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

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

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

Age related decline in female lar gibbon great call performance suggests that call features correlate with physical condition

Background: White-handed gibbons (Hylobates lar) are small Asian apes known for living in stable territories and producing loud, elaborate vocalizations (songs), often in well-coordinated male/female duets. The female great call, the most conspicuous phrase of the repertoire, has been hypothesized to function in intra-sexual territorial defense. We therefore predicted that characteristics of the great call would correlate with a caller’s physical condition, and thus might honestly reflect resource holding potential (RHP). Because measurement of RHP is virtually impossible for wild animals, we used age as a proxy, hypothesizing that great call climaxes are difficult to produce and maintain over time, and that older adults will therefore perform lower quality great calls than young adults. To test this we analyzed the great call climaxes of 15 wild lar gibbon females at Khao Yai National Park, Thailand and 2 captive females at Leo Conservation Center, Greenwich, CT. Results: Findings show that call climaxes correlate with female age, as young animals (n = 8, mean age: 12.9 years) produced climaxes with a higher frequency range (delta F0), maximum F0 frequency and duty cycle than old animals (n = 9, mean age: 29.6 years). A permuted discriminant function analysis also correctly classified calls by age group. During long song bouts the maximum F0 frequency of great call climaxes’ also decreased. Additional data support the hypothesis that short high notes, associated with rapid inhalation as an individual catches its breath, reflect increased caller effort. Older females produced more high notes than younger females, but the difference only approached statistical significance, suggesting that calling effort may be similar across different ages. Finally, for the first time in this species, we measured peak intensity of calls in captive females. They were capable of producing climaxes in excess of 100 dB at close range (2.7 m). Conclusions: Age and within-bout differences in the lar gibbon great call climax suggest that call features correlate with physical condition and thus the call may have evolved as an honest signal in the context of intra-sexual territorial defense and possibly also in male mate choice via sexual selection, although further testing of these hypotheses is necessary. Results: Findings show that call climaxes correlate with female age, as young animals (n = 8, mean age: 12.9 years) produced climaxes with a higher frequency range (delta F0), maximum F0 frequency and duty cycle than old animals (n = 9, mean age: 29.6 years). A permuted discriminant function analysis also correctly classified calls by age group. During long song bouts the maximum F0 frequency of great call climaxes’ also decreased. Additional data support the hypothesis that short high notes, associated with rapid inhalation as an individual catches its breath, reflect increased caller effort. Older females produced more high notes than younger females, but the difference only approached statistical significance, suggesting that calling effort may be similar across different ages. Finally, for the first time in this species, we measured peak intensity of calls in captive females. They were capable of producing climaxes in excess of 100 dB at close range (2.7 m). Conclusions: Age and within-bout differences in the lar gibbon great call climax suggest that call features correlate with physical condition and thus the call may have evolved as an honest signal in the context of intra-sexual territorial defense and possibly also in male mate choice via sexual selection, although further testing of these hypotheses is necessary

I Know My Neighbour: Individual Recognition in Octopus vulgaris

Background: Little is known about individual recognition (IR) in octopuses, although they have been abundantly studied for their sophisticated behaviour and learning capacities. Indeed, the ability of octopuses to recognise conspecifics is suggested by a number of clues emerging from both laboratory studies (where they appear to form and maintain dominance hierarchies) and field observations (octopuses of neighbouring dens display little agonism between each other). To fill this gap in knowledge, we investigated the behaviour of 24 size-matched pairs of Octopus vulgaris in laboratory conditions. Methodology/Principal Findings: The experimental design was composed of 3 phases: Phase 1 (acclimatization): 12 ‘‘sightallowed’’ (and 12 ‘‘isolated’’) pairs were maintained for 3 days in contiguous tanks separated by a transparent (and opaque) partition to allow (and block) the vision of the conspecific; Phase 2 (cohabitation): members of each pair (both sight-allowed and isolated) were transferred into an experimental tank and were allowed to interact for 15 min every day for 3 consecutive days; Phase 3 (test): each pair (both sight-allowed and isolated) was subject to a switch of an octopus to form pairs composed of either familiar (‘‘sham switches’’) or unfamiliar conspecifics (‘‘real switches’’). Longer latencies (i.e. the time elapsed from the first interaction) and fewer physical contacts in the familiar pairs as opposed to the unfamiliar pairs were used as proxies for recognition. Conclusions: Octopuses appear able to recognise conspecifics and to remember the individual previously met for at leas