Infanticide and infant defence by males--modelling the conditions in primate multi-male groups

Infanticide by primate males was considered rare if groups contain more than one adult male because, owing to lower paternity certainty, a male should be less likely to benefit from infanticide. Guided by recent evidence for strong variation of infanticide in primate multi-male groups, we modelled the conditions for when infanticide should occur for a group with a resident and an immigrant male. Setting the parameters (e.g. infant mortality, reduction of interbirth interval, life-time reproductive success, genetic representation) to fit the conditions most commonly found in nature, we develop a game-theoretic model to explore the influence of age and dominance on the occurrence of infanticide and infant defence. Male age strongly impacts the likelihood of an attack which is modified by the father's defence. If the new male is dominant he is likely to attack under most circumstances whereas a subordinate male will only attack if the father does not defend. These model scenarios fit the conditions under which infanticide is known to occur in primate multi-male groups and offer an explanation why infanticide is common in some multi-male groups and rare in others. Overall, the benefits for infanticidal males are strongly governed by a reduced interbirth interval while advantages via improved genetic representation in the gene pool contribute but a minor fraction

Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in huntingtin. There are no treatments that are known to slow the neurodegeneration caused by this mutation. Mutant huntingtin causes disease via a toxic gain-of-function mechanism and has the propensity to aggregate and form intraneuronal inclusions. One therapeutic approach for HD is to enhance the degradation of the mutant protein. We have shown that this can be achieved by upregulating autophagy, using the drug rapamycin. In order to find safer ways of inducing autophagy for clinical purposes, we previously screened United States Food and Drug Administration-approved drugs for their autophagy-stimulating potential. This screen suggested that rilmenidine, a well tolerated, safe, centrally acting anti-hypertensive drug, could induce autophagy in cell culture via a pathway that was independent of the mammalian target of rapamycin. Here we have shown that rilmenidine induces autophagy in mice and in primary neuronal culture. Rilmenidine administration attenuated the signs of disease in a HD mouse model and reduced levels of the mutant huntingtin fragment. As rilmenidine has a long safety record and is designed for chronic use, our data suggests that it should be considered for the treatment of HD and related conditions