Ethal odor dose, respectively. b Food aversion induced by 1 l ccBA of naive and ccBA-preconditioned (1 l for four h) animals at diverse time points. c Meals aversion induced by 4 l of ccDA of naive and ccDA-preconditioned (four l for four h) animals at different time points. d Survival of naive and ccBA-preconditioned worms 14 h just after a 3-h GlyT1 manufacturer exposure to 8 l ccBA. e Survival of naive and ccDA-preconditioned worms 14 h right after a 3-h exposure to 16 l ccDA. Data are expressed as mean SEM. N, quantity of independent experiments. p values were obtained by one-way ANOVA with Fisher’s LSD post hoc test. n.s., not significant; p 0.05; p 0.01; p 0.Hajdet al. BMC Biology(2021) 19:Page six ofsurvival decline on ccDA (Fig. 2d, e), representing a protective (hormetic) effect of ccBA and a debilitating (distressing) effect of ccDA preconditioning. Hormesis and distress are well-known phenomena in tension biology and suggest efficient or insufficient physiological responses for the tension induced by ccBA or ccDA exposures, respectively [17]. These findings are constant with these on Fig. 1, i.e., equivalent survival rates of animals around the respective odors, displaying a recovery of CXCR1 supplier ccBA-exposed worms from a transient early paralysis in comparison to the progressive decline soon after modest initial paralysis of ccDA-exposed worms (cf. Fig. 1e , two h of exposure). Therefore, ccBA preconditioning induces behavioral and physiological anxiety tolerance, whilst ccDA preconditioning induces behavioral sensitization and physiological distress. These benefits suggest that nematodes can mount effective physiological protection against ccBA, but can only engage more alert behavioral defense via sensitization against ccDA.Undiluted benzaldehyde, but not diacetyl, activates specific systemic cytoprotective responsesRNAi, although that of gst-4 was abolished by skn-1 RNAi (Fig. 3c, d). Importantly, ccBA did not activate a number of other pressure reporters, such as the HSF-1 and DAF-16 target hsp-16.2, the HSF-1 target and endoplasmic reticulum unfolded protein response (UPR) reporter hsp-4, the SKN-1-dependent gcs-1, and also the DAF-16dependent sod-3 reporter (Added File 1: Fig. S3c). These findings demonstrate that a distinct stress and detoxification response involving a subset of DAF-16- and SKN-1-activated genes participate in the molecular defense against ccBA toxicity. In contrast, no apparent strain responses were detected upon ccDA exposure.ccBA-induced cytoprotective responses confer behavioral tolerance to ccBA, but to not ccDANext, we asked if the efficient vs. insufficient physiological protection against ccBA and ccDA exposure may possibly be reflected inside the differential mobilization of cellular defense responses for the respective toxic stresses. In agreement with our findings on the toxicity of ccBA, prior studies demonstrated that BA induced oxidative strain [26]. Therefore, we tested different oxidative strain response pathways that may be involved in the physiological adaptation to ccBA. Applying the TJ356 strain expressing GFP-tagged DAF-16, we observed that the identical ccBA dose applied for preconditioning induced a robust nuclear translocation of DAF-16 immediately after 30 min, comparable to that induced by heat pressure. Even so, DAF-16 remained cytosolic in response to ccDA (Fig. 3a and Extra File 1: Fig. S3a). The shift in DAF-16 localization exhibited a clear BA dose dependence (Further File 1: Fig. S3b). These congruent ccBA dosedependent changes in DAF-16 translocation and food avoidance (cf.