Effects of developmental exposure to neurotoxic algal metabolites on predator-prey interactions in larval Pimephales promelas.

Harmful algal blooms are a growing environmental concern in aquatic systems. Although it is known that some of the secondary metabolites produced by cyanobacteria can alter predator-prey dynamics in aquatic communities by reducing foraging and/or predator evasion success, the mechanisms underpinning such responses are largely unknown. In this study, we examined the effects of a potent algal neurotoxin, ß-N-methylamino-L-alanine (BMAA), on the development and behavior of larval Fathead Minnows, Pimephales promelas, during predator-prey interactions. We exposed eggs and larvae to environmentally relevant concentrations of BMAA for 21 days, then tested subjects in prey-capture and predator-evasion assays designed to isolate the effects of exposure at sequential points of the stimulus-response pathway. Exposure was associated with changes in the ability of larvae to detect and respond to environmental stimuli (i.e., a live prey item and a simulated vibrational predator), as well as changes in behavior and locomotor performance during the response. Our findings suggest that chronic exposure to neurodegenerative cyanotoxins could alter the outcomes of predator-prey interactions in natural systems by impairing an animal's ability to perceive, process, and respond to relevant biotic stimuli.

Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster analysis.

Importance: Prurigo nodularis (PN) is a chronic heterogeneous inflammatory skin disease. Objective: To elucidate which components of type 2 inflammation are dysregulated systemically in PN. Design: Whole blood was obtained from PN patients with uncontrolled disease and control patients without pruritus. Plasma was assayed for IL-4, IL-5, IL-13, IgE, and periostin. ANOVA was utilized to compare PN and control patients and multiple-hypothesis adjusted p-value was calculated with the significance threshold at 0.05. Clustering was performed using K-means clustering. Participants: PN patients (n = 29) and controls (n = 18) from Johns Hopkins Dermatology had similar age sex, and race distributions. Results: Single-plex assays of the biomarkers demonstrated elevated circulating plasma IL-13 (0.13 vs. 0.006 pg/mL, p = 0.0008) and periostin (80.3 vs. 60.2 ng/mL, p = 0.012) in PN compared to controls. IL-4 (0.11 vs. 0.02 pg/mL, p = 0.30) and IL-5 (0.75 vs. 0.40 pg/mL, p = 0.10) were not significantly elevated, while IgE approached significance (1202.0 vs. 432.7 ng/mL, p = 0.08). Clustering of PN and control patients together revealed two clusters. Cluster 1 (n = 36) consisted of 18 PN patients and 18 controls. Cluster 2 (n = 11) consisted entirely of PN patients (p < 0.01). Cluster 2 had higher levels of IL-13 (0.33 vs. 0.008 pg/mL, p = 0.0001) and IL-5 (1.22 vs. 0.43 pg/mL, p = 0.03) compared to cluster 1. Conclusion and relevance: This study demonstrates elevation of IL-13 and periostin in the blood of PN patients, with distinct clusters with varying degrees of type 2 inflammation. Given this heterogeneity, future precision medicine approaches should be explored in the management of PN.