Defining Life: The Virus Viewpoint

Are viruses alive? Until very recently, answering this question was often negative and viruses were not considered in discussions on the origin and definition of life. This situation is rapidly changing, following several discoveries that have modified our vision of viruses. It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism—the virus—producing virions. I suggest here to define life (an historical process) as the mode of existence of ribosome encoding organisms (cells) and capsid encoding organisms (viruses) and their ancestors. I propose to define an organism as an ensemble of integrated organs (molecular or cellular) producing individuals evolving through natural selection. The origin of life on our planet would correspond to the establishment of the first organism corresponding to this definition

Why Do Species Co-Occur? A Test of Alternative Hypotheses Describing Abiotic Differences in Sympatry versus Allopatry Using Spadefoot Toads

Areas of co-occurrence between two species (sympatry) are often thought to arise in regions where abiotic conditions are conducive to both species and are therefore intermediate between regions where either species occurs alone (allopatry). Depending on historical factors or interactions between species, however, sympatry might not differ from allopatry, or, alternatively, sympatry might actually be more extreme in abiotic conditions relative to allopatry. Here, we evaluate these three hypothesized patterns for how sympatry compares to allopatry in abiotic conditions. We use two species of congeneric spadefoot toads, Spea multiplicata and S. bombifrons, as our study system. To test these hypotheses, we created ecological niche models (specifically using Maxent) for both species to create a map of the joint probability of occurrence of both species. Using the results of these models, we identified three types of locations: two where either species was predicted to occur alone (i.e., allopatry for S. multiplicata and allopatry for S. bombifrons) and one where both species were predicted to co-occur (i.e., sympatry). We then compared the abiotic environment between these three location types and found that sympatry was significantly hotter and drier than the allopatric regions. Thus, sympatry was not intermediate between the alternative allopatric sites. Instead, sympatry occurred at one extreme of the conditions occupied by both species. We hypothesize that biotic interactions in these extreme environments facilitate co-occurrence. Specifically, hybridization between S. bombifrons females and S. multiplicata males may facilitate co-occurrence by decreasing development time of tadpoles. Additionally, the presence of alternative food resources in more extreme conditions may preclude competitive exclusion of one species by the other. This work has implications for predicting how interacting species will respond to climate change, because species interactions may facilitate survival in extreme habitats

Author Correction: c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis

Correction to: Nature Metabolism https://doi.org/10.1038/s42255-020-00306-2, published online 9 November 2020. In the version of this article initially published, in the ×40 diseased human kidney images in Supplementary Fig. 1, the FSGS image duplicated the DN image. The error has been corrected in the HTML version of the article

c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis

Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic activities of hepatocytes and macrophages and identify Pfkfb3 as the key downstream metabolic mediator of this response. Independent deletions of Rel in hepatocytes or macrophages suppressed liver fibrosis induced by carbon tetrachloride, while combined deletion had an additive anti-fibrogenic effect. In transforming growth factor-β1-induced hepatocytes, c-Rel regulates expression of a pro-fibrogenic secretome comprising inflammatory molecules and connective tissue growth factor, the latter promoting collagen secretion from HMs. Macrophages lacking c-Rel fail to polarize to M1 or M2 states, explaining reduced fibrosis in RelΔLysM mice. Pharmacological inhibition of c-Rel attenuated multi-organ fibrosis in both murine and human fibrosis. In conclusion, activation of c-Rel/Pfkfb3 in damaged tissue instigates a paracrine signalling network among epithelial, myeloid and mesenchymal cells to stimulate fibrogenesis. Targeting the c-Rel–Pfkfb3 axis has potential for therapeutic applications in fibrotic disease