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  • 1
    Publication Date: 2018-04-24
    Description: Invariant NKT (iNKT) cells have been shown to help B cells in a cognate or noncognate manner; however, whether cognate iNKT cell help induces B cell memory responses remains controversial, and the underlying mechanisms are still unclear. In this study, we demonstrated that, in the absence of follicular helper T cells, cognate iNKT cell help could promote B cell memory responses in mice that were dependent on the formation of memory follicular helper iNKT (iNKT FH ) cells and their interactions with memory B cells in recall responses. Generation of memory iNKT FH cells required lipid Ag presentation by dendritic cells but not by B cells. Upon rechallenge, memory iNKT FH cells recognized lipid Ags presented by memory B cells, which recalled iNKT FH effector cells and elicited B cell memory responses. However, LPS, which promoted the synthesis of self-lipids, failed to elicit recall responses in the absence of exogenous lipid Ags.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Publication Date: 2012-12-04
    Description: Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high messenger RNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a range of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25-nucleotide 'TINCR box' motif that is strongly enriched in interacting mRNAs and required for TINCR binding. A high-throughput screen to analyse TINCR binding capacity to approximately 9,400 human recombinant proteins revealed direct binding of TINCR RNA to the staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay, however, did not have differentiation effects. Instead, the TINCR-STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through lncRNA binding to differentiation mRNAs to ensure their expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674581/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kretz, Markus -- Siprashvili, Zurab -- Chu, Ci -- Webster, Dan E -- Zehnder, Ashley -- Qu, Kun -- Lee, Carolyn S -- Flockhart, Ross J -- Groff, Abigail F -- Chow, Jennifer -- Johnston, Danielle -- Kim, Grace E -- Spitale, Robert C -- Flynn, Ryan A -- Zheng, Grace X Y -- Aiyer, Subhadra -- Raj, Arjun -- Rinn, John L -- Chang, Howard Y -- Khavari, Paul A -- AR49737/AR/NIAMS NIH HHS/ -- DP2 OD008514/OD/NIH HHS/ -- P30 CA124435/CA/NCI NIH HHS/ -- R01 AR049737/AR/NIAMS NIH HHS/ -- R01 HG004361/HG/NHGRI NIH HHS/ -- R01-HG004361/HG/NHGRI NIH HHS/ -- T32 AR007422/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jan 10;493(7431):231-5. doi: 10.1038/nature11661. Epub 2012 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23201690" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Differentiation/*genetics ; Cells, Cultured ; Cytoskeletal Proteins/metabolism ; Epidermis/*cytology/*metabolism ; Gene Expression Regulation ; High-Throughput Screening Assays ; Humans ; Keratinocytes ; Mutation ; Nucleotide Motifs/genetics ; Protein Binding ; RNA Stability/genetics ; RNA, Long Noncoding/*genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/metabolism ; Skin Diseases/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    Nature Publishing Group (NPG)
    Publication Date: 2013-07-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connor, Jingmai -- Zheng, Xiaoting -- Zhou, Zhonghe -- England -- Nature. 2013 Jul 11;499(7457):E1-2. doi: 10.1038/nature12368.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Vertebrate Evolution and Human Origin, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China. jingmai.oconnor@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23846662" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Birds/*anatomy & histology/*physiology ; Female ; *Fossils ; Ovarian Follicle/*anatomy & histology/*physiology ; Reproduction/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-10-04
