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  • 1
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    The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family (2016)
    Oxford University Press
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    Publication Date: 2016-05-06
    Description: The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3'-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3' UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Developmental regulation of N-terminal H2B methylation in Drosophila melanogaster (2012)
    Oxford University Press
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    Publication Date: 2012-02-28
    Description: Histone post-translational modifications play an important role in regulating chromatin structure and gene expression in vivo . Extensive studies investigated the post-translational modifications of the core histones H3 and H4 or the linker histone H1. Much less is known on the regulation of H2A and H2B modifications. Here, we show that a major modification of H2B in Drosophila melanogaster is the methylation of the N-terminal proline, which increases during fly development. Experiments performed in cultured cells revealed higher levels of H2B methylation when cells are dense, regardless of their cell cycle distribution. We identified dNTMT (CG1675) as the enzyme responsible for H2B methylation. We also found that the level of N-terminal methylation is regulated by dART8, an arginine methyltransferase that physically interacts with dNTMT and asymmetrically methylates H3R2. Our results demonstrate the existence of a complex containing two methyltransferases enzymes, which negatively influence each other’s activity.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Identification of frequent La Niña events during the early 1800s in the east equatorial Pacific (2015)
    Wiley-Blackwell
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    Publication Date: 2015-02-17
    Description: We report measurements of near-monthly Δ 14 C and δ 18 O during selected decades from an east equatorial Pacific coral that grew during the past four centuries. We find that El Niño events occurred regularly during the late 1700s. During the early 1800s, El Niño events occurred less often, and La Niña conditions prevailed, which were accompanied by unprecedented, low cool season Δ 14 C values and high cool season δ 18 O values. These results indicate that shallow overturning water (e.g. Central Mode Water) from the North Pacific was likely an important source of water to the Galapagos area during the early 1800s.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 4
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    Signal integration by the CYP1A1 promoter -- a quantitative study (2015)
    Oxford University Press
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    Publication Date: 2015-06-24
    Description: Genes involved in detoxification of foreign compounds exhibit complex spatiotemporal expression patterns in liver. Cytochrome P450 1A1 ( CYP1A1 ), for example, is restricted to the pericentral region of liver lobules in response to the interplay between aryl hydrocarbon receptor (AhR) and Wnt/β-catenin signaling pathways. However, the mechanisms by which the two pathways orchestrate gene expression are still poorly understood. With the help of 29 mutant constructs of the human CYP1A1 promoter and a mathematical model that combines Wnt/β-catenin and AhR signaling with the statistical mechanics of the promoter, we systematically quantified the regulatory influence of different transcription factor binding sites on gene induction within the promoter. The model unveils how different binding sites cooperate and how they establish the promoter logic; it quantitatively predicts two-dimensional stimulus-response curves. Furthermore, it shows that crosstalk between Wnt/β-catenin and AhR signaling is crucial to understand the complex zonated expression patterns found in liver lobules. This study exemplifies how statistical mechanical modeling together with combinatorial reporter assays has the capacity to disentangle the promoter logic that establishes physiological gene expression patterns.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Modern Deposition Rates and Patterns of Organic Carbon Burial in Fiordland, New Zealand (2016)
    Wiley-Blackwell
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    Publication Date: 2016-11-10
    Description: Fjords are disproportionately important for global organic carbon (OC) burial relative to their spatial extent, and may be important in sequestering atmospheric CO2, providing a negative climate feedback. Within fjords, multiple locally variable delivery mechanisms control mineral sediment deposition, which in turn modulates OC burial. Sediment and OC sources in Fiordland, New Zealand include terrigenous input at fjord heads, sediment reworking over fjord-mouth sills, and landslide events from steep fjord walls. Box cores were analyzed for sedimentary texture, sediment accumulation rate, and OC content to evaluate the relative importance of each delivery mechanism. Sediment accumulation was up to 3.4 mm/yr in proximal and distal fjord areas, with lower rates in medial reaches. X-radiograph and 210Pb stratigraphy indicate mass wasting and surface-sediment bioturbation throughout the fjords. Sediment accumulation rates are inversely correlated with %OC. Spatial heterogeneity in sediment depositional processes and rates is important when evaluating OC burial within fjords.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 6
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    New insights into saline water evaporation from porous media: Complex interaction between evaporation rates, precipitation and surface temperature (2017)
    Wiley-Blackwell
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    Publication Date: 2017-05-24
    Description: Understanding salt transport and deposition patterns during evaporation from porous media is important in many engineering and hydrological processes such as soil salinization, ecosystem functioning and land-atmosphere interaction. As evaporation proceeds, salt concentration increases until it exceeds solubility limits, locally, and crystals precipitate. The interplay between transport processes, crystallization and evaporation influences where crystallization occurs. During early stages, the precipitated salt creates an evolving porous structure affecting the evaporation kinetics. We conducted a comprehensive series of experiments to investigate how the salt concentration and precipitation influence evaporation dynamics. Our results illustrate the contribution of the evolving salt crust to the evaporative mass losses. High-resolution thermal imaging enabled us to investigate the complex temperature dynamics at the surface of precipitated salt, providing further confirmation of salt crust contribution to the evaporation. We identify different phases of saline water evaporation from porous media with the corresponding dominant mechanisms in each phase and extend the physical understanding of such processes.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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