Glycosylphosphatidylinositols: More than just an anchor?

There is increasing interest in the role of glycosylphosphatidylinositol (GPI) anchors that attach some proteins to cell membranes. Far from being biologically inert, GPIs influence the targeting, intracellular trafficking and function of the attached protein. Our recent paper demonstrated the role of sialic acid on the GPI of the cellular prion protein (PrPC). The “prion diseases” arise following the conversion of PrPC to a disease-associated isoform called PrPSc or “prion”. Our paper showed that desialylated PrPC inhibited PrPSc formation. Aggregated PrPSc creates a signaling platform in the cell membrane incorporating and activating cytoplasmic phospholipase A2 (cPLA2), an enzyme that regulates PrPC trafficking and hence PrPSc formation. The presence of desialylated PrPC caused the dissociation of cPLA2 from PrP-containing platforms, reduced the activation of cPLA2 and inhibited PrPSc production. We concluded that sialic acid contained within the GPI attached to PrPC modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrPSc formation

Unveiling the Circumstellar Envelope and Disk: A Sub-Arcsecond Survey of Circumstellar Structures

We present the results of a 2.7 mm continuum interferometric survey of 24 young stellar objects in 11 fields. The target objects range from deeply embedded Class 0 sources to optical T Tauri sources. This is the first sub-arcsecond survey of the 2.7 mm dust continuum emission from young, embedded stellar systems. The images show a diversity of structure and complexity. The optically visible T Tauri stars (DG Tauri, HL Tauri, GG Tauri,and GM Aurigae) have continuum emission dominated by compact, less than 1", circumstellar disks. The more embedded near-infrared sources (SVS13 and L1551 IRS5) have continuum emission that is extended and compact. The embedded sources (L1448 IRS3, NGC1333 IRAS2, NGC1333 IRAS4, VLA1623, and IRAS 16293-2422) have continuum emission dominated by the extended envelope, typically more than 85%. In fact, in many of the deeply embedded systems it is difficult to uniquely isolate the disk emission component from the envelope extending inward to AU size scales. All of the target embedded objects are in multiple systems with separations on scales of 30" or less. Based on the system separation, we place the objects into three categories: separate envelope (separation > 6500 AU), common envelope (separation 150-3000 AU), and common disk (separation < 100 AU). These three groups can be linked with fragmentation events during the star formation process: separate envelopes from prompt initial fragmentation and the separate collapse of a loosely condensed cloud, common envelopes from fragmentation of a moderately centrally condensed spherical system, and common disk from fragmentation of a high angular momentum circumstellar disk.Comment: 47 Pages, 18 Figures, ApJ accepte

The Stellar Population of the Chamaeleon I Star-Forming Region

I present a new census of the stellar population in the Chamaeleon I star-forming region. Using optical and near-IR photometry and followup spectroscopy, I have discovered 50 new members of Chamaeleon I, expanding the census of known members to 226 objects. Fourteen of these new members have spectral types later than M6, which doubles the number of known members that are likely to be substellar. I have estimated extinctions, luminosities, and effective temperatures for the known members, used these data to construct an H-R diagram for the cluster, and inferred individual masses and ages with the theoretical evolutionary models of Baraffe and Chabrier. The distribution of isochronal ages indicates that star formation began 3-4 and 5-6 Myr ago in the southern and northern subclusters, respectively, and has continued to the present time at a declining rate. The IMF in Chamaeleon I reaches a maximum at a mass of 0.1-0.15 M_sun, and thus closely resembles the IMFs in IC 348 and the Orion Nebula Cluster. In logarithmic units where the Salpeter slope is 1.35, the IMF is roughly flat in the substellar regime and shows no indication of reaching a minimum down to a completeness limit of 0.01 M_sun. The low-mass stars are more widely distributed than members at other masses in the northern subcluster, but this is not the case in the southern subcluster. Meanwhile, the brown dwarfs have the same spatial distribution as the stars out to a radius of 3 deg (8.5 pc) from the center of Chamaeleon I

Star formation at very low metallicity. II: On the insignificance of metal-line cooling during the early stages of gravitational collapse

We study the influence of low levels of metal enrichment on the cooling and collapse of ionized gas in small protogalactic halos using three-dimensional, smoothed particle hydrodynamics simulations. Our initial conditions represent protogalaxies forming within a fossil HII region -- a previously ionized HII region which has not yet had time to cool and recombine. Prior to cosmological reionization, such regions should be relatively common, since the characteristic lifetimes of the likely ionizing sources are significantly shorter than a Hubble time. We show that in these regions, H_2 is the dominant and most effective coolant, and that it is the amount of H_2 formed that determines whether or not the gas can collapse and form stars. At the low metallicities (Z < 10^{-3} Z_sun) thought to be associated with the transition from population III to early population II star formation, metal line cooling has an almost negligible effect on the evolution of low density gas, altering the density and temperature evolution of the gas by less than 1% compared to the metal-free case at densities below 1 cm^{-3} and temperatures above 2000 K. Although there is evidence that metal line cooling becomes more effective at higher density, we find no significant differences in behaviour from the metal-free case at any density below our sink particle creation threshold at n = 500 cm^{-3}. Increasing the metallicity also increases the importance of metal line cooling, but it does not significantly affect the dynamical evolution of the low density gas until Z = 0.1 Z_sun. This result holds regardless of whether or not an ultraviolet background is present.Comment: 38 pages, 8 figures, AASTex. Accepted by ApJ. Corrected typos and reference

Mining multi-item drug adverse effect associations in spontaneous reporting systems