    Description: Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617611/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617611/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sudmant, Peter H -- Rausch, Tobias -- Gardner, Eugene J -- Handsaker, Robert E -- Abyzov, Alexej -- Huddleston, John -- Zhang, Yan -- Ye, Kai -- Jun, Goo -- Hsi-Yang Fritz, Markus -- Konkel, Miriam K -- Malhotra, Ankit -- Stutz, Adrian M -- Shi, Xinghua -- Paolo Casale, Francesco -- Chen, Jieming -- Hormozdiari, Fereydoun -- Dayama, Gargi -- Chen, Ken -- Malig, Maika -- Chaisson, Mark J P -- Walter, Klaudia -- Meiers, Sascha -- Kashin, Seva -- Garrison, Erik -- Auton, Adam -- Lam, Hugo Y K -- Jasmine Mu, Xinmeng -- Alkan, Can -- Antaki, Danny -- Bae, Taejeong -- Cerveira, Eliza -- Chines, Peter -- Chong, Zechen -- Clarke, Laura -- Dal, Elif -- Ding, Li -- Emery, Sarah -- Fan, Xian -- Gujral, Madhusudan -- Kahveci, Fatma -- Kidd, Jeffrey M -- Kong, Yu -- Lameijer, Eric-Wubbo -- McCarthy, Shane -- Flicek, Paul -- Gibbs, Richard A -- Marth, Gabor -- Mason, Christopher E -- Menelaou, Androniki -- Muzny, Donna M -- Nelson, Bradley J -- Noor, Amina -- Parrish, Nicholas F -- Pendleton, Matthew -- Quitadamo, Andrew -- Raeder, Benjamin -- Schadt, Eric E -- Romanovitch, Mallory -- Schlattl, Andreas -- Sebra, Robert -- Shabalin, Andrey A -- Untergasser, Andreas -- Walker, Jerilyn A -- Wang, Min -- Yu, Fuli -- Zhang, Chengsheng -- Zhang, Jing -- Zheng-Bradley, Xiangqun -- Zhou, Wanding -- Zichner, Thomas -- Sebat, Jonathan -- Batzer, Mark A -- McCarroll, Steven A -- 1000 Genomes Project Consortium -- Mills, Ryan E -- Gerstein, Mark B -- Bashir, Ali -- Stegle, Oliver -- Devine, Scott E -- Lee, Charles -- Eichler, Evan E -- Korbel, Jan O -- P01HG007497/HG/NHGRI NIH HHS/ -- R01 CA166661/CA/NCI NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- R01 HG002898/HG/NHGRI NIH HHS/ -- R01CA166661/CA/NCI NIH HHS/ -- R01GM59290/GM/NIGMS NIH HHS/ -- R01HG002898/HG/NHGRI NIH HHS/ -- R01HG007068/HG/NHGRI NIH HHS/ -- RR029676-01/RR/NCRR NIH HHS/ -- RR19895/RR/NCRR NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- U41 HG007497/HG/NHGRI NIH HHS/ -- U41HG007497/HG/NHGRI NIH HHS/ -- WT085532/Z/08/Z/Wellcome Trust/United Kingdom -- WT104947/Z/14/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Oct 1;526(7571):75-81. doi: 10.1038/nature15394.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, 3720 15th Avenue NE, Seattle, Washington 98195-5065, USA. ; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Institute for Genome Sciences, University of Maryland School of Medicine, 801 W Baltimore Street, Baltimore, Maryland 21201, USA. ; Department of Genetics, Harvard Medical School, Boston, 25 Shattuck Street, Boston, Massachusetts 02115, USA. ; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. ; Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA. ; Program in Computational Biology and Bioinformatics, Yale University, BASS 432 &437, 266 Whitney Avenue, New Haven, Connecticut 06520, USA. ; Department of Molecular Biophysics and Biochemistry, School of Medicine, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA. ; The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Department of Genetics, Washington University in St Louis, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA. ; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, 1200 Pressler St., Houston, Texas 77030, USA. ; Department of Biological Sciences, Louisiana State University, 202 Life Sciences Building, Baton Rouge, Louisiana 70803, USA. ; The Jackson Laboratory for Genomic Medicine, 10 Discovery 263 Farmington Avenue, Farmington, Connecticut 06030, USA. ; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, North Carolina 28223, USA. ; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, Connecticut 06520, USA. ; Department of Computational Medicine &Bioinformatics, University of Michigan, 500 S. State Street, Ann Arbor, Michigan 48109, USA. ; The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. ; Department of Biology, Boston College, 355 Higgins Hall, 140 Commonwealth