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  • 1
    Publication Date: 2018-04-14
    Description: Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating the nucleocytoplasmic translocation of proteins through the NPC. In this study, we found that karyopherin α6 (KPNA6; also known as importin α7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm. The KPNA6 protein level in virus-infected cells was much higher than that in mock-infected controls, whereas the KPNA6 transcript remains stable. Viral infection blocked the ubiquitin-proteasomal degradation of KPNA6, which led to an extension of the KPNA6 half-life and the elevation of the KPNA6 level in comparison to mock-infected cells. PRRSV nsp12 protein induced KPNA6 stabilization. KPNA6 silencing was detrimental to the replication of PRRSV, and KPNA6 knockout impaired ZIKV replication. Moreover, KPNA6 knockout blocked the nuclear translocation of PRRSV nsp1β but had a minimal effect on two other PRRSV proteins with nuclear localization. Exogenous restitution of KPNA6 expression in the KPNA6-knockout cells results in restoration of the nuclear translocation of PRRSV nsp1β and the replication of ZIKV. These results indicate that KPNA6 is an important cellular factor for the replication of PRRSV and ZIKV. IMPORTANCE Positive-sense, single-stranded RNA (+ssRNA) viruses replicate in the cytoplasm of infected cells. The roles of transport factors in the nucleocytoplasmic trafficking system for the replication of +ssRNA viruses are not known. In this study, we discovered that PRRSV and ZIKV viruses needed karyopherin α6 (KPNA6), one of the transport factors, to enhance the virus replication. Our data showed that viral infection induced an elevation of the KPNA6 protein level due to an extension of the KPNA6 half-life via viral interference of the ubiquitin-proteasomal degradation of KPNA6. Notably, KPNA6 silencing or knockout dramatically reduced the replication of PRRSV and ZIKV. PRRSV nsp1β depended on KPNA6 to translocate into the nucleus. In addition, exogenous restitution of KPNA6 expression in KPNA6-knockout cells led to the restoration of nsp1β nuclear translocation and ZIKV replication. These results reveal a new aspect in the virus-cell interaction and may facilitate the development of novel antiviral therapeutics.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 2
    Publication Date: 2011-09-29
    Description: Retinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic pathogen recognition receptor that recognizes pathogen-associated molecular pattern (PAMP) motifs to differentiate between viral and cellular RNAs. RIG-I is activated by blunt-ended double-stranded (ds)RNA with or without a 5'-triphosphate (ppp), by single-stranded RNA marked by a 5'-ppp and by polyuridine sequences. Upon binding to such PAMP motifs, RIG-I initiates a signalling cascade that induces innate immune defences and inflammatory cytokines to establish an antiviral state. The RIG-I pathway is highly regulated and aberrant signalling leads to apoptosis, altered cell differentiation, inflammation, autoimmune diseases and cancer. The helicase and repressor domains (RD) of RIG-I recognize dsRNA and 5'-ppp RNA to activate the two amino-terminal caspase recruitment domains (CARDs) for signalling. Here, to understand the synergy between the helicase and the RD for RNA binding, and the contribution of ATP hydrolysis to RIG-I activation, we determined the structure of human RIG-I helicase-RD in complex with dsRNA and an ATP analogue. The helicase-RD organizes into a ring around dsRNA, capping one end, while contacting both strands using previously uncharacterized motifs to recognize dsRNA. Small-angle X-ray scattering, limited proteolysis and differential scanning fluorimetry indicate that RIG-I is in an extended and flexible conformation that compacts upon binding RNA. These results provide a detailed view of the role of helicase in dsRNA recognition, the synergy between the RD and the helicase for RNA binding and the organization of full-length RIG-I bound to dsRNA, and provide evidence of a conformational change upon RNA binding. The RIG-I helicase-RD structure is consistent with dsRNA translocation without unwinding and cooperative binding to RNA. The structure yields unprecedented insight into innate immunity and has a broader impact on other areas of biology, including RNA interference and DNA repair, which utilize homologous helicase domains within DICER and FANCM.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430514/" 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/PMC3430514/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Fuguo -- Ramanathan, Anand -- Miller, Matthew T -- Tang, Guo-Qing -- Gale, Michael Jr -- Patel, Smita S -- Marcotrigiano, Joseph -- AI080659/AI/NIAID NIH HHS/ -- GM55310/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI060389/AI/NIAID NIH HHS/ -- R01 AI060389-11/AI/NIAID NIH HHS/ -- R01 AI080659/AI/NIAID NIH HHS/ -- England -- Nature. 2011 Sep 25;479(7373):423-7. doi: 10.1038/nature10537.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, 679 Hoes Lane West, Piscataway, New Jersey 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21947008" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/analogs & derivatives/chemistry/metabolism ; DEAD-box RNA Helicases/*chemistry/immunology/*metabolism ; Enzyme Activation ; Fluorometry ; Humans ; Immunity, Innate/*immunology ; Models, Molecular ; Nucleic Acid Conformation ; Pliability ; Protein Binding ; Protein Structure, Tertiary ; Proteolysis ; RNA, Double-Stranded/chemistry/*metabolism ; RNA-Binding Proteins/chemistry/immunology/metabolism ; Scattering, Small Angle ; Structure-Activity Relationship ; Substrate Specificity ; Trypsin/metabolism ; X-Ray Diffraction
    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: 2014-09-05
    Description: Agriculture faces great challenges to ensure global food security by increasing yields while reducing environmental costs. Here we address this challenge by conducting a total of 153 site-year field experiments covering the main agro-ecological areas for rice, wheat and maize production in China. A set of integrated soil-crop system management practices based on a modern understanding of crop ecophysiology and soil biogeochemistry increases average yields for rice, wheat and maize from 7.2 million grams per hectare (Mg ha(-1)), 7.2 Mg ha(-1) and 10.5 Mg ha(-1) to 8.5 Mg ha(-1), 8.9 Mg ha(-1) and 14.2 Mg ha(-1), respectively, without any increase in nitrogen fertilizer. Model simulation and life-cycle assessment show that reactive nitrogen losses and greenhouse gas emissions are reduced substantially by integrated soil-crop system management. If farmers in China could achieve average grain yields equivalent to 80% of this treatment by 2030, over the same planting area as in 2012, total production of rice, wheat and maize in China would be more than enough to meet the demand for direct human consumption and a substantially increased demand for animal feed, while decreasing the environmental costs of intensive agriculture.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Xinping -- Cui, Zhenling -- Fan, Mingsheng -- Vitousek, Peter -- Zhao, Ming -- Ma, Wenqi -- Wang, Zhenlin -- Zhang, Weijian -- Yan, Xiaoyuan -- Yang, Jianchang -- Deng, Xiping -- Gao, Qiang -- Zhang, Qiang -- Guo, Shiwei -- Ren, Jun -- Li, Shiqing -- Ye, Youliang -- Wang, Zhaohui -- Huang, Jianliang -- Tang, Qiyuan -- Sun, Yixiang -- Peng, Xianlong -- Zhang, Jiwang -- He, Mingrong -- Zhu, Yunji -- Xue, Jiquan -- Wang, Guiliang -- Wu, Liang -- An, Ning -- Wu, Liangquan -- Ma, Lin -- Zhang, Weifeng -- Zhang, Fusuo -- England -- Nature. 2014 Oct 23;514(7523):486-9. doi: 10.1038/nature13609. Epub 2014 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] College of Resources &Environmental Sciences, China Agricultural University, Beijing 100193, China [2]. ; College of Resources &Environmental Sciences, China Agricultural University, Beijing 100193, China. ; Department of Biology, Stanford University, Stanford, California 94305, USA. ; Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China. ; College of Resources &Environmental Sciences, Agricultural University of Hebei, Baoding 071001, China. ; College of Agronomy, Shandong Agricultural University, Tai'an 271000, China. ; Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, China. ; Key Laboratory of Crop Genetics and Physiology of Jiangsu Province, Yangzhou University, Yangzhou 225009, China. ; State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, Northwest Agriculture and Forestry University, Yangling 712100, China. ; College of Resources &Environmental Sciences, Jilin Agricultural University, Changchun 130118, China. ; Institute of Agricultural Environment and Resource, Shanxi