Observational constraints on annihilation sites in 1E 1740.7-2942 and Nova Muscae

The region of the Galactic center contains several sources which demonstrate their activity at various wavelengths and particularly above several hundred keV. Escape of positrons from such a source or several sources into the interstellar medium, where they slow down and annihilate, can account for the 511 keV narrow line observed from this direction. 1E 1740.7-2942 object has been proposed as the most likely candidate to be responsible for this variable source of positrons. Besides, Nova Muscae shows a spectrum which is consistent with Comptonization by a thermal plasma kT<100 keV in its hard X-ray part, while a relatively narrow annihilation line observed by SIGMA on January 20-21, 1991 implies that positrons annihilate in a much colder medium. We estimate the electron number density and the size of the emitting regions suggesting that annihilation features observed by SIGMA from Nova Muscae and 1E 1740.7-2942 are due to the positron slowing down and annihilation in thermal plasma. We show that in the case of Nova Muscae the observed radiation is coming from a pair plasma stream, N(e+)~N(e-), rather than from a gas cloud. We argue that two models are probably relevant to the 1E source: annihilation in (hydrogen) plasma N(e+)<~N(e-) at rest, and annihilation in the pair plasma stream, which involves matter from the source environment.Comment: 5 pages including 2 figures, latex, aipproc.sty, aipproc.cls, epsfig.sty. To be published in Proc. of 4th Compton Symp., 1997 (27-30 April, Williamsburg, Virginia

Propagation of chaos for rank-based interacting diffusions and long time behaviour of a scalar quasilinear parabolic equation

We study a quasilinear parabolic Cauchy problem with a cumulative distribution function on the real line as an initial condition. We call 'probabilistic solution' a weak solution which remains a cumulative distribution function at all times. We prove the uniqueness of such a solution and we deduce the existence from a propagation of chaos result on a system of scalar diffusion processes, the interactions of which only depend on their ranking. We then investigate the long time behaviour of the solution. Using a probabilistic argument and under weak assumptions, we show that the flow of the Wasserstein distance between two solutions is contractive. Under more stringent conditions ensuring the regularity of the probabilistic solutions, we finally derive an explicit formula for the time derivative of the flow and we deduce the convergence of solutions to equilibrium.Comment: Stochastic partial differential equations: analysis and computations (2013) http://dx.doi.org/10.1007/s40072-013-0014-

Fission yeast sec3 bridges the exocyst complex to the actin cytoskeleton.

The exocyst complex tethers post-Golgi secretory vesicles to the plasma membrane prior to docking and fusion. In this study, we identify Sec3, the missing component of the Schizosaccharomyces pombe exocyst complex (SpSec3). SpSec3 shares many properties with its orthologs, and its mutants are rescued by human Sec3/EXOC1. Although involved in exocytosis, SpSec3 does not appear to mark the site of exocyst complex assembly at the plasma membrane. It does, however, mark the sites of actin cytoskeleton recruitment and controls the organization of all three yeast actin structures: the actin cables, endocytic actin patches and actomyosin ring. Specifically, SpSec3 physically interacts with For3 and sec3 mutants have no actin cables as a result of a failure to polarize this nucleating formin. SpSec3 also interacts with actin patch components and sec3 mutants have depolarized actin patches of reduced endocytic capacity. Finally, the constriction and disassembly of the cytokinetic actomyosin ring is compromised in these sec3 mutant cells. We propose that a role of SpSec3 is to spatially couple actin machineries and their independently polarized regulators. As a consequence of its dual role in secretion and actin organization, Sec3 appears as a major co-ordinator of cell morphology in fission yeast.This work was supported by Cancer Research UK (T. T.)

Fission yeast Nod1 is a component of cortical nodes involved in cell size control and division site placement.

Most cells enter mitosis once they have reached a defined size. In the fission yeast Schizosaccharomyces pombe, mitotic entry is orchestrated by a geometry-sensing mechanism that involves the Cdk1/Cdc2-inhibiting Wee1 kinase. The factors upstream of Wee1 gather together in interphase to form a characteristic medial and cortical belt of nodes. Nodes are also considered to be precursors of the cytokinesis contractile actomyosin ring (CAR). Here we describe a new component of the interphase nodes and cytokinesis rings, which we named Nod1. Consistent with its role in cell size control at division, nod1Δ cells were elongated and epistatic with regulators of Wee1. Through biochemical and localisation studies, we placed Nod1 in a complex with the Rho-guanine nucleotide exchange factor Gef2. Nod1 and Gef2 mutually recruited each other in nodes and Nod1 also assembles Gef2 in rings. Like gef2Δ, nod1Δ cells showed a mild displacement of their division plane and this phenotype was severely exacerbated when the parallel Polo kinase pathway was also compromised. We conclude that Nod1 specifies the division site by localising Gef2 to the mitotic cell middle. Previous work showed that Gef2 in turn anchors factors that control the spatio-temporal recruitment of the actin nucleation machinery. It is believed that the actin filaments originated from the nodes pull nodes together into a single contractile ring. Surprisingly however, we found that node proteins could form pre-ring helical filaments in a cdc12-112 mutant in which nucleation of the actin ring is impaired. Furthermore, the deletion of either nod1 or gef2 created an un-expected situation where different ring components were recruited sequentially rather than simultaneously. At later stages of cytokinesis, these various rings appeared inter-fitted rather than merged. This study brings a new slant to the understanding of CAR assembly and function.This work was supported by a Core grant from Cancer Research UK (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Exocyst Complex in Health and Disease

Exocytosis involves the fusion of intracellular secretory vesicles with the plasma membrane, thereby delivering integral membrane proteins to the cell surface and releasing material into the extracellular space. Importantly, exocytosis also provides a source of lipid moieties for membrane extension. The tethering of the secretory vesicle before docking and fusion with the plasma membrane is mediated by the exocyst complex, an evolutionary conserved octameric complex of proteins. Recent findings indicate that the exocyst complex also takes part in other intra-cellular processes besides secretion. These various functions seem to converge toward defining a direction of membrane growth in a range of systems from fungi to plants and from neurons to cilia. In this review we summarize the current knowledge of exocyst function in cell polarity, signaling and cell-cell communication and discuss implications for plant and animal health and disease

L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade.

Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade