Distinctive communication networks in inactive states of β2-adrenergic receptor: Mutual information and entropy transfer analysis

Mutual information and entropy transfer analysis employed on two inactive states of human beta-2 adrenergic receptor (β₂-AR) unraveled distinct communication pathways. Previously, a so-called “highly” inactive state of the receptor was observed during 1.5 microsecond long molecular dynamics simulation where the largest intracellular loop (ICL3) was swiftly packed onto the G-protein binding cavity, becoming entirely inaccessible. Mutual information quantifying the degree of correspondence between backbone-C_α fluctuations was mostly shared between intra- and extra-cellular loop regions in the original inactive state, but shifted to entirely different regions in this latest inactive state. Interestingly, the largest amount of mutual information was always shared among the mobile regions. Irrespective of the conformational state, polar residues always contributed more to mutual information than hydrophobic residues, and also the number of polar-polar residue pairs shared the highest degree of mutual information compared to those incorporating hydrophobic residues. Entropy transfer, quantifying the correspondence between backbone-C_α fluctuations at different timesteps, revealed a distinctive pathway directed from the extracellular site toward intracellular portions in this recently exposed inactive state for which the direction of information flow was the reverse of that observed in the original inactive state where the mobile ICL3 and its intracellular surroundings drove the future fluctuations of extracellular regions.     

Actuarial senescence in laboratory and field populations of Lepidoptera

1. Recent observations of actuarial senescence – an increase in mortality rate with age – have challenged the assertion that the brevity of adult insect life spans precludes ageing. 2. Here the rate of senescence in 22 species of Lepidoptera was quantified by fitting demographic models to adult survivorship data drawn from a range of field and laboratory studies. 3. Senescence was evident in all 22 species investigated, with a model of age‐related mortality consistently fitting the survivorship curves significantly better than an alternative model which assumes constant mortality. 4. The rates of senescence varied significantly among species. The rates of senescence also differed significantly between sexes for all species tested, but not in a consistent way.