Academy of Agricultural Sciences, Taiyuan 030031, China. ; College of Resources &Environmental Sciences, Nanjing Agricultural University, Nanjing 210095, China. ; Research Center of Agricultural Environment &Resources, Jilin Academy of Agricultural Sciences, Changchun 130033, China. ; College of Resources &Environmental Sciences, Henan Agricultural University, Zhengzhou 450000, China. ; Northwest Agriculture and Forestry University, Yangling 712100, China. ; College of Plant Science &Technology, Huazhong Agricultural University, Wuhan 430070, China. ; Crop Physiology, Ecology &Production Center, Hunan Agricultural University, Changsha 410128, China. ; Soil &Fertilizer Research Institute, Anhui Academy of Agricultural Sciences, Hefei 230031, China. ; College of Resources &Environmental Sciences, Northeast Agricultural University, Harbin 150030, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186728" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*methods ; Animal Feed ; China ; Edible Grain/*growth & development/*supply & distribution ; *Environment ; Fertilizers/utilization ; Greenhouse Effect/statistics & numerical data ; Nitrogen/metabolism
    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: 2015-11-26
    Description: DNase I hypersensitive sites (DHSs) provide important information on the presence of transcriptional regulatory elements and the state of chromatin in mammalian cells. Conventional DNase sequencing (DNase-seq) for genome-wide DHSs profiling is limited by the requirement of millions of cells. Here we report an ultrasensitive strategy, called single-cell DNase sequencing (scDNase-seq) for detection of genome-wide DHSs in single cells. We show that DHS patterns at the single-cell level are highly reproducible among individual cells. Among different single cells, highly expressed gene promoters and enhancers associated with multiple active histone modifications display constitutive DHS whereas chromatin regions with fewer histone modifications exhibit high variation of DHS. Furthermore, the single-cell DHSs predict enhancers that regulate cell-specific gene expression programs and the cell-to-cell variations of DHS are predictive of gene expression. Finally, we apply scDNase-seq to pools of tumour cells and pools of normal cells, dissected from formalin-fixed paraffin-embedded tissue slides from patients with thyroid cancer, and detect thousands of tumour-specific DHSs. Many of these DHSs are associated with promoters and enhancers critically involved in cancer development. Analysis of the DHS sequences uncovers one mutation (chr18: 52417839G〉C) in the tumour cells of a patient with follicular thyroid carcinoma, which affects the binding of the tumour suppressor protein p53 and correlates with decreased expression of its target gene TXNL1. In conclusion, scDNase-seq can reliably detect DHSs in single cells, greatly extending the range of applications of DHS analysis both for basic and for translational research, and may provide critical information for personalized medicine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697938/" 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/PMC4697938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jin, Wenfei -- Tang, Qingsong -- Wan, Mimi -- Cui, Kairong -- Zhang, Yi -- Ren, Gang -- Ni, Bing -- Sklar, Jeffrey -- Przytycka, Teresa M -- Childs, Richard -- Levens, David -- Zhao, Keji -- Z01 HL005801-05/Intramural NIH HHS/ -- England -- Nature. 2015 Dec 3;528(7580):142-6. doi: 10.1038/nature15740.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Systems Biology Center, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; Institute of Immunology, Third Military Medical University of the People's Liberation Army, Chongqing 400038, China. ; College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. ; Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26605532" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma, Follicular/genetics/pathology ; Animals ; Chromatin/*genetics/*metabolism ; Deoxyribonuclease I/*metabolism ; Enhancer Elements, Genetic/genetics ; *Formaldehyde ; Gene Expression Profiling ; Genome/*genetics ; Histones/metabolism ; Humans ; Mice ; Mutation/genetics ; NIH 3T3 Cells ; *Paraffin Embedding ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Single-Cell Analysis/*methods ; Thioredoxins/genetics ; Thyroid Neoplasms/genetics/pathology ; *Tissue Fixation ; Tumor Suppressor Protein p53/metabolism
