When does cyclic dominance lead to stable spiral waves?

Species diversity in ecosystems is often accompanied by characteristic spatio-temporal patterns. Here, we consider a generic two-dimensional population model and study the spiraling patterns arising from the combined effects of cyclic dominance of three species, mutation, pair-exchange and individual hopping. The dynamics is characterized by nonlinear mobility and a Hopf bifurcation around which the system's four-phase state diagram is inferred from a complex Ginzburg-Landau equation derived using a perturbative multiscale expansion. While the dynamics is generally characterized by spiraling patterns, we show that spiral waves are stable in only one of the four phases. Furthermore, we characterize a phase where nonlinearity leads to the annihilation of spirals and to the spatially uniform dominance of each species in turn. Away from the Hopf bifurcation, when the coexistence fixed point is unstable, the spiraling patterns are also affected by the nonlinear diffusion

Patterns of cell death, apoptosis and necrosis and the question of recovery in light induced retinal degeneration in the rat

The purpose of this study was to investigate the early structural changes and the pattern of recovery in the rat retina after light damage. Methods: Albino rats were dark adapted for 36 hours. The control animals were sacrificed at the end of the dark adaptation period. The experimental animals were exposed for 2 hours to 1000 lux of white light, divided into 5 groups and killed at the following intervals: at the end of light exposure (0), 24, 48, 72 and 144 hours later. The right eyes were fixed in glutaraldehyde and processed for light and electron microscopy. The left eyes were processed for agarose gel electrophoresis of extracted retinal DNA to examine the pattern of DNA fragmentation occurring in various types of cell death. Results: Irreversible photoreceptor damage, observed after two hours of light exposure was observed in the lower temporal retina. It was characterized by condensation of cytoplasm, densification of outer segments and inner segments, including synapses, and pyknosis of the photoreceptor nuclei. Mitochondria, cilia and intracellular organelles and the arrangement of rod outer segment disks were, however, well preserved. Extensive auto and heterophagy (Muller cells) was observed but there was no inflammation. These changes were consistent with programmed cell death (apoptosis), which was confirmed by agarose gel electrophoresis showing a ladder formation characteristic for apoptosis up to 48 hours after light damage. Within 24 hours numerous photoreceptors showed, however, swelling and lysis of the inner segments, changes consistent with necrosis. Within a week chorioretinal adhesion was formed. Cell death in the retinal pigment epithelium was observed 24 hours after light exposure. The loss of the retinal pigment epithelium was followed by a breakdown of the blood retinal barrier resulting in serous retinal detachments and microcystic retinal oedema at its maximum 48 hours after exposure. Proliferation of cells in the inner nuclear layer was noted and an influx of macrophages, but no other inflammatory cells, was most pronounced between 48 and 72 hours after light damage. Lower nasal retina which primarily showed vesicular alterations of the rod outer segments as an acute response recovered normal morphology within one week. Conclusion: Diffuse white light can trigger regional retinal degeneration in a rat. Apoptosis of photoreceptors is an immediate retinal response to toxic light levels in albino rat retinae undergoing degeneration. Necrosis which was also recorded may be secondary in nature. In contrast, morphological recovery is observed in the regions in which vesicular alterations of disk membranes of photoreceptor outer segments were predominant. Such changes may signify disfunction of outer segment membranes and are enhanced by glutaraldehyde fixation

The favorable kinetics and balance of nebivolol-stimulated nitric oxide and peroxynitrite release in human endothelial cells

Background: Nebivolol is a third-generation beta-blocker used to treat hypertension. The vasodilation properties of nebivolol have been attributed to nitric oxide (NO) release. However, the kinetics and mechanism of nebivolol-stimulated bioavailable NO are not fully understood. Methods: Using amperometric NO and peroxynitrite (ONOO-) nanosensors, β3-receptor (agonist: L-755,507; antagonists: SR59230A and L-748,337), ATP efflux (the mechanosensitive ATP channel blocker, gadolinium) and P2Y-receptor (agonists: ATP and 2-MeSATP; antagonist: suramin) modulators, superoxide dismutase and a NADPH oxidase inhibitor (VAS2870), we evaluated the kinetics and balance of NO and ONOO- stimulated by nebivolol in human umbilical vein endothelial cells (HUVECs). NO and ONOO- were measured with nanosensors (diameter ~ 300 nm) placed 5 ± 2 μm from the cell membrane and ATP levels were determined with a bioluminescent method. The kinetics and balance of nebivolol-stimulated NO and ONOO- were compared with those of ATP, 2-MeSATP, and L-755,507. Results: Nebivolol stimulates endothelial NO release through β3-receptor and ATP-dependent, P2Y-receptor activation with relatively slow kinetics (75 ± 5 nM/s) as compared to the kinetics of ATP (194 ± 10 nM/s), L-755,507 (108 ± 6 nM/s), and 2-MeSATP (105 ± 5 nM/s). The balance between cytoprotective NO and cytotoxic ONOO- was expressed as the ratio of [NO]/[ONOO-] concentrations. This ratio for nebivolol was 1.80 ± 0.10 and significantly higher than that for ATP (0.80 ± 0.08), L-755,507 (1.08 ± 0.08), and 2-MeSATP (1.09 ± 0.09). Nebivolol induced ATP release in a concentration-dependent manner. Conclusion: The two major pathways (ATP efflux/P2Y receptors and β3 receptors) and several steps of nebivolol-induced NO and ONOO- stimulation are mainly responsible for the slow kinetics of NO release and low ONOO-. The net effect of this slow kinetics of NO is reflected by a favorable high ratio of [NO]/[ONOO-] which may explain the beneficial effects of nebivolol in the treatment of endothelial dysfunction, hypertension, heart failure, and angiogenesis

Plasmodium falciparum translational machinery condones polyadenosine repeats

Plasmodium falciparum is a causative agent of human malaria. Sixty percent of mRNAs from its extremely AT-rich (81%) genome harbor long polyadenosine (polyA) runs within their ORFs, distinguishing the parasite from its hosts and other sequenced organisms. Recent studies indicate polyA runs cause ribosome stalling and frameshifting, triggering mRNA surveillance pathways and attenuating protein synthesis. Here, we show that P. falciparum is an exception to this rule. We demonstrate that both endogenous genes and reporter sequences containing long polyA runs are efficiently and accurately translated in P. falciparum cells. We show that polyA runs do not elicit any response from No Go Decay (NGD) or result in the production of frameshifted proteins. This is in stark contrast to what we observe in human cells or T. thermophila, an organism with similar AT-content. Finally, using stalling reporters we show that Plasmodium cells evolved not to have a fully functional NGD pathway

Two novel C-terminal frameshift mutations in the β-globin gene lead to rapid mRNA decay

BACKGROUND: The thalassemia syndromes are classified according to the globin chain or chains whose production is affected. β-thalassemias are caused by point mutations or, more rarely, deletions or insertions of a few nucleotides in the β-globin gene or its immediate flanking sequences. These mutations interfere with the gene function either at the transcriptional, translational or posttranslational level. METHODS: Two cases of Polish patients with hereditary hemolytic anemia suspected of thalassemia were studied. DNA sequencing and mRNA quantification were performed. Stable human cell lines which express wild-type HBB and mutated versions were used to verify that detected mutation are responsible for mRNA degradation. RESULTS: We identified two different frameshift mutations positioned in the third exon of HBB. Both patients harboring these mutations present the clinical phenotype of thalassemia intermedia and showed dominant pattern of inheritance. In both cases the mutations do not generate premature stop codon. Instead, slightly longer protein with unnatural C-terminus could be produced. Interestingly, although detected mutations are not expected to induce NMD, the mutant version of mRNA is not detectable. Restoring of the open reading frame brought back the RNA to that of the wild-type level. CONCLUSION: Our results show that a lack of natural stop codon due to the frameshift in exon 3 of β-globin gene causes rapid degradation of its mRNA and indicate existence of novel surveillance pathway

Hox-controlled reorganisation of intrasegmental patterning cues underlies Drosophila posterior spiracle organogenesis

10 páginas, 8 figuras. Material complementario del artículo esta disponible en http://dev.biologists.org/cgi/content/full/132/13/3093/DC1Hox proteins provide axial positional information and control segment morphology in development and evolution. Yet how they specify morphological traits that confer segment identity and how axial positional information interferes with intrasegmental patterning cues during organogenesis remain poorly understood. We have investigated the control of Drosophila posterior spiracle morphogenesis, a segment-specific structure that forms under Abdominal-B (AbdB) Hox control in the eighth abdominal segment (A8). We show that the Hedgehog (Hh), Wingless (Wg) and Epidermal Growth Factor Receptor (Egfr) pathways provide specific inputs for posterior spiracle morphogenesis and act in a genetic network made of multiple and rapidly evolving Hox/signalling interplays. A major function of AbdB during posterior spiracle organogenesis is to reset A8 intrasegmental patterning cues, first by reshaping wg and rhomboid expression patterns, then by reallocating the Hh signal and later by initiating de novo expression of the posterior compartment gene engrailed in anterior compartment cells. These changes in expression patterns confer axial specificity to otherwise reiteratively used segmental patterning cues, linking intrasegmental polarity and acquisition of segment identity.This work was supported by the `Centre National de la Recherche Scientifique' (CNRS), grants from `la Ligue Nationale Contre Le Cancer (équipe labellisée La Ligue)', `l'Association pour la Recherche contre le Cancer' (ARC), The Royal Society, The Welcome Trust, the `Minesterio de education y ciencia (BFU 2004 0 96) and ARC and EMBO long term fellowships to S. Merabet.Peer reviewe

