Centimeter Imaging of the R Coronae Australis Region

The R CrA region was observed in the 3.5 and 6.2 cm continuum with high angular resolutions (0.6--1.7 arcseconds) using the Very Large Array. Archival data sets were also analyzed for comparison, which provided angular resolutions up to 0.3 arcseconds. A cluster of young stellar objects was detected, and a rich array of star forming activities was revealed. IRS 7A showed an enhanced outflow activity recently. The main peak of IRS 7A positionally coincides with an X-ray source, which suggests that the X-ray emission is directly related to the central protostar. The Class 0 source SMA 2 is associated with a double radio source, B 9a and 9b, and seems to be driving two outflows. The B 9 complex is probably a multiple-protostar system. Both B 9a and 9b are nonthermal radio sources with negative spectral indices. IRS 7B is a compact radio source surrounded by an extended structure. The compact source corresponds to the Class 0/I source SMA 1, and it is also closely associated with an X-ray source, suggesting that magnetic activities start early in the protostellar stage of evolution. The extended structure of IRS 7B may be a bipolar outflow. IRS 5 was resolved into two sources with a separation of 0.9 arcseconds. Both IRS 5a and 5b display radio flares and X-ray emission, suggesting that energetic magnetic processes are active in both members. The month-scale active phase of IRS 5b implies that the flare activity must involve large-scale magnetic fields. During the strong flare event of IRS 5b in 1998, IRS 5a also showed an enhanced level of radio emission. This concurrent activity suggests that IRS 5 may be an interacting young binary system, but the interaction mechanism is unknown. Alternatively, what was seen in the radio images could be a circumbinary halo.Comment: To appear in the Astrophysical Journa

Glutathione-S-transferases in lung and sputum specimens, effects of smoking and COPD severity

<p>Abstract</p> <p>Background</p> <p>Oxidative stress plays a potential role in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Glutathione S-transferases (GSTs) detoxify toxic compounds in tobacco smoke via glutathione-dependent mechanisms. Little is known about the regulation and expression of GSTs in COPD lung and their presence in airway secretions.</p> <p>Methods</p> <p>GST alpha, pi and mu were investigated by immunohistochemistry in 72 lung tissue specimens and by Western analysis in total lung homogenates and induced sputum supernatants from non-smokers, smokers and patients with variable stages of COPD severity.</p> <p>Results</p> <p>GST alpha was expressed mainly in the airway epithelium. The percentage of GST alpha positive epithelial cells was lower in the central airways of patients with very severe (Stage IV) COPD compared to mild/moderate COPD (p = 0.02). GST alpha by Western analysis was higher in the total lung homogenates in mild/moderate COPD compared to cases of very severe disease (p < 0.001). GST pi was present in airway and alveolar epithelium as well as in alveolar macrophages. GST mu was expressed mainly in the epithelium. Both GST alpha and pi were detectable in sputum supernatants especially in patients with COPD.</p> <p>Conclusion</p> <p>This study indicates the presence of GST alpha and pi especially in the epithelium and sputum supernatants in mild/moderate COPD and low expression of GST alpha in the epithelium in cases of very severe COPD. The presence of GSTs in the airway secretions points to their potential protective role both as intracellular and extracellular mediators in human lung.</p

On the Identification of High Mass Star Forming Regions using IRAS: Contamination by Low-Mass Protostars

We present the results of a survey of a small sample (14) of low-mass protostars (L_IR < 10^3 Lsun) for 6.7 GHz methanol maser emission performed using the ATNF Parkes radio telescope. No new masers were discovered. We find that the lower luminosity limit for maser emission is near 10^3 Lsun, by comparison of the sources in our sample with previously detected methanol maser sources. We examine the IRAS properties of our sample and compare them with sources previously observed for methanol maser emission, almost all of which satisfy the Wood & Churchwell criterion for selecting candidate UCHII regions. We find that about half of our sample satisfy this criterion, and in addition almost all of this subgroup have integrated fluxes between 25 and 60 microns that are similar to sources with detectable methanol maser emission. By identifying a number of low-mass protostars in this work and from the literature that satisfy the Wood & Churchwell criterion for candidate UCHII regions, we show conclusively for the first time that the fainter flux end of their sample is contaminated by lower-mass non-ionizing sources, confirming the suggestion by van der Walt and Ramesh & Sridharan.Comment: 8 pages with 2 figures. Accepted by Ap

Radio and X-ray variability of Young Stellar Objects in the Coronet Cluster

The Coronet Cluster in the nearby R CrA dark cloud offers the rare opportunity to study at least four "class I" protostellar sources as well as one candidate "class 0" source, a Herbig Ae star, and a candidate brown dwarf within a few square arcminutes - most of them detected at radio- and X-ray wavelengths. These sources were observed with the Very Large Array (VLA) at 3.5cm on nine occasions in 1998, spread over nearly four months. The source IRS 5, earlier shown to emit circularly polarized radio emission, was observed to undergo a flux increase accompanied by changes in its polarization properties. Comparison with VLA measurements taken in January 1997 allows for some analysis of longer-term variability. In addition to this radio monitoring, we analyze archival Chandra and XMM-Newton X-ray data of these sources. Three class I protostars are bright enough for X-ray spectroscopy, and we perform a variability analysis for these sources, covering a total of 154 ksec spread over more than two and a half years. Also in X-rays, IRS 5 shows the most pronounced variability, whilst the other two class I protostars IRS 1 and IRS 2 have more stable emission. X-ray data is also analyzed for the recently identified candidate class 0 source IRS 7E, which shows strong variability as well as for the Herbig Ae star R CrA for which we find extremely hot X-ray-emitting plasma. For IRS 1,2 and 5, the hydrogen column densities derived from the X-ray spectra are at about half the values derived with near-infrared techniques, a situation similar to what has been observed towards some other young stellar objects.Comment: 17 pages, 11 figures, accepted for publication in A&

