Molecular Correlates of Social Dominance: A Novel Role for Ependymin in Aggression

Theoretical and empirical studies have sought to explain the formation and maintenance of social relationships within groups. The resulting dominance hierarchies have significant fitness and survival consequences dependent upon social status. We hypothesised that each position or rank within a group has a distinctive brain gene expression profile that correlates with behavioural phenotype. Furthermore, transitions in rank position should determine which genes shift in expression concurrent with the new dominance status. We used a custom cDNA microarray to profile brain transcript expression in a model species, the rainbow trout, which forms tractable linear hierarchies. Dominant, subdominant and submissive individuals had distinctive transcript profiles with 110 gene probes identified using conservative statistical analyses. By removing the dominant, we characterised the changes in transcript expression in sub-dominant individuals that became dominant demonstrating that the molecular transition occurred within 48 hours. A strong, novel candidate gene, ependymin, which was highly expressed in both the transcript and protein in subdominants relative to dominants, was tested further. Using antibody injection to inactivate ependymin in pairs of dominant and subdominant zebrafish, the subdominant fish exhibited a substantial increase in aggression in parallel with an enhanced competitive ability. This is the first study to characterise the molecular signatures of dominance status within groups and the first to implicate ependymin in control of aggressive behaviour. It also provides evidence for indirect genetic effect models in which genotype/phenotype of an individual is influenced by conspecific interactions within a group. The variation in the molecular profile of each individual within a group may offer a new explanation of intraspecific variation in gene expression within undefined groups of animals and provides new candidates for empirical study

The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways

Desatando a trama das redes assistenciais sobre drogas: uma revisão narrativa da literatura

Acalorados debates sobre determinados modelos de tratamento para usuários de drogas ocorrem no âmbito da academia, das políticas públicas, além da mídia. A rede assistencial sobre drogas é apresentada neste contexto como um importante mecanismo, mas sua construção torna-se um desafio. Assim, realizou-se uma análise crítica da literatura acadêmica acerca das redes assistenciais sobre drogas, na forma de uma revisão narrativa, visando levantar seus desafios e possibilidades de consolidação. Os resultados encontrados foram: a) uma escassez de estudos específicos sobre a rede assistencial sobre drogas; b) cobertura insuficiente e desintegrada frente à demanda de tratamento; c) necessidade de se repensar o papel dos Centros de Atenção Psicossocial para Álcool e outras Drogas, visando seu fortalecimento, expansão, melhoria estrutural e readequação de práticas; d) ausência de análises críticas sobre o processo de construção dos modelos assistenciais sobre drogas nos serviços públicos; e, e) responsabilidade do Estado em fornecer melhores alternativas ao panorama encontrado, avançando no fortalecimento das ações intersetoriais, articulação do cuidado e no aprimoramento das condições de trabalho