Disruption of Growth Hormone Receptor Prevents Calorie Restriction from Improving Insulin Action and Longevity

Most mutations that delay aging and prolong lifespan in the mouse are related to somatotropic and/or insulin signaling. Calorie restriction (CR) is the only intervention that reliably increases mouse longevity. There is considerable phenotypic overlap between long-lived mutant mice and normal mice on chronic CR. Therefore, we investigated the interactive effects of CR and targeted disruption or knock out of the growth hormone receptor (GHRKO) in mice on longevity and the insulin signaling cascade. Every other day feeding corresponds to a mild (i.e. 15%) CR which increased median lifespan in normal mice but not in GHRKO mice corroborating our previous findings on the effects of moderate (30%) CR on the longevity of these animals. To determine why insulin sensitivity improves in normal but not GHRKO mice in response to 30% CR, we conducted insulin stimulation experiments after one year of CR. In normal mice, CR increased the insulin stimulated activation of the insulin signaling cascade (IR/IRS/PI3K/AKT) in liver and muscle. Livers of GHRKO mice responded to insulin by increased activation of the early steps of insulin signaling, which was dissipated by altered PI3K subunit abundance which putatively inhibited AKT activation. In the muscle of GHRKO mice, there was elevated downstream activation of the insulin signaling cascade (IRS/PI3K/AKT) in the absence of elevated IR activation. Further, we found a major reduction of inhibitory Ser phosphorylation of IRS-1 seen exclusively in GHRKO muscle which may underpin their elevated insulin sensitivity. Chronic CR failed to further modify the alterations in insulin signaling in GHRKO mice as compared to normal mice, likely explaining or contributing to the absence of CR effects on insulin sensitivity and longevity in these long-lived mice

Paternity and Dominance Loss in Male Breeders: The Cost of Helpers in a Cooperatively Breeding Mammal

Paternity insurance and dominance tenure length are two important components of male reproductive success, particularly in species where reproduction is highly skewed towards a few individuals. Identifying the factors affecting these two components is crucial to better understand the pattern of variation in reproductive success among males. In social species, the social context (i.e. group size and composition) is likely to influence the ability of males to secure dominance and to monopolize reproduction. Most studies have analyzed the factors affecting paternity insurance and dominance tenure separately. We use a long term data set on Alpine marmots to investigate the effect of the number of subordinate males on both paternity insurance and tenure of dominant males. We show that individuals which are unable to monopolize reproduction in their family groups in the presence of many subordinate males are likely to lose dominance the following year. We also report that dominant males lose body mass in the year they lose both paternity and dominance. Our results suggest that controlling many subordinate males is energetically costly for dominant males, and those unable to support this cost lose the control over both reproduction and dominance. A large number of subordinate males in social groups is therefore costly for dominant males in terms of fitness

How to prove the existence of God: an argument for conjoined panentheism

This article offers an argument for a form of panentheism in which the divine is conceived as both ‘God the World’ and ‘God the Good’. ‘God the World’ captures the notion that the totality of everything which exists is ‘in’ God, while acknowledging that, given evil and suffering, not everything is ‘of’ God. ‘God the Good’ encompasses the idea that God is also the universal concept of Goodness, akin to Plato’s Form of the Good as developed by Iris Murdoch, which is inextricably conjoined with God the World because it is the nature of the world which determines the nature of perfect Goodness. This form of ‘conjoined’ panentheism yields a concept of divine personhood which includes both divine agency and human/divine engagement. God the Good is an agent of change by providing human persons with a standard of Goodness against which to measure the goodness of their own actions, while God the World provides the physical embodiment through which God acts. Human engagement with the divine may take a number of forms and may lead to moral action, the means by which the divine acts upon the world and changes it for the better

Gait optimization and energetics of ballistic walking for an underactuated biped with knees

In this paper, we study gait optimization of ballistic walking in order to understand the natural dynamics of an underactuated biped with knees. We also propose applications for our understandings. Our optimization problem is solved by fixing energy levels, and then, we attempt to explain how optimal gaits are formed by examining the role of each joint in speeding up. In addition, we explain some natural characteristics of walking. Based on the results, we propose a new cost function to generate various walking gaits, including the optimum. Finally, we evaluate and discuss the energy efficiency of our ballistic walker and other bipedal walkers including humans.clos