Faeces' odours attract gregarious locust hoppers.

Collective motion is one of the most impressive common features of gregarious locusts: once formed, bands and swarms get moving for long distances. It was shown that visual perception of neighbours plays a key role in maintaining marching behaviour at a local scale. But at a larger scale, mechanisms underlying band cohesion are less understood. It was shown in several field studies that individuals separated from the band were able to get back to the group, even after being separated since a night. In this context, faeces' odours could be a possible indicator of the recent passage of a group. In this study, we tested if nymphs are attracted by faeces' odours and if this effect is modulated by the age of the faeces. To this end, we conducted individual olfactometric behavioural assays of 3rd instar hoppers of desert locust, Schistocerca gregaria, exposed to odours of 1 h-old and 24 h-old faeces. We also used Gas Chromatography-Mass Spectrometry (GC-MS) to identify odours' volatile organic compounds from faeces. The results of behavioural assays indicated a strong attractive effect of faeces, with no preference for one of the two faecal age classes. Nymphs spent significantly more time in the side of the olfactometer where the faeces' odours came from, and 72.7% of tested individuals chose this side first. We filtered and annotated 11 volatile organic compounds present in both fresh and old faeces in GC-MS analyses, including guaiacol and phenol, which are known to cause an aggregative effect on desert locusts. As the attractive effect lasted over 24 h, band's faeces could still have an attractive effect when individuals are separated from the band since one day. In this situation, latecomers individuals would be able to get back to the group by following the traces of their predecessors.

Importance of interindividual interactions in eco-evolutionary population dynamics: The rise of demo-genetic agent-based models.

The study of eco-evolutionary dynamics, that is of the intertwinning between ecological and evolutionary processes when they occur at comparable time scales, is of growing interest in the current context of global change. However, many eco-evolutionary studies overlook the role of interindividual interactions, which are hard to predict and yet central to selective values. Here, we aimed at putting forward models that simulate interindividual interactions in an eco-evolutionary framework: the demo-genetic agent-based models (DG-ABMs). Being demo-genetic, DG-ABMs consider the feedback loop between ecological and evolutionary processes. Being agent-based, DG-ABMs follow populations of interacting individuals with sets of traits that vary among the individuals. We argue that the ability of DG-ABMs to take into account the genetic heterogeneity-that affects individual decisions/traits related to local and instantaneous conditions-differentiates them from analytical models, another type of model largely used by evolutionary biologists to investigate eco-evolutionary feedback loops. Based on the review of studies employing DG-ABMs and explicitly or implicitly accounting for competitive, cooperative or reproductive interactions, we illustrate that DG-ABMs are particularly relevant for the exploration of fundamental, yet pressing, questions in evolutionary ecology across various levels of organization. By jointly modelling the effects of management practices and other eco-evolutionary processes on interindividual interactions and population dynamics, DG-ABMs are also effective prospective and decision support tools to evaluate the short- and long-term evolutionary costs and benefits of management strategies and to assess potential trade-offs. Finally, we provide a list of the recent practical advances of the ABM community that should facilitate the development of DG-ABMs.

Allosteric inhibition of PPM1D serine/threonine phosphatase via an altered conformational state.

PPM1D encodes a serine/threonine phosphatase that regulates numerous pathways including the DNA damage response and p53. Activating mutations and amplification of PPM1D are found across numerous cancer types. GSK2830371 is a potent and selective allosteric inhibitor of PPM1D, but its mechanism of binding and inhibition of catalytic activity are unknown. Here we use computational, biochemical and functional genetic studies to elucidate the molecular basis of GSK2830371 activity. These data confirm that GSK2830371 binds an allosteric site of PPM1D with high affinity. By further incorporating data from hydrogen deuterium exchange mass spectrometry and sedimentation velocity analytical ultracentrifugation, we demonstrate that PPM1D exists in an equilibrium between two conformations that are defined by the movement of the flap domain, which is required for substrate recognition. A hinge region was identified that is critical for switching between the two conformations and was directly implicated in the high-affinity binding of GSK2830371 to PPM1D. We propose that the two conformations represent active and inactive forms of the protein reflected by the position of the flap, and that binding of GSK2830371 shifts the equilibrium to the inactive form. Finally, we found that C-terminal truncating mutations proximal to residue 400 result in destabilization of the protein via loss of a stabilizing N- and C-terminal interaction, consistent with the observation from human genetic data that nearly all PPM1D mutations in cancer are truncating and occur distal to residue 400. Taken together, our findings elucidate the mechanism by which binding of a small molecule to an allosteric site of PPM1D inhibits its activity and provides insights into the biology of PPM1D.