Type 2 diabetes mellitus (T2DM) is believed to be irreversible although no component of the pathophysiology is irreversible. We show here with a network model that the apparent irreversibility is contributed by the structure of the network of inter-organ signalling. A network model comprising all known inter-organ signals in T2DM showed bi-stability with one insulin sensitive and one insulin resistant attractor. The bi-stability was made robust by multiple positive feedback loops suggesting an evolved allostatic system rather than a homeostatic system. In the absence of the complete network, impaired insulin signalling alone failed to give a stable insulin resistant or hyperglycemic state. The model made a number of correlational predictions many of which were validated by empirical data. The current treatment practice targeting obesity, insulin resistance, beta cell function and normalization of plasma glucose failed to reverse T2DM in the model. However certain behavioural and neuro-endocrine interventions ensured a reversal. These results suggest novel prevention and treatment approaches which need to be tested empirically.
In high-risk environments with frequent predator encounters, efficient antipredator behavior is key to survival. Parental effects are a powerful mechanism to prepare offspring for coping with such environments, yet clear evidence for adaptive parental effects on offspring antipredator behaviors is missing. Rapid escape reflexes, or “C-start reflexes,” are a key adaptation in fish and amphibians to escape predator strikes. We hypothesized that mothers living in high-risk environments might induce faster C-start reflexes in offspring by modifying egg composition. Here, we show that offspring of the cichlid fish Neolamprologus pulcher developed faster C-start reflexes and were more risk averse if their parents had been exposed to cues of their most dangerous natural predator during egg production. This effect was mediated by differences in egg composition. Eggs of predator-exposed mothers were heavier with higher net protein content, and the resulting offspring were heavier and had lower igf-1 gene expression than control offspring shortly after hatching. Thus, changes in egg composition can relay multiple putative pathways by which mothers can influence adaptive antipredator behaviors such as faster escape reflexes.
For many species, the Mediterranean region harbors distinct lineages that are of conservation concerns. However, many of these are threatened by habitat degradation and by the introduction of non-native species. Here, we assess the status of the native threespine stickleback (Gasterosteus aculeatus) in the Lake Bracciano region in Italy, where stickleback have been historically present. During a dedicated sampling campaign in summer 2015, surveying the potential habitats that sticklebacks commonly occupy, we could not confirm the presence of this species but found introduced species to be often most abundant. Stickleback are thus likely to either have become extinct over the last decades or be on the verge to extinction in the Lake Bracciano region.
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