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  • 1
    Publication Date: 2011-02-04
    Description: Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression. Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFbeta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" 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/PMC3753179/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Zhihu -- Wu, Chang-Jiun -- Chu, Gerald C -- Xiao, Yonghong -- Ho, Dennis -- Zhang, Jingfang -- Perry, Samuel R -- Labrot, Emma S -- Wu, Xiaoqiu -- Lis, Rosina -- Hoshida, Yujin -- Hiller, David -- Hu, Baoli -- Jiang, Shan -- Zheng, Hongwu -- Stegh, Alexander H -- Scott, Kenneth L -- Signoretti, Sabina -- Bardeesy, Nabeel -- Wang, Y Alan -- Hill, David E -- Golub, Todd R -- Stampfer, Meir J -- Wong, Wing H -- Loda, Massimo -- Mucci, Lorelei -- Chin, Lynda -- DePinho, Ronald A -- P50 CA090381/CA/NCI NIH HHS/ -- P50 CA090381-08/CA/NCI NIH HHS/ -- P50 CA90381/CA/NCI NIH HHS/ -- R01 5R01CA136578/CA/NCI NIH HHS/ -- R01 CA131945/CA/NCI NIH HHS/ -- R01CA131945/CA/NCI NIH HHS/ -- R01CA141298/CA/NCI NIH HHS/ -- U01-CA84313/CA/NCI NIH HHS/ -- England -- Nature. 2011 Feb 10;470(7333):269-73. doi: 10.1038/nature09677. Epub 2011 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21289624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Proliferation ; Cyclin D1/genetics/metabolism ; *Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor/physiology ; Humans ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Mice ; Mice, Transgenic ; Models, Biological ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/*pathology ; Osteopontin/genetics/metabolism ; PTEN Phosphohydrolase/deficiency/genetics ; Penetrance ; Prognosis ; Prostate/metabolism ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/diagnosis/genetics/*pathology ; Smad4 Protein/deficiency/genetics/*metabolism ; Transforming Growth Factor beta
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-11-11
    Description: DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B, and the methylation patterns vary with developmental stages and cell types. DNA methyltransferase 3-like protein (DNMT3L) is a catalytically inactive paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a. Recent studies have established a connection between DNA methylation and histone modifications, and revealed a histone-guided mechanism for the establishment of DNA methylation. The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes unmethylated histone H3 (H3K4me0). The histone H3 tail stimulates the enzymatic activity of Dnmt3a in vitro, whereas the molecular mechanism remains elusive. Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3 tail stimulates its activity in a DNMT3L-independent manner. We determine the crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3 (active form) complexes at 3.82 and 2.90 A resolution, respectively. Structural and biochemical analyses indicate that the ADD domain of DNMT3A interacts with and inhibits enzymatic activity of the catalytic domain (CD) through blocking its DNA-binding affinity. Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. The finding adds another layer of regulation of DNA methylation to ensure that the enzyme is mainly activated at proper targeting loci when unmethylated H3K4 is present, and strongly supports a negative correlation between H3K4me3 and DNA methylation across the mammalian genome. Our study provides a new insight into an unexpected autoinhibition and histone H3-induced activation of the de novo DNA methyltransferase after its initial genomic positioning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Xue -- Wang, Ling -- Li, Jie -- Ding, Zhanyu -- Xiao, Jianxiong -- Yin, Xiaotong -- He, Shuang -- Shi, Pan -- Dong, Liping -- Li, Guohong -- Tian, Changlin -- Wang, Jiawei -- Cong, Yao -- Xu, Yanhui -- England -- Nature. 2015 Jan 29;517(7536):640-4. doi: 10.1038/nature13899. Epub 2014 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China [2] State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China. ; Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. ; National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. ; 1] High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China [2] National Laboratory for Physical Science at the Microscale, University of Science and Technology of China, Hefei 230026, China [3] School of Life Sciences, University of Science and Technology of China, Hefei 230026, China. ; 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China [2] University of Chinese Academy of Science, Beijing 100049, China. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China. ; State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383530" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalytic Domain ; Crystallography, X-Ray ; DNA/metabolism ; DNA (Cytosine-5-)-Methyltransferase/*antagonists & ; inhibitors/*chemistry/*metabolism ; DNA Methylation ; Enzyme Activation ; Histones/*chemistry/*metabolism ; Humans ; Mice ; Models, Molecular ; Protein Structure, Tertiary ; Xenopus laevis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2011-09-03
