An evolutionary model explaining the Neolithic transition from egalitarianism to leadership and despotism.

The Neolithic was marked by a transition from small and relatively egalitarian groups, to much larger groups with increased stratification. But the dynamics of thisremain poorly understood. It is hard to see how despotism can arise without coercion, yet coercion could not easily have occurred in an egalitarian setting. Using a quanti-tative model of evolution in a patch-structured population, we demonstrate that the interaction between demographic and ecological factors can overcome this conundrum.We model the co-evolution of individual preferences for hierarchy alongside the degree of despotism of leaders, and the dispersal preferences of followers. We show that voluntary leadership without coercion can evolve in small groups, when leaders help to solve coordination problems related to resource production. An example is coordinating construction of an irrigation system. Our model predicts that the transition to larger despotic groups will then occur when: 1. surplus resources lead to demographicexpansion of groups, removing the viability of an acephalous niche in the same areaand so locking individuals into hierarchy; 2. high dispersal costs limit followers' abilityto escape a despot. Empirical evidence suggests that these conditions were likely metfor the first time during the subsistence intensification of the Neolithic

The Spread of Inequality

The causes of socioeconomic inequality have been debated since the time of Plato. Many reasons for the development of stratification have been proposed, from the need for hierarchical control over large-scale irrigation systems to the accumulation of small differences in wealth over time via inheritance processes. However, none of these explains how unequal societies came to completely displace egalitarian cultural norms over time. Our study models demographic consequences associated with the unequal distribution of resources in stratified societies. Agent-based simulation results show that in constant environments, unequal access to resources can be demographically destabilizing, resulting in the outward migration and spread of such societies even when population size is relatively small. In variable environments, stratified societies spread more and are also better able to survive resource shortages by sequestering mortality in the lower classes. The predictions of our simulation are provided modest support by a range of existing empirical studies. In short, the fact that stratified societies today vastly outnumber egalitarian societies may not be due to the transformation of egalitarian norms and structures, but may instead reflect the more rapid migration of stratified societies and consequent conquest or displacement of egalitarian societies over time

Multivalent ligands control stem cell behaviour in vitro and in vivo

There is broad interest in designing nanostructured materials that can interact with cells and regulate key downstream functions. In particular, materials with nanoscale features may enable control over multivalent interactions, which involve the simultaneous binding of multiple ligands on one entity to multiple receptors on another and are ubiquitous throughout biology. Cellular signal transduction of growth factor and morphogen cues (which have critical roles in regulating cell function and fate) often begins with such multivalent binding of ligands, either secreted or cell-surface-tethered to target cell receptors, leading to receptor clustering. Cellular mechanisms that orchestrate ligand-receptor oligomerization are complex, however, so the capacity to control multivalent interactions and thereby modulate key signalling events within living systems is currently very limited. Here, we demonstrate the design of potent multivalent conjugates that can organize stem cell receptors into nanoscale clusters and control stem cell behaviour in vitro and in vivo. The ectodomain of ephrin-B2, normally an integral membrane protein ligand, was conjugated to a soluble biopolymer to yield multivalent nanoscale conjugates that potently induce signalling in neural stem cells and promote their neuronal differentiation both in culture and within the brain. Super-resolution microscopy analysis yielded insights into the organization of the receptor-ligand clusters at the nanoscale. We also found that synthetic multivalent conjugates of ephrin-B1 strongly enhance human embryonic and induced pluripotent stem cell differentiation into functional dopaminergic neurons. Multivalent bioconjugates are therefore powerful tools and potential nanoscale therapeutics for controlling the behaviour of target stem cells in vitro and in vivo

Attenuation artifacts in light sheet fluorescence microscopy corrected by OPTiSPIM

Light sheet fluorescence microscopy (LSFM) is rapidly becoming an essential technology for mesoscopic imaging of samples such as embryos and adult mouse organs. However, LSFM can suffer from optical artifacts for which there is no intrinsic solution. The attenuation of light due to absorbing material causes "shadow" artifacts along both the illumination and detection paths. Several approaches have been introduced to reduce this problem, including scanning illumination and multi-view imaging. However, neither of these approaches completely eliminates the problem. If the distribution of the absorbing material is complex, shadows cannot be avoided. We introduce a new approach that relies on multi-modal integration of two very different mesoscopic techniques. Unlike LSFM, optical projection tomography (OPT) can operate in transmission mode to create a voxel map of the 3D distribution of the sample's optical attenuation. Here, we demonstrate a hybrid instrument (OPTiSPIM) that can quantify this attenuation and use the information to correct the shadow artifacts of LSFM.The research was funded in part by the European Union’s 7th Framework VIBRANT project (No. 228933 of the FP7-NMP) and the Sinergia project (CRII3_125477) of the Swiss National Science Foundation (SNSF). We acknowledge support from the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013–2017” and from the CERCA Programme/Generalitat de Catalunya