<p>Abstract</p> <p>Background</p> <p>Multi-item adverse drug event (ADE) associations are associations relating multiple drugs to possibly multiple adverse events. The current standard in pharmacovigilance is bivariate association analysis, where each single drug-adverse effect combination is studied separately. The importance and difficulty in the detection of multi-item ADE associations was noted in several prominent pharmacovigilance studies. In this paper we examine the application of a well established data mining method known as association rule mining, which we tailored to the above problem, and demonstrate its value. The method was applied to the FDAs spontaneous adverse event reporting system (AERS) with minimal restrictions and expectations on its output, an experiment that has not been previously done on the scale and generality proposed in this work.</p> <p>Results</p> <p>Based on a set of 162,744 reports of suspected ADEs reported to AERS and published in the year 2008, our method identified 1167 multi-item ADE associations. A taxonomy that characterizes the associations was developed based on a representative sample. A significant number (67% of the total) of potential multi-item ADE associations identified were characterized and clinically validated by a domain expert as previously recognized ADE associations. Several potentially novel ADEs were also identified. A smaller proportion (4%) of associations were characterized and validated as known drug-drug interactions.</p> <p>Conclusions</p> <p>Our findings demonstrate that multi-item ADEs are present and can be extracted from the FDA’s adverse effect reporting system using our methodology, suggesting that our method is a valid approach for the initial identification of multi-item ADEs. The study also revealed several limitations and challenges that can be attributed to both the method and quality of data.</p

The evolution of gravitationally unstable protoplanetary disks: fragmentation and possible giant planet formation

We carry out a large set of very high resolution, three dimensional smoothed particle hydrodynamics (SPH) simulations describing the evolution of gravitationally unstable gaseous protoplanetary disks. We consider a broad range of initial disk parameters. Disk masses out to 20 AU range from 0.075 to 0.125 $M_{\odot}$, roughly consistent with the high-end of the mass distribution inferred for disks around T Tauri stars. The initial disks span minimum $Q$ parameters between 0.8 and 2, with most models being around $\sim 1.4$. The disks are evolved assuming either a locally isothermal equation of state or an adiabatic equation of state with varying $\gamma$. When overdensities above a specific threshold appear as a result of gravitational instability in a locally isothermal calculation, the equation of state is switched to adiabatic to account for the increased optical depth. We show that when a disk has a minimum $Q$ parameter less than 1.4 strong trailing spiral instabilities, typically three or four armed modes, form and grow until fragmentation occurs along the arms after about 5 mean disk orbital times. The resulting clumps contract quickly to densities several orders of magnitude higher than the initial disk density, and the densest of them survive even under adiabatic conditions. These clumps are stable to tidal disruption and merge quickly, leaving 2-3 protoplanets on fairly eccentric orbits (the mean eccentricity being around 0.2) with masses between 0.7 and more than $7 M_{Jup}$, well in agreement with those of detected extrasolar planets.after $\sim 10^3$ years. Fragmentation is not strongly dependent on whether the disk starts from a marginally unstable state or gradually achieves it, as shown by a test where the disk gradually achieves the critical $Q$ by growing in mass.Comment: 48 pages, 18 figures, submitted to ApJ. Abstract considerably reduced, see paper. PostScript file including hi-res figures and movies of the simulations can be dowloaded at http://www.astro.washington.edu/mayer

The masses of Local Group dwarf spheroidal galaxies: The death of the universal mass profile

We investigate the claim that all dwarf spheroidal galaxies (dSphs) reside within halos that share a common, universal mass profile as has been derived for dSphs of the Galaxy. By folding in kinematic information for 25 Andromeda dSphs, more than doubling the previous sample size, we find that a singular mass profile can not be found to fit all the observations well. Further, the best-fit dark matter density profile measured for solely the Milky Way dSphs is marginally discrepant (at just beyond the 1 sigma level) with that of the Andromeda dSphs, where a profile with lower maximum circular velocity, and hence mass, is preferred. The agreement is significantly better when three extreme Andromeda outliers, And XIX, XXI and XXV, all of which have large half-light radii (>600pc) and low velocity dispersions (sigma_v < 5km/s) are omitted from the sample. We argue that the unusual properties of these outliers are likely caused by tidal interactions with the host galaxy.Comment: ApJ in press, 16 pages, 7 figures. Updated to address referee comment

A kinematic study of the Andromeda dwarf spheroidal system

We present a homogeneous kinematic analysis of red giant branch stars within 18 of the 28 Andromeda dwarf spheroidal (dSph) galaxies, obtained using the Keck I LRIS and Keck II DEIMOS spectrographs. Based on their g-i colors (taken with the CFHT MegaCam imager), physical positions on the sky, and radial velocities, we assign probabilities of dSph membership to each observed star. Using this information, the velocity dispersions, central masses and central densities of the dark matter halos are calculated for these objects, and compared with the properties of the Milky Way dSph population. We also measure the average metallicity ([Fe/H]) from the co-added spectra of member stars for each M31 dSph and find that they are consistent with the trend of decreasing [Fe/H] with luminosity observed in the Milky Way population. We find that three of our studied M31 dSphs appear as significant outliers in terms of their central velocity dispersion, And XIX, XXI and XXV, all of which have large half-light radii (>700 pc) and low velocity dispersions (sigma_v<5 km/s). In addition, And XXV has a mass-to-light ratio within its half-light radius of just [M/L]_{half}=10.3^{+7.0}_{-6.7}, making it consistent with a simple stellar system with no appreciable dark matter component within its 1 sigma uncertainties. We suggest that the structure of the dark matter halos of these outliers have been significantly altered by tides.Comment: 41 pages, 23 figures. Accepted for publication in Ap