[
Journal of Gerontology,
1998]
Vanfleteren and colleagues present an interesting example of environmental conditions altering the kinetics of survival. Most previous studies of survival in C. elegans have used abundant bacteria as a food source. Such studies have found that the Gompertz function (exponential growth in mortality rate with age) gives a relatively good fit to survival curves, but that there is some deceleration in the rate of growth of mortality later in the life span. Yulong Yang and I have completed dozens of studies of small populations of the wild-type strain, N2, as well as strains TJ401, TJ411, TJ412,and BA713 in the presence of abundant bacteria in liquid or on agar. Survival curves were better fit by Gompertz more often than by Weibull or logistic functions (unpublished observations).
[
RNA Biol,
2014]
Small RNA programmed Argonautes are sophisticated cellular effector platforms known to be involved in a diverse array of functions ranging from mRNA cleavage, translational inhibition, DNA elimination, epigenetic silencing, alternative splicing and even gene activation. First observed in human cells, small RNA-induced gene activation, also known as RNAa, involves the targeted recruitment of Argonaute proteins to specific promoter sequences followed by induction of stable epigenetic changes which promote transcription. The existence of RNAa remains contentious due to its elusive mechanism. A string of recent studies in C. elegans provides unequivocal evidence for RNAa's fundamental role in sculpting the epigenetic landscape and maintaining active transcription of endogenous genes and supports the presence of a functionally sophisticated network of small RNA-Argonaute pathways consisting of opposite yet complementary "yin and yang" regulatory elements. In this review, we summarize key findings from recent studies of endogenous RNAa in C. elegans, with an emphasis on the Argonaute protein CSR-1.
[
Metabolites,
2018]
While progress has been made in discerning genetic associations with Parkinson's disease (PD), identifying elusive environmental contributors necessitates the application of unconventional hypotheses and experimental strategies. Here, we provide an overview of studies that we conducted on a neurotoxic metabolite produced by a species of common soil bacteria, <i>Streptomyces venezuelae (S. ven</i>), indicating that the toxicity displayed by this bacterium causes stress in diverse cellular mechanisms, such as the ubiquitin proteasome system and mitochondrial homeostasis. This dysfunction eventually leads to age and dose-dependent neurodegeneration in the nematode <i>Caenorhabditis elegans</i>. Notably, dopaminergic neurons have heightened susceptibility, but all of the neuronal classes eventually degenerate following exposure. Toxicity further extends to human SH-SY5Y cells, which also degenerate following exposure. Additionally, the neurons of nematodes expressing heterologous aggregation-prone proteins display enhanced metabolite vulnerability. These mechanistic analyses collectively reveal a unique metabolomic fingerprint for this bacterially-derived neurotoxin. In considering that epidemiological distinctions in locales influence the incidence of PD, we surveyed soils from diverse regions of Alabama, and found that exposure to ~30% of isolated <i>Streptomyces</i> species caused worm dopaminergic neurons to die. In addition to aging, one of the few established contributors to PD appears to be a rural lifestyle, where exposure to soil on a regular basis might increase the risk of interaction with bacteria producing such toxins. Taken together, these data suggest that a novel toxicant within the <i>Streptomyces</i> genus might represent an environmental contributor to the progressive neurodegeneration that is associated with PD.