Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain

<p>Abstract</p> <p>Background</p> <p>Mechanisms driving cancer-induced bone pain are poorly understood. A central factor implicated to be a key player in the process of tumorigenesis, osteoclastogenesis and nociception is p38 MAPK. We determined the role of p38 MAPK in a mouse model of breast cancer induced bone pain in which mixed osteolytic and osteoblastic remodeling occurs.</p> <p>Results</p> <p>In cancer-treated mice, acute as well as chronic inhibition of p38 MAPK with SB203580 blocked flinching and guarding behaviors in a dose-dependent manner whereas no effect on thresholds to tactile stimuli was observed. Radiographic analyses of bones demonstrated that chronic inhibition of p38 MAPK reduced bone loss and incidence of spontaneous fracture in cancer-treated mice. Histological analysis of bones collected from mice treated with the p38 MAPK inhibitor showed complete absence of osteoblastic growth in the intramedullary space as well as significantly reduced tumor burden.</p> <p>Conclusions</p> <p>Blockade of non-evoked pain behaviors but not hypersensitivity suggests differences in the underlying mechanisms of specific components of the pain syndrome and a possibility to individualize aspects of pain management. While it is not known whether the role of p38 MAPK signaling can be expanded to other cancers, the data suggest a need for understanding molecular mechanisms and cellular events that initiate and maintain cancer-induced bone pain for effective management for both ongoing pain as well as breakthrough pain.</p

Sex-biased parental care and sexual size dimorphism in a provisioning arthropod

The diverse selection pressures driving the evolution of sexual size dimorphism (SSD) have long been debated. While the balance between fecundity selection and sexual selection has received much attention, explanations based on sex-specific ecology have proven harder to test. In ectotherms, females are typically larger than males, and this is frequently thought to be because size constrains female fecundity more than it constrains male mating success. However, SSD could additionally reflect maternal care strategies. Under this hypothesis, females are relatively larger where reproduction requires greater maximum maternal effort – for example where mothers transport heavy provisions to nests. To test this hypothesis we focussed on digger wasps (Hymenoptera: Ammophilini), a relatively homogeneous group in which only females provision offspring. In some species, a single large prey item, up to 10 times the mother’s weight, must be carried to each burrow on foot; other species provide many small prey, each flown individually to the nest. We found more pronounced female-biased SSD in species where females carry single, heavy prey. More generally, SSD was negatively correlated with numbers of prey provided per offspring. Females provisioning multiple small items had longer wings and thoraxes, probably because smaller prey are carried in flight. Despite much theorising, few empirical studies have tested how sex-biased parental care can affect SSD. Our study reveals that such costs can be associated with the evolution of dimorphism, and this should be investigated in other clades where parental care costs differ between sexes and species

Does size matter for horny beetles? A geometric morphometric analysis of interspecific and intersexual size and shape variation in Colophon haughtoni Barnard, 1929, and C. kawaii Mizukami, 1997 (Coleoptera: Lucanidae)

Colophon is an understudied, rare and endangered stag beetle genus with all species endemic to isolated mountain peaks in South Africa’s Western Cape. Geometric morphometrics was used to analyse intersexual and interspecific variation of size and shape in the mandibles, heads, pronota and elytra of two sympatric species: Colophon haughtoni and Colophon kawaii. All measured structures showed significant sexual dimorphism, which may result from male-male competition for females. Female mandibles were too small and featureless for analysis, but male Colophon beetles possess large, ornate mandibles for fighting. Males had significantly larger heads and pronota that demonstrated shape changes which may relate to resource diversion to the mandibles and their supporting structures. Females are indistinguishable across species, but males were accurately identified using mandibles, heads and pronota. Male C. kawaii were significantly larger than C. haughtoni for all structures. These results support the species status of C. kawaii, which is currently in doubt due to its hybridisation with C. haughtoni. We also demonstrate the value of geometric morphometrics as a tool which may aid Colophon conservation by providing biological and phylogenetic insights and enabling species identification

The contrasting role of male relatedness in different mechanisms of sexual selection in red junglefowl

In structured populations, competition for reproductive opportunities should be relaxed among related males. The few tests of this prediction often neglect the fact that sexual selection acts through multiple mechanisms, both before and after mating. We performed experiments to study the role of within-group male relatedness across pre- and postcopulatory mechanisms of sexual selection in social groups of red junglefowl, Gallus gallus, in which two related males and one unrelated male competed over females unrelated to all the males. We confirm theoretical expectations that, after controlling for male social status, competition over mating was reduced among related males. However, this effect was contrasted by other sexual selection mechanisms. First, females biased male mating in favor of the unrelated male, and might also favor his inseminations after mating. Second, males invested more—rather than fewer—sperm in postcopulatory competition with relatives. A number of factors may contribute to explain this counterintuitive pattern of sperm allocation, including trade-offs between male investment in pre- versus postcopulatory competition, differences in the relative relatedness of pre- versus postcopulatory competitors, and female bias in sperm utilization in response to male relatedness. Collectively, these results reveal that within-group male relatedness may have contrasting effects in different mechanisms of sexual selection

