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  • Artikel  (19)
  • Wiley-Blackwell  (15)
  • The American Society for Biochemistry and Molecular Biology (ASBMB)  (4)
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  • Artikel  (19)
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  • 1
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    catena-Poly[[(tetrahydrofuran-κO)potassium]-μ-(η5:η5)-2,3,4,5-tetramethyl-1-n-pentylcyclopentadienyl] (2013)
    Wiley-Blackwell
    Details
    Publikationsdatum: 2013-05-10
    Beschreibung: 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
    Digitale ISSN: 1600-5759
    Thema: Chemie und Pharmazie , Geologie und Paläontologie , Physik
    Publiziert von Wiley-Blackwell im Namen von International Union of Crystallography (IUCr).
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  • 2
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    Axisymmetric circulation driven by marginal heating in ice-covered lakes (2015)
    Wiley-Blackwell
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    Publikationsdatum: 2015-04-01
    Beschreibung: Below the temperature of maximum density (TMD) in freshwater lakes, heating at the lateral margins produces gravity currents along the bottom slope, akin to katabatic winds in the atmosphere and currents on continental shelves. We describe axisymmetric basin-scale circulation driven by heat flux at the shorelines in polar Lake Kilpisjärvi. A dense underflow originating near the shore converges towards the lake center, where it produces warm upwelling and return flow across the bulk of lake water column. The return flow, being subject to Coriolis force, creates a lake-wide anticyclonic gyre with velocities of 2-4 cm s -1 . While warm underflows are common on ice-covered lakes, the key finding is the basin-scale anticyclonic gyre with warm upwelling in the core. This circulation mechanism provides a key to understanding transport processes in (semi-) enclosed basins subject to negative buoyancy flux due to heating (or cooling at temperatures above TMD) at their lateral boundaries.
    Print ISSN: 0094-8276
    Digitale ISSN: 1944-8007
    Thema: Geologie und Paläontologie , Physik
    Publiziert von Wiley-Blackwell im Namen von American Geophysical Union (AGU).
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  • 3
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    Ichthyosis as the dermatological phenotype associated to TTC7A mutations (2016)
    Wiley-Blackwell
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    Publikationsdatum: 2016-04-06
    Beschreibung: The phenotype associated to spontaneous mutation in the Tetratricopeptide Repeat Domain 7A (TTC7A) in the flaky skin ( fsn ) mice 1 combines gastric hyperplasia, hyperproliferative immune disorder and skin anomalies. All fsn mice progressively develop thick white scales and patchy alopecia that turns into papulo-squamous lesions, marked hyperkeratosis and hypergranulosis associated to a dermal mixed inflammatory infiltrate on skin biopsy 2,3 . To date, the fsn mouse constitutes a model for human psoriasis vulgaris 3 . This article is protected by copyright. All rights reserved.
    Print ISSN: 0007-0963
    Digitale ISSN: 1365-2133
    Thema: Medizin
    Publiziert von Wiley-Blackwell
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  • 4
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    Yap Localization during Mechanosensing Requires Filamentous Actin [Cell Biology] (2016)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publikationsdatum: 2016-03-19
    Beschreibung: Cell-cell contact inhibition and the mechanical environment of cells have both been shown to regulate YAP nuclear localization to modulate cell proliferation. Changes in cellular contractility by genetic, pharmacological, and matrix stiffness perturbations regulate YAP nuclear localization. However, because contractility and F-actin organization are interconnected cytoskeletal properties, it remains unclear which of these distinctly regulates YAP localization. Here we show that in the absence of cell-cell contact, actomyosin contractility suppresses YAP phosphorylation at Ser112, however, neither loss of contractility nor increase in YAP phosphorylation is sufficient for its nuclear exclusion. We find that actin cytoskeletal integrity is essential for YAP nuclear localization, and can override phosphoregulation or contractility-mediated regulation of YAP nuclear localization. This actin-mediated regulation is conserved during mechanotransduction, as substrate compliance increased YAP phosphorylation and reduced cytoskeletal integrity leading to nuclear exclusion of both YAP and Ser(P)112-YAP. These data provide evidence for two actin-mediated pathways for YAP regulation; one in which actomyosin contractility regulates YAP phosphorylation, and a second that involves cytoskeletal integrity-mediated regulation of YAP nuclear localization independent of contractility. We suggest that in non-contact inhibited cells, this latter mechanism may be important in low stiffness regimes, such as may be encountered in physiological environments.
    Print ISSN: 0021-9258
    Digitale ISSN: 1083-351X
    Thema: Biologie , Chemie und Pharmazie
    Publiziert von The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 5
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    Species-specific Activation of Human TRPA1 by Protons [Neurobiology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publikationsdatum: 2013-07-13
    Beschreibung: The surveillance of acid-base homeostasis is concerted by diverse mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory neurons is mainly mediated by the capsaicin receptor TRPV1 and acid-sensing ion channels. In this study, we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor TRPA1 (hTRPA1). Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at physiological acidic pH values, were concentration-dependent, and were blocked by the selective TRPA1 antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons lacking TRPV1 only responded to protons when hTRPA1 was expressed heterologously. This species-specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular N-terminal cysteines known as important interaction sites for electrophilic TRPA1 agonists. Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule for proton-evoked pain and inflammation. The species specificity of this property is unique among known endogenous TRPA1 agonists, possibly indicating that evolutionary pressure enforced TRPA1 to inherit the role as an acid sensor in human sensory neurons.
    Print ISSN: 0021-9258
    Digitale ISSN: 1083-351X
    Thema: Biologie , Chemie und Pharmazie
    Publiziert von The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 6
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    Equations of state in the Fe–FeSi system at high pressures and temperatures (2014)
    Wiley-Blackwell
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    Publikationsdatum: 2014-03-16
    Beschreibung: 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
    Thema: Geologie und Paläontologie , Physik
    Publiziert von Wiley-Blackwell im Namen von American Geophysical Union (AGU).
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  • 7
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    Sca-1 expression defines developmental stages of mouse pDCs that show functional heterogeneity in the endosomal but not lysosomal TLR9 response (2013)
    Wiley-Blackwell
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    Publikationsdatum: 2013-08-07
    Beschreibung: 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
    Digitale ISSN: 1521-4141
    Thema: Medizin
    Publiziert von Wiley-Blackwell
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  • 8
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    Characterization of the CagA-CagF Interaction [Molecular Biophysics] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publikationsdatum: 2013-11-16
    Beschreibung: CagA is a virulence factor that Helicobacter pylori inject into gastric epithelial cells through a type IV secretion system where it can cause gastric adenocarcinoma. Translocation is dependent on the presence of secretion signals found in both the N- and C-terminal domains of CagA and an interaction with the accessory protein CagF. However, the molecular basis of this essential protein-protein interaction is not fully understood. Herein we report, using isothermal titration calorimetry, that CagA forms a 1:1 complex with a monomer of CagF with nm affinity. Peptide arrays and isothermal titration calorimetry both show that CagF binds to all five domains of CagA, each with μm affinity. More specifically, a coiled coil domain and a C-terminal helix within CagF contacts domains II-III and domain IV of CagA, respectively. In vivo complementation assays of H. pylori with a double mutant, L36A/I39A, in the coiled coil region of CagF showed a severe weakening of the CagA-CagF interaction to such an extent that it was nearly undetectable. However, it had no apparent effect on CagA translocation. Deletion of the C-terminal helix of CagF also weakened the interaction with CagA but likewise had no effect on translocation. These results indicate that the CagA-CagF interface is distributed broadly across the molecular surfaces of these two proteins to provide maximal protection of the highly labile effector protein CagA.