Avenue, Chestnut Hill, Massachusetts 02467, USA. ; Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, New York 10461, USA. ; Bina Technologies, Roche Sequencing, 555 Twin Dolphin Drive, Redwood City, California 94065, USA. ; Cancer Program, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; Department of Computer Engineering, Bilkent University, 06800 Ankara, Turkey. ; University of California San Diego (UCSD), 9500 Gilman Drive, La Jolla, California 92093, USA. ; National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 USA. ; Department of Medicine, Washington University in St Louis, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Siteman Cancer Center, 660 South Euclid Avenue, St Louis, Missouri 63110, USA. ; Department of Human Genetics, University of Michigan, 1241 Catherine Street, Ann Arbor, Michigan 48109, USA. ; Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RA, The Netherlands. ; Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA. ; The Department of Physiology and Biophysics and the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, 1305 York Avenue, Weill Cornell Medical College, New York, New York 10065, USA. ; The Feil Family Brain and Mind Research Institute, 413 East 69th St, Weill Cornell Medical College, New York, New York 10065, USA. ; University of Oxford, 1 South Parks Road, Oxford OX3 9DS, UK. ; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands. ; Department of Genetics and Genomic Sciences, Icahn School of Medicine, New York School of Natural Sciences, 1428 Madison Avenue, New York, New York 10029, USA. ; Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. ; Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, 1112 East Clay Street, McGuire Hall, Richmond, Virginia 23298-0581, USA. ; Zentrum fur Molekulare Biologie, University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. ; Department of Computer Science, Yale University, 51 Prospect Street, New Haven, Connecticut 06511, USA. ; Department of Graduate Studies - Life Sciences, Ewha Womans University, Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, South Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26432246" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Genetic Predisposition to Disease ; Genetic Variation/*genetics ; Genetics, Medical ; Genetics, Population ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genomics ; Genotype ; Haplotypes/genetics ; Homozygote ; Humans ; Molecular Sequence Data ; Mutation Rate ; *Physical Chromosome Mapping ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Sequence Analysis, DNA ; Sequence Deletion/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Yi-Gang -- Shi, Wei-Feng -- Liu, Di -- Qian, Jun -- Liang, Long -- Bo, Xiao-Chen -- Liu, Jun -- Ren, Hong-Guang -- Fan, Hang -- Ni, Ming -- Sun, Yang -- Jin, Yuan -- Teng, Yue -- Li, Zhen -- Kargbo, David -- Dafae, Foday -- Kanu, Alex -- Chen, Cheng-Chao -- Lan, Zhi-Heng -- Jiang, Hui -- Luo, Yang -- Lu, Hui-Jun -- Zhang, Xiao-Guang -- Yang, Fan -- Hu, Yi -- Cao, Yu-Xi -- Deng, Yong-Qiang -- Su, Hao-Xiang -- Sun, Yu -- Liu, Wen-Sen -- Wang, Zhuang -- Wang, Cheng-Yu -- Bu, Zhao-Yang -- Guo, Zhen-Dong -- Zhang, Liu-Bo -- Nie, Wei-Min -- Bai, Chang-Qing -- Sun, Chun-Hua -- An, Xiao-Ping -- Xu, Pei-Song -- Zhang, Xiang-Li-Lan -- Huang, Yong -- Mi, Zhi-Qiang -- Yu, Dong -- Yao, Hong-Wu -- Feng, Yong -- Xia, Zhi-Ping -- Zheng, Xue-Xing -- Yang, Song-Tao -- Lu, Bing -- Jiang, Jia-Fu -- Kargbo, Brima -- He, Fu-Chu -- Gao, George F -- Cao, Wu-Chun -- China Mobile Laboratory Testing Team in Sierra Leone -- England -- Nature. 2015 Oct 22;526(7574):595. doi: 10.1038/nature15255. Epub 2015 Aug 26.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26308898" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2015-05-15