Transgressive phenotypes and generalist pollination in the floral evolution of Nicotiana polyploids

This is the author's proofThe file attached is the Accepted/final draft post-refereeing version of the article. 6 month embargo now lapsed

Fecundity selection theory: concepts and evidence

Fitness results from the optimal balance between survival, mating success and fecundity. The interactions between these three components of fitness vary importantly depending on the selective context, from positive covariation between them, to antagonistic pleiotropic relationships when fitness increases in one reduce fitness of others. Therefore, elucidating the routes through which selection shapes life history and phenotypic adaptations via these fitness components is of primary significance to understand ecological and evolutionary dynamics. However, while the fitness components mediated by natural (survival) and sexual (mating success) selection have extensively been debated from most possible perspectives, fecundity selection remains considerably less studied. Here, we review the theory, evidence and implications of fecundity selection as a driver of sex-specific adaptive evolution. Based on accumulating literature on the life-history, phenotypic and ecological aspects of fecundity, we (i) suggest that ‘fecundity’ is restricted to refer to brood size per reproductive episode, while ‘annual’ and ‘lifetime fecundity’ should not be used interchangeably with ‘fecundity’ as they represent different life history parameters; (ii) provide a generalized redefinition of fecundity selection that encompasses any traits that influence fecundity in any direction (from high to low) and in either sex; (iii) review the (macro)ecological basis of fecundity selection (e.g., ecological pressures that influence predictable spatial variation in fecundity); (iv) suggest that most ecological theories of fecundity selection should be tested in organisms other than birds; (v) argue that the longstanding fecundity selection hypothesis of female-biased sexual size dimorphism (SSD) has gained inconsistent support, that strong fecundity selection does not necessarily drive female-biased SSD, and that this form of SSD can be driven by other selective pressures; and (vi) discuss cases in which fecundity selection operates on males

Crayfish Recognize the Faces of Fight Opponents

The capacity to associate stimuli underlies many cognitive abilities, including recognition, in humans and other animals. Vertebrates process different categories of information separately and then reassemble the distilled information for unique identification, storage and recall. Invertebrates have fewer neural networks and fewer neural processing options so study of their behavior may reveal underlying mechanisms still not fully understood for any animal. Some invertebrates form complex social colonies and are capable of visual memory–bees and wasps, for example. This ability would not be predicted in species that interact in random pairs without strong social cohesion; for example, crayfish. They have chemical memory but the extent to which they remember visual features is unknown. Here we demonstrate that the crayfish Cherax destructor is capable of visual recognition of individuals. The simplicity of their interactions allowed us to examine the behavior and some characteristics of the visual features involved. We showed that facial features are learned during face-to-face fights, that highly variable cues are used, that the type of variability is important, and that the learning is context-dependent. We also tested whether it is possible to engineer false identifications and for animals to distinguish between twin opponents

Sex Promotes Spatial and Dietary Segregation in a Migratory Shorebird during the Non-Breeding Season

Several expressions of sexual segregation have been described in animals, especially in those exhibiting conspicuous dimorphism. Outside the breeding season, segregation has been mostly attributed to size or age-mediated dominance or to trophic niche divergence. Regardless of the recognized implications for population dynamics, the ecological causes and consequences of sexual segregation are still poorly understood. We investigate the foraging habits of a shorebird showing reversed sexual dimorphism, the black-tailed godwit Limosa limosa, during the winter season, and found extensive segregation between sexes in spatial distribution, microhabitat use and dietary composition. Males and females exhibited high site-fidelity but differed in their distributions at estuary-scale. Male godwits (shorter-billed) foraged more frequently in exposed mudflats than in patches with higher water levels, and consumed more bivalves and gastropods and fewer polychaetes than females. Females tended to be more frequently involved and to win more aggressive interactions than males. However, the number of aggressions recorded was low, suggesting that sexual dominance plays a lesser role in segregation, although its importance cannot be ruled out. Dimorphism in the feeding apparatus has been used to explain sex differences in foraging ecology and behaviour of many avian species, but few studies confirmed that morphologic characteristics drive individual differences within each sex. We found a relationship between resource use and bill size when pooling data from males and females. However, this relationship did not hold for either sex separately, suggesting that differences in foraging habits of godwits are primarily a function of sex, rather than bill size. Hence, the exact mechanisms through which this segregation operates are still unknown. The recorded differences in spatial distribution and resource use might expose male and female to distinct threats, thus affecting population dynamics through differential mortality. Therefore, population models and effective conservation strategies should increasingly take sex-specific requirements into consideration