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  • 1
    Keywords: EXPRESSION ; RISK ; COMPLEXES ; AMPLIFICATION ; OVARIAN-CANCER ; MUTATIONS ; VARIANT ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIATION ; CONFERS SUSCEPTIBILITY
    Abstract: A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) 〉/= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (Ptrend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. Cancer Res; 74(20); 5808-18. (c)2014 AACR.
    Type of Publication: Journal article published
    PubMed ID: 25320178
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  • 2
    Publication Date: 2011-09-06
    Description: Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming after fertilization. The paternal genome in a zygote undergoes active DNA demethylation before the first mitosis. The biological significance and mechanisms of this paternal epigenome remodelling have remained unclear. Here we report that, within mouse zygotes, oxidation of 5-methylcytosine (5mC) occurs on the paternal genome, changing 5mC into 5-hydroxymethylcytosine (5hmC). Furthermore, we demonstrate that the dioxygenase Tet3 (ref. 5) is enriched specifically in the male pronucleus. In Tet3-deficient zygotes from conditional knockout mice, paternal-genome conversion of 5mC into 5hmC fails to occur and the level of 5mC remains constant. Deficiency of Tet3 also impedes the demethylation process of the paternal Oct4 and Nanog genes and delays the subsequent activation of a paternally derived Oct4 transgene in early embryos. Female mice depleted of Tet3 in the germ line show severely reduced fecundity and their heterozygous mutant offspring lacking maternal Tet3 suffer an increased incidence of developmental failure. Oocytes lacking Tet3 also seem to have a reduced ability to reprogram the injected nuclei from somatic cells. Therefore, Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gu, Tian-Peng -- Guo, Fan -- Yang, Hui -- Wu, Hai-Ping -- Xu, Gui-Fang -- Liu, Wei -- Xie, Zhi-Guo -- Shi, Linyu -- He, Xinyi -- Jin, Seung-gi -- Iqbal, Khursheed -- Shi, Yujiang Geno -- Deng, Zixin -- Szabo, Piroska E -- Pfeifer, Gerd P -- Li, Jinsong -- Xu, Guo-Liang -- GM078458/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Sep 4;477(7366):606-10. doi: 10.1038/nature10443.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21892189" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Alleles ; Animals ; *Cellular Reprogramming ; Cytosine/analogs & derivatives/metabolism ; DNA/chemistry/genetics/metabolism ; DNA Methylation/genetics ; DNA-Binding Proteins/deficiency/genetics/*metabolism ; Dioxygenases/genetics/*metabolism ; Embryo, Mammalian/embryology/metabolism ; Embryonic Development ; *Epigenesis, Genetic ; Female ; Fertility/genetics ; Gene Expression Regulation, Developmental ; Germ Cells/metabolism ; Male ; Mice ; Octamer Transcription Factor-3/genetics ; Oocytes/cytology/*enzymology/*metabolism ; Oxidation-Reduction ; Proto-Oncogene Proteins/deficiency/genetics/*metabolism ; Zygote/cytology/metabolism
    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: 2018-09-13
    Description: The exact role of lithium ions (Li + ) in controlling alkali–silica reaction is still unclear. Thus, the effects of Li + on the reaction between reactive silica (quartz glass) and hydroxyl in alkaline solution with or without Ca were investigated by quartz glass powder or slice immersion experiments. When quartz glass was immersed in lithium-containing alkaline solutions, only Li 2 SiO 3 was produced with the absence of Ca, but Li 2 SiO 3 and calcium silicate hydrate (CSH) were formed with the presence of Ca. The quartz glass slice immersion experiment indicated that the mass loss of quartz slices was less than 1% only when Ca was present in the lithium-containing alkaline solution. This was because a dense, low-porosity and strongly bonded production layer mainly composed of CSH and Li 2 SiO 3 crystals was formed on the glass surface and served as a barrier against the diffusion of OH – and alkali ions to the substrate glass.