    Description: A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 x 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 x 10(-3) to 1.41 x 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Yi-Gang -- Shi, Wei-Feng -- Liu, Di -- Qian, Jun -- Liang, Long -- Bo, Xiao-Chen -- Liu, Jun -- Ren, Hong-Guang -- Fan, Hang -- Ni, Ming -- Sun, Yang -- Jin, Yuan -- Teng, Yue -- Li, Zhen -- Kargbo, David -- Dafae, Foday -- Kanu, Alex -- Chen, Cheng-Chao -- Lan, Zhi-Heng -- Jiang, Hui -- Luo, Yang -- Lu, Hui-Jun -- Zhang, Xiao-Guang -- Yang, Fan -- Hu, Yi -- Cao, Yu-Xi -- Deng, Yong-Qiang -- Su, Hao-Xiang -- Sun, Yu -- Liu, Wen-Sen -- Wang, Zhuang -- Wang, Cheng-Yu -- Bu, Zhao-Yang -- Guo, Zhen-Dong -- Zhang, Liu-Bo -- Nie, Wei-Min -- Bai, Chang-Qing -- Sun, Chun-Hua -- An, Xiao-Ping -- Xu, Pei-Song -- Zhang, Xiang-Li-Lan -- Huang, Yong -- Mi, Zhi-Qiang -- Yu, Dong -- Yao, Hong-Wu -- Feng, Yong -- Xia, Zhi-Ping -- Zheng, Xue-Xing -- Yang, Song-Tao -- Lu, Bing -- Jiang, Jia-Fu -- Kargbo, Brima -- He, Fu-Chu -- Gao, George F -- Cao, Wu-Chun -- China Mobile Laboratory Testing Team in Sierra Leone -- England -- Nature. 2015 Aug 6;524(7563):93-6. doi: 10.1038/nature14490. Epub 2015 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China. ; Institute of Pathogen Biology, Taishan Medical College, Taian 271000, China. ; Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. ; Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122, China. ; Beijing Key Laboratory of New Molecular Diagnostics Technology, Beijing 100850, China. ; Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. ; Sierra Leone Ministry of Health and Sanitation, Freetown, Sierra Leone. ; Sierra Leone-China Friendship Hospital, Freetown, Sierra Leone. ; BGI-Shenzhen, Shenzhen 518083, China. ; Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK. ; Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100730, China. ; Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing 100021, China. ; The No. 302 Hospital, Beijing 100039, China. ; The No. 307 Hospital, Beijing 100071, China. ; Department of international cooperation, National Health and Family Planning Commission, Beijing 100044, China. ; State Key Laboratory of Proteomics, Beijing 102206, China. ; 1] Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China [2] Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China [3] Chinese Center for Disease Control and Prevention, Beijing 102206, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25970247" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-03-17
    Description: CD8(+) T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment. Reactivating the cytotoxicity of CD8(+) T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8(+) T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme, led to potentiated effector function and enhanced proliferation of CD8(+) but not CD4(+) T cells. This is due to the increase in the plasma membrane cholesterol level of CD8(+) T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8(+) T cells were better than wild-type CD8(+) T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851431/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851431/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Wei -- Bai, Yibing -- Xiong, Ying -- Zhang, Jin -- Chen, Shuokai -- Zheng, Xiaojun -- Meng, Xiangbo -- Li, Lunyi -- Wang, Jing -- Xu, Chenguang -- Yan, Chengsong -- Wang, Lijuan -- Chang, Catharine C Y -- Chang, Ta-Yuan -- Zhang, Ti -- Zhou, Penghui -- Song, Bao-Liang -- Liu, Wanli -- Sun, Shao-cong -- Liu, Xiaolong -- Li, Bo-liang -- Xu, Chenqi -- HL 60306./HL/NHLBI NIH HHS/ -- R01 HL060306/HL/NHLBI NIH HHS/ -- England -- Nature. 2016 Mar 31;531(7596):651-5. doi: 10.1038/nature17412. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Science Research Center, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; MOE Key Laboratory of Protein Science, School of Life Sciences, Collaborative Innovation Center for Infectious Diseases, Tsinghua University, Beijing 100084, China. ; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Haven 03755, USA. ; Rheumatology and Immunology Department of ChangZheng Hospital, Second Military Medical University, Shanghai 200433, China. ; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. ; College of Life Sciences, Wuhan University, Wuhan, Hubei Province 430072, China. ; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA. ; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982734" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates/*pharmacology/therapeutic use ; Acetyl-CoA C-Acetyltransferase/antagonists & ; inhibitors/deficiency/genetics/metabolism ; Animals ; Atherosclerosis/drug therapy ; CD8-Positive T-Lymphocytes/*drug effects/*immunology/metabolism ; Cell Membrane/drug effects/metabolism ; Cholesterol/*metabolism ; Esterification/drug effects ; Female ; Immunological Synapses/drug effects/immunology/metabolism ; Immunotherapy/*methods ; Male ; Melanoma/*drug therapy/*immunology/metabolism/pathology ; Mice ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; Receptors, Antigen, T-Cell/immunology/metabolism ; Signal Transduction/drug effects ; Sulfonic Acids/*pharmacology/therapeutic use
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2016-05-27
    Description: Haematopoietic stem cells (HSCs) are derived early from embryonic precursors, such as haemogenic endothelial cells and pre-haematopoietic stem cells (pre-HSCs), the molecular identity of which still remains elusive. Here we use potent surface markers to capture the nascent pre-HSCs at high purity, as rigorously validated by single-cell-initiated serial transplantation. Then we apply single-cell RNA sequencing to analyse endothelial cells, CD45(-) and CD45(+) pre-HSCs in the aorta-gonad-mesonephros region, and HSCs in fetal liver. Pre-HSCs show unique features in transcriptional machinery, arterial signature, metabolism state, signalling pathway, and transcription factor network. Functionally, activation of mechanistic targets of rapamycin (mTOR) is shown to be indispensable for the emergence of HSCs but not haematopoietic progenitors. Transcriptome data-based functional analysis reveals remarkable heterogeneity in cell-cycle status of pre-HSCs. Finally, the core molecular signature of pre-HSCs is identified. Collectively, our work paves the way for dissection of complex molecular mechanisms regulating stepwise generation of HSCs in vivo, informing future efforts to engineer HSCs for clinical applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Fan -- Li, Xianlong -- Wang, Weili -- Zhu, Ping -- Zhou, Jie -- He, Wenyan -- Ding, Meng -- Xiong, Fuyin -- Zheng, Xiaona -- Li, Zhuan -- Ni, Yanli -- Mu, Xiaohuan -- Wen, Lu -- Cheng, Tao -- Lan, Yu -- Yuan, Weiping -- Tang, Fuchou -- Liu, Bing -- England -- Nature. 2016 May 18;533(7604):487-92. doi: 10.1038/nature17997.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Proteomics, Translational Medicine Center of Stem Cells, 307-Ivy Translational Medicine Center, Laboratory of Oncology, Affiliated Hospital, Academy of Military Medical Sciences, Beijing 100071, China. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. ; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin 300020, China. ; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ; Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China. ; Collaborative Innovation Center for Cancer Medicine, National Institute of Biological Sciences, Tianjin 300020, China. ; State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, China. ; Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. ; Institute of Hematology, Medical College of Jinan University, Guangzhou 510632, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27225119" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-10-18
