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Neuroendocrine cells react to physical, chemical, and synaptic signals originating from tissues and the nervous system, releasing hormones that regulate various body functions beyond the synapse. Neuroendocrine cells are often embedded in complex tissues making direct tests of their activation mechanisms and signaling effects difficult to study. In the nematode wormCaenorhabditis elegans, four uterine-vulval (uv1) neuroendocrine cells sit above the vulval canal next to the egg-laying circuit, releasing tyramine and neuropeptides that feedback to inhibit egg laying. We have previously shown uv1 cells are mechanically deformed during egg laying, driving uv1 Ca²⁺transients. However, whether egg-laying circuit activity, vulval opening, and/or egg release triggered uv1 Ca²⁺activity was unclear. Here, we show uv1 responds directly to mechanical activation. Optogenetic vulval muscle stimulation triggers uv1 Ca²⁺activity following muscle contraction even in sterile animals. Direct mechanical prodding with a glass probe placed against the worm cuticle triggers robust uv1 Ca²⁺activity similar to that seen during egg laying. Direct mechanical activation of uv1 cells does not require other cells in the egg-laying circuit, synaptic or peptidergic neurotransmission, or transient receptor potential vanilloid and Piezo channels. EGL-19 L-type Ca²⁺channels, but not P/Q/N-type or ryanodine receptor Ca²⁺channels, promote uv1 Ca²⁺activity following mechanical activation. L-type channels also facilitate the coordinated activation of uv1 cells across the vulva, suggesting mechanical stimulation of one uv1 cell cross-activates the other. Our findings show how neuroendocrine cells like uv1 report on the mechanics of tissue deformation and muscle contraction, facilitating feedback to local circuits to coordinate behavior. 

Previous work has shown that spherical CuO nanomaterials show negative effects on cell and animal physiology. The biological effects of Cu 2 O materials, which possess unique chemical features compared to CuO nanomaterials and can be synthesized in a similarly large variety of shapes and sizes, are comparatively less studied. Here, we synthesized truncated octahedral Cu 2 O particles and characterized their structure, stability, and physiological effects in the nematode worm animal model, Caenorhabditis elegans . Cu 2 O particles were found to be generally stable in aqueous media, although the particles did show signs of oxidation and leaching of Cu 2+ within hours in worm growth media. The particles were found to be especially sensitive to inorganic phosphate (PO 4 3− ) found in standard NGM nematode growth medium. Cu 2 O particles were observed being taken up into the nematode pharynx and detected in the lumen of the gut. Toxicity experiments revealed that treatment with Cu 2 O particles caused a significant reduction in animal size and lifespan. These toxic effects resembled treatment with Cu 2+ , but measurements of Cu leaching, worm size, and long-term behavior experiments show the particles are more toxic than expected from Cu ion leaching alone. These results suggest worm ingestion of intact Cu 2 O particles enhances their toxicity and behavior effects while particle exposure to environmental phosphate precipitates leached Cu 2+ into biounavailable phosphate salts. Interestingly, the worms showed an acute avoidance of bacterial food with Cu 2 O particles, suggesting that animals can detect chemical features of the particles and/or their breakdown products and actively avoid areas with them. These results will help to understand how specific, chemically-defined particles proposed for use in polluted soil and wastewater remediation affect animal toxicity and behaviors in their natural environment.