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Metabolic phenotyping of mouse mutants in the German Mouse Clinic

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Integrative Zoology 2006年第3期1卷 122-125页

作者： Ralf ELVERT Nicole EHRHARDT Martin TAUBE Martin KLINGENSPOR Valerie GAILUSDURNER Helmut FUCHS Martin Hrabe DE ANGELIS Veronique BLANQUET Gerhard HELDMAIER Institute of experimental genetics German Mouse ClinicNeuherbergMunichGermany Department of Biology Philipps University of MarburgMarburgGermany Laboratory of Molecular experimental genetics Institute of TransgenoseOrleansFrance

The German Mouse Clinic was established as a phenotyping center to provide the scientific community with systematic standardized phenotyping of mouse models from various genetic *** found metabolic phenotypes in nine out of 20 mutant lines screened in a primary *** on these findings,the mutants were analyzed in secondary and tertiary *** of a sample mutant line,isolated from the ENU-screen at the National Research Center for Environment and Health in Munich,were found to have lower body weight,consume less food,but have higher ratios of metabolized energy per unit body weight compared with their wild-type *** metabolic rate and heat production were simultaneously increased by 16–18%,whereas body fat content was reduced by 11–16%.The combination of various parameters of energy consumption,expenditure and energy storage illustrate the metabolic demands of the sample mutant mouse line and demonstrate the utility of the powerful phenotyping tool used at the German Mouse Clinic.

关键词： calorimetry energy metabolism metabolic phenotyping mouse mutant telemetry

Regulation of RNase E during the UV stress response in the cyanobacterium Synechocystis *** 6803

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mLife 2023年第1期2卷 43-57页

作者： Satoru Watanabe Damir Stazic Jens Georg Shota Ohtake Yutaka Sakamaki Megumi Numakura Munehiko Asayama Taku Chibazakura Annegret Wilde Claudia Steglich Wolfgang R.Hess Faculty of Biology Genetics and Experimental BioinformaticsUniversity of FreiburgFreiburgGermany Department of Bioscience Tokyo University of AgricultureSetagayakuTokyoJapan School of Agriculture Molecular GeneticsIbaraki UniversityIbarakiJapan Faculty of Biology Molecular GeneticsUniversity of FreiburgFreiburgGermany Nexxiot Prime Tower(Hardstrasse 201)ZurichSwitzerland.

Endoribonucleases govern the maturation and degradation of RNA and are indispensable in the posttranscriptional regulation of gene expression.A key endoribonuclease in Gram-negative bacteria is RNase *** ensure an appropriate supply of RNase E,some bacteria,such as Escherichia coli,feedback-regulate RNase E expression via the rne 5′-untranslated region(5′UTR)in ***,the mechanisms involved in the control of RNase E in other bacteria largely remain *** rely on solar light as an energy source for photosynthesis,despite the inherent ultraviolet(UV)*** this study,we first investigated globally the changes in gene expression in the cyanobacterium Synechocystis *** ^(6)803 after a brief exposure to *** the 407 responding genes 2 h after UV exposure was a prominent upregulation of rne mRNA ***,the enzymatic activity of RNase E rapidly increased as well,although the protein stability *** unique response was underpinned by the increased accumulation of full-length rne mRNA caused by the stabilization of its 5′UTR and suppression of premature transcriptional termination,but not by an increased transcription *** of RNA 3′ends and in vitro cleavage assays revealed that RNase E cleaves within a stretch of six consecutive uridine residues within the rne 5′UTR,indicating *** observations suggest that RNase E in cyanobacteria contributes to reshaping the transcriptome during the UV stress response and that its required activity level is secured at the RNA level despite the enhanced turnover of the protein.

