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  • 1
    In: Biochemical Journal, Portland Press Ltd., Vol. 457, No. 3 ( 2014-02-01), p. 379-390
    Abstract: The major birch pollen allergen Bet v 1 is the main elicitor of airborne type I allergies and belongs to the PR-10 family (pathogenesis-related proteins 10). Bet v 1 is the most extensively studied allergen, and is well characterized at a biochemical and immunological level; however, its physiological function remains elusive. In the present study, we identify Q3OS (quercetin-3-O-sophoroside) as the natural ligand of Bet v 1. We isolated Q3OS bound to Bet v 1 from mature birch pollen and confirmed its binding by reconstitution of the Bet v 1–Q3OS complex. Fluorescence and UV–visible spectroscopy experiments, as well as HSQC (heteronuclear single-quantum coherence) titration, and the comparison with model compounds, such as quercetin, indicated the specificity of Q3OS binding. Elucidation of the binding site by NMR combined with a computational model resulted in a more detailed understanding and shed light on the physiological function of Bet v 1. We postulate that the binding of Q3OS to Bet v 1 plays an important, but as yet unclear, role during the inflammation response and Bet v 1 recognition by IgE.
    Type of Medium: Online Resource
    ISSN: 0264-6021 , 1470-8728
    RVK:
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2014
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    detail.hit.zdb_id: 2969-5
    SSG: 12
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  • 2
    In: Proteins: Structure, Function, and Bioinformatics, Wiley, Vol. 82, No. 3 ( 2014-03), p. 375-385
    Abstract: Reverse transcriptases (RTs) are pivotal in the life cycle of retroviruses and convert the genomic viral RNA into double‐stranded DNA. The RT polymerase domain is subdivided into fingers, palm, thumb, and the connection subdomain, which links the polymerase to the C‐terminal RNase H domain. In contrast to orthoretroviruses, mature RT of foamy viruses harbors the protease (PR) domain at its N‐terminus (PR‐RT). Therefore and due to low homology to other RTs, it is difficult to define the boundaries and functions of the (sub)domains. We introduced N‐ and C‐terminal deletions into simian foamy virus PR‐RT to investigate the impact of the truncations on the catalytic activities. Both, the RNase H domain and the connection subdomain contribute substantially to polymerase integrity and stability as well as to polymerase activity and substrate binding. The 42 amino acids long region C‐terminal of the PR is important for polymerase stability and activity. PR activation via binding of PR‐RT to viral RNA requires the presence of the full length PR‐RT including the RNase H domain. In vitro , the cleavage efficiencies of FV PR for the Gag and Pol cleavage site are comparable, even though in virus particles only the Pol site is cleaved to completion suggesting that additional factors control PR activity and that virus maturation needs to be strictly regulated. Proteins 2014; 82:375–385. © 2013 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0887-3585 , 1097-0134
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 1475032-6
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2022
    In:  Journal of Biomedical Materials Research Part B: Applied Biomaterials Vol. 110, No. 5 ( 2022-05), p. 1165-1177
    In: Journal of Biomedical Materials Research Part B: Applied Biomaterials, Wiley, Vol. 110, No. 5 ( 2022-05), p. 1165-1177
    Abstract: The development of multifunctional biomaterials as both tissue regeneration and drug delivery devices is currently a major focus in biomedical research. Tannic Acid (TA), a naturally occurring plant polyphenol, displays unique medicinal abilities as an antioxidant, an antibiotic, and as an anticancer agent. TA has applications in biomaterials acting as a crosslinker in polymer hydrogels improving thermal stability and mechanical properties. We have developed injectable cell seeded collagen beads crosslinked with TA for breast reconstruction and anticancer activity following lumpectomy. This study determined the longevity of the bead implants by establishing a degradation time line and TA release profile in vivo. Beads crosslinked with 0.1% TA and 1% TA were compared to observe the differences in TA concentration on degradation and release. We found collagen/TA beads degrade at similar rates in vivo, yet are resistant to complete degradation after 16 weeks. TA is released over time in vivo through diffusion and cellular activity. Changes in mechanical properties in collagen/TA beads before implantation to after 8 weeks in vivo also indicate loss of TA over a longer period of time. Elastic moduli decreased uniformly in both 0.1% and 1% TA beads. This study establishes that collagen/TA materials can act as a drug delivery system, rapidly releasing TA within the first week following implantation. However, the beads retain TA long term allowing them to resist degradation and remain in situ acting as a cell scaffold and tissue filler. This confirms its potential use as an anticancer and minimally invasive breast reconstructive device following lumpectomy.
