278 research outputs found

    A Mycobacterium ESX-1–Secreted Virulence Factor with Unique Requirements for Export

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    Specialized secretion systems of pathogenic bacteria commonly transport multiple effectors that act in concert to control and exploit the host cell as a replication-permissive niche. Both the Mycobacterium marinum and the Mycobacterium tuberculosis genomes contain an extended region of difference 1 (extRD1) locus that encodes one such pathway, the early secretory antigenic target 6 (ESAT-6) system 1 (ESX-1) secretion apparatus. ESX-1 is required for virulence and for secretion of the proteins ESAT-6, culture filtrate protein 10 (CFP-10), and EspA. Here, we show that both Rv3881c and its M. marinum homolog, Mh3881c, are secreted proteins, and disruption of RD1 in either organism blocks secretion. We have renamed the Rv3881c/Mh3881c gene espB for ESX-1 substrate protein B. Secretion of M. marinum EspB (EspBM) requires both the Mh3879c and Mh3871 genes within RD1, while CFP-10 secretion is not affected by disruption of Mh3879c. In contrast, disruption of Mh3866 or Mh3867 within the extRD1 locus prevents CFP-10 secretion without effect on EspBM. Mutants that fail to secrete only EspBM or only CFP-10 are less attenuated in macrophages than mutants failing to secrete both substrates. EspBM physically interacts with Mh3879c; the M. tuberculosis homolog, EspBT, physically interacts with Rv3879c; and mutants of EspBM that fail to bind Mh3879c fail to be secreted. We also found interaction between Rv3879c and Rv3871, a component of the ESX-1 machine, suggesting a mechanism for the secretion of EspB. The results establish EspB as a substrate of ESX-1 that is required for virulence and growth in macrophages and suggests that the contribution of ESX-1 to virulence may arise from the secretion of multiple independent substrates

    Prevalence, Treatment, and Outcomes of Coexistent Pulmonary Hypertension and Interstitial Lung Disease in Systemic Sclerosis

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150609/1/art40862.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150609/2/art40862_am.pd

    Synthesis and Detection of Oxygen-18 Labeled Phosphate

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    Phosphorus (P) has only one stable isotope and therefore tracking P dynamics in ecosystems and inferring sources of P loading to water bodies have been difficult. Researchers have recently employed the natural abundance of the ratio of 18O/16O of phosphate to elucidate P dynamics. In addition, phosphate highly enriched in oxygen-18 also has potential to be an effective tool for tracking specific sources of P in the environment, but has so far been used sparingly, possibly due to unavailability of oxygen-18 labeled phosphate (OLP) and uncertainty in synthesis and detection. One objective of this research was to develop a simple procedure to synthesize highly enriched OLP. Synthesized OLP is made up of a collection of species that contain between zero and four oxygen-18 atoms and, as a result, the second objective of this research was to develop a method to detect and quantify each OLP species. OLP was synthesized by reacting either PCl5 or POCl3 with water enriched with 97 atom % oxygen-18 in ambient atmosphere under a fume hood. Unlike previous reports, we observed no loss of oxygen-18 enrichment during synthesis. Electrospray ionization mass spectrometertry (ESI-MS) was used to detect and quantify each species present in OLP. OLP synthesized from POCl3 contained 1.2% P18O16O3, 18.2% P18O216O2, 67.7% P18O316O, and 12.9% P18O4, and OLP synthesized from PCl5 contained 0.7% P16O4, 9.3% P18O316O, and 90.0% P18O4. We found that OLP can be synthesized using a simple procedure in ambient atmosphere without the loss of oxygen-18 enrichment and ESI-MS is an effective tool to detect and quantify OLP that sheds light on the dynamics of synthesis in ways that standard detection methods cannot

    Blueberry Progress Reports

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    The 1979 edition of the Blueberry Progress Reports was prepared for the Maine Blueberry Commission and the University of Maine Blueberry Advisory Committee by researchers with the Maine Life Sciences and Agriculture Experiment Station and Maine Cooperative Extension Service at the University of Maine, Orono. Projects in this report include: 1. Cooperative Extension Activities 2. Plan of Work - FY 1980 3. Weed Control in Lowbush Blueberry Fields 4. Pruning of Blueberries 5. Integrated Management of Blueberry Fields 6. Physiology and Culture of the Lowbush Blueberry 7. Effect of Plant-Water Stress on Lowbush Blueberry Growth, Yield and Quality 8. Blueberry Pathology 9. Botrytis Blossom Blight of Lowbush Blueberries 10. Insects Affecting the Blueberr

    The ACS Virgo Cluster Survey. XII. The Luminosity Function of Globular Clusters in Early Type Galaxies