关键词： cyanobacteria protein turnover ribonuclease stress response

Customized molecular tools to strengthen metabolic engineering of cyanobacteria

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Green Carbon 2024年第2期2卷 149-163页

作者： Stephan Klähn Franz Opel Wolfgang R.Hess Department of Solar Materials Biotechnology Helmholtz Centre for Environmental Research–UFZLeipzig 04318Germany genetics and experimental bioinformatics Albert-Ludwig University FreiburgFreiburg im Breisgau 79104Germany

Cyanobacteria are promising oxygenic phototrophs for the production of various *** their(photo)biotechnological exploitation,molecular tools are required,such as,for the introduction and expression of heterologous genes,or the modulation of enzyme activities or entire *** and strategies for the development of photosynthetic biomanufacturing technologies based on cyanobacteria have been extensively reviewed,as well as certain specialized aspects of their genetic ***,options for metabolic engineering of specific cyanobacterial cells are still less developed than those for other bacteria of biotechnological *** addition to the standard genetic toolbox for“classical”metabolic engineering,we emphasize certain aspects,including recently developed vector systems for the extrachromosomal maintenance of genes and approaches based on clustered regularly interspaced short palindromic repeats(CRISPR)*** highlight the development of custom molecular tools for specific strains or products,discuss the emerging use of small regulatory proteins that appear promising for advanced metabolic engineering approaches to promote specific product formation,and provide an overview of suitable online ***,we discuss the current trends in this field and indicate their potential,such as using suitable product sensors that enable systematic screening,and optimization approaches.

关键词： Metabolic engineering Cyanobacteria Synthetic plasmids Regulatory proteins Sensors

Overdose the addiction—A new strategy to ablate cancer cells

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Science China(Life Sciences) 2015年第11期58卷 1169-1170页

作者： LI Lei Department of experimental Radiation Oncology Department of Genetics The University of Texas M.D.Anderson Cancer Center

In the field of antitumor drug development, it is common to see paired images of cultured cancer cells： one mock- treated, and the other subjected to a small molecular drug that leads to cell death or growth suppression （Figure 1）. One＇s common perception is that an inhibitor is at work to inactivate a critical factor or pathway essential for cancer cell survival. In the August issue of Cancer Cell [1], how- ever, a team of researchers from Baylor College of Medi- cine led by Dr. Bert O＇Malley described a completely op- posite path for the annihilation of tumors. Instead of using drugs to inhibit the oncogene targets, they used an activator molecule to overstimulate them. The apparent effectiveness and selectiveness of cancer cell killing are astounding.

关键词：癌细胞小分子药物药物开发肿瘤细胞抗肿瘤生长抑制细胞死亡细胞生存

Single-cell omics: experimental workflow, data analyses and applications

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Science China(Life Sciences) 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University(The Second People’s Hospital of Wuhu City)Wuhu 241000China Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration(Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200082China Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200082China Research Institute of Intelligent Computing Zhejiang LabHangzhou 311121China Shanghai Research Institute for Intelligent Autonomous Systems Shanghai 201210China Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of MedicineShanghai 200025China National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314103China Center for bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology(CQB)Peking UniversityBeijing 100871China Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal U

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular *** exploration of how the genomes orchestrate the formation and maintenance of each cell,and control the cellular phenotypes of various organismsis,is both captivating and *** the inception of the first single-cell RNA technology,technologies related to single-cell sequencing have experienced rapid advancements in recent *** technologies have expanded horizontally to include single-cell genome,epigenome,proteome,and metabolome,while vertically,they have progressed to integrate multiple omics data and incorporate additional information such as spatial scRNA-seq and CRISPR ***-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases,including ***,we comprehensively summarize recent advances in single-cell omics technologies,with a specific focus on the methodology *** overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

Crop Epigenomics： Identifying, Unlocking, and Harnessing Cryptic Variation in Crop Genomes

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Molecular Plant 2015年第6期8卷 860-870页

作者： Lexiang Ji Drexel A. Neumann Robert J. Schmitz Department of genetics University of Georgia Athens GA 30602 USA Institute of bioinformatics University of Georgia Athens GA 30602 USA These authors contributed equally to this article.

DNA methylation is a key chromatin modification in plant genomes that is meiotically and mitotically her- itable, and at times is associated with gene expression and morphological variation. Benefiting from the increased availability of high-quality reference genome assemblies and methods to profile single-base res- olution DNA methylation states, DNA methylomes for many crop species are available. These efforts are making it possible to begin answering crucial questions, including understanding the role of DNA methyl- ation in developmental processes, its role in crop species evolution, and whether DNA methylation is dynamically altered and heritable in response to changes in the environment. These genome-wide maps provide evidence for the existence of silent epialleles in plant genomes which, once identified, can be tar- geted for reactivation leading to phenotypic variation.

