Biology subjects

De-Souza, E. A.

Publications and source records attributed to De-Souza, E. A..

4 recordsLinked to original sources

bioRxiv2022

Tissue-specific overexpression of the double-stranded RNA transporter SID-1 limits lifespan in C. elegans

Intertissue RNA transport has emerged as a novel signaling mechanism. In C. elegans, this is conferred by the systemic RNAi pathway, in which the limiting step is the cellular import of extracellular RNAs via SID-1. To better understand the physiological role of systemic RNAi in vivo, we modified the function of SID-1 through loss-of-function mutation and tissue-specific overexpression of sid-1 in C. elegans. We observed that sid-1 loss-of-function mutants are as healthy as wild-type worms. Conversely, overexpression of sid-1 in intestine, muscle, or neurons rendered worms short-lived. The effects of intestinal sid-1 overexpression were reversed by silencing the components of the systemic RNAi pathway sid-1, sid-2 and sid-5, thus implicating RNA transport. Moreover, silencing the miRNA biogenesis proteins pash-1 and dcr-1 rendered the lifespan of worms with intestinal sid-1 overexpression similar to controls. Lastly, we observed that the lifespan decrease produced by tissue-specific sid-1 overexpression was dependent on the bacterial food source. Collectively, our data support the notion that systemic RNA signaling is tightly regulated, and unbalancing that process provokes a reduction in lifespan.

molecular biology↗

bioRxiv2022

The Nuclear RNAi Pathway Regulates DAF-16/FOXO to Control C. elegans Longevity and Dauer Entry

Caenorhabditis elegans with impaired insulin/IGF-1 receptor signalling (IIS) or with germline ablation live longer and this phenomenon is entirely dependent on the transcription factor DAF-16 - the C. elegans homolog of the class O of the forkhead box transcription factors (FoxO). In a candidate RNAi screen designed to search for new modifiers of DAF-16 function among genes involved in histone modification and/or small RNA-mediated silencing pathways, we found nrde-1, wago-1, and adr-1 as positive regulators of DAF-16. We confirmed by several methods and in different models that DAF-16 translocation to the nucleus and, subsequently, its function is tightly controlled by these genes and narrowed down to components of the NRDE complex and the nuclear RNAi pathway as key DAF-16 modulators. Importantly, we found that the NRDE pathway controls DAF-16-mediated longevity and dauer entry. Our epistasis data indicate that nrde-1 interacts with akt-1 to control lifespan. We also demonstrated that NRDE-1 acts downstream of AGE-1/PI3K and partially requires mTORC2 and AKT-1 to control DAF-16 translocation. These results unveil a mechanism of regulation of dauer formation and longevity in C. elegans via nuclear RNAi-mediated modulation of DAF-16 function in a manner that involves the mTORC2-AKT axis.

genetics↗

bioRxiv2022

Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation

Animals rely on chemosensory cues to survive in pathogen-rich environments. In C. elegans, pathogenic bacteria are known to trigger aversive behaviors through neuronal perception, and to activate molecular defenses throughout the animal. This suggests that neurons may be able to coordinate the activation of organism-wide defensive responses upon pathogen perception. We find that exposure to volatile pathogen-associated compounds induces cell non-autonomous activation of the endoplasmic reticulum unfolded protein response (UPRER) in peripheral tissues following xbp-1 splicing in neurons. This odorant-induced UPRER activation is dependent upon transforming growth factor beta (TGF-{beta}) signaling and leads to extended lifespan and enhanced clearance of toxic proteins. Our data suggest that the cell non-autonomous UPRER rewires organismal proteostasis in response to pathogen detection, pre-empting the arrival of proteotoxic stress. Thus, chemosensation of particular odors may be a novel way to manipulate stress responses and longevity.

cell biology↗

bioRxiv2019

Comparing quality of reporting between preprints and peer-reviewed articles in the biomedical literature

BackgroundPreprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the readers ability to independently interpret data and reproduce findings. MethodsIn this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons between preprints from bioRxiv to their own peer-reviewed versions in journals. ResultsPeer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication. ConclusionsOur results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions.

scientific communication and education↗