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  • 1
    Language: English
    In: Sci Rep, 2017, Vol.7(1), pp.9328-9328
    Description: Many pathogenic bacteria utilize specialized secretion systems to deliver proteins called effectors into eukaryotic cells for manipulation of host pathways. The vast majority of known effector targets are host proteins, whereas a potential targeting of host nucleic acids remains little explored. There is only one family of effectors known to target DNA directly, and effectors binding host RNA are unknown. Here, we take a two-pronged approach to search for RNA-binding effectors, combining biocomputational prediction of RNA-binding domains (RBDs) in a newly assembled comprehensive dataset of bacterial secreted proteins, and experimental screening for RNA binding in mammalian cells. Only a small subset of effectors were predicted to carry an RBD, indicating that if RNA targeting was common, it would likely involve new types of RBDs. Our experimental evaluation of effectors with predicted RBDs further argues for a general paucity of RNA binding activities amongst bacterial effectors. We obtained evidence that PipB2 and Lpg2844, effector proteins of Salmonella and Legionella species, respectively, may harbor novel biochemical activities. Our study presenting the first systematic evaluation of the RNA-targeting potential of bacterial effectors offers a basis for discussion of whether or not host RNA is a prominent target of secreted bacterial proteins.
    Keywords: Bacterial Proteins -- Metabolism ; Eukaryotic Cells -- Metabolism ; Legionella -- Metabolism ; RNA -- Metabolism ; RNA-Binding Proteins -- Metabolism ; Salmonella -- Metabolism ; Virulence Factors -- Metabolism;
    ISSN: 2045-2322
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  • 2
    In: Scientific Reports, 2016, Vol.6
    Description: Escherichia coli O104:H4 (E. coli O104:H4), which caused a massive outbreak of acute gastroenteritis and hemolytic uremic syndrome in 2011, carries an aggregative adherence fimbriae I (AAF/I) encoding virulence plasmid, pAA. The importance of pAA in host-pathogen interaction and disease severity has been demonstrated, however, not much is known about its transcriptional organization and gene regulation. Here, we analyzed the pAA primary transcriptome using differential RNA sequencing, which allows for the high-throughput mapping of transcription start site (TSS) and non-coding RNA candidates. We identified 248 TSS candidates in the 74-kb pAA and only 21% of them could be assigned as TSS of annotated genes. We detected TSS for the majority of pAA-encoded virulence factors. Interestingly, we mapped TSS, which could allow for the transcriptional uncoupling of the AAF/I operon, and potentially regulatory antisense RNA candidates against the genes encoding dispersin and the serine protease SepA. Moreover, a computational search for transcription factor binding sites suggested for AggR-mediated activation of SepA expression, which was additionally experimentally validated. This work advances our understanding of the molecular basis of E. coli O104:H4 pathogenicity and provides a valuable resource for further characterization of pAA virulence gene regulation.
    Keywords: Biology;
    E-ISSN: 2045-2322
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  • 3
    In: Scientific Reports, 2019, Vol.9
    Description: Contradictory evidence exists regarding whether and to which extend roots change soil structure in their vicinity. Here we attempt to reconcile disparate views allowing for the two-way interaction between soil structure and root traits, i.e. changes...
    Keywords: Article ; Environmental Sciences ; Imaging Techniques ; Image Processing ; Patterning ; Tropism
    E-ISSN: 2045-2322
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  • 4
    In: Scientific Reports, 2013, Vol.3
    Description: Substrate-exploring functions of filopodia were previously suggested based on cell studies on flat surfaces, but their role in topography sensing especially within nanofibrillar environments remained elusive. Here we have grown highly flexible hairy silicon nanowires on micropatterned islands on otherwise flat glass surfaces and coated them both with the extracellular matrix (ECM) protein fibronectin. This allowed us to visualize how filopodia steer fundamental cell functions such as cell adhesion, spreading, migration and division in the absence of lamellipodia. Shortly after seeding, transient filopodia protrude from the still spherical cells. Once filopodia contact nanowires, they bend and align them, while most filopodia peel off from flat surfaces. A zipping mechanism regulated by traction forces is proposed to explain how force-induced changes in filopodia-substrate contact angles enable topography sensing, including the still elusive phenomenon of contact guidance. Filopodia thus play a central role in steering transient topographic preferences.
