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  • Articles  (17)
  • Oxford University Press  (8)
  • Wiley-Blackwell  (8)
  • The American Association for Cancer Research (AACR)  (1)
  • 2010-2014  (17)
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  • Articles  (17)
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  • 1
    Publication Date: 2012-05-23
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2012-04-24
    Description: The transcription factors Gli2 (glioma-associated factor 2), which is a transactivator of Sonic Hedgehog (Shh) signalling, and myocyte enhancer factor 2C (MEF2C) play important roles in the development of embryonic heart muscle and enhance cardiomyogenesis in stem cells. Although the physiological importance of Shh signalling and MEF2 factors in heart development is well known, the mechanistic understanding of their roles is unclear. Here, we demonstrate that Gli2 and MEF2C activated each other's expression while enhancing cardiomyogenesis in differentiating P19 EC cells. Furthermore, dominant-negative mutant proteins of either Gli2 or MEF2C repressed each other's expression, while impairing cardiomyogenesis in P19 EC cells. In addition, chromatin immunoprecipitation (ChIP) revealed association of Gli2 to the Mef2c gene, and of MEF2C to the Gli2 gene in differentiating P19 cells. Finally, co-immunoprecipitation studies showed that Gli2 and MEF2C proteins formed a complex, capable of synergizing on cardiomyogenesis-related promoters containing both Gli- and MEF2-binding elements. We propose a model whereby Gli2 and MEF2C bind each other's regulatory elements, activate each other's expression and form a protein complex that synergistically activates transcription, enhancing cardiac muscle development. This model links Shh signalling to MEF2C function during cardiomyogenesis and offers mechanistic insight into their in vivo functions.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2013-07-17
    Description: The reconstruction of the history of rearrangements and the reconstruction of ancestral genomes are some of the challenges of bioinformatics today. Many algorithms already exist, treating one or the other question but none treating both. These reconstructions are interdependent and we argue on the interest of treating both problems in parallel to lead to a richer and more complete output. We also argue on the importance of redefining several steps of these algorithms to improve both reconstructions: the identification of synteny blocks has to be as precise as possible, and the treatment of multiple genomes has to be based on pairwise comparisons to ensure the most detailed reconstructions. In this article, we highlight novel solutions to these points and focus on the need of explicitly treating overlapping, included, duplicated and unsigned synteny blocks. To do so, we introduce the new notion of synteny pack , which is a representation of local hypothetical intermediate ancestral genomes. We discuss a number of examples on yeast genomes to illustrate the importance of such a definition.
    Print ISSN: 0955-792X
    Electronic ISSN: 1465-363X
    Topics: Computer Science , Mathematics
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  • 4
    Publication Date: 2013-05-10
    Description: The title compound, [K(C 14 H 23 )(C 4 H 8 O)] n , comprises zigzag chains of alternating bridging 2,3,4,5-tetramethyl-1- n -pentylcyclopentadienyl ligands and potassium ions, with an ancillary tetrahydrofuran ligand in the coordination environment of potassium. The coordination polymer strands so formed extend by 2 1 screw symmetry in the b -axis direction. The chemically modified cyclopentadienyl ligand, with a tethered n -pentyl group, was synthesized from 2,3,4,5-tetramethylcyclopent-2-enone by a Grignard reaction.
