Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish

Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to P. aeruginosa infection. sod2 is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro, and sod2 knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections.     

Structured Sequence Learning: Animal Abilities,Cognitive Operations,and Language Evolution

Human language is a salient example of a neurocognitive system that is specialized to process complex dependencies between sensory events distributed in time, yet how this system evolved and specialized remains unclear. Artificial Grammar Learning (AGL) studies have generated a wealth of insights into how human adults and infants process different types of sequencing dependencies of varying complexity. The AGL paradigm has also been adopted to examine the sequence processing abilities of nonhuman animals. We critically evaluate this growing literature in species ranging from mammals (primates and rats) to birds (pigeons, songbirds, and parrots) considering also cross‐species comparisons. The findings are contrasted with seminal studies in human infants that motivated the work in nonhuman animals. This synopsis identifies advances in knowledge and where uncertainty remains regarding the various strategies that nonhuman animals can adopt for processing sequencing dependencies. The paucity of evidence in the few species studied to date and the need for follow‐up experiments indicate that we do not yet understand the limits of animal sequence processing capacities and thereby the evolutionary pattern. This vibrant, yet still budding, field of research carries substantial promise for advancing knowledge on animal abilities, cognitive substrates, and language evolution.