Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the redox status of the soluble guanylyl cyclase.

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Some COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS-driven oxidative stress on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, this superoxide increase did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide scavenger mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseases.

Ants resort to heuristics when facing relational-learning tasks they cannot solve.

We humans sort the world around us into conceptual groups, such as 'the same' or 'different', which facilitates many cognitive tasks. Applying such abstract concepts can improve problem-solving success and is therefore worth the cognitive investment. In this study, we investigated whether ants (Lasius niger) can learn the relational rule of 'the same' or 'different' by training them in an odour match-to-sample test over 48 visits. While ants in the 'different' treatment improved significantly over time, reaching around 65% correct decisions, ants in the 'same' treatment did not. Ants did not seem able to learn such abstract relational concepts, but instead created their own individual strategy to try to solve the problem: some ants decided to 'always go left', others preferred a 'go to the more salient cue' heuristic which systematically biased their decisions. These heuristics even occasionally lowered the success rate in the experiment below chance, indicating that following any rule may be more desirable then making truly random decisions. As the finding that ants resort to heuristics when facing hard-to-solve decisions was discovered post-hoc, we strongly encourage other researchers to ask whether employing heuristics in the face of challenging tasks is a widespread phenomenon in insects.