The Vega Debris Disk -- A Surprise from Spitzer

We present high spatial resolution mid- and far-infrared images of the Vega debris disk obtained with the Multiband Imaging Photometer for Spitzer (MIPS). The disk is well resolved and its angular size is much larger than found previously. The radius of the disk is at least 43" (330 AU), 70"(543 AU), and 105" (815 AU) in extent at 24, 70 and 160 um, respectively. The disk images are circular, smooth and without clumpiness at all three wavelengths. The radial surface brightness profiles imply an inner boundary at a radius of 11"+/-2" (86 AU). Assuming an amalgam of amorphous silicate and carbonaceous grains, the disk can be modeled as an axially symmetric and geometrically thin disk, viewed face-on, with the surface particle number density following an r^-1 power law. The disk radiometric properties are consistent with a range of models using grains of sizes ~1 to ~50 um. We find that a ring, containing grains larger than 180 um and at radii of 86-200 AU from the star, can reproduce the observed 850 um flux, while its emission does not violate the observed MIPS profiles. This ring could be associated with a population of larger asteroidal bodies analogous to our own Kuiper Belt. Cascades of collisions starting with encounters amongthese large bodies in the ring produce the small debris that is blown outward by radiation pressure to much larger distances where we detect its thermal emission. The dust production rate is >~10^15 g/s based on the MIPS results. This rate would require a very massive asteroidal reservoir for the dust to be produced in a steady state throughout Vega's life. Instead, we suggest that the disk we imaged is ephemeral and that we are witnessing the aftermath of a large and relatively recent collisional event, and subsequent collisional cascade.Comment: 13 pages, 17 figures, accepted for publication in ApJ. (Figures 2, 3a, 3b and 4 have been degraded to lower resolutions.

The Primordial Binary Population - I: A near-infrared adaptive optics search for close visual companions to A star members of Scorpius OB2

We present the results of a near-infrared adaptive optics survey with the aim to detect close companions to Hipparcos members in the three subgroups of the nearby OB association Sco OB2: Upper Scorpius (US), Upper Centaurus Lupus (UCL) and Lower Centaurus Crux (LCC). We have targeted 199 A-type and late B-type stars in the Ks band, and a subset also in the J and H band. We find 151 stellar components other than the target stars. A brightness criterion is used to separate these components into 77 background stars and 74 candidate physical companion stars. Out of these 74 candidate companions, 41 have not been reported before (14 in US; 13 in UCL; 14 in LCC). Companion star masses range from 0.1 to 3 Msun. The mass ratio distribution follows f(q) = q^-0.33, which excludes random pairing. No close (rho < 3.75'') companion stars or background stars are found in the magnitude range 12 < Ks < 14. The lack of stars with these properties cannot be explained by low-number statistics, and may imply a lower limit on the companion mass of ~ 0.1 Msun. Close stellar components with Ks > 14 are observed. If these components are very low-mass companion stars, a gap in the companion mass distribution might be present. The small number of close low-mass companion stars could support the embryo-ejection formation scenario for brown dwarfs. Our findings are compared with and complementary to visual, spectroscopic, and astrometric data on binarity in Sco OB2. We find an overall companion star fraction of 0.52 in this association. This paper is the first step toward our goal to derive the primordial binary population in Sco OB2.Comment: 27 pages, to accepted by A&

The accuracy of stellar atmospheric parameter determinations: a case study with HD 32115 and HD 37594

We present detailed parameter determinations of two chemically normal late A-type stars, HD 32115 and HD 37594, to uncover the reasons behind large discrepancies between two previous analyses of these stars performed with a semi-automatic procedure and a "classical" analysis. Our study is based on high resolution, high signal-to-noise spectra obtained at the McDonald Observatory. Our method is based on the simultaneous use of all available observables: multicolor photometry, pressure-sensitive magnesium lines, metallic lines and Balmer line profiles. Our final set of fundamental parameters fits, within the error bars, all available observables. It differs from the published results obtained with a semi-automatic procedure. A direct comparison between our new observational material and the spectra previously used by other authors shows that the quality of the data is not the origin of the discrepancies. As the two stars require a substantial macroturbulence velocity to fit the line profiles, we concluded that neglecting this additional broadening in the semi-automatic analysis is one origin of discrepancy. The use of FeI excitation equilibrium and of the Fe ionisation equilibrium, to derive effective temperature and surface gravity, respectively, neglecting all other indicators leads to a systematically erroneously high effective temperature. We deduce that the results obtained using only one parameter indicator might be biased and that those results need to be cautiously taken when performing further detailed analyses, such as modelling of the asteroseismic frequencies or characterising transiting exoplanets.Comment: Accepted for publication by MNRA

Differential Requirements for Clathrin-dependent Endocytosis at Sites of Cell–Substrate Adhesion

Little is known about the influences of cell–substrate attachment in clathrin-mediated endocytosis. We find that cell–substrate adhesion reduces the rate of endocytosis. In addition, we demonstrate that actin assembly is differentially required for efficient endocytosis, with a stronger requirement for actin dynamics at sites of adhesion

