特征。采用受试者工作特征(ROC)曲线确定临床诊断BRAF基因突变型颅咽管瘤所需的最少MRI诊断特征。结果52例患者中8例为BRAF基因突变型颅咽管瘤,44例为野生型颅咽管瘤,二者临床特征无显著差异。两位神经影像学专家的MRI数据分析结果具有较高的一致性,Kappa一致性检验(κ值)为0.65~0.97。与野生型颅咽管瘤相比,BRAF基因突变型颅咽管瘤表现为向鞍上生长(P<0.001)、呈球形(P=0.005)、主要为实性结构(P=0.003)、均匀强化(P<0.001)和垂体柄增粗(P=0.014)等5项MRI特征。当这5项特征中至少存在3项时可诊断为BRAF基因突变型颅咽管瘤,其灵敏度为100%、特异度为91%,ROC曲线下面积为0.989(P<0.001)。结论通过MRI特征诊断BRAF基因突变型颅咽管瘤具有较高的敏感性和特异性,从而为BRAF基因突变抑制剂的术前应用提供指导意见。

关键词：突变型颅咽管瘤 MRI

Gene expression responses in zebrafish to short-term high-hydrostatic pressure

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Zoological research 2022年第2期43卷 188-191页

作者： Ming-Liang Hu Bao-Sheng Wu Wen-Jie Xu Cheng-Long Zhu Yuan Yuan Wen-Qi Lv Qiang Qiu Hai-Bin Zhang Kun Wang Chen-Guang Feng School of Ecology and Environment Northwestern Polytechnical UniversityXi’anShaanxi 710072China Key laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences Institute of HydrobiologyChinese Academy of SciencesWuhanHubei 430072China Institute of Deep-Sea Science and Engineering Chinese Academy of SciencesSanyaHainan 572000China University of Chinese Academy of Sciences Beijing 100049China

Hydrostatic pressure is one of the main factors limiting the vertical range of marine ***,little is known about the level of hydrostatic pressure that shallow-water fish can tolerate or how they respond to this potential ***,we applied high-hydrostatic pressure treatment to wild-type AB line zebrafish(Danio rerio)and analyzed transcriptome data following treatment.

关键词： fish treatment hydrostatic

Kisspeptin stimulates oocyte maturation,and food deprivation modulates the abundance of kisspeptin system in zebrafish gonads

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Aquaculture and Fisheries 2022年第5期7卷 484-493页

作者： Azadeh Hatef Jithine Jayakumar Rajeswari Suraj Unniappan laboratory of Integrative Neuroendocrinology Department of Veterinary Biomedical SciencesWestern College of Veterinary MedicineUniversity of SaskatchewanSaskatoonSaskatchewanS7N 5B4Canada Toxicology Centre University of SaskatchewanSaskatoonSaskatchewanS7N 5B4Canada

Kisspeptin is a hormone involved in the neuroendocrine control of reproduction in *** hypothesized that kisspeptin stimulates oocyte maturation and modulates other reproductive hormones in zebrafish;and the gonadal kisspeptin system in zebrafish is affected during energy *** main goals of this research were to test in vitro effects of kisspeptin on oocyte maturation and mRNA abundance in zebrafish ovarian follicles and determine how short-term feed restriction affects kisspeptin and its receptors in zebrafish testis and *** study demonstrates the presence of kisspeptin and its receptors in zebrafish(Danio rerio)gonads and its direct action on ovarian follicles in ***(10 ng/mL)induced oocyte maturation,as indicated by germinal vesicle break down at 18-and 24-hours *** significantly increased the abundance of mRNAs encoding reproductive hormones and its receptors in zebrafish *** suggests that kisspeptin-10 affects ovarian functions by modulating other *** is a process that requires ***,whether energy availability affects the kisspeptin system in zebrafish gonads was *** deprivation modulated kisspeptin expression differently in zebrafish testis and ***2 and kiss1ra were upregulated while kiss1rb was downregulated in the testis post-food ***,no changes in kiss in the ovary were found after food ***,kiss1rb was downregulated in unfed fish at 3-and 7-days post-food ***,our results suggest sex-and tissue-specific changes in the gonadal abundance of the kisspeptin system in *** fine tuning of reproduction during energy fluctuations in fish is likely mediated via changes in hormones,including kisspeptin as shown in this research.

关键词： Oocyte Kisspeptin Food deprivation GVBD Gonadotropin Testis Ovary zebrafish Oocyte maturation