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    We analyze the luminosity function of the globular clusters (GCs) belonging to the early-type galaxies observed in the ACS Virgo Cluster Survey. We have obtained estimates for a Gaussian representation of the GC luminosity function (GCLF) for 89 galaxies. We have also fit the GCLFs with an "evolved Schechter function", which is meant to reflect the preferential depletion of low-mass GCs, primarily by evaporation due to two-body relaxation, from an initial Schechter mass function similar to that of young massive clusters. We find a significant trend of the GCLF dispersion with galaxy luminosity, in the sense that smaller galaxies have narrower GCLFs. We show that this narrowing of the GCLF in a Gaussian description is driven by a steepening of the GC mass function above the turnover mass, as one moves to smaller host galaxies. We argue that this behavior at the high-mass end of the GC mass function is most likely a consequence of systematic variations of the initial cluster mass function. The GCLF turnover mass M_TO is roughly constant, at ~ 2.2 x 10^5 M_sun in bright galaxies, but it decreases slightly in dwarfs with M_B >~ -18. We show that part of the variation could arise from the shorter dynamical friction timescales in smaller galaxies. We probe the variation of the GCLF to projected galactocentric radii of 20-35 kpc in the Virgo giants M49 and M87, finding that M_TO is essentially constant over these spatial scales. Our fits of evolved Schechter functions imply average dynamical mass losses (Delta) over a Hubble time that fall in the range 2 x 10^5 <~ (Delta/M_sun) < 10^6 per GC. We agree with previous suggestions that if the full GCLF is to be understood in more detail GCLF models will have to include self-consistent treatments of dynamical evolution inside time-dependent galaxy potentials. (Abridged)Comment: 46 pages, 20 figures, 6 tables. Accepted for publication in ApJS. Also available at http://www1.cadc-ccda.hia-iha.nrc-cnrc.gc.ca/community/ACSVCS/publications.htm

    The ACS Virgo Cluster Survey. VII. Resolving the Connection Between Globular Clusters and Ultra-Compact Dwarf Galaxies

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    We investigate the connection between globular clusters and ultra-compact dwarf galaxies (UCDs) by examining the properties of several compact objects associated with M87, all of which were previously classified as globular clusters. Combining imaging from the Hubble Space Telescope with ground-based Keck spectroscopy, we find two objects to have half-light radii, velocity dispersions and mass-to-light ratios that are consistent with the predictions of population synthesis models for old, metal-rich, luminous globular clusters. Three other objects are much larger, with half-light radii of approximately 20pc, and have V-band mass-to-light ratios in the range 6-9. These objects, which we consider to be UCDs, resemble the nuclei of nucleated dwarf elliptical galaxies in Virgo, having similar mass-to-light ratios, luminosities and colors. These UCDs are found to obey the extrapolated scaling relations of galaxies more closely than those of Galactic globular clusters. There appears to be a transition between the two types of stellar systems at a mass of about two million solar masses. If the UCDs are gravitationally bound, then we suggest that the presence of dark matter is the fundamental property distinguishing globular clusters from UCDs. More than half of the UCD candidates uncovered in the ACS Virgo Cluster Survey are associated with a single galaxy -- M87 -- which suggests that proximity to the Virgo center may be of critical importance for the formation of these objects. These results show that distinguishing bonafide UCDs from bright globular clusters requires a careful analysis of their detailed structural and dynamical properties, particularly their mass-to-light ratios. (ABRIDGED)Comment: 56 pages, with 17 postscript figures. Accepted for publication in ApJ. Also available at: http://www.physics.rutgers.edu/~pcote/acs/publications.htm

    The ACS Virgo Cluster Survey X. Half-light Radii of Globular Clusters in Early-Type Galaxies: Environmental Dependencies and a Standard Ruler for Distance Estimation

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    We have measured half-light radii, r_h, for globular clusters (GCs) belonging to the 100 early-type galaxies observed in the ACS Virgo Cluster Survey and the elliptical galaxy NGC 4697. An analysis of the dependencies of the measured r_h on both the properties of the GCs themselves and their host galaxies reveals that the average r_h increases with increasing galactocentric distance or, alternatively, with decreasing galaxy surface brightness. For the first time, we find that the average r_h decreases with the host galaxy color. We also show that there is no evidence for a variation of r_h with the luminosity of the GCs. Finally, we find in agreement with previous observations that the average r_h depends on the color of GCs, with red GCs being ~17% smaller than their blue counterparts. We show that this difference is probably a consequence of an intrinsic mechanism, rather than projection effects, and that it is in good agreement with the mechanism proposed in Jordan (2004). We discuss these findings in light of two simple pictures for the origin of the r_h of GCs and show that both lead to a behavior in rough agreement with the observations. After accounting for the dependencies found we show that the average GC half-light radii can be successfully used as a standard ruler for distance estimation. We outline the methodology, and provide a calibration for its use. We find = 2.7 +- 0.35 pc for GCs with (g-z)=1.2 mag in a galaxy with color (g-z)_{gal}=1.5 mag and at an underlying surface z-band brightness of mu_z = 21 mag arcsec^{-2}. Using this technique, we place an upper limit of 3.4 Mpc on the 1-sigma line-of-sight depth of the Virgo Cluster. Finally, we examine the form of the r_h distribution for our sample galaxies and provide an analytic expression which successfully describes this distribution. (Abridged)Comment: 18 pages, 13 figures. Accepted for publication in ApJ. Also available at http://www.physics.rutgers.edu/~pcote/acs/publications.htm
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