A Search for Wolf-Rayet Stars in the Small Magellanic Cloud

We conducted an extensive search for Wolf-Rayet stars (W-Rs) in the SMC, using the same interference filter imaging techniques that have proved successful in finding W-Rs in more distant members of the Local Group. Photometry of some 1.6 million stellar images resulted in some 20 good candidates, which we then examined spectroscopically. Two of these indeed proved to be newly found W-Rs, bringing the total known in the SMC from 9 to 11. Other finds included previously unknown Of-type stars (one as early as O5f?p)),the recovery of the Luminous Blue Variable S18, and the discovery of a previously unknown SMC symbiotic star. More important, however, is the fact that there does not exist a significant number of W-Rs waiting to be discovered in the SMC. The number of W-Rs in the SMC is a factor of 3 lower than in the LMC (per unit luminosity), and we argue this is the result of the SMC's low metallicity on the evolution of the most massive stars.Comment: Accepted by Astrophysical Journal. Postscript version available via ftp.lowell.edu/pub/massey/smcwr.ps.gz Revised version contains slightly revised spectral types for the Of stars but is otherwise unchange

Synthetic High-Resolution Line Spectra of Star-Forming Galaxies Below 1200A

We have generated a set of far-ultraviolet stellar libraries using spectra of OB and Wolf-Rayet stars in the Galaxy and the Large and Small Magellanic Cloud. The spectra were collected with the Far Ultraviolet Spectroscopic Explorer and cover a wavelength range from 1003.1 to 1182.7A at a resolution of 0.127A. The libraries extend from the earliest O- to late-O and early-B stars for the Magellanic Cloud and Galactic libraries, respectively. Attention is paid to the complex blending of stellar and interstellar lines, which can be significant, especially in models using Galactic stars. The most severe contamination is due to molecular hydrogen. Using a simple model for the H$_2$ line strength, we were able to remove the molecular hydrogen lines in a subset of Magellanic Cloud stars. Variations of the photospheric and wind features of CIII 1176, OVI 1032, 1038, PV 1118, 1128, and SIV 1063, 1073, 1074 are discussed as a function of temperature and luminosity class. The spectral libraries were implemented into the LavalSB and Starburst99 packages and used to compute a standard set of synthetic spectra of star-forming galaxies. Representative spectra are presented for various initial mass functions and star formation histories. The valid parameter space is confined to the youngest ages of less than 10 Myr for an instantaneous burst, prior to the age when incompleteness of spectral types in the libraries sets in. For a continuous burst at solar metallicity, the parameter space is not limited. The suite of models is useful for interpreting the restframe far-ultraviolet in local and high-redshift galaxies.Comment: 33 pages including 13 figures, accepted for publication in Ap

Neutrino Oscillations and the Supernova 1987A Signal

We study the impact of neutrino oscillations on the interpretation of the supernova (SN) 1987A neutrino signal by means of a maximum-likelihood analysis. We focus on oscillations between $\overline\nu_e$ with $\overline\nu_\mu$ or $\overline\nu_\tau$ with those mixing parameters that would solve the solar neutrino problem. For the small-angle MSW solution ($\Delta m^2\approx10^{-5}\,\rm eV^2$, $\sin^22\Theta_0\approx0.007$), there are no significant oscillation effects on the Kelvin-Helmholtz cooling signal; we confirm previous best-fit values for the neutron-star binding energy and average spectral $\overline\nu_e$ temperature. There is only marginal overlap between the upper end of the 95.4\% CL inferred range of $\langle E_{\overline\nu_e}\rangle$ and the lower end of the range of theoretical predictions. Any admixture of the stiffer $\overline\nu_\mu$ spectrum by oscillations aggravates the conflict between experimentally inferred and theoretically predicted spectral properties. For mixing parameters in the neighborhood of the large-angle MSW solution ($\Delta m^2\approx10^{-5}\,\rm eV^2$, $\sin^22\Theta_0\approx0.7$) the oscillations in the SN are adiabatic, but one needs to include the regeneration effect in the Earth which causes the Kamiokande and IMB detectors to observe different $\overline\nu_e$ spectra. For the solar vacuum solution ($\Delta m^2\approx10^{-10}\,\rm eV^2$, $\sin^22\Theta_0\approx1$) the oscillations in the SN are nonadiabatic; vacuum oscillations take place between the SN and the detector. If either of the large-angle solutions were borne out by the upcoming round of solar neutrino experiments, one would have to conclude that the SN~1987A $\overline\nu_\mu$ and/or $\overline\nu_e$ spectra had been much softer than predicted by currentComment: Final version with very minor wording changes, to be published in Phys. Rev.

