Reddening law and interstellar dust properties along Magellanic sight-lines

This study establishes that SMC, LMC and Milky Way extinction curves obey the same extinction law which depends on the 2200A bump size and one parameter, and generalizes the Cardelli, Clayton and Mathis (1989) relationship. This suggests that extinction in all three galaxies is of the same nature. The role of linear reddening laws over all the visible/UV wavelength range, particularly important in the SMC but also present in the LMC and in the Milky Way, is also highlighted and discussed.Comment: accepted for publication in Astrophysics and Space Science. 16 pages, 12 figures. Some figures are colour plot

Molecular architecture of Gαo and the structural basis for RGS16-mediated deactivation

Heterotrimeric G proteins relay extracellular cues from heptahelical transmembrane receptors to downstream effector molecules. Composed of an α subunit with intrinsic GTPase activity and a βγ heterodimer, the trimeric complex dissociates upon receptor-mediated nucleotide exchange on the α subunit, enabling each component to engage downstream effector targets for either activation or inhibition as dictated in a particular pathway. To mitigate excessive effector engagement and concomitant signal transmission, the Gα subunit's intrinsic activation timer (the rate of GTP hydrolysis) is regulated spatially and temporally by a class of GTPase accelerating proteins (GAPs) known as the regulator of G protein signaling (RGS) family. The array of G protein-coupled receptors, Gα subunits, RGS proteins and downstream effectors in mammalian systems is vast. Understanding the molecular determinants of specificity is critical for a comprehensive mapping of the G protein system. Here, we present the 2.9 Å crystal structure of the enigmatic, neuronal G protein Gαo in the GTP hydrolytic transition state, complexed with RGS16. Comparison with the 1.89 Å structure of apo-RGS16, also presented here, reveals plasticity upon Gαo binding, the determinants for GAP activity, and the structurally unique features of Gαo that likely distinguish it physiologically from other members of the larger Gαi family, affording insight to receptor, GAP and effector specificity

GPCR-OKB: the G protein coupled receptor oligomer knowledge base

Rapid expansion of available data about G Protein Coupled Receptor (GPCR) dimers/oligomers over the past few years requires an effective system to organize this information electronically. Based on an ontology derived from a community dialog involving colleagues using experimental and computational methodologies, we developed the GPCR-Oligomerization Knowledge Base (GPCR-OKB). GPCR-OKB is a system that supports browsing and searching for GPCR oligomer data. Such data were manually derived from the literature. While focused on GPCR oligomers, GPCR-OKB is seamlessly connected to GPCRDB, facilitating the correlation of information about GPCR protomers and oligomers

Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis

The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway represents a promising therapeutic target to prevent fibrosis. We have tested the effects of new pharmacological inhibitors of MRTF/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 μM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues

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

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.

A Gold Standard Dataset for the Reviewer Assignment Problem

Many peer-review venues are either using or looking to use algorithms to assign submissions to reviewers. The crux of such automated approaches is the notion of the "similarity score"--a numerical estimate of the expertise of a reviewer in reviewing a paper--and many algorithms have been proposed to compute these scores. However, these algorithms have not been subjected to a principled comparison, making it difficult for stakeholders to choose the algorithm in an evidence-based manner. The key challenge in comparing existing algorithms and developing better algorithms is the lack of the publicly available gold-standard data that would be needed to perform reproducible research. We address this challenge by collecting a novel dataset of similarity scores that we release to the research community. Our dataset consists of 477 self-reported expertise scores provided by 58 researchers who evaluated their expertise in reviewing papers they have read previously. We use this data to compare several popular algorithms employed in computer science conferences and come up with recommendations for stakeholders. Our main findings are as follows. First, all algorithms make a non-trivial amount of error. For the task of ordering two papers in terms of their relevance for a reviewer, the error rates range from 12%-30% in easy cases to 36%-43% in hard cases, highlighting the vital need for more research on the similarity-computation problem. Second, most existing algorithms are designed to work with titles and abstracts of papers, and in this regime the Specter+MFR algorithm performs best. Third, to improve performance, it may be important to develop modern deep-learning based algorithms that can make use of the full texts of papers: the classical TD-IDF algorithm enhanced with full texts of papers is on par with the deep-learning based Specter+MFR that cannot make use of this information

Kinetics of M1 muscarinic receptor and G protein signaling to phospholipase C in living cells

G protein–coupled receptors (GPCRs) mediate responses to external stimuli in various cell types. Early events, such as the binding of ligand and G proteins to the receptor, nucleotide exchange (NX), and GTPase activity at the Gα subunit, are common for many different GPCRs. For Gq-coupled M1 muscarinic (acetylcholine) receptors (M1Rs), we recently measured time courses of intermediate steps in the signaling cascade using Förster resonance energy transfer (FRET). The expression of FRET probes changes the density of signaling molecules. To provide a full quantitative description of M1R signaling that includes a simulation of kinetics in native (tsA201) cells, we now determine the density of FRET probes and construct a kinetic model of M1R signaling through Gq to activation of phospholipase C (PLC). Downstream effects on the trace membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) and PIP2-dependent KCNQ2/3 current are considered in our companion paper in this issue (Falkenburger et al. 2010. J. Gen. Physiol. doi:10.1085/jgp.200910345). By calibrating their fluorescence intensity, we found that we selected transfected cells for our experiments with ∼3,000 fluorescently labeled receptors, G proteins, or PLC molecules per µm2 of plasma membrane. Endogenous levels are much lower, 1–40 per µm2. Our kinetic model reproduces the time courses and concentration–response relationships measured by FRET and explains observed delays. It predicts affinities and rate constants that align well with literature values. In native tsA201 cells, much of the delay between ligand binding and PLC activation reflects slow binding of G proteins to receptors. With M1R and Gβ FRET probes overexpressed, 10% of receptors have G proteins bound at rest, rising to 73% in the presence of agonist. In agreement with previous work, the model suggests that binding of PLC to Gαq greatly speeds up NX and GTPase activity, and that PLC is maintained in the active state by cycles of rapid GTP hydrolysis and NX on Gαq subunits bound to PLC

Generic realignments in Maxillariinae (Orchidaceae): Corrigenda et adenda

UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Jardín Botánico Lankester (JBL