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Berlin Brandenburg

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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 24 July 2018, Vol.115(30), pp.E7053-E7062
    Description: Lens epithelium-derived growth factor/p75 (LEDGF/p75, or PSIP1) is a transcriptional coactivator that tethers other proteins to gene bodies. The chromatin tethering function of LEDGF/p75 is hijacked by HIV integrase to ensure viral integration at sites of active transcription. LEDGF/p75 is also important for the development of mixed-lineage leukemia (MLL), where it tethers the MLL1 fusion complex at aberrant MLL targets, inducing malignant transformation. However, little is known about how the LEDGF/p75 protein interaction network is regulated. Here, we obtained solution structures of the complete interfaces between the LEDGF/p75 integrase binding domain (IBD) and its cellular binding partners and validated another binding partner, Mediator subunit 1 (MED1). We reveal that structurally conserved IBD-binding motifs (IBMs) on known LEDGF/p75 binding partners can be regulated by phosphorylation, permitting switching between low- and high-affinity states. Finally, we show that elimination of IBM phosphorylation sites on MLL1 disrupts the oncogenic potential of primary MLL1-rearranged leukemic cells. Our results demonstrate that kinase-dependent phosphorylation of MLL1 represents a previously unknown oncogenic dependency that may be harnessed in the treatment of MLL-rearranged leukemia.
    Keywords: Ledgf/P75 ; Disordered Proteins ; Leukemia ; Phosphorylation ; Protein–Protein Interactions ; Adaptor Proteins, Signal Transducing -- Metabolism ; Transcription Factors -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    In: Geochimica et Cosmochimica Acta, 01 December 2017, Vol.218, pp.237-256
    Description: The formation of realgar (As S ) has recently been identified as a prominent As sequestration pathway in the naturally As-enriched wetland soil at the Mokrsko geochemical anomaly (Czech Republic). Here we used bulk soil and pore water analyses, synchrotron X-ray absorption spectroscopy, S isotopes, and DNA extractions to determine the distribution and speciation of As as a function of soil depth and metabolic properties of microbial communities in wetland soil profiles. Total solid-phase analyses showed that As was strongly correlated with organic matter, caused by a considerable As accumulation (up to 21 g kg ) in an organic-rich soil horizon artificially buried in 1980 at a depth of ∼80 cm. Extended X-ray absorption fine structure spectroscopy revealed that As in the buried organic horizon was predominantly present as realgar occurring as nanocrystallites (50–100 nm) in millimeter-scale deposits associated with particulate organic matter. The realgar was depleted in the S isotope by 9–12.5‰ relative to the aqueous sulfate supplied to the soil, implying its biologically induced formation. Analysis of the microbial communities by 16S rDNA sequencing showed that realgar deposits formed in strictly anaerobic organic-rich domains dominated by sulfate-reducing and fermenting metabolisms. In contrast, realgar deposits were not observed in similar domains with even small contributions of oxidative metabolisms. No association of realgar with specific microbial species was observed. Our investigation shows that strongly reducing microenvironments associated with buried organic matter are significant biogeochemical traps for As, with an estimated As accumulation rate of 61 g As m yr . Nevertheless the production of biologically induced realgar in these microenvironments is too slow to lower As groundwater concentrations at our field site (∼6790 mg L ). Our study demonstrates the intricate link between geochemistry and microbial community dynamics in wetland soils, and provides insights into the conditions necessary to promote As sulfide precipitation in engineered wetlands for the treatment of As-rich waters.
    Keywords: Arsenic Speciation ; Realgar ; Wetland Soil ; X-Ray Absorption Spectroscopy ; Sulfur Isotopes ; Microbial Communities ; Geology
    ISSN: 0016-7037
    E-ISSN: 1872-9533
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  • 3
    Language: English
    In: Applied Surface Science, 15 June 2018, Vol.443, pp.244-254
    Description: In the current work, chemical derivatization of amine (NH ) groups with trifluoroacetic anhydride (TFAA) as an analytical method to improve the information scope of X-ray photoelectron spectroscopy (XPS) is investigated. TFAA is known to successfully label hydroxyl (OH) groups. With the introduction of a newly developed gas-phase derivatization protocol conducted at ambient pressure and using a catalyst also NH groups can now efficiently be labelled with a high yield and without the formation of unwanted by-products. By establishing a comprehensive and self-consistent database of reference binding energies for XPS a promising approach for distinguishing hydroxyl from amine groups is presented. The protocol was verified on different polymers, including poly(allylamine), poly(ethyleneimine), poly(vinylalcohol) and chitosan, the latter one containing both types of addressed chemical groups.