RGS4 negatively modulates Nociceptin/Orphanin FQ opioid receptor signaling: implication for L-Dopa induced dyskinesia

Background and purpose Regulator of G-protein signal 4 (RGS4) is a signal transduction protein that accelerates intrinsic GTPase activity of Gαi/o and Gαq subunits, suppressing GPCR signaling. Here we investigate whether RGS4 modulates nociceptin/orphanin FQ (N/OFQ) opioid (NOP) receptor signaling and this modulation has relevance for L-Dopa-induced dyskinesia. Experimental approach HEK293T cells transfected with NOP, NOP/RGS4 or NOP/RGS19 were challenged with N/OFQ and the small molecule NOP agonist AT-403, using D1-stimulated cAMP levels as a readout. Primary rat striatal neurons and adult mouse striatal slices were challenged with N/OFQ or AT-403 in the presence of the experimental RGS4 chemical probe, CCG-203920, and D1-stimulated cAMP or phosphorylated extracellular signal regulated kinase 1/2 (pERK) responses were monitored. In vivo, CCG-203920 was co-administered with AT-403 and L-Dopa to 6-hydroxydopamine hemilesioned rats, and dyskinetic movements, striatal biochemical correlates of dyskinesia (pERK and pGluR1 levels) and striatal RGS4 levels were measured. Key results RGS4 expression reduced NOFQ and AT-403 potency and efficacy in HEK293T cells. CCG-203920 increased N/OFQ potency in primary rat striatal neurons, and potentiated AT-403 response in mouse striatal slices. CCG-203920 enhanced AT-403 mediated inhibition of dyskinesia and its biochemical correlates, without compromising its motor-improving effects. Unilateral dopamine depletion caused bilateral reduction of RGS4 levels, which was reversed by L-Dopa. L-Dopa acutely upregulated RGS4 in the lesioned striatum. Conclusions and Implications RGS4 physiologically inhibits NOP receptor signaling. CCG-203920 enhanced NOP responses and improved the antidyskinetic potential of NOP receptor agonists, mitigating the effects of striatal RGS4 upregulation occurring during dyskinesia expression

Phagocyte-derived catecholamines enhance acute inflammatory injury

It is becoming increasingly clear that the autonomic nervous system and the immune system demonstrate cross-talk during inflammation by means of sympathetic and parasympathetic pathways(1,2). We investigated whether phagocytes are capable of de novo production of catecholamines, suggesting an autocrine/paracrine self-regulatory mechanism by catecholamines during inflammation, as has been described for lymphocytes(3). Here we show that exposure of phagocytes to lipopolysaccharide led to a release of catecholamines and an induction of catecholamine-generating and degrading enzymes, indicating the presence of the complete intracellular machinery for the generation, release and inactivation of catecholamines. To assess the importance of these findings in vivo, we chose two models of acute lung injury. Blockade of alpha(2)-adrenoreceptors or catecholamine-generating enzymes greatly suppressed lung inflammation, whereas the opposite was the case either for an alpha(2)-adrenoreceptor agonist or for inhibition of catecholamine-degrading enzymes. We were able to exclude T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Our studies identify phagocytes as a new source of catecholamines, which enhance the inflammatory response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62733/1/nature06185.pd