    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: 2018-10-25
    Description: Biochars were produced from long-root Eichhornia crassipes at four temperatures: 200, 300, 400 and 500°C, referred to as LEC200, LEC300, LEC400 and LEC500, respectively. The sorption ability of lead, zinc, copper and cadmium from aqueous solutions by four kinds of biochars was investigated. All the biochars had lower values of CEC and higher values of pH. LEC500 was the best one to bind toxic metals which can be reflected in the results of SEM, BET and elemental analyser. It was also found that alkyl, carboxyl, phosphate and cyano groups in the biochars can play a role in binding metals. In addition, the sorption processes of four metals by the biochars in different metal concentration were all excellently represented by the pseudo-second-order model with all correlation coefficients R 2 〉 0.95. And the sorption processes of four metals in different temperatures could be described satisfactorily by the Langmuir isotherms. According to calculated results by the Langmuir equation, the maximum removal capacities of Pb(II), Zn(II), Cu(II) and Cd(II) at 298 K were 39.09 mg g –1 , 45.40 mg g –1 , 48.20 mg g –1 and 44.04 mg g –1 , respectively. The positive value of the H 0 confirmed the adsorption process was endothermic and the negative value of G 0 confirmed the adsorption process was spontaneous. The sorption capacities were compared with several other lignocellulosic materials which implied the potential of long-root Eichhornia crassipes waste as an economic and excellent biosorbent for eliminating metal ions from contaminated waters.
    Keywords: environmental chemistry
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 6
    Publication Date: 2011-08-13
    Description: Methane and ethane are the most abundant hydrocarbons in the atmosphere and they affect both atmospheric chemistry and climate. Both gases are emitted from fossil fuels and biomass burning, whereas methane (CH(4)) alone has large sources from wetlands, agriculture, landfills and waste water. Here we use measurements in firn (perennial snowpack) air from Greenland and Antarctica to reconstruct the atmospheric variability of ethane (C(2)H(6)) during the twentieth century. Ethane levels rose from early in the century until the 1980s, when the trend reversed, with a period of decline over the next 20 years. We find that this variability was primarily driven by changes in ethane emissions from fossil fuels; these emissions peaked in the 1960s and 1970s at 14-16 teragrams per year (1 Tg = 10(12) g) and dropped to 8-10 Tg yr(-1) by the turn of the century. The reduction in fossil-fuel sources is probably related to changes in light hydrocarbon emissions associated with petroleum production and use. The ethane-based fossil-fuel emission history is strikingly different from bottom-up estimates of methane emissions from fossil-fuel use, and implies that the fossil-fuel source of methane started to decline in the 1980s and probably caused the late twentieth century slow-down in the growth rate of atmospheric methane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aydin, Murat -- Verhulst, Kristal R -- Saltzman, Eric S -- Battle, Mark O -- Montzka, Stephen A -- Blake, Donald R -- Tang, Qi -- Prather, Michael J -- England -- Nature. 2011 Aug 10;476(7359):198-201. doi: 10.1038/nature10352.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth System Science, University of California, Irvine, California 92697, USA. maydin@uci.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833087" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Atmosphere/*chemistry ; Biofuels ; Biomass ; Ethane/*analysis ; Fires ; *Fossil Fuels/history/utilization ; Geography ; Greenland ; History, 20th Century ; History, 21st Century ; Ice/analysis ; Methane/*analysis ; Models, Theoretical ; Snow/*chemistry
    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: 2018-03-28
    Description: Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC 24 /MIC) of 〉400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC 24 values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC 24 . A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC 24 /MIC of 〉400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC 24 /MIC of 〉400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.