    Print ISSN: 0108-2701
    Electronic ISSN: 1600-5759
    Topics: Chemistry and Pharmacology , Geosciences , Physics
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  • 5
    Publication Date: 2014-03-16
    Description: Earth's core is an iron-rich alloy containing several weight percent of light element(s), possibly including silicon. Therefore the high pressure-temperature equations of state of iron–silicon alloys can provide understanding of the properties of Earth's core. We performed X-ray diffraction experiments using laser-heated diamond anvil cells to achieve simultaneous high pressures and temperatures, up to ~200 GPa for Fe–9wt%Si alloy and ~145 GPa for stoichiometric FeSi. We determined equations of state of the D0 3 , hcp + B2, and hcp phases of Fe–9Si, and the B20 and B2 phases of FeSi. We also calculated equations of state of Fe, Fe 11 Si, Fe 5 Si, Fe 3 Si, and FeSi using ab initio methods, finding that iron and silicon atoms have similar volumes at high pressures. By comparing our experimentally-determined equations of state to the observed core density deficit, we find that the maximum amount of silicon in the outer core is ~11 wt%, while the maximum amount in the inner core is 6–8 wt%, for a purely Fe–Si–Ni core. Bulk sound speeds predicted from our equations of state also match those of the inner and outer core for similar ranges of compositions. We find a compositional contrast between the inner and outer core of 3.5–5.6 wt% silicon, depending on the seismological model used. Theoretical and experimental equations of state agree at high pressures. We find a good match to the observed density, density profile, and sound speed of the Earth's core, suggesting that silicon is a viable candidate for the dominant light element.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
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  • 6
    Publication Date: 2013-08-07
    Description: Plasmacytoid dendritic cells (pDCs) play an important role in innate and adaptive immunity and were shown to be identical to previously described natural IFN-α-producing (NIP) cells. Here, we describe two functionally distinct pDC subpopulations that are characterized by the differential expression of stem cell antigen-1 (Sca-1; Ly-6A/E). Sca-1 − pDCs are mainly found in the bone marrow, appear first during development, show a higher proliferative activity and represent the more precursor phenotype. Sca-1 + pDCs are mostly located in secondary lymphoid organs and represent a later developmental stage. Sca-1 − pDCs give rise to a Sca-1 + subset upon activation or in response to endogenous type I IFN. Interestingly, in contrast to Sca-1 − pDCs, Sca-1 + pDCs are defective in IFN-α production upon endosomal TLR9 stimulation, whereas lysosomal signaling via TLR9 is functional in both subsets. Gene expression analysis revealed that osteopontin (Opn) is strongly upregulated in Sca-1 − pDCs. These data provide evidence for the molecular basis of the observed functional heterogeneity, as the intracellular isoform of Opn couples TLR9 signaling to IFN-α expression. Taken together, our results indicate that Sca-1 − pDCs are an early developmental stage of pDCs with distinct innate functions representing the true murine NIP cell.
    Print ISSN: 0014-2980
    Electronic ISSN: 1521-4141
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 7
    Publication Date: 2012-04-16
    Description: Purpose: To evaluate the feasibility of semiquantitative measurement of liver perfusion from analysis of ferucarbotran induced signal-dynamics in double-contrast liver MR-imaging (DC-MRI). Materials and Methods: In total 31 patients (21 men; 58 ± 10 years) including 18 patients with biopsy proven liver cirrhosis prospectively underwent clinically indicated DC-MRI at 1.5 Tesla (T) with dynamic T2*-weighted gradient-echo imaging after ferucarbotran bolus injection. Breathing artefacts in tissue and input time curves were reduced by Savitzky-Golay-filtering and semiquantitative perfusion maps were calculated using a model free approach. Hepatic blood flow index (HBFI) and splenic blood flow index (SBFI) were determined by normalization of arbitrary perfusion values to the perfusion of the erector spinae muscle resulting in a semiquantitative perfusion measure. Results: In 30 of 31 patients the evaluated protocol could successfully be applied. Mean HBF was 7.7 ± 2.46 (range, 4.6–12.8) and mean SBF was 13.20 ± 2.57 (range, 8.5–17.8). A significantly lower total HBF was seen in patients with cirrhotic livers as compared to patients with noncirrhotic livers ( P 〈 0.05). In contrast, similar SBF was observed in cirrhotic and noncirrhotic patients ( P = 0.11). Conclusion: Capturing the signal dynamics during bolus injection of ferucarbotran in DC-MRI of the liver allows for semiquantitative assessment of hepatic perfusion that may be helpful for a more precise characterisation of liver cirrhosis and focal liver lesions. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 8