    Description: The atomic nucleus is composed of two different kinds of fermions: protons and neutrons. If the protons and neutrons did not interact, the Pauli exclusion principle would force the majority of fermions (usually neutrons) to have a higher average momentum. Our high-energy electron-scattering measurements using (12)C, (27)Al, (56)Fe, and (208)Pb targets show that even in heavy, neutron-rich nuclei, short-range interactions between the fermions form correlated high-momentum neutron-proton pairs. Thus, in neutron-rich nuclei, protons have a greater probability than neutrons to have momentum greater than the Fermi momentum. This finding has implications ranging from nuclear few-body systems to neutron stars and may also be observable experimentally in two-spin-state, ultracold atomic gas systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hen, O -- Sargsian, M -- Weinstein, L B -- Piasetzky, E -- Hakobyan, H -- Higinbotham, D W -- Braverman, M -- Brooks, W K -- Gilad, S -- Adhikari, K P -- Arrington, J -- Asryan, G -- Avakian, H -- Ball, J -- Baltzell, N A -- Battaglieri, M -- Beck, A -- May-Tal Beck, S -- Bedlinskiy, I -- Bertozzi, W -- Biselli, A -- Burkert, V D -- Cao, T -- Carman, D S -- Celentano, A -- Chandavar, S -- Colaneri, L -- Cole, P L -- Crede, V -- D'Angelo, A -- De Vita, R -- Deur, A -- Djalali, C -- Doughty, D -- Dugger, M -- Dupre, R -- Egiyan, H -- El Alaoui, A -- El Fassi, L -- Elouadrhiri, L -- Fedotov, G -- Fegan, S -- Forest, T -- Garillon, B -- Garcon, M -- Gevorgyan, N -- Ghandilyan, Y -- Gilfoyle, G P -- Girod, F X -- Goetz, J T -- Gothe, R W -- Griffioen, K A -- Guidal, M -- Guo, L -- Hafidi, K -- Hanretty, C -- Hattawy, M -- Hicks, K -- Holtrop, M -- Hyde, C E -- Ilieva, Y -- Ireland, D G -- Ishkanov, B I -- Isupov, E L -- Jiang, H -- Jo, H S -- Joo, K -- Keller, D -- Khandaker, M -- Kim, A -- Kim, W -- Klein, F J -- Koirala, S -- Korover, I -- Kuhn, S E -- Kubarovsky, V -- Lenisa, P -- Levine, W I -- Livingston, K -- Lowry, M -- Lu, H Y -- MacGregor, I J D -- Markov, N -- Mayer, M -- McKinnon, B -- Mineeva, T -- Mokeev, V -- Movsisyan, A -- Munoz Camacho, C -- Mustapha, B -- Nadel-Turonski, P -- Niccolai, S -- Niculescu, G -- Niculescu, I -- Osipenko, M -- Pappalardo, L L -- Paremuzyan, R -- Park, K -- Pasyuk, E -- Phelps, W -- Pisano, S -- Pogorelko, O -- Price, J W -- Procureur, S -- Prok, Y -- Protopopescu, D -- Puckett, A J R -- Rimal, D -- Ripani, M -- Ritchie, B G -- Rizzo, A -- Rosner, G -- Roy, P -- Rossi, P -- Sabatie, F -- Schott, D -- Schumacher, R A -- Sharabian, Y G -- Smith, G D -- Shneor, R -- Sokhan, D -- Stepanyan, S S -- Stepanyan, S -- Stoler, P -- Strauch, S -- Sytnik, V -- Taiuti, M -- Tkachenko, S -- Ungaro, M -- Vlassov, A V -- Voutier, E -- Walford, N K -- Wei, X -- Wood, M H -- Wood, S A -- Zachariou, N -- Zana, L -- Zhao, Z W -- Zheng, X -- Zonta, I -- Jefferson Lab CLAS Collaboration -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):614-7. doi: 10.1126/science.1256785. Epub 2014 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tel Aviv University, Tel Aviv 69978, Israel. or.chen@mail.huji.ac.il. ; Florida International University, Miami, FL 33199, USA. ; Old Dominion University, Norfolk, VA 23529, USA. ; Tel Aviv University, Tel Aviv 69978, Israel. ; Universidad Tecnica Federico Santa Maria, Casilla 110-V Valparaiso, Chile. Yerevan Physics Institute, 375036 Yerevan, Armenia. ; Thomas Jefferson National Accelerator Facility, Newport News, VA 23606, USA. ; Universidad Tecnica Federico Santa Maria, Casilla 110-V Valparaiso, Chile. ; Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Argonne National Laboratory, Argonne, IL 60439, USA. ; Yerevan Physics Institute, 375036 Yerevan, Armenia. ; Commissariat a l'Energie Atomique et aux Energies Alternatives, Centre de Saclay, Irfu/Service de Physique Nucleaire, 91191 Gif-sur-Yvette, France. ; Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Genova, 16146 Genova, Italy. ; Tel Aviv University, Tel Aviv 69978, Israel. Nuclear Research Center Negev, P.O. Box 9001, Beer-Sheva 84190, Israel. ; Institute of Theoretical and Experimental Physics, Moscow, 117259, Russia. ; Fairfield University, Fairfield, CT 06824, USA. ; University of South Carolina, Columbia, SC 29208, USA. ; Ohio University, Athens, OH 45701, USA. ; INFN, Sezione di Roma Tor Vergata, 00133 