    Print ISSN: 0066-4804
    Electronic ISSN: 1098-6596
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2014-03-29
    Description: Cancer cells induce a set of adaptive response pathways to survive in the face of stressors due to inadequate vascularization. One such adaptive pathway is the unfolded protein (UPR) or endoplasmic reticulum (ER) stress response mediated in part by the ER-localized transmembrane sensor IRE1 (ref. 2) and its substrate XBP1 (ref. 3). Previous studies report UPR activation in various human tumours, but the role of XBP1 in cancer progression in mammary epithelial cells is largely unknown. Triple-negative breast cancer (TNBC)--a form of breast cancer in which tumour cells do not express the genes for oestrogen receptor, progesterone receptor and HER2 (also called ERBB2 or NEU)--is a highly aggressive malignancy with limited treatment options. Here we report that XBP1 is activated in TNBC and has a pivotal role in the tumorigenicity and progression of this human breast cancer subtype. In breast cancer cell line models, depletion of XBP1 inhibited tumour growth and tumour relapse and reduced the CD44(high)CD24(low) population. Hypoxia-inducing factor 1alpha (HIF1alpha) is known to be hyperactivated in TNBCs. Genome-wide mapping of the XBP1 transcriptional regulatory network revealed that XBP1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1alpha that regulates the expression of HIF1alpha targets via the recruitment of RNA polymerase II. Analysis of independent cohorts of patients with TNBC revealed a specific XBP1 gene expression signature that was highly correlated with HIF1alpha and hypoxia-driven signatures and that strongly associated with poor prognosis. Our findings reveal a key function for the XBP1 branch of the UPR in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105133/" 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/PMC4105133/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Xi -- Iliopoulos, Dimitrios -- Zhang, Qing -- Tang, Qianzi -- Greenblatt, Matthew B -- Hatziapostolou, Maria -- Lim, Elgene -- Tam, Wai Leong -- Ni, Min -- Chen, Yiwen -- Mai, Junhua -- Shen, Haifa -- Hu, Dorothy Z -- Adoro, Stanley -- Hu, Bella -- Song, Minkyung -- Tan, Chen -- Landis, Melissa D -- Ferrari, Mauro -- Shin, Sandra J -- Brown, Myles -- Chang, Jenny C -- Liu, X Shirley -- Glimcher, Laurie H -- AI32412/AI/NIAID NIH HHS/ -- CA112663/CA/NCI NIH HHS/ -- K99 CA175290/CA/NCI NIH HHS/ -- K99CA175290/CA/NCI NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- R00 CA160351/CA/NCI NIH HHS/ -- R01 AI032412/AI/NIAID NIH HHS/ -- R01 CA112663/CA/NCI NIH HHS/ -- R01 HG004069/HG/NHGRI NIH HHS/ -- R01HG004069/HG/NHGRI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Apr 3;508(7494):103-7. doi: 10.1038/nature13119. Epub 2014 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Sandra and Edward Meyer Cancer Center of Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA [2] Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA. ; 1] Center for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA [2] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [3]. ; 1] Lineberger Comprehensive Cancer Center, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2]. ; 1] Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China [2] Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Ya'an, Sichuan 625014, China [3]. ; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; 1] Center for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA [2] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02215, USA. ; Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA. ; 1] Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA [2] Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA. ; Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts 02115, USA. ; Houston Methodist Cancer Center, Houston, Texas 77030, USA. ; 1] Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA [2] Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA. ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA. ; 1] Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA [2] Houston Methodist Cancer Center, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670641" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD24/metabolism ; Antigens, CD44/metabolism ; Cell Hypoxia/genetics ; Cell Line, Tumor ; Cell Proliferation ; DNA-Binding Proteins/deficiency/genetics/*metabolism ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Gene Silencing ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Mice ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prognosis ; RNA Polymerase II/metabolism ; Transcription Factors/deficiency/genetics/*metabolism ; Transcription, Genetic ; Triple Negative Breast Neoplasms/blood supply/genetics/*metabolism/*pathology ; Unfolded Protein Response