    Description: In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions. Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise. Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines--including CCL11 (also known as eotaxin)--the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170097/" 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/PMC3170097/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Villeda, Saul A -- Luo, Jian -- Mosher, Kira I -- Zou, Bende -- Britschgi, Markus -- Bieri, Gregor -- Stan, Trisha M -- Fainberg, Nina -- Ding, Zhaoqing -- Eggel, Alexander -- Lucin, Kurt M -- Czirr, Eva -- Park, Jeong-Soo -- Couillard-Despres, Sebastien -- Aigner, Ludwig -- Li, Ge -- Peskind, Elaine R -- Kaye, Jeffrey A -- Quinn, Joseph F -- Galasko, Douglas R -- Xie, Xinmin S -- Rando, Thomas A -- Wyss-Coray, Tony -- 1 F31 AG034045-01/AG/NIA NIH HHS/ -- 1 F31 NS066676-01A1/NS/NINDS NIH HHS/ -- DP1 OD000392/OD/NIH HHS/ -- DP1 OD000392-01/OD/NIH HHS/ -- DP1 OD000392-02/OD/NIH HHS/ -- DP1 OD000392-03/OD/NIH HHS/ -- DP1 OD000392-04/OD/NIH HHS/ -- DP1 OD000392-05/OD/NIH HHS/ -- F31 AG034045/AG/NIA NIH HHS/ -- F31 AG034045-01/AG/NIA NIH HHS/ -- F31 AG034045-02/AG/NIA NIH HHS/ -- F31 AG034045-03/AG/NIA NIH HHS/ -- P30AG08017/AG/NIA NIH HHS/ -- P50 AG005136/AG/NIA NIH HHS/ -- R01 AG027505/AG/NIA NIH HHS/ -- R01 AG027505-01A1/AG/NIA NIH HHS/ -- R01 AG027505-02/AG/NIA NIH HHS/ -- R01 AG027505-03/AG/NIA NIH HHS/ -- R01 AG027505-04/AG/NIA NIH HHS/ -- R01 AG027505-05/AG/NIA NIH HHS/ -- R01 AR056849/AR/NIAMS NIH HHS/ -- R01 MH078194/MH/NIMH NIH HHS/ -- R01AG027505/AG/NIA NIH HHS/ -- T32 AI007290/AI/NIAID NIH HHS/ -- England -- Nature. 2011 Aug 31;477(7362):90-4. doi: 10.1038/nature10357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neurological Sciences, 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/21886162" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Chemokine CCL11/blood/cerebrospinal fluid/metabolism/pharmacology ; Chemokines/*blood/cerebrospinal fluid/*metabolism ; Female ; Learning/drug effects/*physiology ; Learning Disorders/blood/cerebrospinal fluid/physiopathology ; Male ; Memory Disorders/blood/cerebrospinal fluid/physiopathology ; Mice ; Mice, Inbred C57BL ; Neurogenesis/drug effects/*physiology ; Parabiosis ; Plasma/chemistry ; Time Factors
    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: 2018-09-14
    Description: Although organic photovoltaic (OPV) cells have many advantages, their performance still lags far behind that of other photovoltaic platforms. A fundamental reason for their low performance is the low charge mobility of organic materials, leading to a limit on the active-layer thickness and efficient light absorption. In this work, guided by a semi-empirical model analysis and using the tandem cell strategy to overcome such issues, and taking advantage of the high diversity and easily tunable band structure of organic materials, a record and certified 17.29% power conversion efficiency for a two-terminal monolithic solution-processed tandem OPV is achieved.
    Keywords: Chemistry, Materials Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2018-10-13
    Description: Molecular transistors operating in the quantum tunneling regime represent potential electronic building blocks for future integrated circuits. However, due to their complex fabrication processes and poor stability, traditional molecular transistors can only operate stably at cryogenic temperatures. Here, through a combined experimental and theoretical investigation, we demonstrate a new design of vertical molecular tunneling transistors, with stable switching operations up to room temperature, formed from cross-plane graphene/self-assembled monolayer (SAM)/gold heterostructures. We show that vertical molecular junctions formed from pseudo- p -bis((4-(acetylthio)phenyl)ethynyl)- p -[2,2]cyclophane (PCP) SAMs exhibit destructive quantum interference (QI) effects, which are absent in 1,4-bis(((4-acetylthio)phenyl)ethynyl)benzene (OPE3) SAMs. Consequently, the zero-bias differential conductance of the former is only about 2% of the latter, resulting in an enhanced on-off current ratio for (PCP) SAMs. Field-effect control is achieved using an ionic liquid gate, whose strong vertical electric field penetrates through the graphene layer and tunes the energy levels of the SAMs. The resulting on-off current ratio achieved in PCP SAMs can reach up to ~330, about one order of magnitude higher than that of OPE3 SAMs. The demonstration of molecular junctions with combined QI effect and gate tunability represents a critical step toward functional devices in future molecular-scale electronics.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 6
    Publication Date: 2015-05-02
    Description: Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1alpha and nuclear lamina-heterochromatin anchoring protein LAP2beta. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494668/" 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/PMC4494668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Weiqi -- Li, Jingyi -- Suzuki, Keiichiro -- Qu, Jing -- Wang, Ping -- Zhou, Junzhi -- Liu, Xiaomeng -- Ren, Ruotong -- Xu, Xiuling -- Ocampo, Alejandro -- Yuan, Tingting -- Yang, Jiping -- Li, Ying -- Shi, Liang -- Guan, Dee -- Pan, Huize -- Duan, Shunlei -- Ding, Zhichao -- Li, Mo -- Yi, Fei -- Bai, Ruijun -- Wang, Yayu -- Chen, Chang -- Yang, Fuquan -- Li, Xiaoyu -- Wang, Zimei -- Aizawa, Emi -- Goebl, April -- Soligalla, Rupa Devi -- Reddy, Pradeep -- Esteban, Concepcion Rodriguez -- Tang, Fuchou -- Liu, Guang-Hui -- Belmonte, Juan Carlos Izpisua -- F32 AG047770/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1160-3. doi: 10.1126/science.aaa1356. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; Diagnosis and Treatment Center for Oral Disease, the 306th Hospital of the PLA, Beijing, China. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; College of Life Sciences, Peking University, Beijing 100871, China. ; The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Universidad Catolica San Antonio de Murcia, Campus de los Jeronimos s/n, 30107 Guadalupe, Murcia, Spain. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Beijing Institute for Brain Disorders, Beijing 100069, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931448" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*metabolism ; Animals ; *Cell Aging ; Cell Differentiation ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; DNA-Binding Proteins/metabolism ; Epigenesis, Genetic ; Exodeoxyribonucleases/genetics/*metabolism ; Gene Knockout Techniques ; HEK293 Cells ; Heterochromatin/chemistry/*metabolism ; Humans ; Membrane Proteins/metabolism ; Mesenchymal Stromal Cells/*metabolism ; Methyltransferases/genetics/metabolism ; Mice ; Models, Biological ; RecQ Helicases/genetics/*metabolism ; Repressor Proteins/genetics/metabolism ; Werner Syndrome/genetics/*metabolism
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2015-08-26
    Description: The identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens ("mini-HAs") based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to those of full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever after sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bound a wide range of HAs, competed with human bnAbs for HA stem binding, neutralized H5N1 viruses, and mediated antibody-dependent effector activity. These results represent a proof of concept for the design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Impagliazzo, Antonietta -- Milder, Fin -- Kuipers, Harmjan -- Wagner, Michelle V -- Zhu, Xueyong -- Hoffman, Ryan M B -- van Meersbergen, Ruud -- Huizingh, Jeroen -- Wanningen, Patrick -- Verspuij, Johan -- de Man, Martijn -- Ding, Zhaoqing -- Apetri, Adrian -- Kukrer, Basak -- Sneekes-Vriese, Eveline -- Tomkiewicz, Danuta -- Laursen, Nick S -- Lee, Peter S -- Zakrzewska, Anna -- Dekking, Liesbeth -- Tolboom, Jeroen -- Tettero, Lisanne -- van Meerten, Sander -- Yu, Wenli -- Koudstaal, Wouter -- Goudsmit, Jaap -- Ward, Andrew B -- Meijberg, Wim -- Wilson, Ian A -- Radosevic, Katarina -- P41GM103393/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1301-6. doi: 10.1126/science.aac7263. Epub 2015 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands. aimpagli@its.jnj.com wilson@scripps.edu. ; Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands. ; Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 3210 Merryfield Row, San Diego, CA 92121, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. aimpagli@its.jnj.com wilson@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26303961" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*immunology ; Humans ; Influenza A Virus, H1N1 Subtype/*immunology ; Influenza A Virus, H5N1 Subtype/*immunology ; Influenza Vaccines/*immunology ; Influenza, Human/*prevention & control ; Mice ; Protein Multimerization ; Protein Structure, Secondary
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    facet.materialart.
    Unknown
    German Medical Science GMS Publishing House; Düsseldorf
    In:  29. Jahrestagung der Retinologischen Gesellschaft; 20160617-20160618; Berlin; DOC16rg14 /20160616/
    Publication Date: 2016-06-18
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 9
    Keywords: TRANSCRIPTION FACTOR ; CRYSTAL-STRUCTURE ; BRLF1 PROMOTER ; STRUCTURAL BASIS ; ZEBRA PROTEIN ; LYTIC CYCLE GENES ; BURKITTS-LYMPHOMA ; IMMEDIATE-EARLY PROMOTER ; LEUCINE ZIPPER ; VIRAL GENOME
    Abstract: ZEBReplication Activator (ZEBRA), a viral basic zipper protein that initiates the Epstein-Barr viral lytic cycle, binds to DNA and activates transcription through heptamer ZEBRA response elements (ZREs) related to AP-1 sites. A component of the biologic action of ZEBRA is attributable to binding methylated CpGs in ZREs present in the promoters of viral lytic cycle genes. Residue S186 of ZEBRA, Z(S186), which is absolutely required for disruption of latency, participates in the recognition of methylated DNA. We find that mutant cellular AP-1 proteins, Jun(A266S) and Fos(A151S), with alanine-to-serine substitutions homologous to Z(S186), exhibit altered DNA-binding affinity and preferentially bind methylated ZREs. These mutant AP-1 proteins acquire functions of ZEBRA; they activate expression of many viral early lytic cycle gene transcripts in cells harboring latent EBV but are selectively defective in activating expression of some viral proteins and are unable to promote viral DNA replication. Transcriptional activation by mutant c-Jun and c-Fos that have acquired the capacity to bind methylated CpG challenges the paradigm that DNA methylation represses gene expression.
    Type of Publication: Journal article published
    PubMed ID: 23625009
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Polyhedron 13 (1994), S. 2679-2681 
    ISSN: 0277-5387
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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