Quantitative Spectroscopy of O Stars at Low Metallicity. O Dwarfs in NGC 346

We present the results of a detailed UV and optical spectral analysis of the properties of 6 dwarf O-type stars in the SMC H II region NGC 346. Stellar parameters, chemical abundances, and wind parameters have been determined using NLTE line blanketed models calculated with the photospheric code, Tlusty, and with the wind code, CMFGEN. The results, in particular iron abundances, obtained with the two NLTE codes compare very favorably, demonstrating that basic photospheric parameters of O dwarfs can be reliably determined using NLTE static model atmospheres. The two NLTE codes require a microturbulent velocity to match the observed spectra. Our results hint at a decrease of the microturbulent velocity from early O stars to late O stars. Similarly to several recent studies of galactic, LMC and SMC stars, we derive effective temperatures lower than predicted from the widely-used relation between spectral type and Teff, resulting in lower stellar luminosities and lower ionizing fluxes. From evolutionary tracks in the HR diagram, we find an age of 3 10^6 years for NGC 346. A majority of the stars in our sample reveal CNO-cycle processed material at their surface during the MS stage, indicating thus fast stellar rotation and/or very efficient mixing processes. We obtain an overall metallicity, Z = 0.2 Zsun, in good agreement with other recent analyses of SMC stars. The derived mass loss rate of the three most luminous stars agrees with recent theoretical predictions. However, the three other stars of our sample reveal very weak wind signatures. We obtain mass loss rates that are significantly lower than 10^{-8} Msun/yr, which is below the predictions of radiative line-driven wind theory by an order of magnitude or more. (abridged version)Comment: 61 pages, 17 figures; to appear in ApJ, 595 (Oct 1, 2003); minor revisions and addition

Tiny-Scale Molecular Structures in the Magellanic Clouds (Part 1)

We report on the {\small FUSE} detections of the HD and CO molecules {\bf on the lines of sight towards three Large Magellanic stars}: Sk $-$67D05, Sk $-$68D135, and Sk $-$69D246. HD is also detected for the first time {\bf on the lines of sight towards two Small Magellanic Cloud stars}: AV 95 and Sk 159. While the HD and CO abundances are expected to be lower in the Large Magellanic Cloud where molecular fractions are a third of the Galactic value and where the photodissociation flux is up to thousands times larger, we report an average HD/H$_2$ ratio of 1.4$\pm$0.5 ppm and CO/H$_2$ ratio ranging from 0.8 to 2.7 ppm similar to the Galactic ones. We tentatively identify a deuterium reservoir (hereafter D--reservoir) towards the Small Magellanic Cloud, along the light path to AV 95. We derive a D/H ratio ranging from 1. 10$^{-6}$ to 1.1 10$^{-5}$.Comment: 34 pages, 10 tables, 12 figures, accepted for publication in A&

Community guidelines for GPCR ligand bias: IUPHAR review 32

GPCRs modulate a plethora of physiological processes and mediate the effects of one-third of FDA-approved drugs. Depending on which ligand activates a receptor, it can engage different intracellular transducers. This ‘biased signalling’ paradigm requires that we now characterize physiological signalling not just by receptors but by ligand–receptor pairs. Ligands eliciting biased signalling may constitute better drugs with higher efficacy and fewer adverse effects. However, ligand bias is very complex, making reproducibility and description challenging. Here, we provide guidelines and terminology for any scientists to design and report ligand bias experiments. The guidelines will aid consistency and clarity, as the basic receptor research and drug discovery communities continue to advance our understanding and exploitation of ligand bias. Scientific insight, biosensors, and analytical methods are still evolving and should benefit from and contribute to the implementation of the guidelines, together improving translation from in vitro to disease-relevant in vivo models

G-protein signaling: back to the future

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways