Radiation induced bystander signals are independent of DNA damage and DNA repair capacity of the irradiated cells.

Evidence is accumulating that irradiated cells produce signals, which interact with non-exposed cells in the same population. Here, we analysed the mechanism for bystander signal arising in wild-type CHO cells and repair deficient varients, focussing on the relationship between DNA repair capacity and bystander signal arising in irradiated cells. In order to investigate the bystander effect, we carried out medium transfer experiments after X-irradiation where micronuclei were scored in non-targeted DSB repair deficient xrs5 cells. When conditioned medium from irradiated cells was transferred to unirradiated xrs5 cells, the level of induction was independent of whether the medium came from irradiated wild-type, ssb or dsb repair deficient cells. This result suggests that the activation of a bystander signal is independent of the DNA repair capacity of the irradiated cells. Also, pre-treatment of the irradiated cells with 0.5% DMSO, which suppresses micronuclei induction in CHO but not in xrs5 cells, suppressed bystander effects completely in both conditioned media, suggesting that DMSO is effective for suppression of bystander signal arising independently of DNA damage in irradiated cells. Overall the work presented here adds to the understanding that it is the repair phenotype of the cells receiving bystander signals, which determines overall response rather than that of the cell producing the bystander signal.

Ca(2+) signals coordinate zygotic polarization and cell cycle progression in the brown alga Fucus serratus

Zygotes of the fucoid brown algae provide excellent models for addressing fundamental questions about zygotic symmetry breaking. Although the acquisition of polarity is tightly coordinated with the timing and orientation of the first asymmetric division-with zygotes having to pass through a G1/S-phase checkpoint before the polarization axis can be fixed -the mechanisms behind the interdependence of polarization and cell cycle progression remain unclear. In this study, we combine in vivo Ca(2+) imaging, single cell monitoring of S-phase progression and multivariate analysis of high-throughput intracellular Ca(2+) buffer loading to demonstrate that Ca(2+) signals coordinate polarization and cell cycle progression in the Fucus serratus zygote. Consistent with earlier studies on this organism, and in contrast to animal models, we observe no fast Ca(2+) wave following fertilization. Rather, we show distinct slow localized Ca(2+) elevations associated with both fertilization and S-phase progression, and we show that both S-phase and zygotic polarization are dependent on pre-S-phase Ca(2+) increases. Surprisingly, this Ca(2+) requirement cannot be explained by co-dependence on a single G1/ S-phase checkpoint, as S phase and zygotic polarization are differentially sensitive to pre-S-phase Ca(2+) elevations and can be uncoupled. Furthermore, subsequent cell cycle progression through M phase is independent of localized actin polymerization and zygotic polarization. This absence of a morphogenesis checkpoint, together with the observed Ca(2+)dependences of S phase and polarization, show that the regulation of zygotic division in the brown algae differs from that in other eukaryotic model systems, such as yeast and Drosophila.

Vitamin D Receptor Modulates the Neoplastic Phenotype Through Antagonistic Growth Regulatory Signals

Vitamin D receptor (VDR) can modulate functionally antagonistic growth regulatory pathways, involving beta-catenin/E-cadherin on one hand and osteopontin (OPN) on the other. This study investigates effects of VDR ligand treatment on the balance of these discordant signals and on associated cell behavior. Treatment of Rama 37 or SW480 cells by 1 alpha,25-(OH)(2) D-3 or analogs suppressed beta-catenin/Lef-1/Tcf signaling and upregulated E-cadherin, consistent with a cancer-inhibitory action. Conversely, treatment also increased transcription of OPN that may be implicated in tumor progression. Molecular crosstalk was observed between the antagonistic VDR-dependent signals, in that beta-catenin/Lef-1/Tcf molecules modulated VDR activation of OPN. Treatment effects on cell growth were related to a constitutive balance of OPN and E-cadherin expression. No growth effects were observed in Rama 37 cells that have low OPN and high E-cadherin expression. Conversely, treatment of Rama 37 stably transfected subclones that had high OPN and/or low level E-cadherin induced small but significant increases of cell attachment to fibronectin, anchorage-independent growth or invasion. This study shows that relative expression levels of key VDR downstream genes may influence growth regulation by 1 alpha,25-(OH)(2) D-3 or analogs. These findings may be relevant to the cell- or tissue-specificity of vitamin D growth regulation. (C) 2009 Wiley-Liss, Inc.

Motivation matters: cheliped extension displays in the hermit crab, Pagurus bernhardus, are honest signals of hunger

Whether animal signals convey honest information is a central evolutionary question, since selection pressures could, in some circumstances, favour dishonesty. A prior study of signalling in hermit crabs proposed that the cheliped extension display of Pagurus bernhardus might represent such an instance of dishonesty. A limitation of this conclusion, however, was that honesty was defined in the context of size assessment, neglecting the potential information that displays might transmit about signallers' variable internal states. Recent analyses of signalling in this same species have shown that its displays provide reliable information about the amount of risk crabs are prepared to tolerate, which therefore might enable signallers to use these displays to honestly convey their motivation to take such risks. Here we test this 'honest advertisement of motivation' hypothesis by varying crabs' need for food and analysing their signalling during simulated feeding conflicts against a model. When crabs were starved for 1-5 days, they dropped significantly in weight. Despite this decrement in resource-holding potential and energy reserves, crabs were more likely to perform cheliped extension displays the longer they were food deprived. Longer-starved crabs, whose subjective resource value was greater, also displayed at a higher rate and were more likely to risk seizing the food from the model. We conclude that cheliped extension is a reliable indicator of crabs' internal state and suggest how this honest signal might operate in conflicts over a variety of other resources in addition to food. We propose that future studies detecting apparent dishonesty should analyse many possible signal-state correlations before concluding a signal is actually dishonest. (c) 2008 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Signals of need in a cooperatively breeding mammal with mobile offspring

In many bird species with biparental care for young in the nest, hungry chicks beg repeatedly and parents adjust their feeding rate to the call rate of young. Repetitive calling also occurs in fledglings and in some mammals where offspring follow provisioners. It is not yet clear whether, in mobile systems with dispersed young where adults cannot compare the vocal behaviour of all young simultaneously, the calls represent a signal of need. We investigated repetitive begging by cooperatively reared meerkat, Suricata suricatta, pups that foraged with the group. Pups produced two types of begging calls: repeat calls over long periods and high-pitched calls mainly confined to feeding events. Food-deprived pups stayed closer to feeders, and begged for longer and more intensely by calling at a higher rate. Hungry pups increased both the rate of repeat calls, which were given continually, and the number of high-pitched bouts, but adults increased their food allocation only in relation to the rate of repeat calls. Our study indicates that hunger may lead to several changes in vocal behaviour, only some of which may be used by adults to assess need.