Differential effects of cytokines and corticosteroids on Toll-like receptor 2 expression and activity in human airway epithelia

<p>Abstract</p> <p>Background</p> <p>The recognition of microbial molecular patterns via Toll-like receptors (TLRs) is critical for mucosal defenses.</p> <p>Methods</p> <p>Using well-differentiated primary cultures of human airway epithelia, we investigated the effects of exposure of the cells to cytokines (TNF-α and IFN-γ) and dexamethasone (dex) on responsiveness to the TLR2/TLR1 ligand Pam3CSK4. Production of IL-8, CCL20, and airway surface liquid antimicrobial activity were used as endpoints.</p> <p>Results</p> <p>Microarray expression profiling in human airway epithelia revealed that first response cytokines markedly induced TLR2 expression. Real-time PCR confirmed that cytokines (TNF-α and IFN-γ), dexamethasone (dex), or cytokines + dex increased TLR2 mRNA abundance. A synergistic increase was seen with cytokines + dex. To assess TLR2 function, epithelia pre-treated with cytokines ± dex were exposed to the TLR2/TLR1 ligand Pam3CSK4 for 24 hours. While cells pre-treated with cytokines alone exhibited significantly enhanced IL-8 and CCL20 secretion following Pam3CSK4, mean IL-8 and CCL20 release decreased in Pam3CSK4 stimulated cells following cytokines + dex pre-treatment. This marked increase in inflammatory gene expression seen after treatment with cytokines followed by the TLR2 ligand did not correlate well with NF-κB, Stat1, or p38 MAP kinase pathway activation. Cytokines also enhanced TLR2 agonist-induced beta-defensin 2 mRNA expression and increased the antimicrobial activity of airway surface liquid. Dex blocked these effects.</p> <p>Conclusion</p> <p>While dex treatment enhanced TLR2 expression, co-administration of dex with cytokines inhibited airway epithelial cell responsiveness to TLR2/TLR1 ligand over cytokines alone. Enhanced functional TLR2 expression following exposure to TNF-α and IFN-γ may serve as a dynamic means to amplify epithelial innate immune responses during infectious or inflammatory pulmonary diseases.</p

Triose Phosphate Isomerase Deficiency Is Caused by Altered Dimerization–Not Catalytic Inactivity–of the Mutant Enzymes

Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disorder caused by various mutations in the gene encoding the key glycolytic enzyme TPI. A drastic decrease in TPI activity and an increased level of its substrate, dihydroxyacetone phosphate, have been measured in unpurified cell extracts of affected individuals. These observations allowed concluding that the different mutations in the TPI alleles result in catalytically inactive enzymes. However, despite a high occurrence of TPI null alleles within several human populations, the frequency of this disorder is exceptionally rare. In order to address this apparent discrepancy, we generated a yeast model allowing us to perform comparative in vivo analyses of the enzymatic and functional properties of the different enzyme variants. We discovered that the majority of these variants exhibit no reduced catalytic activity per se. Instead, we observed, the dimerization behavior of TPI is influenced by the particular mutations investigated, and by the use of a potential alternative translation initiation site in the TPI gene. Additionally, we demonstrated that the overexpression of the most frequent TPI variant, Glu104Asp, which displays altered dimerization features, results in diminished endogenous TPI levels in mammalian cells. Thus, our results reveal that enzyme deregulation attributable to aberrant dimerization of TPI, rather than direct catalytic inactivation of the enzyme, underlies the pathogenesis of TPI deficiency. Finally, we discovered that yeast cells expressing a TPI variant exhibiting reduced catalytic activity are more resistant against oxidative stress caused by the thiol-oxidizing reagent diamide. This observed advantage might serve to explain the high allelic frequency of TPI null alleles detected among human populations

Bordetella pertussis Infection Exacerbates Influenza Virus Infection through Pertussis Toxin-Mediated Suppression of Innate Immunity

Pertussis (whooping cough) is frequently complicated by concomitant infections with respiratory viruses. Here we report the effect of Bordetella pertussis infection on subsequent influenza virus (PR8) infection in mouse models and the role of pertussis toxin (PT) in this effect. BALB/c mice infected with a wild-type strain of B. pertussis (WT) and subsequently (up to 14 days later) infected with PR8 had significantly increased pulmonary viral titers, lung pathology and mortality compared to mice similarly infected with a PT-deficient mutant strain (ΔPT) and PR8. Substitution of WT infection by intranasal treatment with purified active PT was sufficient to replicate the exacerbating effects on PR8 infection in BALB/c and C57/BL6 mice, but the effects of PT were lost when toxin was administered 24 h after virus inoculation. PT had no effect on virus titers in primary cultures of murine tracheal epithelial cells (mTECs) in vitro, suggesting the toxin targets an early immune response to increase viral titers in the mouse model. However, type I interferon responses were not affected by PT. Whole genome microarray analysis of gene expression in lung tissue from PT-treated and control PR8-infected mice at 12 and 36 h post-virus inoculation revealed that PT treatment suppressed numerous genes associated with communication between innate and adaptive immune responses. In mice depleted of alveolar macrophages, increase of pulmonary viral titers by PT treatment was lost. PT also suppressed levels of IL-1β, IL-12, IFN-γ, IL-6, KC, MCP-1 and TNF-α in the airways after PR8 infection. Furthermore PT treatment inhibited early recruitment of neutrophils and NK cells to the airways. Together these findings demonstrate that infection with B. pertussis through PT activity predisposes the host to exacerbated influenza infection by countering protective innate immune responses that control virus titers