The manuscript is overall very well written and the authors provide extensive data which has apparently been subjected to comprehensive and sound statistical analyses. The data is presented in an attractive manner. Main manuscript figures are supported by extensive supplementary material including the presentation of extensive control data, which is greatly appreciated. In some cases the figure descriptions or legends should be extended. Due to the vast amount of data condensed in the figures, the descriptions (at least in the text) should be detailed enough for a wide readership to follow the authors through their argumentation.