关键词： epigenomics DNA methylation whole-genome bisulfite sequencing (WGBS) crops comparativegenomics

Expression and responses to dehydration and salinity stresses of V-PPase gene members in wheat

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Journal of genetics and Genomics 2009年第12期36卷 711-720页

作者： Yuezhi Wang Haibin Xu Guangxiang Zhang Huilan Zhu Lixia Zhang Zhengzhi Zhang Caiqin Zhang Zhengqiang Ma The Applied Plant Genomics Laboratory Crop Genomics and Bioinformatics Center & National Key Lab of Crop Genetics and Germplasm Enhancement Nanjing Agricultural University Nanjing 210095 China

Vacuolar H^＋-translocating pyrophosphatase （V-PPase） is a key enzyme related to plant growth as well as abiotic stress tolerance. In this work, wheat V-PPase genes TaVP1, TaVP2 and TaVP3 were identified. TaVP1 and TaVP2 are more similar to each other than to TaVP3. Their deduced polypeptide sequences preserve the topological structure and essential residues of V-PPases. Phylogenetic studies suggested that monocot plants, at least monocot grasses, have three VP paralogs. TaVP3 transcripts were only detected in developing seeds, and no TaVP2 transcripts were found in germinating seeds. TaVP2 was mainly expressed in shoot tissues and down-regulated in leaves under dehydration. Its expression was up-regulated in roots under high salinity. TaVP1 was relatively more ubiquitously and evenly expressed than TaVP2. Its expression level in roots was highest among the tissues examined, and was inducible by salinity stress. These results indicated that the V-PPase gene paralogs in wheat are differentially regulated spatially and in response to dehydration and salinity stresses.

关键词： vacuolar H^+-pyrophosphatase abiotic stress phylogenetic analysis

Protein Subcellular Localization Prediction and Genomic Polymorphism Analysis of the SARS Coronavirus

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Tsinghua Science and Technology 2004年第4期9卷 384-390页

作者：季星来柳树群李岭孙之荣 Institute of bioinformatics Department of Biological Sciences and BiotechnologyTsinghua University Beijing 100084 China Department of Medical genetics China Medical University Shenyang 110001China

The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavi-rus (CoV). Several sequences of the complete genome of SARS-CoV have been determined. The subcellu-lar localization (SubLocation) of annotated open-reading frames of the SARS-CoV genome was predicted using a support vector machine. Several gene products were predicted to locate in the Golgi body and cell nucleus. The SubLocation information was combined with predicted transmembrane information to develop a model of the viral life cycle. The results show that this information can be used to predict the functions of genes and even the virus pathogenesis. In addition, the entire SARS viral genome sequences currently available in GenBank were compared to identify the sequence variations among different isolates. Some variations in the Hong Kong strains may be related to the special clinical manifestations and provide clues for understanding the relationship between gene functions and evolution. These variations reflect the evolu-tion of the SARS virus in human populations and may help development of a vaccine.

关键词： severe acute respiratory syndrome (SARS) subcellular localization viral life cycle genomic polymorphism

Highly Regional Genes:graph-based gene selection for single-cell RNA-seq data

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Journal of genetics and Genomics 2022年第9期49卷 891-899页

作者： Yanhong Wu Qifan Hu Shicheng Wang Changyi Liu Yiran Shan Wenbo Guo Rui Jiang Xiaowo Wang Jin Gu MOE Key Laboratory of bioinformatics BNRIST Bioinformatics DivisionDepartment of AutomationTsinghua UniversityBeijing 100084China

Gene selection is an indispensable step for analyzing noisy and high-dimensional single-cell RNA-seq(scRNA-seq)*** with the commonly used variance-based methods,by mimicking the human maker selection in the 2D visualization of cells,a new feature selection method called HRG(Highly Regional Genes)is proposed to find the informative genes,which show regional expression patterns in the cell-cell similarity *** mathematically find the optimal expression patterns that can maximize the proposed scoring *** comparison with several unsupervised methods,HRG shows high accuracy and robustness,and can increase the performance of downstream cell clustering and gene correlation ***,it is applicable for selecting informative genes of sequencing-based spatial transcriptomic data.

关键词： Single-cell RNA-sequencing Feature selection Spatially resolved transcriptomic data Regional patterns Graphical models