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Berlin Brandenburg

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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 08 February 2011, Vol.108(6), pp.2480-5
    Description: Inducible cAMP early repressor (ICER) is a transcriptional repressor, which, because of alternate promoter use, is generated from the 3' region of the cAMP response modulator (Crem) gene. Its expression and nuclear occurrence are elevated by high cAMP levels in naturally occurring regulatory T cells (nTregs). Using two mouse models, we demonstrate that nTregs control the cellular localization of ICER/CREM, and thereby inhibit IL-2 synthesis in conventional CD4(+) T cells. Ablation of nTregs in depletion of regulatory T-cell (DEREG) mice resulted in cytosolic localization of ICER/CREM and increased IL-2 synthesis upon stimulation. Direct contacts between nTregs and conventional CD4(+) T cells led to nuclear accumulation of ICER/CREM and suppression of IL-2 synthesis on administration of CD28 superagonistic (CD28SA) Ab. In a similar way, nTregs communicated with B cells and induced the cAMP-driven nuclear localization of ICER/CREM. High levels of ICER suppressed the induction of nuclear factor of activated T cell c1 (Nfatc1) gene in T cells whose inducible Nfatc1 P1 promoter bears two highly conserved cAMP-responsive elements to which ICER/CREM can bind. These findings suggest that nTregs suppress T-cell responses by the cAMP-dependent nuclear accumulation of ICER/CREM and inhibition of NFATc1 and IL-2 induction.
    Keywords: Cell Nucleus -- Immunology ; Cyclic Amp Response Element Modulator -- Immunology ; Lymphocyte Activation -- Immunology ; Nfatc Transcription Factors -- Immunology ; Response Elements -- Immunology ; T-Lymphocytes, Regulatory -- Immunology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 10 September 2013, Vol.110(37), pp.15019-24
    Description: Robust cytotoxic CD8(+) T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8(+) T-cell response to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4(-/-)) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenes-specific CD8(+) T cells with impaired effector phenotype and function. Transfer of wild-type CD8(+) T cells into Irf4(-/-) mice improved bacterial clearance, suggesting an intrinsic defect of CD8(+) T cells in Irf4(-/-) mice. Following transfer into wild-type recipients, Irf4(-/-) CD8(+) T cells became activated and showed initial proliferation upon L. monocytogenes infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-γ and TNF-α, and failed to acquire cytotoxic function. Forced IRF4 expression in Irf4(-/-) CD8(+) T cells rescued the defect. During acute infection, Irf4(-/-) CD8(+) T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4(-/-) CD8(+) T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3, Irf4(-/-) CD8(+) T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4(+) T-cell differentiation, the identification of its decisive role in peripheral CD8(+) T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.
    Keywords: Interferon Regulatory Factors -- Immunology ; T-Lymphocytes, Cytotoxic -- Immunology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 3
    Language: English
    In: Langmuir : the ACS journal of surfaces and colloids, 10 March 2015, Vol.31(9), pp.2655-61
    Description: For several decades, nonaqueous dispersions of PMMA particles have played an important role in colloid research. They have found application as colloidal model systems, which are used to probe glassy dynamics or to explore crystal nucleation. To date, most research has focused on spherical particles, in which only translational motion can be investigated. Recently, however, there has been a surge of interest in analyzing also rotational dynamics. In this contribution, we introduce a new class of core-shell particles, which can be used as rotational probes. The colloids described herein are composed of shape anisotropic, fluorescent cores covered with nonfluorescent PMMA shells. The core-shell particles are built up in four steps. In a first step, we produce fluorescent and photo-cross-linkable PMMA colloids. In the second step, these particles are thermomechanically elongated and fixed in defined ellipsoidal shapes by photo-cross-linking. Subsequently, we cover the cross-linked, fluorescent core with a nonfluorescent PMMA shell. The shape of the resulting core-shell colloids is tunable between the initial anisotropic and perfect spherical shape. For shaping, we apply a simple solvent swelling procedure. As one option, this method yields perfect PMMA spheres with ellipsoidal, fluorescent centers. We also report morphological particle characterization using various fluorescence microscopy techniques. Finally, we demonstrate that the rotational dynamics of individual colloids can be tracked and analyzed.
