Erickson, G. | Search bioRxiv

bioRxiv2022

Sinking a giant: quantitative macroevolutionary comparative methods debunk qualitative assumptions

Myhrvold et al.1 suggest that our inference of subaqueous foraging among spinosaurids2 is undermined by selective bone sampling, inadequate statistical procedures, and use of inaccurate ecological categorizations. Myhrvold et al.1 ignore major details of our analyses and results, and instead choose to portray our inferences as if they were based on qualitative interpretations of our plots, without providing additional analyses to support their claims. In this manuscript, we thoroughly discuss all the concerns exposed by Myhrvold et al.1. Additional analyses based on our original datasets2 and novel data presented by Myhrvold et al.1 do not change our original interpretations: while the spinosaurid dinosaurs Spinosaurus and Baryonyx are recovered as subaqueous foragers, Suchomimus is inferred as a non-diving animal.

paleontology↗

bioRxiv2019

Myt Transcription Factors prevent stress-response gene over-activation to enable postnatal pancreatic β cell proliferation and function

Although stress response maintains cell function and survival under adverse conditions, over-activation of late-stage stress-gene effectors causes dysfunction and death. Here we show that the Myelin Transcription Factors (Myt 1, 2, and 3 TFs) prevent this over-activation. Co-inactivating Myt TFs in mouse pancreatic progenitors compromised postnatal {beta}-cell function, proliferation, and survival, preceded by upregulation of late-stage stress-response genes Activating Transcription Factors (e.g., Atf4) and Heat Shock Proteins (Hsps). Myt1 binds the putative enhancers of Atf4 and Hsps, whose over-expression in mouse {beta} cells largely recapitulated the Myt mutant phenotypes. Moreover, Myt(MYT)-TF levels were upregulated in functional mouse and human {beta} cells by metabolic stress but downregulated in those of type 2 diabetic islets that display ATF4 and HSP over-activation. Lastly, human MYT knockdown caused stress-gene over-activation and death in Endo-{beta}H1 cells. These findings suggest that the Myt TFs restrict stress-response to physiologically tolerable levels in mice and human.

developmental biology↗