Rome, Italy. ; Thomas Jefferson National Accelerator Facility, Newport News, VA 23606, USA. Idaho State University, Pocatello, ID 83209, USA. Catholic University of America, Washington, DC 20064, USA. ; Florida State University, Tallahassee, FL 32306, USA. ; INFN, Sezione di Roma Tor Vergata, 00133 Rome, Italy. Universita di Roma Tor Vergata, 00133 Rome, Italy. ; University of South Carolina, Columbia, SC 29208, USA. University of Iowa, Iowa City, IA 52242, USA. ; Thomas Jefferson National Accelerator Facility, Newport News, VA 23606, USA. Christopher Newport University, Newport News, VA 23606, USA. ; Arizona State University, Tempe, AZ 85287-1504, USA. ; Institut de Physique Nucleaire ORSAY, Orsay, France. ; University of South Carolina, Columbia, SC 29208, USA. Skobeltsyn Institute of Nuclear Physics, Lomonosov, Russia. ; Idaho State University, Pocatello, ID 83209, USA. ; University of Richmond, Richmond, VA 23173, USA. ; College of William and Mary, Williamsburg, VA 23187-8795, USA. ; Florida International University, Miami, FL 33199, USA. Thomas Jefferson National Accelerator Facility, Newport News, VA 23606, USA. ; University of Virginia, Charlottesville, VA 22901, USA. ; University of New Hampshire, Durham, NH 03824-3568, USA. ; University of South Carolina, Columbia, SC 29208, USA. The George Washington University, Washington, DC 20052, USA. ; University of Glasgow, Glasgow G12 8QQ, UK. ; Skobeltsyn Institute of Nuclear Physics, Lomonosov, Russia. ; University of Connecticut, Storrs, CT 06269, USA. ; Idaho State University, Pocatello, ID 83209, USA. Norfolk State University, Norfolk, VA 23504, USA. ; Kyungpook National University, Daegu 702-701, Republic of Korea. ; Catholic University of America, Washington, DC 20064, USA. ; INFN, Sezione di Ferrara, 44100 Ferrara, Italy. ; Carnegie Mellon University, Pittsburgh, PA 15213, USA. ; Thomas Jefferson National Accelerator Facility, Newport News, VA 23606, USA. Institut de Physique Nucleaire ORSAY, Orsay, France. Moscow State University, Moscow, 119234, Russia. ; James Madison University, Harrisonburg, VA 22807, USA. ; INFN, Sezione di Ferrara, 44100 Ferrara, Italy. Universita di Ferrara, 44122 Ferrara, Italy. ; Yerevan Physics Institute, 375036 Yerevan, Armenia. University of New Hampshire, Durham, NH 03824-3568, USA. ; Thomas Jefferson National Accelerator Facility, Newport News, VA 23606, USA. Kyungpook National University, Daegu 702-701, Republic of Korea. ; INFN, Laboratori Nazionali di Frascati, 00044 Frascati, Italy. ; California State University, Dominguez Hills, Carson, CA 90747, USA. ; Old Dominion University, Norfolk, VA 23529, USA. University of Virginia, Charlottesville, VA 22901, USA. ; The George Washington University, Washington, DC 20052, USA. ; Edinburgh University, Edinburgh EH9 3JZ, UK. ; Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA. ; Universita di Genova, 16146 Genova, Italy. ; Laboratoire de Physique Subatomique et de Cosmologie, Universite Joseph Fourier, CNRS/IN2P3, Institut National Polytechnique, Grenoble, France. ; University of South Carolina, Columbia, SC 29208, USA. Canisius College, Buffalo, NY 14208, USA. ; University of New Hampshire, Durham, NH 03824-3568, USA. Edinburgh University, Edinburgh EH9 3JZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25323697" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-07-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Xiaoyan -- Lv, Yibing -- England -- Nature. 2015 Jul 16;523(7560):290. doi: 10.1038/523290e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉China National Environmental Monitoring Center, Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26178953" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Cities ; Environmental Monitoring/*instrumentation ; Environmental Policy/*legislation & jurisprudence ; Environmental Pollution/*analysis/statistics & numerical data
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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