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  • 1
    Publication Date: 2013-06-04
    Description: DNA damage activates a signalling network that blocks cell-cycle progression, recruits DNA repair factors and/or triggers senescence or programmed cell death. Alterations in chromatin structure are implicated in the initiation and propagation of the DNA damage response. Here we further investigate the role of chromatin structure in the DNA damage response by monitoring ionizing-radiation-induced signalling and response events with a high-content multiplex RNA-mediated interference screen of chromatin-modifying and -interacting genes. We discover that an isoform of Brd4, a bromodomain and extra-terminal (BET) family member, functions as an endogenous inhibitor of DNA damage response signalling by recruiting the condensin II chromatin remodelling complex to acetylated histones through bromodomain interactions. Loss of this isoform results in relaxed chromatin structure, rapid cell-cycle checkpoint recovery and enhanced survival after irradiation, whereas functional gain of this isoform compacted chromatin, attenuated DNA damage response signalling and enhanced radiation-induced lethality. These data implicate Brd4, previously known for its role in transcriptional control, as an insulator of chromatin that can modulate the signalling response to DNA damage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683358/" 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/PMC3683358/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Floyd, Scott R -- Pacold, Michael E -- Huang, Qiuying -- Clarke, Scott M -- Lam, Fred C -- Cannell, Ian G -- Bryson, Bryan D -- Rameseder, Jonathan -- Lee, Michael J -- Blake, Emily J -- Fydrych, Anna -- Ho, Richard -- Greenberger, Benjamin A -- Chen, Grace C -- Maffa, Amanda -- Del Rosario, Amanda M -- Root, David E -- Carpenter, Anne E -- Hahn, William C -- Sabatini, David M -- Chen, Clark C -- White, Forest M -- Bradner, James E -- Yaffe, Michael B -- 1-U54-CA112967-04/CA/NCI NIH HHS/ -- ES-002109/ES/NIEHS NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- P30 ES002109/ES/NIEHS NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- R01 ES015339/ES/NIEHS NIH HHS/ -- R01-ES15339/ES/NIEHS NIH HHS/ -- R21 CA109661/CA/NCI NIH HHS/ -- R21 NS063917/NS/NINDS NIH HHS/ -- R21-NS063917/NS/NINDS NIH HHS/ -- U54 CA112967/CA/NCI NIH HHS/ -- England -- Nature. 2013 Jun 13;498(7453):246-50. doi: 10.1038/nature12147. Epub 2013 Jun 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23728299" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Adenosine Triphosphatases/metabolism ; Cell Cycle Checkpoints/radiation effects ; Cell Line, Tumor ; Cell Survival/radiation effects ; Chromatin/chemistry/*metabolism/radiation effects ; *Chromatin Assembly and Disassembly/radiation effects ; *DNA Damage ; DNA Repair/radiation effects ; DNA-Binding Proteins/metabolism ; Histones/chemistry/metabolism ; Humans ; Lysine/chemistry/metabolism ; Multiprotein Complexes/metabolism ; Nuclear Proteins/chemistry/deficiency/genetics/*metabolism ; Phosphorylation/radiation effects ; Positive Transcriptional Elongation Factor B/metabolism ; Protein Isoforms/metabolism ; Radiation, Ionizing ; *Signal Transduction/radiation effects ; Transcription Factors/chemistry/deficiency/genetics/*metabolism
    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: 2018-02-16
    Description: Purpose: The comprehensive understanding of mechanisms involved in the tumor metastasis is urgently needed for discovering novel metastasis-related genes for developing effective diagnoses and treatments for lung cancer. Experimental Design: FAM198B was identified from an isogenic lung cancer metastasis cell model by microarray analysis. To investigate the clinical relevance of FAM198B, the FAM198B expression of 95 Taiwan lung adenocarcinoma patients was analyzed by quantitative real-time PCR and correlated to patients' survivals. The impact of FAM198B on cell invasion, metastasis, and tumor growth was examined by in vitro cellular assays and in vivo mouse models. In addition, the N-glycosylation–defective FAM198B mutants generated by site-directed mutagenesis were used to study protein stability and subcellular localization of FAM198B. Finally, the microarray and pathway analyses were used to elucidate the underlying mechanisms of FAM198B-mediated tumor suppression. Results: We found that the high expression of FAM198B was associated with favorable survival in Taiwan lung adenocarcinoma patients and in a lung cancer public database. Enforced expression of FAM198B inhibited cell invasion, migration, mobility, proliferation, and anchorage-independent growth, and FAM198B silencing exhibited opposite activities in vitro . FAM198B also attenuated tumor growth and metastasis in vivo . We further identified MMP-1 as a critical downstream target of FAM198B. The FAM198B-mediated MMP-1 downregulation was via inhibition of the phosphorylation of ERK. Interestingly deglycosylation nearly eliminated the metastasis suppression activity of FAM198B due to a decrease of protein stability. Conclusions: Our results implicate FAM198B as a potential tumor suppressor and to be a prognostic marker in lung adenocarcinoma. Clin Cancer Res; 24(4); 916–26. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Carbohydrate Research 50 (1976), S. 53-62 
    ISSN: 0008-6215
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0649
    Keywords: 82.50
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract 13C separation at a laboratory scaled-up level by the13C-selective InfraRed MultiPhoton Dissociation (IRMPD) of CHClF2 in the presence of Br2 has been investigated in a flow reactor. With a complete scaled-up system including a flow reactor, an industrially reliable TEA CO2 laser with longer pulse duration and a product-separation set-up for13C separation, it has been attempted to optimize the parameters suitable for large-scale production of the carbon isotope. The optimization of13C separation parameters, such as laser fluence, laser frequency and the partial pressure of CHClF2 and Br2 was tested under static conditions. By irradiation with longer pulses, a lower optimum pressure for a high13C-production rate was determined. Furthermore, the separation process was scaled in the flow system to examine the13C-production rates,13C atomic fractions in the CBr2F2 products and13C depletions in the CHClF2 reactants at different flow rates and laser repetition frequencies. The data obtained from the flow tests demonstrated a 40 mg/h production rate for CBr2F2 at 65%13C by using a 40 W (4 J, 10 Hz) laser beam focused with a lens of 120 cm focal length. If the reliable TEA CO2 laser is operated with 100 W (10 J, 10 Hz) output, the production rate of CBr2F2 for13C at 60% of 200 mg/h can be attained. The measurements of the spatial profile of the focused laser beam imply a 2 g/h production rate for the 60%13C product for an incident power of 200 W (20 J, 10 Hz).
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-4838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The antimicrobial ceramics (AC) based on hydroxyapatite (HA) were made in a wet chemical process with additions of AgNO3, Cu(NO3)2 · 3H2O and Zn(NO3)2 · 6H2O. The ACs were composed of metal-ion substituted hydroxyapatite and nitrate–apatite, which was identified by X-ray diffraction. The viable count and turbidity measurement was adopted to observe the antimicrobial effects of the various ACs. The aerobic Escherichia coli was used in the study. An obvious antimicrobial effect against E. coli was observed in Ag+ AC. In contrast to Ag+ AC, it was difficult to ascertain any bactericidal effect in the case of Cu2+ and Zn2+ AC. The bactericidal effect of Ag+ was observed using a dialysis tube experiment. This suggests that Ag+ dissolved out and reacted with E. coli, thus inhibiting its growth. © 1998 Chapman & Hall
    Type of Medium: Electronic Resource
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