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  • Articles  (22)
  • Wiley-Blackwell  (15)
  • National Academy of Sciences  (5)
  • The American Association for Cancer Research (AACR)  (2)
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  • Articles  (22)
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  • 1
    Publication Date: 2012-04-25
    Description: Differentiated cells can be forced to change identity, either to directly adopt another differentiated identity or to revert to a pluripotent state. Direct reprogramming events can also occur naturally. We recently characterized such an event in Caenorhabditis elegans, in which a rectal cell switches to a neuronal cell. Here we have used this single-cell paradigm to investigate the molecular requirements of direct cell-type conversion, with a focus on the early steps. Our genetic analyses revealed the requirement of sem-4/Sall, egl-27/Mta, and ceh-6/Oct, members of the NODE complex recently identified in embryonic stem (ES) cells, and of the OCT4 partner sox-2, for the initiation of this natural direct reprogramming event. These four factors have been shown to individually impact on ES cell pluripotency; however, whether they act together to control cellular potential during development remained an open question. We further found that, in addition to acting at the same time, these factors physically associate, suggesting that they could act together as a NODE-like complex during this in vivo process. Finally, we have elucidated the functional domains in EGL-27/MTA that mediate its reprogramming activity in this system and have found that modulation of the posterior HOX protein EGL-5 is a downstream event to allow the initiation of Y identity change. Our data reveal unique in vivo functions in a natural direct reprogramming event for these genes that impact on ES cells pluripotency and suggest that conserved nuclear events could be shared between different cell plasticity phenomena across phyla.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    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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  • 3
    Publication Date: 2015-04-01
    Description: 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
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
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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: 2014-02-12
    Description: Mucociliary transport (MCT) is an innate defense mechanism that removes particulates, noxious material, and microorganisms from the lung. Several airway diseases exhibit abnormal MCT, including asthma, chronic bronchitis, and cystic fibrosis. However, it remains uncertain whether MCT abnormalities contribute to the genesis of disease or whether they are secondary manifestations...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    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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  • 7
    Publication Date: 2013-08-07
    Description: 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
    Electronic ISSN: 1521-4141
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 8
    Publication Date: 2017-04-23
    Description: 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
    Electronic ISSN: 1522-2594
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 9
    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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  • 10
    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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