Spirals and heteroclinic cycles in a spatially extended Rock-Paper-Scissors model of cyclic dominance

Spatially extended versions of the cyclic-dominance Rock-Paper-Scissors model have traveling wave (in one dimension) and spiral (in two dimensions) behaviour. The far field of the spirals behave like traveling waves, which themselves have profiles reminiscent of heteroclinic cycles. We compute numerically a nonlinear dispersion relation between the wavelength and wavespeed of the traveling waves, and, together with insight from heteroclinic bifurcation theory and further numerical results from 2D simulations, we are able to make predictions about the overall structure and stability of spiral waves in 2D cyclic dominance models

Characterization of spiraling patterns in spatial rock-paper-scissors games

The spatiotemporal arrangement of interacting populations often influences the maintenance of species diversity and is a subject of intense research. Here, we study the spatiotemporal patterns arising from the cyclic competition between three species in two dimensions. Inspired by recent experiments, we consider a generic metapopulation model comprising “rock-paper-scissors” interactions via dominance removal and replacement, reproduction, mutations, pair exchange, and hopping of individuals. By combining analytical and numerical methods, we obtain the model's phase diagram near its Hopf bifurcation and quantitatively characterize the properties of the spiraling patterns arising in each phase. The phases characterizing the cyclic competition away from the Hopf bifurcation (at low mutation rate) are also investigated. Our analytical approach relies on the careful analysis of the properties of the complex Ginzburg-Landau equation derived through a controlled (perturbative) multiscale expansion around the model's Hopf bifurcation. Our results allow us to clarify when spatial “rock-paper-scissors” competition leads to stable spiral waves and under which circumstances they are influenced by nonlinear mobility

Production and characterization of recombinant protein preparations of Endonuclease G-homologs from yeast, C. elegans and humans

Nuc1p, CPS-6, EndoG and EXOG are evolutionary conserved mitochondrial nucleases from yeast, Caenorhabditis elegans and humans, respectively. These enzymes play an important role in programmed cell death as well as mitochondrial DNA-repair and recombination. Whereas a significant interest has been given to the cell biology of these proteins, in particular their recruitment during caspase-independent apoptosis, determination of their biochemical properties has lagged behind. In part, biochemical as well as structural analysis of mitochondrial nucleases has been hampered by the fact that upon cloning and overexpression in Escherichia coli these enzymes can exert considerable toxicity and tend to aggregate and form inclusion bodies. We have, therefore, established a uniform E. coli expression system allowing us to obtain these four evolutionary related nucleases in active form from the soluble as well as insoluble fractions of E. coli cell lysates. Using preparations of recombinant Nuc1p, CPS-6, EndoG and EXOG we have compared biochemical properties and the substrate specificities of these related nucleases on selected substrates in parallel. Whereas Nuc1p and EXOG in addition to their endonuclease activity exert 5'-3'- exonuclease activity, CPS-6 and EndoG predominantly are endonucleases. These findings allow speculating that the mechanisms of action of these related nucleases in cell death as well as DNA-repair and recombination differ according to their enzyme activities and substrate specificities. © 2010 Elsevier Inc. All rights reserved

Effects of noise on convergent game learning dynamics

We study stochastic effects on the lagging anchor dynamics, a reinforcement learning algorithm used to learn successful strategies in iterated games, which is known to converge to Nash points in the absence of noise. The dynamics is stochastic when players only have limited information about their opponents' strategic propensities. The effects of this noise are studied analytically in the case where it is small but finite, and we show that the statistics and correlation properties of fluctuations can be computed to a high accuracy. We find that the system can exhibit quasicycles, driven by intrinsic noise. If players are asymmetric and use different parameters for their learning, a net payoff advantage can be achieved due to these stochastic oscillations around the deterministic equilibrium.Comment: 17 pages, 8 figure