cAMP-Inhibits Cytoplasmic Phospholipase A(2) and Protects Neurons against Amyloid-beta-Induced Synapse Damage

A key event in Alzheimer’s disease (AD) is the production of amyloid-β (Aβ) peptides and the loss of synapses. In cultured neurons Aβ triggered synapse damage as measured by the loss of synaptic proteins. α-synuclein (αSN), aggregates of which accumulate in Parkinson’s disease, also caused synapse damage. Synapse damage was associated with activation of cytoplasmic phospholipase A2 (cPLA2), an enzyme that regulates synapse function and structure, and the production of prostaglandin (PG) E2. In synaptosomes PGE2 increased concentrations of cyclic adenosine monophosphate (cAMP) which suppressed the activation of cPLA2 demonstrating an inhibitory feedback system. Thus, Aβ/αSN-induced activated cPLA2 produces PGE2 which increases cAMP which in turn suppresses cPLA2 and, hence, its own production. Neurons pre-treated with pentoxifylline and caffeine (broad spectrum phosphodiesterase (PDE) inhibitors) or the PDE4 specific inhibitor rolipram significantly increased the Aβ/αSN-induced increase in cAMP and consequently protected neurons against synapse damage. The addition of cAMP analogues also inhibited cPLA2 and protected neurons against synapse damage. These results suggest that drugs that inhibit Aβ-induced activation of cPLA2 and cross the blood–brain barrier may reduce synapse damage in AD

Collapse of a Molecular Cloud Core to Stellar Densities: The First Three-Dimensional Calculations

We present results from the first three-dimensional calculations ever to follow the collapse of a molecular cloud core (~ 10^{-18} g cm^{-3}) to stellar densities (> 0.01 g cm^{-3}). The calculations resolve structures over 7 orders of magnitude in spatial extent (~ 5000 AU - 0.1 R_\odot), and over 17 orders of magnitude in density contrast. With these calculations, we consider whether fragmentation to form a close binary stellar system can occur during the second collapse phase. We find that, if the quasistatic core that forms before the second collapse phase is dynamically unstable to the growth of non-axisymmetric perturbations, the angular momentum extracted from the central regions of the core, via gravitational torques, is sufficient to prevent fragmentation and the formation of a close binary during the subsequent second collapse.Comment: ApJ Letters, in press (will appear in Nov 20 issue; available from the ApJ Rapid Release web page). 7 pages, incl. 5 figures. Also available at http://www.mpia-hd.mpg.de/theory/bat

The Origin of the Initial Mass Function and Its Dependence on the Mean Jeans Mass in Molecular Clouds

We investigate the dependence of stellar properties on the mean thermal Jeans mass in molecular clouds. We compare the results from the two largest hydrodynamical simulations of star formation to resolve the fragmentation process down to the opacity limit, the first of which was reported by Bate, Bonnell & Bromm. The initial conditions of the two calculations are identical except for the radii of the clouds, which are chosen so that the mean densities and mean thermal Jeans masses of the clouds differ by factors of nine and three, respectively. We find that the denser cloud, with the lower mean thermal Jeans mass, produces a higher proportion of brown dwarfs and has a lower characteristic (median) mass of the stars and brown dwarfs. This dependence of the initial mass function (IMF) on the density of the cloud may explain the observation that the Taurus star-forming region appears to be deficient in brown dwarfs when compared with the Orion Trapezium cluster. The new calculation also produces wide binaries (separations >20 AU), one of which is a wide binary brown dwarf system. Based on the hydrodynamical calculations, we develop a simple accretion/ejection model for the origin of the IMF. In the model, all stars and brown dwarfs begin with the same mass (set by the opacity limit for fragmentation) and grow in mass until their accretion is terminated stochastically by their ejection from the cloud through dynamically interactions. The model predicts that the main variation of the IMF in different star-forming environments should be in the location of the peak (due to variations in the mean thermal Jeans mass of the cloud) and in the substellar regime. However, the slope of the IMF at high-masses may depend on the dispersion in the accretion rates of protostars.Comment: 22 pages, 14 figures, accepted for publication in MNRAS. Paper with high-resolution figures and animations available from http://www.astro.ex.ac.uk/people/mbate/ Replacement removes inconsistent definitions of base 10 logarithm

The Formation Mechanism of Brown Dwarfs

We present results from the first hydrodynamical star formation calculation to demonstrate that brown dwarfs are a natural and frequent product of the collapse and fragmentation of a turbulent molecular cloud. The brown dwarfs form via the fragmentation of dense molecular gas in unstable multiple systems and are ejected from the dense gas before they have been able to accrete to stellar masses. Thus, they can be viewed as `failed stars'. Approximately three quarters of the brown dwarfs form in gravitationally-unstable circumstellar discs while the remainder form in collapsing filaments of molecular gas. These formation mechanisms are very efficient, producing roughly the same number of brown dwarfs as stars, in agreement with recent observations. However, because close dynamical interactions are involved in their formation, we find a very low frequency of binary brown dwarf systems (\lsim 5%) and that those binary brown dwarf systems that do exist must be close \lsim 10 AU. Similarly, we find that young brown dwarfs with large circumstellar discs (radii \gsim 10 AU) are rare ($\approx 5$%).Comment: 5 pages, 2 GIF figures, postscript with figures available at http://www.astro.ex.ac.uk/people/mbat