    Keywords: inorganic chemistry, materials science
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 4
    Publication Date: 2018-10-11
    Description: Nicotinamide adenine dinucleotide (NAD) plays an essential role in all aspects of human life. NAD levels decrease as humans age, and supplementation with NAD precursors plays a protective role against aging and associated disease. Less is known about the effects of decreased NAD on cellular processes, which is the basis for understanding the relationship between cellular NAD levels and aging-associated disease. In the present study, cellular NAD levels were decreased by overexpression of CD38, a NAD hydrolase, or by treating cells with FK866, an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). Quantitative proteomics revealed that declining NAD levels downregulated proteins associated with primary metabolism and suppressed cell growth in culture and nude mice. Decreased glutathione synthesis caused a 4-fold increase in cellular reactive oxygen species levels, and more importantly upregulated proteins related to movement and adhesion. In turn, this significantly changed cell morphology and caused cells to undergo epithelial to mesenchymal transition (EMT). Secretomic analysis also showed that decreased NAD triggered interleukin-6 and transforming growth factor beta (TGFβ) secretion, which activated integrin-β-catenin, TGFβ-MAPK, and inflammation signaling pathways to sustain the signaling required for EMT. We further revealed that decreased NAD inactivated sirtuin 1, resulting in increased signal transducer and activator of transcription 3 (STAT3) acetylation and phosphorylation, and STAT3 activation. Repletion of nicotinamide or nicotinic acid inactivated STAT3 and reversed EMT, as did STAT3 inhibition. Taken together, these results indicate that decreased NAD activates multiple signaling pathways to promote EMT and suggests that age-dependent decreases in NAD may contribute to tumor progression. Consequently, repletion of NAD precursors has potential benefits for inhibiting cancer progression.
    Print ISSN: 1535-9476
    Electronic ISSN: 1535-9484
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2018-02-16
    Description: Purpose: Previous studies revealed diverging results regarding the role of survivin in squamous cell carcinoma of the head and neck (SCCHN). This study aimed to evaluate the clinical significance of survivin expression in SCCHN; the function of survivin in DNA-damage repair following ionizing radiation therapy (RT) in SCCHN cells; and the potential of honokiol to enhance RT through downregulation of survivin. Experimental Design: Expression of survivin in SCCHN patient primary tumor tissues ( n = 100) was analyzed and correlated with clinical parameters. SCCHN cell lines were used to evaluate the function of survivin and the effects of honokiol on survivin expression in vitro and in vivo . Results: Overexpression of survivin was significantly associated with lymph nodes' metastatic status ( P = 0.025), worse overall survival (OS), and disease-free survival (DFS) in patients receiving RT ( n = 65, OS: P = 0.024, DFS: P = 0.006) and in all patients with SCCHN ( n = 100, OS: P = 0.002, DFS: P = 0.003). In SCCHN cells, depletion of survivin led to increased DNA damage and cell death following RT, whereas overexpression of survivin increased clonogenic survival. RT induced nuclear accumulation of survivin and its molecular interaction with -H2AX and DNA-PKCs. Survivin specifically bound to DNA DSB sites induced by I-SceI endonuclease. Honokiol (which downregulates survivin expression) in combination with RT significantly augmented cytotoxicity in SCCHN cells with acquired radioresistance and inhibited growth in SCCHN xenograft tumors. Conclusions: Survivin is a negative prognostic factor and is involved in DNA-damage repair induced by RT. Targeting survivin using honokiol in combination with RT may provide novel therapeutic opportunities. Clin Cancer Res; 24(4); 858–69. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 6
    Publication Date: 2011-04-16
    Description: We present a strategy to design and construct self-assembling DNA nanostructures that define intricate curved surfaces in three-dimensional (3D) space using the DNA origami folding technique. Double-helical DNA is bent to follow the rounded contours of the target object, and potential strand crossovers are subsequently identified. Concentric rings of DNA are used to generate in-plane curvature, constrained to 2D by rationally designed geometries and crossover networks. Out-of-plane curvature is introduced by adjusting the particular position and pattern of crossovers between adjacent DNA double helices, whose conformation often deviates from the natural, B-form twist density. A series of DNA nanostructures with high curvature--such as 2D arrangements of concentric rings and 3D spherical shells, ellipsoidal shells, and a nanoflask--were assembled.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Dongran -- Pal, Suchetan -- Nangreave, Jeanette -- Deng, Zhengtao -- Liu, Yan -- Yan, Hao -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):342-6. doi: 10.1126/science.1202998.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. dongran.han@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493857" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*chemistry ; Models, Molecular ; *Nanostructures ; Nanotechnology ; *Nucleic Acid Conformation
    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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  • 7
    ISSN: 0275-1062
    Keywords: Galaxy-large scale structure-cosmology
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Chinese Astronomy and Astrophysics 9 (1985), S. 20-26 
    ISSN: 0275-1062
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 169 (1992), S. 186-190 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 115 (1986), S. 21-24 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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