Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes.

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways occurs through regulation of activity and availability of mothers against DPP (Drosophila) human homologue (Smad) proteins. METHODS: Human articular chondrocytes isolated from knee joints from patients with osteoarthritis (OA) or normal bovine chondrocytes were cultured in suspension in poly-(2-hydroxyethyl methacrylate)-coated dishes with either 10% fetal bovine serum media or serum-deprived media 6h before treatment with IL-1beta alone, TNF-alpha alone or IL-1beta followed by TGF-beta. Nuclear extracts were examined by electrophoretic mobility-shift assays (EMSA) for nuclear factor-kappa B (NF-kappaB) and Smad3/4 deoxyribonucleic acid (DNA) binding. Nuclear extracts were also subjected to the TranSignal Protein/DNA array (Panomics, Redwood City, CA) enabling the simultaneous semiquantitative assessment of DNA-binding activity of 54 different transcription factors. Nuclear phospho-Smad2/3 and total Smad7 protein expression in whole cell lysates were studied by Western blot. Cytoplasmic Smad7, type II collagen alpha 1 (COL2A1), aggrecan and SRY-related high mobility group-Box gene 9 (SOX-9) mRNA expression were measured by real-time polymerase chain reaction (PCR). RESULTS: The DNA-binding activity of Smad3/4 in the TranSignal Protein/DNA array was downregulated by TNF-alpha (46%) or IL-1beta treatment (42%). EMSA analysis showed a consistent reduction in Smad3/4 DNA-binding activity in human articular chondrocytes treated with IL-1beta or TNF-alpha. TGF-beta-induced Smad3/4 DNA-binding activity and Smad2/3 phosphorylation were also reduced following pretreatment with IL-1beta in human OA and bovine chondrocytes. Real-time PCR and Western blot analysis showed that IL-1beta partially reversed the TGF-beta stimulation of Smad7 mRNA and protein levels in TGF-beta-treated human OA cells. In contrast, TGF-beta-stimulated COL2A1, aggrecan, and SOX-9 mRNA levels were abrogated by IL-1beta. CONCLUSIONS: IL-1beta or TNF-alpha exerted a suppressive effect on Smad3/4 DNA-binding activity in human articular chondrocytes, as well as on TGF-beta-induced stimulation of Smad3/4 DNA-binding activity and Smad2/3 phosphorylation in human OA and bovine articular chondrocytes. IL-1beta partially reversed the increase in TGF-beta-stimulated Smad7 mRNA or protein levels suggesting that Smad7 may not be involved in the suppression of TGF-beta signaling induced by IL-1beta or TNF-alpha in articular chondrocytes. The balance between the IL-1beta or TNF-alpha and the TGF-beta signaling pathways is crucial for maintenance of articular cartilage homeostasis and its disruption likely plays a substantial role in the pathogenesis of OA

Correlating fissure occurrence to rice quality for various drying and tempering treatments

When a rice kernel fissures, it can break in subsequent food processing operations and lose its commercial value. Head rice yield (HRY) is a measure of the percent of kernels that remain whole (at least three-fourths of original length) after rice has been milled. Our experiment was designed to test the effect of a rapid state transition during drying and tempering processes using cultivars Bengal and Cypress. ‘Bengal’ is a medium-size kernel and ‘Cypress’ is a longsize, thinner grained cultivar. Immediately after drying, the rice samples were separated into four sub-samples and tempered for 0, 80, 160, or 240 minutes at the temperature of the drying air. Tempering is a process to allow kernel moisture content gradients to decrease, thereby reducing the stress within the kernel. From each sample, 400 kernels were randomly selected, visually observed, and the percentage of fissured kernels determined. Results showed that the percentage of fissured kernels generally decreased with tempering. However, some samples still showed many fissures even after extended tempering, yet had a high HRY. While HRY is currently the primary index of rice quality, it is known that fissured kernels can severely and detrimentally affect end-use processing operations such as cooking or puffing. Thus, the tempering duration required for preventing kernel fissuring might be longer than the tempering duration required for maintaining a high HRY

Sensitivity analysis of the solar rotation to helioseismic data from GONG, GOLF and MDI observations

Accurate determination of the rotation rate in the radiative zone of the sun from helioseismic observations requires rotational frequency splittings of exceptional quality as well as reliable inversion techniques. We present here inferences based on mode parameters calculated from 2088-days long MDI, GONG and GOLF time series that were fitted to estimate very low frequency rotational splittings (nu < 1.7 mHz). These low frequency modes provide data of exceptional quality, since the width of the mode peaks is much smaller than the rotational splitting and hence it is much easier to separate the rotational splittings from the effects caused by the finite lifetime and the stochastic excitation of the modes. We also have implemented a new inversion methodology that allows us to infer the rotation rate of the radiative interior from mode sets that span l=1 to 25. Our results are compatible with the sun rotating like a rigid solid in most of the radiative zone and slowing down in the core (R_sun < 0.2). A resolution analysis of the inversion was carried out for the solar rotation inverse problem. This analysis effectively establishes a direct relationship between the mode set included in the inversion and the sensitivity and information content of the resulting inferences. We show that such an approach allows us to determine the effect of adding low frequency and low degree p-modes, high frequency and low degree p-modes, as well as some g-modes on the derived rotation rate in the solar radiative zone, and in particular the solar core. We conclude that the level of uncertainties that is needed to infer the dynamical conditions in the core when only p-modes are included is unlikely to be reached in the near future, and hence sustained efforts are needed towards the detection and characterization of g-modes.Comment: Accepted for publication in Astrophysical journal. 15 pages, 19 figure

