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Caenorhabditis elegans must distinguish pathogens from nutritious food sources among the many bacteria to which it is exposed in its environment.sup.1. Here we show that a single exposure to purified small RNAs isolated from pathogenic Pseudomonas aeruginosa (PA14) is sufficient to induce pathogen avoidance in the treated worms and in four subsequent generations of progeny. The RNA interference (RNAi) and PIWI-interacting RNA (piRNA) pathways, the germline and the ASI neuron are all required for avoidance behaviour induced by bacterial small RNAs, and for the transgenerational inheritance of this behaviour. A single P. aeruginosa non-coding RNA, P11, is both necessary and sufficient to convey learned avoidance of PA14, and its C. elegans target, maco-1, is required for avoidance. Our results suggest that this non-coding-RNA-dependent mechanism evolved to survey the microbial environment of the worm, use this information to make appropriate behavioural decisions and pass this information on to its progeny. Exposing Caenorhabditis elegans to non-coding small RNAs from pathogenic Pseudomonas aeruginosa induces avoidance behaviours in treated worms and their progeny, which reveals how C. elegans discriminates between bacterial species in its microbial environment., Author(s): Rachel Kaletsky [sup.1] [sup.2] , Rebecca S. Moore [sup.1] , Geoffrey D. Vrla [sup.1] , Lance R. Parsons [sup.2] , Zemer Gitai [sup.1] , Coleen T. Murphy [sup.1] [sup.2] [...]

The goal of this study was to test the hypothesis that NADPH oxidase contributes importantly to renal cortical oxidative stress and inflammation, as well as renal damage and dysfunction, and increases in arterial pressure. Fifty-four 7- to 8-wk-old Dahl salt-sensitive (S) or R/Rapp strain rats were maintained for 5 wk on a high sodium (8%) or high sodium + apocynin (1.5 mmol/1 in drinking water). Arterial and venous catheters were implanted on day 21. By day 35 in the high-Na S rats, mRNA expression of renal cortical gp91phox, p22phox, p47phox, and p67phox NADPH subunits in S rats increased markedly, and treatment of high-Na S rats with the NADPH oxidase inhibitor apocynin resulted in significant decreases in mRNA expression of these NADPH oxidase subunits. At the same time, in apocynin-treated S rats 1) renal cortical GSH/GSSG ratio increased, 2) renal cortical [O.sub.2.sup.*-] release and NADPH oxidase activity decreased, and 3) renal glomerular and interstitial damage markedly fell. Apocynin also decreased renal cortical monocyte/macrophage infiltration, and apocynin, but not the xanthine oxidase inhibitor allopurinol, attenuated decreases in renal hemodynamics and lowered arterial pressure. These data suggest that NADPH oxidase plays an important role in causing renal cortical oxidative stress and inflammation, which lead to decreases in renal hemodynamics, renal cortical damage, and increases in arterial pressure. renal failure; apocynin; renal hemodynamics; oxidative stress; inflammation

Background: Nonsense mutations in the dystrophin gene usually result in a severe Duchenne muscular dystrophy phenotype. Findings: We describe a 7-year-old boy with a rare pathogenic mutation in exon 29 c.3940C>T p.(Arg1314Ter) resulting in exon skipping, in turn rescuing the phenotype from a severe Duchenne type to a milder Becker muscular dystrophy type. No adults have been described with this mutation to date. Conclusions: Exon skipping of exon 29 results in a higher level of functional dystrophin. Some cases of muscular dystrophy may still require muscle biopsy to determine optimal management and pharmaceutical treatment options. [ABSTRACT FROM AUTHOR]

The goal of this study was to test the hypothesis that NADPH oxidase contributes importantly to renal cortical oxidative stress and inflammation, as well as renal damage and dysfunction, and increases in arterial pressure. Fifty-four 7- to 8-wk-old Dahl salt-sensitive (S) or R/Rapp strain rats were maintained for 5 wk on a high sodium (8%) or high sodium + apocynin (1.5 mmol/l in drinking water). Arterial and venous catheters were implanted on day 21. By day 35 in the high-Na S rats, mRNA expression of renal cortical gp91phox, p22phox, p47phox, and p67phox NADPH subunits in S rats increased markedly, and treatment of high-Na S rats with the NADPH oxidase inhibitor apocynin resulted in significant decreases in mRNA expression of these NADPH oxidase subunits. At the same time, in apocynin-treated S rats 1) renal cortical GSH/GSSG ratio increased, 2) renal cortical O2 release and NADPH oxidase activity decreased, and 3) renal glomerular and interstitial damage markedly fell. Apocynin also decreased renal cortical monocyte/macrophage infiltration, and apocynin, but not the xanthine oxidase inhibitor allopurinol, attenuated decreases in renal hemodynamics and lowered arterial pressure. These data suggest that NADPH oxidase plays an important role in causing renal cortical oxidative stress and inflammation, which lead to decreases in renal hemodynamics, renal cortical damage, and increases in arterial pressure. [ABSTRACT FROM AUTHOR]

