Interleukin-4 (IL-4) enhances and soluble interleukin-4 receptor (sIL-4R) inhibits histamine release from peripheral blood basophils and mast cells in vitro and in vivo

The aim of the study was to analyse the effect of interleukin-4 (IL-4) on allergen and anti-IgE mediated histamine release from basophils and human skin mast cells and to assess whether soluble recombinant interleukin-4 receptor (sIL4R) can inhibit these effects. Anti-IgE stimulated histamine release from peripheral blood basophils and mast cells of atopic donors was enhanced after preincubation with IL-4, whereas after preincubation with sIL-4R it was inhibited. These effects were even more pronounced when samples were stimulated with a clinically relevant allergen. In IL-4 preincubated skin mast cells, there was a similar enhancement of anti-IgE stimulated histamine release, which could again be inhibited by sIL-4R. The effects of IL-4 and sIL4R were dose- and time-dependent. Mice sensitized to ovalbumin and treated with soluble recombinant murine sIL-4R showed significantly reduced immediate-type cutaneous hypersensitivity responses compared with untreated mice. These in vivo effects were IgE independent, since there were no significant differences in total and allergen specific IgE/IgG1 antibody titres between treated and untreated mice. This indicates that IL4 exerts priming effects on histamine release by effector cells of the allergic response and that these effects are potently antagonized by soluble IL-4R both in vitro and in vivo

Measuring the equation of state of a hard-disc fluid

We use video microscopy to study a two-dimensional (2D) model fluid of charged colloidal particles suspended in water and compute the pressure from the measured particle configurations. Direct experimental control over the particle density by means of optical tweezers allows the precise measurement of pressure as a function of density. We compare our data with theoretical predictions for the equation of state, the pair-correlation function and the compressibility of a hard-disc fluid and find good agreement, both for the fluid and the solid phase. In particular the location of the transition point agrees well with results from Monte Carlo simulations.Comment: 7 pages, to appear in EPL, slightly corrected versio

Harmonic lattice behavior of two-dimensional colloidal crystals

Using positional data from video-microscopy and applying the equipartition theorem for harmonic Hamiltonians, we determine the wave-vector-dependent normal mode spring constants of a two-dimensional colloidal model crystal and compare the measured band-structure to predictions of the harmonic lattice theory. We find good agreement for both the transversal and the longitudinal mode. For $q\to 0$, the measured spring constants are consistent with the elastic moduli of the crystal.Comment: 4 pages, 3 figures, submitte

Probing the shape of atoms in real space

The structure of single atoms in real space is investigated by scanning tunneling microscopy. Very high resolution is possible by a dramatic reduction of the tip-sample distance. The instabilities which are normally encountered when using small tip-sample distances are avoided by oscillating the tip of the scanning tunneling microscope vertically with respect to the sample. The surface atoms of Si(111)-(7 x 7) with their well-known electronic configuration are used to image individual samarium, cobalt, iron and silicon atoms. The resulting images resemble the charge density corresponding to 4f, 3d and 3p atomic orbitals.Comment: Submitted to Phys. Rev. B, 17 pages, 7 figure

Why, what, and how? case study on law, risk, and decision making as necessary themes in built environment teaching

The paper considers (and defends) the necessity of including legal studies as a core part of built environment undergraduate and postgraduate curricula. The writer reflects upon his own experience as a lawyer working alongside and advising built environment professionals in complex land remediation and site safety management situations in the United Kingdom and explains how themes of liability, risk, and decision making can be integrated into a practical simulation in order to underpin more traditional lecture-based law teaching. Through reflection upon the writer's experiments with simulation-based teaching, the paper suggests some innovations that may better orientate law teaching to engage these themes and, thereby, enhance the relevance of law studies to the future needs of built environment professionals in practice.</p

In vivo imaging of lymphocytes in the CNS reveals different behaviour of naïve T cells in health and autoimmunity