    Publication Date: 2011-12-16
    Description: Wüstite, Fe1-xO, is an important component in the mineralogy of Earth's lower mantle and may also be a component of the core. Therefore its high pressure-temperature behavior, including its electronic structure, is essential to understanding the nature and evolution of Earth's deep interior. We performed X-ray diffraction and radiometric measurements on wüstite in a laser-heated diamond anvil cell, finding an insulator-metal transition at high pressures and temperatures. Our data show a negative slope for this apparently isostructural phase boundary, which is characterized by a volume decrease and emissivity increase. The metallic phase of FeO is stable at conditions of the lower mantle and core, which has implications for the high P-T character of Fe-O bonds, magnetic field propagation, and lower mantle conductivity.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
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  • 9
    Publication Date: 2011-07-10
    Description: Sea-level rise is a projected consequence of global climate change that will result in complex changes in coastal ecosystems. These changes will cause transitions among coastal habitat types, which will be compounded by human-made barriers to the gradual inland migration of these habitat types. The effect of these changes on the future viability of coastal species will depend on the habitat requirements and population dynamics of these species. Thus, realistic assessments of the impact of sea-level rise (SLR) require linking geomorphological models with habitat and population models. In this study, we implemented a framework that allows this linkage, and demonstrated its feasibility to assess the effect of SLR on the viability of the Snowy Plover population in Florida. The results indicate that SLR will cause a decline in suitable habitat and carrying capacity for this species, and an increase in the risk of its extinction and decline. The model projected that the population size will decline faster than the area of habitat or carrying capacity, demonstrating the necessity of incorporating population dynamics in assessing the impacts of SLR on coastal species. The results were most sensitive to uncertainties in survival rate and fecundity, and suggested that future studies on this species should focus on the average and variability of these demographic rates and their dependence on population density. The effect of SLR on this species’ viability was qualitatively similar with most alternative models that used the extreme values of each uncertain parameter, indicating that the results are robust to uncertainties in the model.
    Print ISSN: 1354-1013
    Electronic ISSN: 1365-2486
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Published by Wiley-Blackwell
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  • 10
    Publication Date: 2013-01-04
    Description: Purpose: The phosphoinositide 3-kinase (PI3K) pathway is fundamental for cell proliferation and survival and is frequently altered and activated in neoplasia, including carcinomas of the lung. In this study, we investigated the potential of targeting the catalytic class I A PI3K isoforms in small cell lung cancer (SCLC), which is the most aggressive of all lung cancer types. Experimental Design: The expression of PI3K isoforms in patient specimens was analyzed. The effects on SCLC cell survival and downstream signaling were determined following PI3K isoform inhibition by selective inhibitors or downregulation by siRNA. Results: Overexpression of the PI3K isoforms p110-α and p110-β and the antiapoptotic protein Bcl-2 was shown by immunohistochemistry in primary SCLC tissue samples. Targeting the PI3K p110-α with RNA interference or selective pharmacologic inhibitors resulted in strongly affected cell proliferation of SCLC cells in vitro and in vivo , whereas targeting p110-β was less effective. Inhibition of p110-α also resulted in increased apoptosis and autophagy, which was accompanied by decreased phosphorylation of Akt and components of the mTOR pathway, such as the ribosomal S6 protein, and the eukaryotic translation initiation factor 4E-binding protein 1. A DNA microarray analysis revealed that p110-α inhibition profoundly affected the balance of pro- and antiapoptotic Bcl-2 family proteins. Finally, p110-α inhibition led to impaired SCLC tumor formation and vascularization in vivo . Conclusion: Together our data show the key involvement of the PI3K isoform p110-α in the regulation of multiple tumor-promoting processes in SCLC. Clin Cancer Res; 19(1); 96–105. ©2012 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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