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  • 1
    Keywords: RISK ; PROSTATE-CANCER ; LOCI ; GENOME-WIDE ASSOCIATION ; COMMON VARIANTS ; CLEAR-CELL CARCINOMA ; MODY
    Abstract: HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR) = 1.13, P = 3.1 x 10(-10)) and clear cell (rs11651755 OR = 0.77, P = 1.6 x 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
    Type of Publication: Journal article published
    PubMed ID: 23535649
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A 54-year-old man presented with features consistent with extrinsic allergic alveolitis occurring after contact with his pet birds. Screening of the serum for avian precipitating antibody was negative but canary precipitins were present. Extrinsic allergic alveolitis to his pet canaries was confirmed by inhalation challenge.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Esters of 2-diazonaphthalenone sulfonic acid were examined by mass spectrometry using electron impact and chemical ionization techniques. Charactristic differences in the fragmentation patterns of positional isomers have been observed. In a manner analogous to photo-induced decompositions, the diazoketo functional groups fragment by elimination of N2 to form an indenoketene ion. An alternative process involves the apparent loss of 26 mass units from the molecular ion. The latter process is explained by evoking the abstraction of two hydrogen atoms following the loss of N2. With deuterium isotope labeling, it has been shown that the hydrogens are abstracted from the surface of the probe tip used for introduction of the samples into the mass spectrometer. It is concluded that an environment rich in hydrogen or proton-donating properties promotes and enhances the incorporation of the hydrogen atoms and formation of the [M-26] species at the expense of the ketene moiety, which is an important intermediate in the photoresist process. By extrapolation it may be inferred that the efficiency of the photolithographic process could be influenced by the availability of protons in the photoresist matrix.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2012-04-12
    Description: Observations with the Venus Express magnetometer and low-energy particle detector revealed magnetic field and plasma behavior in the near-Venus wake that is symptomatic of magnetic reconnection, a process that occurs in Earth's magnetotail but is not expected in the magnetotail of a nonmagnetized planet such as Venus. On 15 May 2006, the plasma flow in this region was toward the planet, and the magnetic field component transverse to the flow was reversed. Magnetic reconnection is a plasma process that changes the topology of the magnetic field and results in energy exchange between the magnetic field and the plasma. Thus, the energetics of the Venus magnetotail resembles that of the terrestrial tail, where energy is stored and later released from the magnetic field to the plasma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, T L -- Lu, Q M -- Baumjohann, W -- Russell, C T -- Fedorov, A -- Barabash, S -- Coates, A J -- Du, A M -- Cao, J B -- Nakamura, R -- Teh, W L -- Wang, R S -- Dou, X K -- Wang, S -- Glassmeier, K H -- Auster, H U -- Balikhin, M -- New York, N.Y. -- Science. 2012 May 4;336(6081):567-70. doi: 10.1126/science.1217013. Epub 2012 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chinese Academy of Sciences Key Laboratory of Geospace Environment, University of Science and Technology of China, Hefei 230026, China. tielong.zhang@oeaw.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491094" 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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  • 5
    Publication Date: 2015-09-30
    Description: The battle for survival between bacteria and the viruses that infect them (phages) has led to the evolution of many bacterial defence systems and phage-encoded antagonists of these systems. Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an adaptive immune system that is one of the most widespread means by which bacteria defend themselves against phages. We identified the first examples of proteins produced by phages that inhibit a CRISPR-Cas system. Here we performed biochemical and in vivo investigations of three of these anti-CRISPR proteins, and show that each inhibits CRISPR-Cas activity through a distinct mechanism. Two block the DNA-binding activity of the CRISPR-Cas complex, yet do this by interacting with different protein subunits, and using steric or non-steric modes of inhibition. The third anti-CRISPR protein operates by binding to the Cas3 helicase-nuclease and preventing its recruitment to the DNA-bound CRISPR-Cas complex. In vivo, this anti-CRISPR can convert the CRISPR-Cas system into a transcriptional repressor, providing the first example-to our knowledge-of modulation of CRISPR-Cas activity by a protein interactor. The diverse sequences and mechanisms of action of these anti-CRISPR proteins imply an independent evolution, and foreshadow the existence of other means by which proteins may alter CRISPR-Cas function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bondy-Denomy, Joseph -- Garcia, Bianca -- Strum, Scott -- Du, Mingjian -- Rollins, MaryClare F -- Hidalgo-Reyes, Yurima -- Wiedenheft, Blake -- Maxwell, Karen L -- Davidson, Alan R -- MOP-130482/Canadian Institutes of Health Research/Canada -- MOP-136845/Canadian Institutes of Health Research/Canada -- P20GM103500/GM/NIGMS NIH HHS/ -- R01GM108888/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Oct 1;526(7571):136-9. doi: 10.1038/nature15254. Epub 2015 Sep 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59717, USA. ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26416740" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*metabolism/*virology ; Bacteriophages/*metabolism ; CRISPR-Associated Proteins/*antagonists & inhibitors/metabolism ; CRISPR-Cas Systems/genetics/*physiology ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; DNA Helicases/antagonists & inhibitors/metabolism ; DNA, Viral/metabolism ; DNA-Binding Proteins/antagonists & inhibitors/metabolism ; Endonucleases/antagonists & inhibitors/metabolism ; *Evolution, Molecular ; Protein Binding ; Protein Subunits/antagonists & inhibitors/metabolism ; Repressor Proteins/genetics/metabolism ; Substrate Specificity ; Viral Proteins/*metabolism