    ISSN: 07437463
    E-ISSN: 1520-5827
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  • 4
    Language: English
    In: Langmuir : the ACS journal of surfaces and colloids, 28 October 2014, Vol.30(42), pp.12457-64
    Description: Colloidal polymer particles are an important class of materials finding use in both everyday and basic research applications. Tailoring their composition, shape, and functionality is of key importance. In this article, we describe a new class of shape-tunable core-shell microparticles. They are composed of a cross-linked polystyrene (PS) core and a poly(methyl methacrylate) (PMMA) shell of varying thickness. In the first step, we prepared highly cross-linked PS cores, which are subsequently transferred into a nonpolar dispersant. They serve as the seed dispersion for a nonaqueous dispersion polymerization to generate the PMMA shell. The shape of the particles can subsequently be manipulated. After the shell growth stage, the spherical PS/PMMA core-shell colloids exhibit an uneven and wrinkled surface. An additional tempering procedure allows for smoothing the surface of the core-shell colloids. This results in polymer core-shell particles with a perfectly spherical shape. In addition to this thermal smoothing of the PMMA shell, we generated a selection of shape-anisotropic core-shell particles using a thermomechanical stretching procedure. Because of the unique constitution, we can selectively interrogate molecular vibrations in the PS core or the PMMA shell of the colloids using nonlinear optical microscopy techniques. This is of great interest because no photobleaching occurs, such that the particles can be tracked in real space over long times.
    Keywords: Chemistry;
    ISSN: 07437463
    E-ISSN: 1520-5827
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  • 5
    In: Headache: The Journal of Head and Face Pain, July 2013, Vol.53(7), pp.1159-1161
    Description: Byline: Matthias Klein, Bianca Woehrl, Grete Zeller, Andreas Straube Keywords: stabbing headache; inflammation; multiple sclerosis; sensitization; nociceptive fiber ***** No abstract is available for this article. ***** Author Affiliation: Article Note: Conflicts of Interest: The authors report no conflicts of interest.
    Keywords: Stabbing Headache ; Inflammation ; Multiple Sclerosis ; Sensitization ; Nociceptive Fiber
    ISSN: 0017-8748
    E-ISSN: 1526-4610
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  • 6
    Language: English
    In: Science, 28 July 2006, Vol.313(5786), pp.502-504
    Description: We observe second-harmonic generation from metamaterials composed of split-ring resonators excited at 1.5-micrometer wavelength. Much larger signals are detected when magnetic-dipole resonances are excited, as compared with purely electric-dipole resonances. The experiments are consistent with calculations based on the magnetic component of the Lorentz force exerted on metal electrons-an intrinsic second-harmonic generation mechanism that plays no role in natural materials. This unusual mechanism becomes relevant in our work as a result of the enhancement and the orientation of the local magnetic fields associated with the magnetic-dipole resonances of the split-ring resonators.
    Keywords: Physical sciences -- Physics -- Mechanics ; Physical sciences -- Physics -- Fundamental forces ; Physical sciences -- Physics -- Mechanics ; Physical sciences -- Physics -- Microphysics ; Physical sciences -- Physics -- Fundamental forces ; Physical sciences -- Physics -- Fundamental forces ; Applied sciences -- Materials science -- Materials ; Physical sciences -- Physics -- Fundamental forces ; Applied sciences -- Materials science -- Materials ; Physical sciences -- Physics -- Optics
    ISSN: 00368075
    E-ISSN: 10959203
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  • 7
    In: Nature, 2015, Vol.528(7580), p.105-107
    Description: Big-Bang nucleosynthesis indicates that baryons account for 5% of the Universe’s total energy content[ 1 ]. In the local Universe, the census of all observed baryons falls short of this estimate by a factor of two[ 2 , 3 ]. Cosmological simulations indicate that the missing baryons have not yet condensed into virialised halos, but reside throughout the filaments of the cosmic web: a low-density plasma at temperature 10 5 –10 7 K known as the warm-hot intergalactic medium (WHIM)[ 3 , 4 , 5 , 6 ]. There have been previous claims of the detection of warm baryons along the line of sight to distant blazars[ 7 , 8 , 9 , 10 ] and hot gas between interacting clusters[ 11 , 12 , 13 , 14 ]. These observations were however unable to trace the large-scale filamentary structure, or to estimate the total amount of warm baryons in a representative volume of the Universe. Here we report X-ray observations of filamentary structures of ten-million-degree gas associated with the galaxy cluster Abell 2744. Previous observations of this cluster[ 15 ] were unable to resolve and remove coincidental X-ray point sources. After subtracting these, we reveal hot gas structures that are coherent over 8 Mpc scales. The filaments coincide with over-densities of galaxies and dark matter, with 5-10% of their mass in baryonic gas. This gas has been heated up by the cluster's gravitational pull and is now feeding its core.