    Keywords: Biology;
    ISSN: 20452322
    E-ISSN: 20452322
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  • 5
    In: Scientific Reports, 2013, Vol.3
    Description: While stem cells can sense and respond to physical properties of their environment, the molecular aspects how physical information is translated into biochemical signals remain unknown. Here we show that human mesenchymal stem cells (hMSCs) harvest and assemble plasma fibronectin into their extracellular matrix (ECM) fibrils within 24 hours. hMSCs pro-actively pull on newly assembled fibronectin ECM fibrils, and the fibers are more stretched on rigid than on soft fibronectin-coated polyacrylamide gels. Culturing hMSCs on single stretched fibronectin fibers upregulates hMSC osteogenesis. Osteogenesis was increased when αvβ3 integrins were blocked on relaxed fibronectin fibers, and decreased when α5β1 integrins were blocked or when epidermal growth factor (EGF) receptor signaling was inhibited on stretched fibronectin fibers. This suggests that hMSCs utilize their own contractile forces to translate environmental cues into differential biochemical signals by stretching fibronectin fibrils. Mechanoregulation of fibronectin fibrils may thus serve as check point to regulate hMSC osteogenesis.
    Keywords: Biology;
    ISSN: 20452322
    E-ISSN: 20452322
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  • 6
    Language: English
    In: Sci Rep, 2017, Vol.7(1), pp.1210-1210
    Description: Glycosaminoglycans are known to bind biological mediators thereby modulating their biological activity. Sulfated hyaluronans (sHA) were reported to strongly interact with transforming growth factor (TGF)-β1 leading to impaired bioactivity in fibroblasts. The underlying mechanism is not fully elucidated yet. Examining the interaction of all components of the TGF-β1:receptor complex with sHA by surface plasmon resonance, we could show that highly sulfated HA (sHA3) blocks binding of TGF-β1 to its TGF-β receptor-I (TβR-I) and -II (TβR-II). However, sequential addition of sHA3 to the TβR-II/TGF-β1 complex led to a significantly stronger recruitment of TβR-I compared to a complex lacking sHA3, indicating that the order of binding events is very important. Molecular modeling suggested a possible molecular mechanism in which sHA3 could potentially favor the association of TβR-I when added sequentially. For the first time bioactivity of TGF-β1 in conjunction with sHA was investigated at the receptor level. TβR-I and, furthermore, Smad2 phosphorylation were decreased in the presence of sHA3 indicating the formation of an inactive signaling complex. The results contribute to an improved understanding of the interference of sHA3 with TGF-β1:receptor complex formation and will help to further improve the design of functional biomaterials that interfere with TGF-β1-driven skin fibrosis.
    Keywords: Adjuvants, Immunologic -- Metabolism ; Hyaluronic Acid -- Metabolism ; Receptors, Transforming Growth Factor Beta -- Metabolism ; Signal Transduction -- Drug Effects ; Transforming Growth Factor Beta1 -- Metabolism;
    ISSN: 2045-2322
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  • 7
  • 8
    In: Scientific Reports, 2016, Vol.6
    Description: The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases ( DUSP genes) and of PPP1R15A , which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.
    Keywords: Article;
    E-ISSN: 2045-2322
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  • 9
    Language: English
    In: Sci Rep, 2017, Vol.7(1), pp.14406-14406
    Description: The uneven representation of frugivorous mammals and birds across tropical regions – high in the New World, low in Madagascar and intermediate in Africa and Asia – represents a long-standing enigma in ecology. Several hypotheses have been proposed to explain these differences but the ultimate drivers remain unclear. Here, we tested the hypothesis that fruits in Madagascar contain insufficient nitrogen to meet primate metabolic requirements, thus constraining the evolution of frugivory. We performed a global analysis of nitrogen in fruits consumed by primates, as collated from 79 studies. Our results showed that average frugivory among lemur communities was lower compared to New World and Asian-African primate communities. Fruits in Madagascar contain lower average nitrogen than those in the New World and Old World. Nitrogen content in the overall diets of primate species did not differ significantly between major taxonomic radiations. There is no relationship between fruit protein and the degree of frugivory among primates either globally or within regions, with the exception of Madagascar. This suggests that low protein availability in fruits influences current lemur communities to select for protein from other sources, whereas in the New World and Old World other factors are more significant in shaping primate communities.
    Keywords: Biological Evolution ; Primates ; Fruit -- Metabolism ; Nitrogen -- Metabolism;
    ISSN: 2045-2322
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