The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

<p>Abstract</p> <p>Background</p> <p>The natural function of the C-C chemokine receptor type 5 (CCR5) is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32) located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD) and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD.</p> <p>Methods</p> <p>We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion.</p> <p>Results</p> <p>12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L.</p> <p>Conclusions</p> <p>Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.</p

Magnetocaloric effect and magnetic cooling near a field-induced quantum-critical point

The presence of a quantum critical point (QCP) can significantly affect the thermodynamic properties of a material at finite temperatures T. This is reflected, e.g., in the entropy landscape S(T, r) in the vicinity of a QCP, yielding particularly strong variations for varying the tuning parameter r such as pressure or magnetic field B. Here we report on the determination of the critical enhancement of $\delta S / \delta B$ near a B-induced QCP via absolute measurements of the magnetocaloric effect (MCE), $(\delta T / \delta B)_S$, and demonstrate that the accumulation of entropy around the QCP can be used for efficient low-temperature magnetic cooling. Our proof of principle is based on measurements and theoretical calculations of the MCE and the cooling performance for a Cu$^{2+}$-containing coordination polymer, which is a very good realization of a spin-1/2 antiferromagnetic Heisenberg chain - one of the simplest quantum-critical systems.Comment: 21 pages, 4 figure

Disruption of LTBP-4 function reduces TGF-β activation and enhances BMP-4 signaling in the lung

Disruption of latent TGF-β binding protein (LTBP)–4 expression in the mouse leads to abnormal lung development and colorectal cancer. Lung fibroblasts from these mice produced decreased amounts of active TGF-β, whereas secretion of latent TGF-β was significantly increased. Expression and secretion of TGF-β2 and -β3 increased considerably. These results suggested that TGF-β activation but not secretion would be severely impaired in LTBP-4 −/− fibroblasts. Microarrays revealed increased expression of bone morphogenic protein (BMP)–4 and decreased expression of its inhibitor gremlin. This finding was accompanied by enhanced expression of BMP-4 target genes, inhibitors of differentiation 1 and 2, and increased deposition of fibronectin-rich extracellular matrix. Accordingly, increased expression of BMP-4 and decreased expression of gremlin were observed in mouse lung. Transfection of LTBP-4 rescued the −/− fibroblast phenotype, while LTBP-1 was inefficient. Treatment with active TGF-β1 rescued BMP-4 and gremlin expression to wild-type levels. Our results indicate that the lack of LTBP-4–mediated targeting and activation of TGF-β1 leads to enhanced BMP-4 signaling in mouse lung

VLTI-MATISSE L- and N-band aperture-synthesis imaging of the unclassified B[e] star FS Canis Majoris

Context. FS Canis Majoris (FS CMa, HD 45677) is an unclassified B[e] star surrounded by an inclined dust disk. The evolutionary stage of FS CMa is still debated. Perpendicular to the circumstellar disk, a bipolar outflow was detected. Infrared aperture-synthesis imaging provides us with a unique opportunity to study the disk structure. Aims: Our aim is to study the intensity distribution of the disk of FS CMa in the mid-infrared L and N bands. Methods: We performed aperture-synthesis imaging of FS CMa with the MATISSE instrument (Multi AperTure mid-Infrared SpectroScopic Experiment) in the low spectral resolution mode to obtain images in the L and N bands. We computed radiative transfer models that reproduce the L- and N-band intensity distributions of the resolved disks. Results: We present L- and N-band aperture-synthesis images of FS CMa reconstructed in the wavelength bands of 3.4-3.8 and 8.6-9.0 μm. In the L-band image, the inner rim region of an inclined circumstellar disk and the central object can be seen with a spatial resolution of 2.7 milliarcsec (mas). An inner disk cavity with an angular diameter of ~6 × 12 mas is resolved. The L-band disk consists of a bright northwestern (NW) disk region and a much fainter southeastern (SE) region. The images suggest that we are looking at the bright inner wall of the NW disk rim, which is on the far side of the disk. In the N band, only the bright NW disk region is seen. In addition to deriving the inclination and the inner disk radius, fitting the reconstructed brightness distributions via radiative transfer modelling allows one to constrain the innermost disk structure, in particular the shape of theinner disk rim. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere within the commissioning of the VLTI-MATISSE instrument (ID 60.A-9257(E))

High angular resolution N-band observation of the silicate carbon star IRAS08002-3803 with the VLTI/MIDI instrument

