Vertebrates possess two paralogs of cytochrome c oxidase (COX) subunit 4: a ubiquitous COX4-1 and a hypoxia-linked COX4-2. Mammalian COX4-2 is thought to have a role in relation to fine-tuning metabolism in low oxygen levels, conferred through both structural differences in the subunit protein structure and regulatory differences in the gene. We sought to elucidate the pervasiveness of this feature across vertebrates. The ratio of COX4-2/4-1 mRNA is generally low in mammals, but this ratio was higher in fish and reptiles, particularly turtles. The COX4-2 gene appeared unresponsive to low oxygen in nonmammalian models (zebrafish, goldfish, tilapia, anoles, and turtles) and fish cell lines. Reporter genes constructed from the amphibian and reptile homologues of the mammalian oxygen-responsive elements and hypoxia-responsive elements did not respond to low oxygen. Unlike the rodent ortholog, the promoter of goldfish COX4-2 did not respond to hypoxia or anoxia. The protein sequences of the COX4-2 peptide showed that the disulfide bridge seen in human and rodent orthologs would be precluded in other mammalian lineages and lower vertebrates, all of which lack the requisite pair of cysteines. The coordinating ligands of the ATP-binding site are largely conserved across mammals and reptiles, but in Xenopus and fish, sequence variations may disrupt the ability of the protein to bind ATP at this site. Collectively, these results suggest that many of the genetic and structural features of COX4-2 that impart responsiveness and benefits in hypoxia may be restricted to the Euarchontoglires lineage that includes primates, lagomorphs, and rodents.
With the spread of internet-based technologies, the sharing economy is emerging as a new and rapidly growing sector of the economy. This sector offers transformative potential for many other sectors of the economy, and possibilities for new economic activity and growth in the developing world. The sharing economy is a misnomer, as while there are possibilities for more cooperative economic approaches, the primary emphasis is on the reduction of transaction costs including the elimination of middlemen in sales between a good/service provider and a customer. In this introductory article to the special edition, we provide an overview of both the positive and negative potential for the contribution of the sharing economy to development. On the one hand, we find that the reduction in transactions costs and the low price of mobiles improves access to goods and services, and reduces the need for economies of scale for marginalized groups who lack access to capital and infrastructure. However, we point to the real obstacles that the poor experience in using internet-based platforms to start businesses or accumulate capital. We discuss the potential for labour substitution of traditional service providers, such as taxi drivers. In juxtaposition to some of its claimants, we find that the sharing economy changes the nature of institutional, regulatory and promotional challenges by the state and social groups, rather than reducing the need for them.
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