The Formation of Close Binary Systems by Dynamical Interactions and Orbital Decay

We present results from the first hydrodynamical star formation calculation to demonstrate that close binary stellar systems (separations \lsim 10 AU) need not be formed directly by fragmentation. Instead, a high frequency of close binaries can be produced through a combination of dynamical interactions in unstable multiple systems and the orbital decay of initially wider binaries. Orbital decay may occur due to gas accretion and/or the interaction of a binary with its circumbinary disc. These three mechanisms avoid the problems associated with the fragmentation of optically-thick gas to form close systems directly. They also result in a preference for close binaries to have roughly equal-mass components because dynamical exchange interactions and the accretion of gas with high specific angular momentum drive mass ratios towards unity. Furthermore, due to the importance of dynamical interactions, we find that stars with greater masses ought to have a higher frequency of close companions, and that many close binaries ought to have wide companions. These properties are in good agreement with the results of observational surveys.Comment: Published in MNRAS, 10 pages, 6 figures (5 degraded). Paper with high-resolution figures and animations available from http://www.astro.ex.ac.uk/people/mbat

Modelling circumstellar discs with 3D radiation hydrodynamics

We present results from combining a grid-based radiative transfer code with a Smoothed Particle Hydrodynamics code to produce a flexible system for modelling radiation hydrodynamics. We use a benchmark model of a circumstellar disc to determine a robust method for constructing a gridded density distribution from SPH particles. The benchmark disc is then used to determine the accuracy of the radiative transfer results. We find that the SED and the temperature distribution within the disc are sensitive to the representation of the disc inner edge, which depends critically on both the grid and SPH resolution. The code is then used to model a circumstellar disc around a T-Tauri star. As the disc adjusts towards equilibrium vertical motions in the disc are induced resulting in scale height enhancements which intercept radiation from the central star. Vertical transport of radiation enables these perturbations to influence the mid-plane temperature of the disc. The vertical motions decay over time and the disc ultimately reaches a state of simultaneous hydrostatic and radiative equilibrium.Comment: MNRAS accepted; 15 pages; 17 figures, 4 in colou

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

The formation of close binary systems

A viable solution to the origin of close binary systems, unaccounted for in recent theories, is presented. Fragmentation, occurring at the end of the secondary collapse phase (during which molecular hydrogen is dissociating), can form binary systems with separations less than 1 au. Two fragmentation modes are found to occur after the collapse is halted. The first consists of the fragmentation of a protostellar disc due to rotational instabilities in a protostellar core, involving both an $m=1$ and an $m=2$ mode. This fragmentation mechanism is found to be insensitive to the initial density distribution: it can occur in both centrally condensed and uniform initial conditions. The second fragmentation mode involves the formation of a rapidly rotating core at the end of the collapse phase which is unstable to the axisymmetric perturbations. This core bounces into a ring which quickly fragments into several components. The binary systems thus formed contain less than 1 per cent of a solar mass and therefore will need to accrete most of their final mass if they are to form a binary star system. Their orbital properties will thus be determined by the properties of the accreted matter.Comment: 6 pages, uuencoded compressed postscript file (containing 2 figures

The efficiency of star formation in clustered and distributed regions

We investigate the formation of both clustered and distributed populations of young stars in a single molecular cloud. We present a numerical simulation of a 10,000 solar mass elongated, turbulent, molecular cloud and the formation of over 2500 stars. The stars form both in stellar clusters and in a distributed mode which is determined by the local gravitational binding of the cloud. A density gradient along the major axis of the cloud produces bound regions that form stellar clusters and unbound regions that form a more distributed population. The initial mass function also depends on the local gravitational binding of the cloud with bound regions forming full IMFs whereas in the unbound, distributed regions the stellar masses cluster around the local Jeans mass and lack both the high-mass and the low-mass stars. The overall efficiency of star formation is ~ 15 % in the cloud when the calculation is terminated, but varies from less than 1 % in the the regions of distributed star formation to ~ 40 % in regions containing large stellar clusters. Considering that large scale surveys are likely to catch clouds at all evolutionary stages, estimates of the (time-averaged) star formation efficiency for the giant molecular cloud reported here is only ~ 4 %. This would lead to the erroneous conclusion of 'slow' star formation when in fact it is occurring on a dynamical timescale.Comment: 9 pages, 8 figures, MNRAS in pres