    Type of Medium: Online Resource
    ISSN: 1552-4973 , 1552-4981
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2130917-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Portland Press Ltd. ; 2010
    In:  Biochemical Journal Vol. 427, No. 2 ( 2010-04-15), p. 197-203
    In: Biochemical Journal, Portland Press Ltd., Vol. 427, No. 2 ( 2010-04-15), p. 197-203
    Abstract: Retroviral proteases have been shown previously to be only active as homodimers. They are essential to form the separate and active proteins from the viral precursors. Spumaretroviruses produce separate precursors for Gag and Pol, rather than a Gag and a Gag–Pol precursor. Nevertheless, processing of Pol into a PR (protease)–RT (reverse transcriptase) and integrase is essential in order to obtain infectious viral particles. We showed recently that the PR–RT from a simian foamy virus, as well as the separate PRshort (protease) domain, exhibit proteolytic activities, although only monomeric forms could be detected. In the present study, we demonstrate that PRshort and PR–RT can be inhibited by the putative dimerization inhibitor cholic acid. Various other inhibitors, including darunavir and tipranavir, known to prevent HIV-1 PR dimerization in cells, had no effect on foamy virus protease in vitro. 1H-15N HSQC (heteronuclear single quantum coherence) NMR analysis of PRshort indicates that cholic acid binds in the proposed PRshort dimerization interface and appears to impair formation of the correct dimer. NMR analysis by paramagnetic relaxation enhancement resulted in elevated transverse relaxation rates of those amino acids predicted to participate in dimer formation. Our results suggest transient PRshort homodimers are formed under native conditions but are only present as a minor transient species, which is not detectable by traditional methods.
    Type of Medium: Online Resource
    ISSN: 0264-6021 , 1470-8728
    RVK:
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2010
    detail.hit.zdb_id: 1473095-9
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 19 ( 2021-05-11)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 19 ( 2021-05-11)
    Abstract: Various microorganisms and some mammalian cells are able to swim in viscous fluids by performing nonreciprocal body deformations, such as rotating attached flagella or by distorting their entire body. In order to perform chemotaxis (i.e., to move toward and to stay at high concentrations of nutrients), they adapt their swimming gaits in a nontrivial manner. Here, we propose a computational model, which features autonomous shape adaptation of microswimmers moving in one dimension toward high field concentrations. As an internal decision-making machinery, we use artificial neural networks, which control the motion of the microswimmer. We present two methods to measure chemical gradients, spatial and temporal sensing, as known for swimming mammalian cells and bacteria, respectively. Using the genetic algorithm NeuroEvolution of Augmenting Topologies, surprisingly simple neural networks evolve. These networks control the shape deformations of the microswimmers and allow them to navigate in static and complex time-dependent chemical environments. By introducing noisy signal transmission in the neural network, the well-known biased run-and-tumble motion emerges. Our work demonstrates that the evolution of a simple and interpretable internal decision-making machinery coupled to the environment allows navigation in diverse chemical landscapes. These findings are of relevance for intracellular biochemical sensing mechanisms of single cells or for the simple nervous system of small multicellular organisms such as Caenorhabditis elegans .
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Informa UK Limited ; 2012
    In:  Journal of Biomolecular Structure and Dynamics Vol. 29, No. 4 ( 2012-02), p. 793-798
    In: Journal of Biomolecular Structure and Dynamics, Informa UK Limited, Vol. 29, No. 4 ( 2012-02), p. 793-798
    Type of Medium: Online Resource
    ISSN: 0739-1102 , 1538-0254
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2085732-9
    SSG: 12
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