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Abstract Environmental stress from ultraviolet radiation, elevated temperatures or metal toxicity can lead to reactive oxygen species in cells, leading to oxidative DNA damage, premature aging, neurodegenerative diseases, and cancer. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activates many cytoprotective proteins within the nucleus to maintain homeostasis during oxidative stress. In vertebrates, Nrf2 levels are regulated by the Kelch-family protein Keap1 (Kelch-like ECH-associated protein 1) in the absence of stress according to a canonical redox control pathway. Little, however, is known about the redox control pathway used in early diverging metazoans. Our study examines the presence of known oxidative stress regulatory elements within non-bilaterian metazoans including free living and parasitic cnidarians, ctenophores, placozoans, and sponges. Cnidarians, with their pivotal position as the sister phylum to bilaterians, play an important role in understanding the evolutionary history of response to oxidative stress. Through comparative genomic and transcriptomic analysis our results show that Nrf homologs evolved early in metazoans, whereas Keap1 appeared later in the last common ancestor of cnidarians and bilaterians. However, key Nrf–Keap1 interacting domains are not conserved within the cnidarian lineage, suggesting this important pathway evolved with the radiation of bilaterians. Several known downstream Nrf targets are present in cnidarians suggesting that cnidarian Nrf plays an important role in oxidative stress response even in the absence of Keap1. Comparative analyses of key oxidative stress sensing and response proteins in early diverging metazoans thus provide important insights into the molecular basis of how these lineages interact with their environment and suggest a shared evolutionary history of regulatory pathways. Exploration of these pathways may prove important for the study of cancer therapeutics and broader research in oxidative stress, senescence, and the functional responses of early diverging metazoans to environmental change.more » « less
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As part of the first stage of a community-based participatory research project with two communities in the Canadian Arctic—Kangiqsujuaq, Nunavik, and Ulukhaktok, Northwest Territories—we conducted 57 interviews eliciting residents’ perceptions of pressing issues facing their communities, problems affecting health and wellbeing, and how researchers or other organized groups could help alleviate those problems. A recurrent theme that emerged during these interviews was having “no one to talk to.” Here, we focus on understanding why communication was a central theme using a grounded-theory approach to develop a model of Inuit stress management. Inuit in both Kangiqsujuaq and Ulukhaktok codify stress as isumaaluttuq, or excess worry, which often manifests physically and leads to social withdrawal. Because stress is believed to accumulate in the body, managing it involves decisions about whether to “Get It Out” or “Keep It In.” Keep It In is a potentially dangerous strategy because, if the problem does not resolve itself, accumulated stress may have harmful consequences. Inuit viewed talking to others as the most effective means to Get It Out, but respondents also identified numerous barriers to doing so. One important reason for this is that stress is transferable: Talking to others about a problem potentially increases the burden of stress on them. Consequently, Inuit may choose to Keep It In to avoid the potential negative consequences (for others or for oneself) of sharing bad thoughts. Based on this preliminary model, we consider questions for further inquiry and implications for community-based mental health programming in Inuit communities.
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1029/2021AV000509