Implications of multiple high-redshift galaxy clusters

To date, 14 high-redshift (z>1.0) galaxy clusters with mass measurements have been observed, spectroscopically confirmed and are reported in the literature. These objects should be exceedingly rare in the standard LCDM model. We conservatively approximate the selection functions of these clusters' parent surveys, and quantify the tension between the abundances of massive clusters as predicted by the standard LCDM model and the observed ones. We alleviate the tension considering non-Gaussian primordial perturbations of the local type, characterized by the parameter fnl and derive constraints on fnl arising from the mere existence of these clusters. At the 95% confidence level, fnl>467 with cosmological parameters fixed to their most likely WMAP5 values, or fnl > 123 (at 95% confidence) if we marginalize over WMAP5 parameters priors. In combination with fnl constraints from Cosmic Microwave Background and halo bias, this determination implies a scale-dependence of fnl at approx. 3 sigma. Given the assumptions made in the analysis, we expect any future improvements to the modeling of the non-Gaussian mass function, survey volumes, or selection functions to increase the significance of fnl>0 found here. In order to reconcile these massive, high-z clusters with an fnl=0, their masses would need to be systematically lowered by 1.5 sigma or the sigma8 parameter should be approx. 3 sigma higher than CMB (and large-scale structure) constraints. The existence of these objects is a puzzle: it either represents a challenge to the LCDM paradigme or it is an indication that the mass estimates of clusters is dramatically more uncertain than we think.Comment: 11 pages, 7 figures, modified to match published versio

X-ray observations of the Compton-thick Seyfert 2 galaxy, NGC 5643

We present results from a ~55 ks long XMM-Newton observation of the obscured AGN, NGC 5643, performed in July 2009. A previous, shorter (about 10 ks) XMM-Newton observation in February 2003 had left two major issues open, the nature of the hard X-ray emission (Compton-thin vs Compton-thick) and of the soft X-ray excess (photoionized vs collisionally ionized matter). The new observation shows that the source is Compton-thick and that the dominant contribution to the soft X-ray emission is by photoionized matter (even if it is still unclear whether collisionally ionized matter may contribute as well). We also studied three bright X-ray sources that are in the field of NGC 5643. The ULX NGC 5643 X-1 was confirmed to be very luminous, even if more than a factor 2 fainter than in 2003. We then provided the first high quality spectrum of the cluster of galaxies Abell 3602. The last source, CXOJ143244.5-442020, is likely an unobscured AGN, possibly belonging to Abell 3602.Comment: 6 pages. Accepted for publication in A&

The Cosmic Neutrino Background and the Age of the Universe

We discuss the cosmological degeneracy between the age of the Universe, the Hubble parameter and the effective number of relativistic particles N_eff. We show that independent determinations of the Hubble parameter H(z) as those recently provided by Simon,Verde, Jimenez (2006), combined with other cosmological data sets can provide the most stringent constraint on N_eff, yielding N_eff=3.7 (-1.2) (+1.1) at 95% confidence level. A neutrino background is detected with high significance: N_eff >1.8 at better than 99% confidence level. Constraints on the age of the universe in the framework of an extra background of relativistic particles are improved by a factor 3.Comment: JCAP, in pres

The star-formation histories of elliptical galaxies across the fundamental plane

We present the first results from a study designed to test whether, given high-quality spectrophotometry spanning the mid-UV--optical wavelength regime, it is possible to distinguish the metal content (Z) and star-formation history (sfh) of individual elliptical galaxies with sufficient accuracy to establish whether their formation history is linked to their detailed morphology and position on the Fundamental Plane. From a detailed analysis of UV-optical spectrophotometry of the `cuspy' elliptical galaxy NGC 3605 and the giant elliptical NGC 5018 we find that: 1) optical spectra with l > 3500 A may not contain sufficient data to robustly uncover all the stellar populations present in individual galaxies, even in such relatively passive objects as ellipticals, 2) the addition of the UV data approaching l = 2500 A holds the key to establishing well-constrained sfhs, from which we can infer a formation and evolution history which is consistent with their photometric properties, 3) despite the superficial similarity of their spectra, the two galaxies have very different `recent' sfhs -- the smaller, cuspy elliptical NGC 3605 contains a high-Z population of age ~= 1 Gyr, and has a position on the fundamental plane typical of the product of a low-z gas-rich merger (most likely at z ~ 0.08), while the giant elliptical NGC 5018, with a sub-solar secondary population, appears to have gained its more recent stars via mass transfer / accretion of gas from its spiral companion, 4) despite these differences in detailed history, more than 85% of the stellar mass of both galaxies is associated with an old (9-12 Gyr) stellar population of near-solar Z. This pilot study provides strong motivation for the construction and analysis of high-quality UV-optical spectra for a substantial sample of ellipticals spanning the Fundamental Plane.Comment: 11 pages, 10 figures, submitted to MNRAS, revised versio