The Effect of OPA1 on Mitochondrial Ca2+ Signaling

The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles. Its mutation is the most prevalent cause of Autosomal Dominant Optic Atrophy. OPA1 controls the diameter of the junctions between the boundary part of the inner membrane and the membrane of cristae and reduces the diffusibility of cytochrome c through these junctions. We postulated that if significant Ca2+ uptake into the matrix occurs from the lumen of the cristae, reduced expression of OPA1 would increase the access of Ca2+ to the transporters in the crista membrane and thus would enhance Ca2+ uptake. In intact H295R adrenocortical and HeLa cells cytosolic Ca2+ signals evoked with K+ and histamine, respectively, were transferred into the mitochondria. The rate and amplitude of mitochondrial [Ca2+] rise (followed with confocal laser scanning microscopy and FRET measurements with fluorescent wide-field microscopy) were increased after knockdown of OPA1, as compared with cells transfected with control RNA or mitofusin1 siRNA. Ca2+ uptake was enhanced despite reduced mitochondrial membrane potential. In permeabilized cells the rate of Ca2+ uptake by depolarized mitochondria was also increased in OPA1-silenced cells. The participation of Na+/Ca2+ and Ca2+/H+ antiporters in this transport process is indicated by pharmacological data. Altogether, our observations reveal the significance of OPA1 in the control of mitochondrial Ca2+ metabolism

Clostridial Glucosylating Toxins Enter Cells via Clathrin-Mediated Endocytosis

Clostridium difficile toxin A (TcdA) and toxin B (TcdB), C. sordellii lethal toxin (TcsL) and C. novyi α-toxin (TcnA) are important pathogenicity factors, which represent the family of the clostridial glucosylating toxins (CGTs). Toxin A and B are associated with antibiotic-associated diarrhea and pseudomembraneous colitis. Lethal toxin is involved in toxic shock syndrome after abortion and α-toxin in gas gangrene development. CGTs enter cells via receptor-mediated endocytosis and require an acidified endosome for translocation of the catalytic domain into the cytosol. Here we studied the endocytic processes that mediate cell internalization of the CGTs. Intoxication of cells was monitored by analyzing cell morphology, status of Rac glucosylation in cell lysates and transepithelial resistance of cell monolayers. We found that the intoxication of cultured cells by CGTs was strongly delayed when cells were preincubated with dynasore, a cell-permeable inhibitor of dynamin, or chlorpromazine, an inhibitor of the clathrin-dependent endocytic pathway. Additional evidence about the role of clathrin in the uptake of the prototypical CGT family member toxin B was achieved by expression of a dominant-negative inhibitor of the clathrin-mediated endocytosis (Eps15 DN) or by siRNA against the clathrin heavy chain. Accordingly, cells that expressed dominant-negative caveolin-1 were not protected from toxin B-induced cell rounding. In addition, lipid rafts impairment by exogenous depletion of sphingomyelin did not decelerate intoxication of HeLa cells by CGTs. Taken together, our data indicate that the endocytic uptake of the CGTs involves a dynamin-dependent process that is mainly governed by clathrin

Crystal structure of nucleotide-free dynamin

Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of human dynamin 1 in the nucleotide-free state with a four-domain architecture comprising the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. Dynamin 1 oligomerized in the crystals via the stalks, which assemble in a criss-cross fashion. The stalks further interact via conserved surfaces with the pleckstrin homology domain and the bundle signalling element of the neighbouring dynamin molecule. This intricate domain interaction rationalizes a number of disease-related mutations in dynamin 2 and suggests a structural model for the mechanochemical coupling that reconciles previous models of dynamin function

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

A Novel Mechanism Is Involved in Cationic Lipid-Mediated Functional siRNA Delivery

A key challenge for therapeutic application of RNA interference is to efficiently deliver synthetic small interfering RNAs (siRNAs) into target cells that will lead to the knockdown of the target transcript (functional siRNA delivery). To facilitate rational development of nonviral carriers, we have investigated by imaging, pharmacological and genetic approaches the mechanisms by which a cationic lipid carrier mediates siRNA delivery into mammalian cells. We show that 95% of siRNA lipoplexes enter the cells through endocytosis and persist in endolysosomes for a prolonged period of time. However, inhibition of clathrin-, caveolin-, or lipid-raft-mediated endocytosis or macropinocytosis fails to inhibit the knockdown of the target transcript. In contrast, depletion of cholesterol from the plasma membrane has little effect on the cellular uptake of siRNA lipoplexes, but it abolishes the target transcript knockdown. Furthermore, functional siRNA delivery occurs within a few hours and is gradually inhibited by lowering temperatures. These results demonstrate that although endocytosis is responsible for the majority of cellular uptake of siRNA lipoplexes, a minor pathway, probably mediated by fusion between siRNA lipoplexes and the plasma membrane, is responsible for the functional siRNA delivery. Our findings suggest possible directions for improving functional siRNA delivery by cationic lipids.National Institutes of Health (U.S.) (NIH Grant AI56267)National Institutes of Health (U.S.) (NIH Grant CA112967)National Institutes of Health (U.S.) (NIH Grant CA119349)Natural Sciences and Engineering Research Council of Canada (NSERC) (Post-doctoral fellowship