Neonicotinoids, a class of insecticides structurally similar to nicotine that target biting and sucking insects, are the most widely used insecticides today, in part due to their supposed low toxicity in other organisms. However, a growing body of research has found that even low doses of neonicotinoids can induce unexpected negative effects on the physiology and survival of a wide range of non-target organisms. Importantly, no work has been done on the commercial formulations of pesticides that include imidacloprid as the active ingredient, but that also contain many other components. The present study examines the sublethal effects of "Tree and Shrub"™ ("T+S"), a commercial insecticide containing the neonicotinoid imidacloprid as its active ingredient, on Caenorhabditis elegans. We discovered that "T+S" significantly stunted the overall growth in wildtype nematodes, an effect that was exacerbated by concurrent exposure to heat stress. "T+S" also negatively impacted fecundity as measured by increased germline apoptosis, a decrease in egg-laying, and fewer viable offspring. Lastly, exposure to "T+S" resulted in degenerative changes in nicotinic cholinergic neurons in wildtype nematodes. As a whole, these findings demonstrate widespread toxic effects of neonicotinoids to critical functions in nematodes.
Environmental toxicants are chemicals that negatively affect human health. Although there are numerous ways to limit exposure, the ubiquitous nature of certain environmental toxicants makes it impossible to avoid them entirely. Consequently, scientists are continuously working toward developing strategies for combating their harmful effects. Using the nematode Caenorhabditis elegans, a model with many genetic and physiological similarities to humans, researchers in the Colaiácovo laboratory have identified several molecular mechanisms by which the toxic agent bisphenol A (BPA) interferes with reproduction. Here, we address their recent discovery that a widely available compound, Coenzyme Q10 (CoQ10), can rescue BPA-induced damage. This work is significant in that it poses a low-cost method for improving reproductive success in humans. The goal of this primer is to assist educators and students with navigating the paper entitled “Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline.” It is ideally suited for integration into an upper-level undergraduate course such as Genetics, Cell and Molecular Biology, Developmental Biology, or Toxicology. The primer provides background information on the history of BPA, the utility of the C. elegans germ line as a model for studying reproductive toxicity, and research methods including assessment of programmed cell death, fluorescent microscopy applications, and assays to quantify gene expression. Questions for deeper exploration in-class or online are provided.Related article in GENETICS: Hornos Carneiro MF, Shin N, Karthikraj R, Barbosa F Jr, Kannan K, Colaiácovo MP. Antioxidant CoQ10 restores fertility by rescuing bisphenol A-induced oxidative DNA damage in the Caenorhabditis elegans Germline. Genetics 214:381–395.
H3K56 acetylation (H3K56Ac) was first identified in yeast and has recently been reported to play important roles in maintaining genomic stability, chromatin assembly, DNA replication, cell cycle progression and DNA repair. Although H3.1K56Ac has been relatively well studied, the function of H3.3K56Ac remains mostly unknown in mammals. In this study, we used H3.3K56Q and H3.3K56R mutants to study the possible function of H3.3K56 acetylation. The K-to-Q substitution mimics a constitutively acetylated lysine, while the K-to-R replacement mimics a constitutively unmodified lysine. We report that cell lines harboring mutation of H3.3K56R exhibit dramatic morphology changes and cell death. Using Tet-Off inducible system, we show an increased population of polyploid/aneuploid cells and a decreased cell viability in H3.3K56R mutant cells. In consistence with these results, H3.3K56R mutant compromised H3.3 incorporation into several pericentric and centric heterochromatin regions we tested. Moreover, mass spectrometry analysis coupled with label free quantification reveal that biological processes regulated by the H3.3-associating proteins, whose interaction with H3.3 is markedly increased by H3.3K56Q mutation but decreased by H3.3K56Q mutation, include sister chromatid cohesion, mitotic nuclear division, and mitotic nuclear envelope disassembly. These results suggest that H3.3K56 acetylation is crucial for chromosome segregation and cell division in mammals. ∼ 30% of total histone H3. However, in mammalian cells its abundance is much lower as it marks less than 1% of total H3 [34]. H3K56Ac is tightly regulated by cell cycle and DNA damage-induced checkpoints [30, 32]. In budding yeast, H3K56 has been reported to be acetylated predominantly during the S phase, but deacetylated rapidly when cells enter the G2/M phase of the cell cycle [32, 43]. Mammalian H3K56 acetylation requires the histone chaperone Asf1 and occurs mainly at the S phase in unstressed cells [37, 42]. Dysregulation of histone H3K56 acetylation leads to increased sensitivity to DNA damage agents and elevated genome instability [37, 44, 45]. Both hyper-and hypo-acetylation of H3K56 result in defects in sister chromatid cohesion , recombination and ribosomal DNA (rDNA) amplification [27, 33].H3K56Ac makes the nucleosome termini more flexible and facilitates nucleosome disassembly [41, 46, 47]. H3K56Ac also alters the substrate specificity of SWR-C, leading to either H2A.Z or H2A being exchanged from nucleosomes [48]. These findings strongly support the important role of H3K56 acetylation in regulating cell cycle progression, DNA damage response, chromatin remodeling, nucleosome assembly following DNA replication and DNA repair.However, all these reports focused on K56Ac of H3, either on H3.1 or without defining which isoform of H3. Studies on K56Ac of the variant H3.3 in mammals in particular are absent and remain to be explored.In this study, to address the function of H3.3K56 acetylation, we made use of H3.3K56Q and H3.3K56R mutants, in which the lysine at...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.