Epidemiologic studies have linked the use of aspirin to a decline in chronic inflammation that underlies many human diseases, including some cancers. Aspirin reduces the levels of cyclooxygenase-mediated pro-inflammatory prostaglandins, promotes the production of pro-resolution molecules, and triggers the production of anti-inflammatory electrophilic mono-oxygenated (EFOX) lipid mediators. We investigated the effects of aspirin in fruit fly models of chronic inflammation. Ectopic Toll/NF-κB and JAK/STAT signaling in mutant D. melanogaster results in overproliferation of hematopoietic blood progenitors resulting in the formation of granuloma-like tumors. Ectopic JAK-STAT signaling also leads to metabolic inflammation. We report that aspirin-treated mutant flies experience reduction in metabolic inflammation, mitosis, ectopic immune signaling, and macrophage infiltration. Moreover, these flies synthesize 13-HODE, and aspirin triggers 13-oxoODE (13-EFOX-L2) production. Providing the precursor of 13-HODE, linoleic acid, or performing targeted knockdown of the transcription factor STAT in inflammatory blood cells, boosts 13-EFOX-L2 levels while decreasing metabolic inflammation. Thus, hematopoietic cells regulate metabolic inflammation in flies, and their effects can be reversed by pharmaceutical or dietary intervention, suggesting deep phylogenetic conservation in the ability of animals to resolve inflammation and repair tissue damage. These findings can help identify novel treatment targets in humans. [ABSTRACT FROM AUTHOR]

The goal of this study was to determine if renal oxidative stress increases renal inflammation in Dahl salt-sensitive hypertension. Dahl salt-sensitive (S) and salt-resistant (R) rats were equipped with arterial and venous catheters and subjected to a 5-week diet of high Na (8% NaCl) or high Na + Vitamins C and E. Mean arterial pressure (MAP) was measured continuously throughout the last 10 days. By the end of week 5, renal cortical O2*- release in S rots was significantly reduced in the S rats with vitamins (1204±100 vs 821±63 RLU/min/mg). At the same time, renal inflammation in the S rats with high Na vitamin treatment group also significantly decreased compared to S high Na group (TNFα, 0.96±0.1 vs 0.59±0.1 pg/mg; MCP-1, 16±1 vs 10±1 pg/mg; monocyte/macrophage infiltration, 15±2 vs 3±1 cells/mm²), but IL-6 was unchanged (4±1 vs 4±0 pg/mg). Interestingly, in the R rat, vitamin treatment decreased renal macrophage infiltration and MCP-1 without a change in MAP. Vitamin treatment in S high Na rats decreased MAP and urinary protein excretion and increased GFR and renal plasma flow. In summary, vitamin C/E treatment in Dahl S rats on high Na intake decreased renal oxidative stress and renal markers of inflammation and improved renal damage and dysfunction. In conclusion, renal oxidative stress is associated with increased renal inflammation in Dahl salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

C. elegans are exposed to a variety of pathogenic and non-pathogenic bacteria species in their natural environment. Correspondingly, C. elegans has evolved an ability to discern between nutritive and infectious bacterial food sources. Here we show that C. elegans can learn to avoid the pathogenic bacteria Pseudomonas fluorescens 15 (PF15), and that this learned avoidance behavior is passed on to progeny for four generations, as we previously demonstrated for Pseudomonas aeruginosa (PA14) and Pseudomonas vranovensis , using similar mechanisms, including the involvement of both the TGF-β ligand DAF-7 and Cer1 retrotransposon-encoded virus-like particles. PF15 small RNAs are both necessary and sufficient to induce this transgenerational avoidance behavior. Unlike PA14 or P. vranovensis , PF15 does not use P11, Pv1, or a small RNA with maco-1 homology for this avoidance; instead, an unrelated PF15 small RNA, Pfs1, that targets the C. elegans vab-1 Ephrin receptor gene is necessary and sufficient for learned avoidance, suggesting the evolution of yet another bacterial sRNA/ C. elegans gene target pair involved in transgenerational inheritance of pathogen avoidance. As VAB-2 Ephrin receptor ligand and MACO-1 knockdown also induce PF15 avoidance, we have begun to understand the genetic pathway involved in small RNA targeted pathogenic avoidance. Moreover, these data show that axon guidance pathway genes (VAB-1 and VAB-2) have previously unknown adult roles in regulating neuronal function. C. elegans may have evolved multiple bacterial specificity-encoded small RNA-dependent mechanisms to avoid different pathogenic bacteria species, thereby providing progeny with a survival advantage in a dynamic environment.

Caenorhabditis elegans is used as a model organism to study a wide range of topics in molecular and cellular biology. Conventional C. elegans assays often require a large sample size with frequent manipulations, rendering them labor-intensive. Automated high-throughput workflows may not be always the best solution to reduce benchwork labor, as they may introduce more complexity. Thus, most assays are carried out manually, where logging and digitizing experimental data can be as time-consuming as picking and scoring worms. Here we report the development of CeAid, C. elegans Application for inputting data, which significantly expedites the data entry process, utilizing swiping gestures and a voice recognition algorithm for logging data using a standard smartphone or Android device. This modular platform can also be adapted for a wide range of assays where recording data is laborious, even beyond worm research., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)