    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: 2011-08-06
    Description: The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462231/" 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/PMC3462231/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Yu-Fei -- Li, Bin-Zhong -- Li, Zheng -- Liu, Peng -- Wang, Yang -- Tang, Qingyu -- Ding, Jianping -- Jia, Yingying -- Chen, Zhangcheng -- Li, Lin -- Sun, Yan -- Li, Xiuxue -- Dai, Qing -- Song, Chun-Xiao -- Zhang, Kangling -- He, Chuan -- Xu, Guo-Liang -- 1S10RR027643-01/RR/NCRR NIH HHS/ -- GM071440/GM/NIGMS NIH HHS/ -- R01 GM071440/GM/NIGMS NIH HHS/ -- S10 RR027643/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2011 Sep 2;333(6047):1303-7. doi: 10.1126/science.1210944. Epub 2011 Aug 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Group of DNA Metabolism, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21817016" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; Cell Line ; Cytosine/*analogs & derivatives/metabolism ; DNA/*metabolism ; DNA Methylation ; DNA-Binding Proteins/genetics/*metabolism ; Embryonic Stem Cells ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Mice ; Oxidation-Reduction ; Proto-Oncogene Proteins/genetics/*metabolism ; RNA, Small Interfering ; Thymine DNA Glycosylase/genetics/*metabolism ; Transfection
    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: 2013-11-10
    Description: The asteroid impact near the Russian city of Chelyabinsk on 15 February 2013 was the largest airburst on Earth since the 1908 Tunguska event, causing a natural disaster in an area with a population exceeding one million. Because it occurred in an era with modern consumer electronics, field sensors, and laboratory techniques, unprecedented measurements were made of the impact event and the meteoroid that caused it. Here, we document the account of what happened, as understood now, using comprehensive data obtained from astronomy, planetary science, geophysics, meteorology, meteoritics, and cosmochemistry and from social science surveys. A good understanding of the Chelyabinsk incident provides an opportunity to calibrate the event, with implications for the study of near-Earth objects and developing hazard mitigation strategies for planetary protection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Popova, Olga P -- Jenniskens, Peter -- Emel'yanenko, Vacheslav -- Kartashova, Anna -- Biryukov, Eugeny -- Khaibrakhmanov, Sergey -- Shuvalov, Valery -- Rybnov, Yurij -- Dudorov, Alexandr -- Grokhovsky, Victor I -- Badyukov, Dmitry D -- Yin, Qing-Zhu -- Gural, Peter S -- Albers, Jim -- Granvik, Mikael -- Evers, Laslo G -- Kuiper, Jacob -- Kharlamov, Vladimir -- Solovyov, Andrey -- Rusakov, Yuri S -- Korotkiy, Stanislav -- Serdyuk, Ilya -- Korochantsev, Alexander V -- Larionov, Michail Yu -- Glazachev, Dmitry -- Mayer, Alexander E -- Gisler, Galen -- Gladkovsky, Sergei V -- Wimpenny, Josh -- Sanborn, Matthew E -- Yamakawa, Akane -- Verosub, Kenneth L -- Rowland, Douglas J -- Roeske, Sarah -- Botto, Nicholas W -- Friedrich, Jon M -- Zolensky, Michael E -- Le, Loan -- Ross, Daniel -- Ziegler, Karen -- Nakamura, Tomoki -- Ahn, Insu -- Lee, Jong Ik -- Zhou, Qin -- Li, Xian-Hua -- Li, Qiu-Li -- Liu, Yu -- Tang, Guo-Qiang -- Hiroi, Takahiro -- Sears, Derek -- Weinstein, Ilya A -- Vokhmintsev, Alexander S -- Ishchenko, Alexei V -- Schmitt-Kopplin, Phillipe -- Hertkorn, Norbert -- Nagao, Keisuke -- Haba, Makiko K -- Komatsu, Mutsumi -- Mikouchi, Takashi -- Chelyabinsk Airburst Consortium -- New York, N.Y. -- Science. 2013 Nov 29;342(6162):1069-73. doi: 10.1126/science.1242642. Epub 2013 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Dynamics of Geospheres of the Russian Academy of Sciences, Leninsky Prospect 38, Building 1, Moscow, 119334, Russia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24200813" target="_blank"〉PubMed〈/a〉
    Keywords: *Accidents ; *Air ; *Explosions ; *Meteoroids ; Russia
    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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