The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialised endfeet, the significance of this interaction is not understood. In contrast, it is well established that vasculature-secreted soluble factors promote lineage progression of committed progenitors. Here we specifically investigated the role of cell-cell contact-dependent signalling in the vascular niche. Unexpectedly, we find that direct cell-cell interactions with endothelial cells enforces quiescence and promotes stem cell identity. Mechanistically, endothelial ephrinB2 and Jagged1 mediate these effects by suppressing cell-cycle entry downstream of mitogens and inducing stemness genes to jointly inhibit differentiation. In vivo, endothelial-specific ablation of either of the genes which encode these proteins, Efnb2 and Jag1 respectively, aberrantly activates quiescent stem cells, resulting in depletion. Thus, we identify the vasculature as a critical niche compartment for stem cell maintenance, furthering our understanding of how anchorage to the niche maintains stem cells within a pro-differentiative microenvironment.
We investigate the backflow effect in elementary quantum mechanics -the phenomenon in which a state consisting entirely of positive momenta may have negative current and the probability flows in the opposite direction to the momentum. We compute the current and flux for states consisting of superpositions of gaussian wave packets. These are experimentally realizable but the amount of backflow is small. Inspired by the numerical results of Penz et al (M.Penz, G.Grübl, S.Kreidl and P.Wagner, J.Phys. A39, 423 (2006)), we find two non-trivial wave functions whose current at any time may be computed analytically and which have periods of significant backflow, in one case with a backwards flux equal to about 70 percent of the maximum possible backflow, a dimensionless number c bm ≈ 0.04, discovered by Bracken and Melloy (A.J.Bracken and G.F.Melloy, J.Phys. A27, 2197 (1994)). This number has the unusual property of being independent of (and also of all other parameters of the model), despite corresponding to an obviously quantum-mechanical effect, and we shed some light on this surprising property by considering the classical limit of backflow. We discuss some specific measurement models in which backflow may be identified in certain measurable probabilities.
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