Desynchronization of cells on the developmental path triggers the formation of spiral waves of cAMP during Dictyostelium aggregation

Whereas it is relatively easy to account for the formation of concentric (target) waves of cAMP in the course of Dictyostelium discoideum aggregation after starvation, the origin of spiral waves remains obscure. We investigate a physiologically plausible mechanism for the spontaneous formation of spiral waves of cAMP in D. discoideum. The scenario relies on the developmental path associated with the continuous changes in the activity of enzymes such as adenylate cyclase and phosphodiesterase observed during the hours that follow starvation. These changes bring the cells successively from a nonexcitable state to an excitable state in which they relay suprathreshold cAMP pulses, and then to autonomous oscillations of cAMP, before the system returns to an excitable state. By analyzing a model for cAMP signaling based on receptor desensitization, we show that the desynchronization of cells on this developmental path triggers the formation of fully developed spirals of cAMP. Developmental paths that do not correspond to the sequence of dynamic transitions no relay-relay-oscillations-relay are less able or fail to give rise to the formation of spirals.

Selection for spiral waves in the social amoebae Dictyostelium

Starving Dictyostelium amoebae emit pulses of the chemoattractant cAMP that are relayed from cell to cell as circular and spiral waves. We have recently modeled spiral wave formation in Dictyostelium. Our model suggests that a secreted protein inhibitor of an extracellular cAMP phosphodiesterase selects for spirals. Herein we test the essential features of this prediction by comparing wave propagation in wild type and inhibitor mutants. We find that mutants rarely form spirals. The territory size of mutant strains is approximately 50 times smaller than wild type, and the mature fruiting bodies are smaller but otherwise normal. These results identify a mechanism for selecting one wave symmetry over another in an excitable system and suggest that the phosphodiesterase inhibitor may be under selection because it helps regulate territory size.

Positive genetic feedback governs cAMP spiral wave formation in Dictyostelium.

The aggregation stage of the life cycle of Dictyostelium discoideum is governed by the chemotactic response of individual amoebae to excitable waves of cAMP. We modeled this process through a recently introduced hybrid automata-continuum scheme and used computer simulation to unravel the role of specific components of this complex developmental process. Our results indicated an essential role for positive feedback between the cAMP signaling and the expression of the genes encoding the signal transduction and response machinery.

The nuclear region of the spiral galaxy M81.

Very-long-baseline radio interferometry images of the nuclear region of the nearby spiral galaxy M81 reveal the most compact galactic core outside the Galaxy of which the size has been determined: 700 x 300 astronomical units (AU). The observations exclude a starburst or supernova interpretation for the core. Instead they favor an active galactic nucleus. There is evidence for a northeastern jet bent by approximately 35 degrees over a length scale from 700 to 4000 AU. The jet is, on average, directed toward an extended emission region, probably a radio lobe, about 1 kiloparsec (kpc) away from the core. A corresponding emission region was found in the southwest at a distance of only 30 pc from the core. The observed jet is extremely stable and likely to be associated with a steady-state channel. There is no detectable motion along the jet beyond the nominal value of -60 +/- 60 km.s-1. The level of activities in the core region of M81 is intermediate between that of SgrA* and that of powerful radio galaxies and quasars.

CT-2576, an inhibitor of phospholipid signaling, suppresses constitutive and induced expression of human immunodeficiency virus.

Viruses such as human immunodeficiency virus (HIV) require cellular activation for expression. Cellular activation in lymphoid cells is associated with augmented accumulation of certain phosphatidic acid (PA) species derived from the hydrolysis of glycan phosphatidylinositol (GPI). This suggests that activation of a phospholipid pathway may play a role in initiation of viral replication. To test this hypothesis, we examined the effect of tat gene expression on the production of cellular PA species, as the Tat protein is essential for HIV expression and has been implicated in activating the expression of multiple host cellular genes. Expression of tat increased the expression of PA. We then tested whether synthetic inhibitors of PA metabolism would inhibit activation of the HIV long terminal repeat by Tat and tumor necrosis factor alpha (TNF-alpha). CT-2576 suppressed both PA generation induced by Tat and HIV long terminal repeat-directed gene expression in response to Tat or TNF-alpha at a posttranscriptional step. CT-2576 also inhibited constitutive as well as TNF-alpha- and interleukin 6-induced expression of HIV p24 antigen in chronically infected U1 cells and in peripheral blood lymphocytes acutely infected with a clinical isolate of HIV. Pharmacological inhibition of synthesis of selected PA species may therefore provide a therapeutic approach to suppression of HIV replication.