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  • Articles  (19)
  • Wiley-Blackwell  (15)
  • The American Society for Biochemistry and Molecular Biology (ASBMB)  (4)
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  • Articles  (19)
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  • 1
    Publication Date: 2014-03-16
    Description: 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
    Topics: Geosciences , Physics
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  • 2
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    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Publication Date: 2013-12-07
    Description: 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
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 3
    Publication Date: 2012-04-16
    Description: Purpose: To evaluate the feasibility of semiquantitative measurement of liver perfusion from analysis of ferucarbotran induced signal-dynamics in double-contrast liver MR-imaging (DC-MRI). Materials and Methods: In total 31 patients (21 men; 58 ± 10 years) including 18 patients with biopsy proven liver cirrhosis prospectively underwent clinically indicated DC-MRI at 1.5 Tesla (T) with dynamic T2*-weighted gradient-echo imaging after ferucarbotran bolus injection. Breathing artefacts in tissue and input time curves were reduced by Savitzky-Golay-filtering and semiquantitative perfusion maps were calculated using a model free approach. Hepatic blood flow index (HBFI) and splenic blood flow index (SBFI) were determined by normalization of arbitrary perfusion values to the perfusion of the erector spinae muscle resulting in a semiquantitative perfusion measure. Results: In 30 of 31 patients the evaluated protocol could successfully be applied. Mean HBF was 7.7 ± 2.46 (range, 4.6–12.8) and mean SBF was 13.20 ± 2.57 (range, 8.5–17.8). A significantly lower total HBF was seen in patients with cirrhotic livers as compared to patients with noncirrhotic livers ( P 〈 0.05). In contrast, similar SBF was observed in cirrhotic and noncirrhotic patients ( P = 0.11). Conclusion: Capturing the signal dynamics during bolus injection of ferucarbotran in DC-MRI of the liver allows for semiquantitative assessment of hepatic perfusion that may be helpful for a more precise characterisation of liver cirrhosis and focal liver lesions. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 4
    Publication Date: 2016-04-06
    Description: 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
    Electronic ISSN: 1365-2133
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 5
    Publication Date: 2016-03-19
    Description: 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
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 6
    Publication Date: 2013-05-10
    Description: 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
    Electronic ISSN: 1600-5759
    Topics: Chemistry and Pharmacology , Geosciences , Physics
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  • 7
    Publication Date: 2013-11-16
    Description: 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
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 8
    Publication Date: 2011-12-16
    Description: Wüstite, Fe1-xO, is an important component in the mineralogy of Earth's lower mantle and may also be a component of the core. Therefore its high pressure-temperature behavior, including its electronic structure, is essential to understanding the nature and evolution of Earth's deep interior. We performed X-ray diffraction and radiometric measurements on wüstite in a laser-heated diamond anvil cell, finding an insulator-metal transition at high pressures and temperatures. Our data show a negative slope for this apparently isostructural phase boundary, which is characterized by a volume decrease and emissivity increase. The metallic phase of FeO is stable at conditions of the lower mantle and core, which has implications for the high P-T character of Fe-O bonds, magnetic field propagation, and lower mantle conductivity.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
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  • 9
    Publication Date: 2011-07-10
    Description: Sea-level rise is a projected consequence of global climate change that will result in complex changes in coastal ecosystems. These changes will cause transitions among coastal habitat types, which will be compounded by human-made barriers to the gradual inland migration of these habitat types. The effect of these changes on the future viability of coastal species will depend on the habitat requirements and population dynamics of these species. Thus, realistic assessments of the impact of sea-level rise (SLR) require linking geomorphological models with habitat and population models. In this study, we implemented a framework that allows this linkage, and demonstrated its feasibility to assess the effect of SLR on the viability of the Snowy Plover population in Florida. The results indicate that SLR will cause a decline in suitable habitat and carrying capacity for this species, and an increase in the risk of its extinction and decline. The model projected that the population size will decline faster than the area of habitat or carrying capacity, demonstrating the necessity of incorporating population dynamics in assessing the impacts of SLR on coastal species. The results were most sensitive to uncertainties in survival rate and fecundity, and suggested that future studies on this species should focus on the average and variability of these demographic rates and their dependence on population density. The effect of SLR on this species’ viability was qualitatively similar with most alternative models that used the extreme values of each uncertain parameter, indicating that the results are robust to uncertainties in the model.
    Print ISSN: 1354-1013
    Electronic ISSN: 1365-2486
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Published by Wiley-Blackwell
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  • 10
    Publication Date: 2013-07-13
    Description: 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
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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