    Keywords: Article
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 8
    Language: English
    In: Nature, 01 December 2015
    Description: Observations of the cosmic microwave background indicate that baryons account for 5% of the Universe's total energy content. In the local Universe, the census of all observed baryons falls short of this estimate by a factor of two. Cosmological simulations indicate that the missing baryons...
    Keywords: Physics ; Astrophysics ; Cosmology and Extra-Galactic Astrophysics ; Sciences (General) ; Biology ; Physics
    ISSN: 0028-0836
    E-ISSN: 1476-4679
    Source: Hyper Article en Ligne (CCSd)
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  • 9
    Language: English
    In: Nature, 03 December 2015, Vol.528(7580), pp.105-7
    Description: Observations of the cosmic microwave background indicate that baryons account for 5 per cent of the Universe's total energy content. In the local Universe, the census of all observed baryons falls short of this estimate by a factor of two. Cosmological simulations indicate that the missing baryons have not condensed into virialized haloes, but reside throughout the filaments of the cosmic web (where matter density is larger than average) as a low-density plasma at temperatures of 10(5)-10(7) kelvin, known as the warm-hot intergalactic medium. There have been previous claims of the detection of warm-hot baryons along the line of sight to distant blazars and of hot gas between interacting clusters. These observations were, however, unable to trace the large-scale filamentary structure, or to estimate the total amount of warm-hot baryons in a representative volume of the Universe. Here we report X-ray observations of filamentary structures of gas at 10(7) kelvin associated with the galaxy cluster Abell 2744. Previous observations of this cluster were unable to resolve and remove coincidental X-ray point sources. After subtracting these, we find hot gas structures that are coherent over scales of 8 megaparsecs. The filaments coincide with over-densities of galaxies and dark matter, with 5-10 per cent of their mass in baryonic gas. This gas has been heated up by the cluster's gravitational pull and is now feeding its core. Our findings strengthen evidence for a picture of the Universe in which a large fraction of the missing baryons reside in the filaments of the cosmic web.
    Keywords: Dark Matter -- Research ; Gravity (Force) -- Analysis ; X-Rays -- Usage;
    ISSN: 00280836
    E-ISSN: 1476-4687
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  • 10
    In: PLoS ONE, 2018, Vol.13(7)
    Description: Background The mortality and neurologic sequelae associated with acute bacterial meningitis (ABM) remain high despite advances in medical care. The main aim of this study was to evaluate short-term outcome in patients treated as bacterial meningitis at a teaching hospital in Ethiopia to identify factors that could be focused on to improve outcome in this setting. Methods A hospital based longitudinal study was conducted at Jimma University Hospital in southwest Ethiopia from March 1, 2013 to December 31, 2015. Participants of this study were patients of age 18 years and older who were treated as confirmed or possible cases of ABM. Patients were followed throughout their hospital stay for change in their clinical course and predefined end points. A multivariable analysis was done to identify factors associated with unfavorable outcomes. Result 90 patients admitted with diagnosis of acute bacterial meningitis were included in the study; cerebrospinal fluid was analysed for 85 (94.4%) of them. Causative bacteria were isolated in 26 (28.9%) patients only; most of these isolates (84.6%) were either Streptococcus pneumoniae or Neisseria meningitidis . Patients managed as cases of ABM at the hospital suffered from a high rate of unfavorable outcome (36.7%) and an overall mortality rate of 22.2%. Impaired level of consciousness (AOR = 0.766, 95% CI = 0.589–0.995), dexamethasone therapy (AOR = 4.676, 95% CI = 1.12–19.50) and fever persisting after two days of admission (AOR = 24.226, 95% CI = 5.24–111.96) were found to be independently associated with unfavorable outcome. Conclusion Outcome in patients treated for ABM at the hospital was found to be poor. Impaired mentation, treatment with adjunctive dexamethasone and persistent fever were found to be associated with poor outcome. Thus, development of clinical guidelines for treatment of ABM that suit the local context is essential to improve patient management and outcome.
    Keywords: Research Article ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; People And Places ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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