    Print ISSN: 0021-9258
    Digitale ISSN: 1083-351X
    Thema: Biologie , Chemie und Pharmazie
    Publiziert von The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 9
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    Metaphosphate Stabilization in the Myosin ATPase [Enzymology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publikationsdatum: 2013-12-07
    Beschreibung: It has been proposed recently that ATP hydrolysis in ATPase enzymes proceeds via an initial intermediate in which the dissociated γ-phosphate of ATP is bound in the protein as a metaphosphate (PγO3−). A combined quantum/classical analysis of this dissociated nucleotide state inside myosin provides a quantitative understanding of how the enzyme stabilizes this unusual metaphosphate. Indeed, in vacuum, the energy of the ADP3−·PγO3−·Mg2+ complex is much higher than that of the undissociated ATP4−. The protein brings it to a surprisingly low value. Energy decomposition reveals how much each interaction in the protein stabilizes the metaphosphate state; backbone peptides of the P-loop contribute 50% of the stabilization energy, and the side chain of Lys-185+ contributes 25%. This can be explained by the fact that these groups make strong favorable interactions with the α- and β-phosphates, thus favoring the charge distribution of the metaphosphate state over that of the ATP state. Further stabilization (16%) is achieved by a hydrogen bond between the backbone C=O of Ser-237 (on loop Switch-1) and a water molecule perfectly positioned to attack the PγO3− in the subsequent hydrolysis step. The planar and singly negative PγO3− is a much better target for the subsequent nucleophilic attack by a negatively charged OH− than the tetrahedral and doubly negative PγO42− group of ATP. Therefore, we argue that the present mechanism of metaphosphate stabilization is common to the large family of nucleotide-hydrolyzing enzymes. Methodologically, this work presents a computational approach that allows us to obtain a truly quantitative conception of enzymatic strategy.
    Print ISSN: 0021-9258
    Digitale ISSN: 1083-351X
    Thema: Biologie , Chemie und Pharmazie
    Publiziert von The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 10
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    Whole-body adipose tissue and lean muscle volumes and their distribution across gender and age: MR-derived normative values in a normal-weight Swiss population (2017)
    Wiley-Blackwell
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    Publikationsdatum: 2017-04-23
    Beschreibung: Purpose To determine age- and gender-dependent whole-body adipose tissue and muscle volumes in healthy Swiss volunteers in Dixon MRI in comparison with anthropometric and bioelectrical impedance (BIA) measurements. Methods Fat–water-separated whole-body 3 Tesla MRI of 80 healthy volunteers (ages 20 to 62 years) with a body mass index (BMI) of 17.5 to 26.2 kg/m 2 (10 men, 10 women per decade). Age and gender-dependent volumes of total adipose tissue (TAT), visceral adipose tissue (VAT), total abdominal subcutaneous adipose tissue (ASAT) and total abdominal adipose tissue (TAAT), and the total lean muscle tissue (TLMT) normalized for body height were determined by semi-automatic segmentation, and correlated with anthropometric and BIA measurements as well as lifestyle parameters. Results The TAT, ASAT, VAT, and TLMT indexes (TATi, ASATi, VATi, and TLMTi, respectively) (L/m 2  ± standard deviation) for women/men were 6.4 ± 1.8/5.3 ± 1.7, 1.6 ± 0.7/1.2 ± 0.5, 0.4 ± 0.2/0.8 ± 0.5, and 5.6 ± 0.6/7.1 ± 0.7, respectively. The TATi correlated strongly with ASATi ( r  〉 0.93), VATi, BMI and BIA ( r  〉 0.70), and TAATi ( r  〉 0.96), and weak with TLMTi for both genders ( r  〉 –0.34). The VAT was the only parameter showing an age dependency ( r  〉 0.32). The BMI and BIA showed strong correlation with all MR-derived adipose tissue volumes. The TAT mass was estimated significantly lower from BIA than from MRI (both genders P  〈 .001; mean bias –5 kg). Conclusions The reported gender-specific MRI-based adipose tissue and muscle volumes might serve as normative values. The estimation of adipose tissue volumes was significantly lower from anthropometric and BIA measurements than from MRI. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
    Print ISSN: 0740-3194
    Digitale ISSN: 1522-2594
    Thema: Medizin
    Publiziert von Wiley-Blackwell
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