    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: 2011-01-08
    Description: Methane was the most abundant hydrocarbon released during the 2010 Deepwater Horizon oil spill in the Gulf of Mexico. Beyond relevancy to this anthropogenic event, this methane release simulates a rapid and relatively short-term natural release from hydrates into deep water. Based on methane and oxygen distributions measured at 207 stations throughout the affected region, we find that within ~120 days from the onset of release ~3.0 x 10(10) to 3.9 x 10(10) moles of oxygen were respired, primarily by methanotrophs, and left behind a residual microbial community containing methanotrophic bacteria. We suggest that a vigorous deepwater bacterial bloom respired nearly all the released methane within this time, and that by analogy, large-scale releases of methane from hydrate in the deep ocean are likely to be met by a similarly rapid methanotrophic response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kessler, John D -- Valentine, David L -- Redmond, Molly C -- Du, Mengran -- Chan, Eric W -- Mendes, Stephanie D -- Quiroz, Erik W -- Villanueva, Christie J -- Shusta, Stephani S -- Werra, Lindsay M -- Yvon-Lewis, Shari A -- Weber, Thomas C -- New York, N.Y. -- Science. 2011 Jan 21;331(6015):312-5. doi: 10.1126/science.1199697. Epub 2011 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oceanography, Texas A&M University, College Station, TX 77843-3146, USA. jkessler@ocean.tamu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21212320" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Bacteria/classification/growth & development/*metabolism ; Biodegradation, Environmental ; *Environmental Pollution ; Hydrocarbons/analysis ; Methane/analysis/*metabolism ; Molecular Sequence Data ; Oxidation-Reduction ; Oxygen/*analysis ; Oxygen Consumption ; *Petroleum ; Phylogeny ; Seawater/chemistry/*microbiology
    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
    Publication Date: 2018-08-09
    Description: G protein–coupled receptor 54 (GPR54), the key receptor for the neuropeptide hormone kisspeptin, plays essential roles in regulating puberty development and cancer metastasis. However, its role in the antiviral innate immune response is unknown. We report that virus-induced type I interferon (IFN-I) production was significantly enhanced in Gpr54 -deficient cells and mice and resulted in restricted viral replication. We found a marked increase of kisspeptin in mouse serum during viral infection, which, in turn, impaired IFN-I production and antiviral immunity through the GPR54/calcineurin axis. Mechanistically, kisspeptin/GPR54 signaling recruited calcineurin and increased its phosphatase activity to dephosphorylate and deactivate TANK [tumor necrosis factor receptor-associated factor (TRAF) family member-associated NF-B activator]–binding kinase 1 (TBK1) in a Ca 2+ -dependent manner. Thus, our data reveal a kisspeptin/GPR54/calcineurin-mediated immune evasion pathway exploited by virus through the negative feedback loop of TBK1 signaling. These findings also provide insights into the function and cross-talk of kisspeptin, a known neuropeptide hormone, in antiviral innate immune response.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 8
    Publication Date: 2018-10-26
    Description: Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry–specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 x 10 –5 ) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene ( SERPINE1 ) and the 3 fibrinogen subunit-encoding genes ( FGA , FGG , and FGB ) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.
    Keywords: Thrombosis and Hemostasis
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 9
    Publication Date: 2018-10-20
    Description: Atomic-level structure engineering can substantially change the chemical and physical properties of materials. However, the effects of structure engineering on the capacitive properties of electrode materials at the atomic scale are poorly understood. Fast transport of ions and electrons to all active sites of electrode materials remains a grand challenge. Here, we report the radical modification of the pseudocapacitive properties of an oxide material, Zn x Co 1– x O, via atomic-level structure engineering, which changes its dominant charge storage mechanism from surface redox reactions to ion intercalation into bulk material. Fast ion and electron transports are simultaneously achieved in this mixed oxide, increasing its capacity almost to the theoretical limit. The resultant Zn x Co 1– x O exhibits high-rate performance with capacitance up to 450 F g –1 at a scan rate of 1 V s –1 , competing with the state-of-the-art transition metal carbides. A symmetric device assembled with Zn x Co 1– x O achieves an energy density of 67.3 watt-hour kg –1 at a power density of 1.67 kW kg –1 , which is the highest value ever reported for symmetric pseudocapacitors. Our finding suggests that the rational design of electrode materials at the atomic scale opens a new opportunity for achieving high power/energy density electrode materials for advanced energy storage devices.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 10
    Publication Date: 2018-11-27
    Description: Actinia -like multifunctional nanocoagulant for single-step removal of water contaminants 〈i〉Actinia〈/i〉-like multifunctional nanocoagulant for single-step removal of water contaminants, Published online: 26 November 2018; doi:10.1038/s41565-018-0307-8 A nanostructure inspired by the sea anemone is very effective in removing a range of water contaminants.
    Print ISSN: 1748-3387
    Electronic ISSN: 1748-3395
    Topics: Physics
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