Crucial cross-talk of interleukin-1β and progesterone in human choriocarcinoma

Copyright @ 2012 Spandidos Publications Ltd. This article can be accessed from the links below.This article has been made available through the Brunel Open Access Publishing Fund.Choriocarcinoma is a highly malignant epithelial tumour that is most often associated with hydatidiform mole and presents the most common emergency medical problem in the management of trophoblast disease. We hypothesise that the hormones/cytokines present within the tumour microenvironment play key roles in the development of choriocarcinoma. In this study we assessed the effects of interleukin-1β (IL-1β) on cell death in the presence or absence of the sex hormone progesterone using two choriocarcinoma cell lines (BeWo and JEG-3) as in vitro experimental models. Although IL-1β induced cell death in both cell lines, the effect was more pronounced in JEG-3 cells, where cell death reached 40% compared to 15% in BeWo cells. Cell death of JEG-3 cells in response to IL-1β was significantly decreased by co-treatment with 100 nM and 1000 nM progesterone and completely abolished at a progesterone concentration of 1000 nM. Progesterone was also able to induce phosphorylation of ERK1/2 in these cells. Pretreatment of JEG-3 cells with a specific MAPK inhibitor (UO126) inhibited progesterone's inhibitory effect on cell death. Collectively, these data provide evidence of cross-talk between progesterone and IL-1β in this aggressive and poorly understood tumour that involves activation of a MAPK pathway and involvement of numerous progesterone receptors.This research was funded by a National Institutes of Health Grant ESO12961. This article is made available through the Brunel Open Access Publishing Fund

Fluctuations and oscillations in a simple epidemic model

We show that the simplest stochastic epidemiological models with spatial correlations exhibit two types of oscillatory behaviour in the endemic phase. In a large parameter range, the oscillations are due to resonant amplification of stochastic fluctuations, a general mechanism first reported for predator-prey dynamics. In a narrow range of parameters that includes many infectious diseases which confer long lasting immunity the oscillations persist for infinite populations. This effect is apparent in simulations of the stochastic process in systems of variable size, and can be understood from the phase diagram of the deterministic pair approximation equations. The two mechanisms combined play a central role in explaining the ubiquity of oscillatory behaviour in real data and in simulation results of epidemic and other related models.Comment: acknowledgments added; a typo in the discussion that follows Eq. (3) is corrected

Benevolent characteristics promote cooperative behaviour among humans

Cooperation is fundamental to the evolution of human society. We regularly observe cooperative behaviour in everyday life and in controlled experiments with anonymous people, even though standard economic models predict that they should deviate from the collective interest and act so as to maximise their own individual payoff. However, there is typically heterogeneity across subjects: some may cooperate, while others may not. Since individual factors promoting cooperation could be used by institutions to indirectly prime cooperation, this heterogeneity raises the important question of who these cooperators are. We have conducted a series of experiments to study whether benevolence, defined as a unilateral act of paying a cost to increase the welfare of someone else beyond one's own, is related to cooperation in a subsequent one-shot anonymous Prisoner's dilemma. Contrary to the predictions of the widely used inequity aversion models, we find that benevolence does exist and a large majority of people behave this way. We also find benevolence to be correlated with cooperative behaviour. Finally, we show a causal link between benevolence and cooperation: priming people to think positively about benevolent behaviour makes them significantly more cooperative than priming them to think malevolently. Thus benevolent people exist and cooperate more

If cooperation is likely punish mildly: Insights from economic experiments based on the snowdrift game

Punishment may deter antisocial behavior. Yet to punish is costly, and the costs often do not offset the gains that are due to elevated levels of cooperation. However, the effectiveness of punishment depends not only on how costly it is, but also on the circumstances defining the social dilemma. Using the snowdrift game as the basis, we have conducted a series of economic experiments to determine whether severe punishment is more effective than mild punishment. We have observed that severe punishment is not necessarily more effective, even if the cost of punishment is identical in both cases. The benefits of severe punishment become evident only under extremely adverse conditions, when to cooperate is highly improbable in the absence of sanctions. If cooperation is likely, mild punishment is not less effective and leads to higher average payoffs, and is thus the much preferred alternative. Presented results suggest that the positive effects of punishment stem not only from imposed fines, but may also have a psychological background. Small fines can do wonders in motivating us to chose cooperation over defection, but without the paralyzing effect that may be brought about by large fines. The later should be utilized only when absolutely necessary.Comment: 15 pages, 6 figures; accepted for publication in PLoS ON

Cluster approximations for infection dynamics on random networks

In this paper, we consider a simple stochastic epidemic model on large regular random graphs and the stochastic process that corresponds to this dynamics in the standard pair approximation. Using the fact that the nodes of a pair are unlikely to share neighbors, we derive the master equation for this process and obtain from the system size expansion the power spectrum of the fluctuations in the quasi-stationary state. We show that whenever the pair approximation deterministic equations give an accurate description of the behavior of the system in the thermodynamic limit, the power spectrum of the fluctuations measured in long simulations is well approximated by the analytical power spectrum. If this assumption breaks down, then the cluster approximation must be carried out beyond the level of pairs. We construct an uncorrelated triplet approximation that captures the behavior of the system in a region of parameter space where the pair approximation fails to give a good quantitative or even qualitative agreement. For these parameter values, the power spectrum of the fluctuations in finite systems can be computed analytically from the master equation of the corresponding stochastic process.Comment: the notation has been changed; Ref. [26] and a new paragraph in Section IV have been adde

Mitochondrial-nuclear epistasis affects fitness within species but does not contribute to fixed incompatibilities between species of \u3ci\u3eDrosophila\u3c/i\u3e

Efficient mitochondrial function requires physical interactions between the proteins encoded by the mitochondrial and nuclear genomes. Co-evolution between these genomes may result in the accumulation of incompatibilities between divergent lineages. We test whether mitochondrialnuclear incompatibilities have accumulated within the Drosophila melanogaster species subgroup by combining divergent mitochondrial and nuclear lineages and quantifying the effects on relative fitness. Precise placement of nine mtDNAs from D. melanogaster, D. simulans and D. mauritiana into two D. melanogaster nuclear genetic backgrounds reveals significant mitochondrial-nuclear epistasis affecting fitness in females. Combining the mitochondrial genomes with three different D. melanogaster X chromosomes reveals significant epistasis for male fitness between X-linked and mitochondrial variation. However, we find no evidence that the more than 500 fixed differences between the mitochondrial genomes of D. melanogaster and the D. simulans species complex are incompatible with the D. melanogaster nuclear genome. Rather, the interactions of largest effect occur between mitochondrial and nuclear polymorphisms that segregate within species of the D. melanogaster species subgroup. We propose that a low mitochondrial substitution rate, resulting from a low mutation rate and/or efficient purifying selection, precludes the accumulation of mitochondrial-nuclear incompatibilities among these Drosophila species

Variation in Herbivore-Mediated Indirect Effects of an Invasive Plant on a Native Plant

Theory predicts that damage by a shared herbivore to a secondary host plant species may either be higher or lower in the vicinity of a preferred host plant species. To evaluate the importance of ecological factors, such as host plant proximity and density, in determining the direction and strength of such herbivore-mediated indirect effects, we quantified oviposition by the exotic weevil Rhinocyllus conicus on the native wavyleaf thistle Cirsium undulatum in midgrass prairie on loam soils in the upper Great Plains, USA. Over three years (2001–2003), the number of eggs laid by R. conicus on C. undulatum always decreased significantly with distance (0–220 m) from a musk thistle (Carduus nutans L.) patch. Neither the level of R. conicus oviposition on C. undulatum nor the strength of the distance effect was predicted by local musk thistle patch density or by local C. undulatum density (≤ 5 m). The results suggest that high R. conicus egg loads on C. undulatum near musk thistle resulted from the native thistle’s co-occurrence with the coevolved preferred exotic host plant and not from the weevil’s response to local host plant density. Mean egg loads on C. undulatum also were greater at sites with higher R. conicus densities. We conclude that both preferred-plant proximity and shared herbivore density strongly affected the herbivore-mediated indirect interaction, suggesting that such interactions are important pathways by which invasive exotic weeds can indirectly impact native plants

Parallax of PSR J1744-1134 and the Local Interstellar Medium

We present the annual trigonometric parallax of PSR J1744-1134 derived from an analysis of pulse times of arrival. The measured parallax, pi = 2.8+/-0.3 mas ranks among the most precisely determined distances to any pulsar. The parallax distance of 357+/-39 pc is over twice that derived from the dispersion measure using the Taylor & Cordes model for the Galactic electron distribution. The mean electron density in the path to the pulsar, n_e = (0.0088 +/- 0.0009) cm^{-3}, is the lowest for any disk pulsar. We have compared the n_e for PSR J1744-1134 with those for another 11 nearby pulsars with independent distance estimates. We conclude that there is a striking asymmetry in the distribution of electrons in the local interstellar medium. The electron column densities for pulsars in the third Galactic quadrant are found to be systematically higher than for those in the first. The former correlate with the position of the well known local HI cavity in quadrant three. The excess electrons within the cavity may be in the form of HII clouds marking a region of interaction between the local hot bubble and a nearby superbubble.Comment: revised version accepted for publication in ApJ Letters; reanalysis of uncertainty in parallax measure and changes to fig