Increasing surface temperatures, Arctic sea-ice loss, and other evidence of anthropogenic global warming (AGW) are acknowledged by every major scientific organization in the world. However, there is a wide gap between this broad scientific consensus and public opinion. Internet blogs have strongly contributed to this consensus gap by fomenting misunderstandings of AGW causes and consequences. Polar bears (Ursus maritimus) have become a “poster species” for AGW, making them a target of those denying AGW evidence. Here, focusing on Arctic sea ice and polar bears, we show that blogs that deny or downplay AGW disregard the overwhelming scientific evidence of Arctic sea-ice loss and polar bear vulnerability. By denying the impacts of AGW on polar bears, bloggers aim to cast doubt on other established ecological consequences of AGW, aggravating the consensus gap. To counter misinformation and reduce this gap, scientists should directly engage the public in the media and blogosphere.
Directed differentiation of human pluripotent stem cells (PSC) into cardiomyocytes via manipulation of Wnt signaling leads to generation of immature cardiomyocytes, more closely resembling a fetal state. It has become increasingly apparent that metabolic parameters regulate of cardiomyocyte maturation. The forkhead box (FOX) family of transcription factors has previously been shown to regulate metabolic phenotype in neonatal cardiomyocytes through a balance between FOXO and FOXM proteins. Therefore, we hypothesized that dysregulation of FOXO-FOXM1 signaling inhibits maturation of iPSC-derived cardiomyocytes (iPSC-CMs). We cultured iPSC-CMs in 3D suspension culture using an orbital shaker. iPSC-CMs were treated with RCM-1 (FOXM1 inhibitor), LOM612 (FOXO nuclear translocator), or AS1842856 (FOXO inhibitor) starting 2 days after onset of beating. We found that inhibition of FOXO with AS1842856 resulted in loss of expression of cardiac-specific markers such as cardiac troponin T as well as loss of spontaneous beating. In contrast, inhibition of FOXM1 with RCM-1 or activation of FOXO with LOM612 resulted in retention of a cardiomyocyte phenotype with continued expression of cardiac troponin T but with significantly increased expression membrane protein expression of Kir2.1 (Figure), the protein largely responsible for maintaining the resting membrane potential in cardiomyocytes. These results suggest that inhibition of FOXM1 and/or activation of FOXO signaling may facilitate maturation of iPSC-derived cardiomyocytes.
Figure.
(A) % of TNNT2+ iPSC-derived cardiomyocytes that express Kir2.1 and (B) Mean fluorescence intensity of Kir2.1 in iPSC-derived cardiomyocytes after treatment with DMSO (vehicle control), RCM-1, LOM612, or AS1842856. *p<0.05, ***p<0.001, ****p<0.0001 by one-way ANOVA with Dunnett’s multiple comparisons test.
This paper has been corrected online and in print in order to clarify Dr. Crockford's scientific expertise and financial links in relation to the arguments made in the paper (BioScience 68: 281-287). The corrected text is as follows: First change: Notably, as of this writing, Crockford has neither conducted any original research nor published any articles in the peer-reviewed literature on the effects of sea ice on the population dynamics of polar bears. Second change: Some of the most prominent AGW deniers, including Crockford, are linked with or receive support from organizations that downplay AGW (e.g., Dr. Crockford has previously been paid for report writing by the Heartland Institute).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.