    Keywords: Chemical Derivatization ; Xps ; Trifluoroacetic Anhydride ; Amino Group ; Hydroxyl Group ; Polymer ; Engineering
    ISSN: 0169-4332
    E-ISSN: 1873-5584
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  • 4
    Language: English
    In: Microbial Ecology, 2016, Vol.72(1), pp.163-174
    Description: Deep sequencing of prokaryotic 16S rDNA regularly reveals thousands of microbial species thriving in many common habitats. It is still unknown how this huge microbial diversity, including many potentially competing organisms, may persist at a single site. One of plausible hypotheses is that a large number of spatially separated microcommunities exist within each complex habitat. Smaller subset of the species may exist in each microcommunity and actually interact with each other. We sampled two groups of microbial stalactites growing at a single acidic mine drainage outlet as a model of multiplicated, low-complexity microhabitat. Samples from six other sites were added for comparison. Both tRFLP and 16S rDNA pyrosequencing showed that microbial communities containing 6 to 51 species-level operational taxonomic units (OTU) inhabited all stalactites. Interestingly, most OTUs including the highly abundant ones unpredictably alternated regardless of physical and environmental distance of the stalactites. As a result, the communities clustered independently on sample site and other variables when using both phylogenetic dissimilarity and OTU abundance metrics. Interestingly, artificial communities generated by pooling the biota of several adjacent stalactites together clustered by the locality more strongly than when the stalactites were analyzed separately. The most probable interpretation is that each stalactite contains likely random selection from the pool of plausible species. Such degree of stochasticity in assembly of extremophilic microbial communities is significantly greater than commonly proposed and requires caution when interpreting microbial diversity.
    Keywords: Acidophiles ; Chemolithotrophy ; Phylogenetic dissimilarity ; Community assembly ; Neutral processes
    ISSN: 0095-3628
    E-ISSN: 1432-184X
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  • 5
    Language: English
    In: Environmental Science and Pollution Research, 2019, Vol.26(18), pp.18766-18776
    Description: Sequestration of arsenic to biogenic sulfide minerals is known from As-contaminated anoxic environments. Despite numerous successful laboratory experiments, the process remains difficult to predict in moderate arsenic conditions. We performed microcosm experiments using naturally contaminated groundwater (containing ca. 6 mg/L As) and natural organic matter (NOM) particles both collected from wetland soil. Macroscopic realgar precipitates, occasionally accompanied by bonazziite, a FeS phase, elementary S, calcite, and whewellite, appeared after 4 to 18 months. Realgar only precipitated in microcosms moderately poisoned by azide or antibiotics and those in which oxidation of hydrogen sulfide to sulfur took place. The biomineralization process was not affected by the presence of additional carbon sources or the diversity, community structure, and functional composition of the microbial community. Hydrogen sulfide concentration was greater in the realgar-free microcosms, suggesting that arsenic thiolation prevented precipitation of realgar. We compared our data to available microbial community data from soils with different rates of realgar precipitation, and found that the communities from realgar-encrusted NOM particles usually showed limited sulfate reduction and the presence of fermentative metabolisms, whereas communities from realgar-free NOM particles were strongly dominated by sulfate reducers. We argue that the limited sulfate supply and intensive fermentation amplify reducing conditions, which make arsenic sulfide precipitation plausible in high-sulfate, low-arsenic groundwaters.
    Keywords: Arsenic ; Microcosm ; Sulfate reduction ; Realgar biomineralization ; Fermentation ; Arsenic thiolation
    ISSN: 0944-1344
    E-ISSN: 1614-7499
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