[
Nature,
1993]
Myth and literature have given human immortality mixed reviews. There is, nonetheless, fairly general agreement that intimations of mortality, in the form of ageing or senescence, are regrettable and should be postponed as long as possible. On page 461 of this issue, Kenyon and co-workers report a mutation of the nematode worm Caenorahbditis elegans that more than doubles its healthy and fertile adult lifespan.
[
Nature,
2001]
The degredation of DNA is one of the hallmarks of programmed cell death (apoptosis). When forced to commit suicide, apoptotic cells - like good secret agents - grimly destroy their "instruction book," chewing up their genomic DNA into tiny morsels. Until now, only two DNA-destroying enzymes (nucleases) with a clear role in cell death were known, one in mammals and one in the nematode worm Caenorhabditis elegans. But, on pages 90-99 of this issue, Li and colleagues and Parrish and co-workers show that another nuclease, endonuclease G (endoG), also contributes to the carnage, and might even influence the likelihood that a cell will live or die.
[
Gut Microbes,
2013]
The fungus Candida albicans and the gram-positive bacterium Enterococcus faecalis are both normal residents of the human gut microbiome and cause opportunistic disseminated infections in immunocompromised individuals. Using a nematode infection model, we recently showed that co-infection resulted in less pathology and less mortality than infection with either species alone and this was partly explained by an interkingdom signaling event in which a bacterial-derived product inhibits hyphal morphogenesis of C. albicans. In this addendum we discuss these findings in the contest of other described bacterial-fungal interactions and recent data suggesting a potentially synergistic relationship between these two species in the mouse gut as well. We suggest that E. faecalis and C. albicans promote a mutually beneficial association with the host, in effect choosing a commensal lifestyle over a pathogenic one.
[
Worm,
2014]
Animal development is driven by robust, cell-specific gene expression programs. Understanding mechanistically how a single transcription factor (TF) can govern distinct programs with exquisite precision is a major challenge. We view TFs as signal integrators, taking information from co-regulator interactions, post-translational modifications, other transcription factors, chromatin state, DNA sequence and in some cases, specific noncovalent ligands, to determine the collection of genes regulated by a TF at any given time. Here, we describe a reductionist approach to combinatorial transcriptional regulation, focusing on a single C. elegans TF, the nuclear hormone receptor NHR-25, and a single post-translational modification, SUMO. We suggest that the ratio of sumoylated to unsumoylated NHR-25 could specify a switch-like cell-fate decision during vulval development. Direct examination of this "SUMO ratio" in vivo is challenging and we discuss possible solutions going forward. We also consider how sumoylation of multiple substrates might be coordinated during vulval development. Finally, we note that iteration of this approach could leverage our sumoylation findings to define the roles of other effectors of NHR-25 in the developing vulva and in other tissues.