<p>Abstract</p> <p>Background</p> <p>Two-photon laser scanning microscopy (TPLSM) has become a powerful tool in the visualization of immune cell dynamics and cellular communication within the complex biological networks of the inflamed central nervous system (CNS). Whereas many previous studies mainly focused on the role of effector or effector memory T cells, the role of naïve T cells as possible key players in immune regulation directly in the CNS is still highly debated.</p> <p>Methods</p> <p>We applied <it>ex vivo </it>and intravital TPLSM to investigate migratory pathways of naïve T cells in the inflamed and non-inflamed CNS. MACS-sorted naïve CD4+ T cells were either applied on healthy CNS slices or intravenously injected into RAG1 -/- mice, which were affected by experimental autoimmune encephalomyelitis (EAE). We further checked for the generation of second harmonic generation (SHG) signals produced by extracellular matrix (ECM) structures.</p> <p>Results</p> <p>By applying TPLSM on living brain slices we could show that the migratory capacity of activated CD4+ T cells is not strongly influenced by antigen specificity and is independent of regulatory or effector T cell phenotype. Naïve T cells, however, cannot find sufficient migratory signals in healthy, non-inflamed CNS parenchyma since they only showed stationary behaviour in this context. This is in contrast to the high motility of naïve CD4+ T cells in lymphoid organs. We observed a highly motile migration pattern for naïve T cells as compared to effector CD4+ T cells in inflamed brain tissue of living EAE-affected mice. Interestingly, in the inflamed CNS we could detect reticular structures by their SHG signal which partially co-localises with naïve CD4+ T cell tracks.</p> <p>Conclusions</p> <p>The activation status rather than antigen specificity or regulatory phenotype is the central requirement for CD4+ T cell migration within healthy CNS tissue. However, under inflammatory conditions naïve CD4+ T cells can get access to CNS parenchyma and partially migrate along inflammation-induced extracellular SHG structures, which are similar to those seen in lymphoid organs. These SHG structures apparently provide essential migratory signals for naïve CD4+ T cells within the diseased CNS.</p

On Synchronization in a Lattice Model of Pulse-Coupled Oscillators

We analyze the collective behavior of a lattice model of pulse-coupled oscillators. By means of computer simulations we find the relation between the intrinsic dynamics of each member of the population and their mutual interaction that ensures, in a general context, the existence of a fully synchronized regime. This condition turns out to be the same than the obtained for the globally coupled population. When the condition is not completely satisfied we find different spatial structures. This also gives some hints about self-organized criticality.Comment: 4 pages, RevTex, 1 PostScript available upon request, To appear in Phys. Rev. Let

GLINT: GlucoCEST in neoplastic tumors at 3 T—clinical results of GlucoCEST in gliomas

Objective: Clinical relevance of dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) imaging has mostly been demonstrated at ultra-high field (UHF) due to low effect size. Results of a cohort study at clinical field strength are shown herein. // Materials and methods: Motion and field inhomogeneity corrected T1ρ‐based DGE (DGE⍴) images were acquired before, during and after a D-glucose injection with 6.3 s temporal resolution to detect accumulation in the brain. Six glioma patients with clear blood–brain barrier (BBB) leakage, two glioma patients with suspected BBB leakage, and three glioma patients without BBB leakage were scanned at 3 T. // Results: In high-grade gliomas with BBB leakage, D-glucose uptake could be detected in the gadolinium (Gd) enhancing region as well as in the tumor necrosis with a maximum increase of ∆DGE⍴ around 0.25%, whereas unaffected white matter did not show any significant DGE⍴ increase. Glioma patients without Gd enhancement showed no detectable DGE⍴ effect within the tumor. // Conclusion: First application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading

Transplacental Passage of Interleukins 4 and 13?

The mechanisms by which prenatal events affect development of adult disease are incompletely characterized. Based on findings in a murine model of maternal transmission of asthma risk, we sought to test the role of the pro-asthmatic cytokines interleukin IL-4 and -13. To assess transplacental passage of functional cytokines, we assayed phosphorylation of STAT-6, a marker of IL-4 and -13 signaling via heterodimeric receptor complexes which require an IL-4 receptor alpha subunit. IL-4 receptor alpha−/− females were mated to wild-type males, and pregnant females were injected with supraphysiologic doses of IL-4 or 13. One hour after injection, the receptor heterozygotic embryos were harvested and tissue nuclear proteins extracts assayed for phosphorylation of STAT-6 by Western blot. While direct injection of embryos produced a robust positive control, no phosphorylation was seen after maternal injection with either IL-4 or -13, indicating that neither crossed the placenta in detectable amounts. The data demonstrate a useful approach to assay for transplacental passage of functional maternal molecules, and indicate that molecules other than IL-4 and IL-13 may mediate transplacental effects in maternal transmission of asthma risk