We present the results of N-band spectro-interferometric observations of the silicate carbon star IRAS08002-3803 with the MID-infrared Interferometric instrument (MIDI) at the Very Large Telescope Interferometer (VLTI) of the European Southern Observatory (ESO). The observations were carried out using two unit telescopes (UT2 and UT3) with projected baseline lengths ranging from 39 to 47 m. Our observations of IRAS08002-3803 have spatially resolved the dusty environment of a silicate carbon star for the first time and revealed an unexpected wavelength dependence of the angular size in the N band: the uniform-disk diameter is found to be constant and ~36 mas (72 Rstar) between 8 and 10 micron, while it steeply increases longward of 10 micron to reach ~53 mas (106 Rstar) at 13 micron. Model calculations with our Monte Carlo radiative transfer code show that neither spherical shell models nor axisymmetric disk models consisting of silicate grains alone can simultaneously explain the observed wavelength dependence of the visibility and the spectral energy distribution (SED). We propose that the circumstellar environment of IRAS08002-3803 may consist of two grain species coexisting in the disk: silicate and a second grain species, for which we consider amorphous carbon, large silicate grains, and metallic iron grains. Comparison of the observed visibilities and SED with our models shows that such disk models can fairly -- though not entirely satisfactorily -- reproduce the observed SED and N-band visibilities. Our MIDI observations and the radiative transfer calculations lend support to the picture where oxygen-rich material around IRAS08002-3803 is stored in a circumbinary disk surrounding the carbon-rich primary star and its putative low-luminosity companion.Comment: 15 pages, 8 figures, accepted for publication in A&

Formation of superdense hadronic matter in high energy heavy-ion collisions

We present the detail of a newly developed relativistic transport model (ART 1.0) for high energy heavy-ion collisions. Using this model, we first study the general collision dynamics between heavy ions at the AGS energies. We then show that in central collisions there exists a large volume of sufficiently long-lived superdense hadronic matter whose local baryon and energy densities exceed the critical densities for the hadronic matter to quark-gluon plasma transition. The size and lifetime of this matter are found to depend strongly on the equation of state. We also investigate the degree and time scale of thermalization as well as the radial flow during the expansion of the superdense hadronic matter. The flow velocity profile and the temperature of the hadronic matter at freeze-out are extracted. The transverse momentum and rapidity distributions of protons, pions and kaons calculated with and without the mean field are compared with each other and also with the preliminary data from the E866/E802 collaboration to search for experimental observables that are sensitive to the equation of state. It is found that these inclusive, single particle observables depend weakly on the equation of state. The difference between results obtained with and without the nuclear mean field is only about 20\%. The baryon transverse collective flow in the reaction plane is also analyzed. It is shown that both the flow parameter and the strength of the ``bounce-off'' effect are very sensitive to the equation of state. In particular, a soft equation of state with a compressibility of 200 MeV results in an increase of the flow parameter by a factor of 2.5 compared to the cascade case without the mean field. This large effect makes it possible to distinguish the predictions from different theoretical models and to detect the signaturesComment: 55 pages, latex, + 39 figures available upon reques

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

Clumpy dust clouds and extended atmosphere of the AGB star W Hydrae revealed with VLT/SPHERE-ZIMPOL and VLTI/AMBER

Context. Dust formation is thought to play an important role in the mass loss from stars at the asymptotic giant branch (AGB); however, where and how dust forms is still open to debate. Aims. We present visible polarimetric imaging observations of the well-studied AGB star W Hya taken with VLT/SPHERE-ZIMPOL as well as high spectral resolution long-baseline interferometric observations taken with the AMBER instrument at the Very Large Telescope Interferometer (VLTI). Our goal is to spatially resolve the dust and molecule formation region within a few stellar radii. Methods. We observed W Hya with VLT/SPHERE-ZIMPOL at three wavelengths in the continuum (645, 748, and 820 nm), in the Hα line at 656.3 nm, and in the TiO band at 717 nm. The VLTI/AMBER observations were carried out in the wavelength region of the CO first overtone lines near 2.3 μm with a spectral resolution of 12000. Results. Taking advantage of the polarimetric imaging capability of SPHERE-ZIMPOL combined with the superb adaptive optics performance, we succeeded in spatially resolving three clumpy dust clouds located at ~50 mas (~2 R⋆) from the central star, revealing dust formation very close to the star. The AMBER data in the individual CO lines suggest a molecular outer atmosphere extending to ~3 R⋆. Furthermore, the SPHERE-ZIMPOL image taken over the Hα line shows emission with a radius of up to ~160 mas (~7 R⋆). We found that dust, molecular gas, and Hα-emitting hot gas coexist within 2–3 R⋆. Our modeling suggests that the observed polarized intensity maps can reasonably be explained by large (0.4–0.5 μm) grains of Al2O3, Mg2SiO4, or MgSiO3 in an optically thin shell (τ550nm = 0.1 ± 0.02) with an inner and outer boundary radius of 1.9–2.0 R⋆ and 3 ± 0.5R⋆, respectively. The observed clumpy structure can be reproduced by a density enhancement of a factor of 4 ± 1. Conclusions. The grain size derived from our modeling of the SPHERE-ZIMPOL polarimetric images is consistent with the prediction of the hydrodynamical models for the mass loss driven by the scattering due to micron-sized grains. The detection of the clumpy dust clouds close to the star lends support to the dust formation induced by pulsation and large convective cells as predicted by the 3D simulations for AGB stars