De novo polyamine synthesis supports metabolic and functional responses in activated murine NK cells.

Cellular metabolism is dynamically regulated in NK cells and strongly influences their responses. Metabolic dysfunction is linked to defective NK cell responses in diseases such as obesity and cancer. The transcription factors, sterol regulatory element binding protein (SREBP) and cMyc, are crucial for controlling NK cell metabolic and functional responses, though the mechanisms involved are not fully understood. This study reveals a new role for SREBP in NK cells in supporting de novo polyamine synthesis through facilitating elevated cMyc expression. Polyamines have diverse roles and their de novo synthesis is required for NK cell glycolytic and oxidative metabolism and to support optimal NK cell effector functions. When NK cells with impaired SREBP activity were supplemented with exogenous polyamines, NK cell metabolic defects were not rescued but these NK cells displayed significant improvement in some effector functions. One role for polyamines is in the control of protein translation where spermidine supports the posttranslational hypusination of translation factor eIF5a. Pharmacological inhibition of hypusination also impacts upon NK cell metabolism and effector function. Considering recent evidence that cholesterol-rich tumor microenvironments inhibit SREBP activation and drive lymphocyte dysfunction, this study provides key mechanistic insight into this tumor-evasion strategy.

Experiencing regret about a choice helps children learn to delay gratification.

Children (6- and 7-year-olds) decided whether to wait for a short delay to win a prize or for a longer period to win a different prize. Those who chose to take their prize after a short delay won two candies but were shown that they would have won four candies if they had waited longer. We measured whether children regretted their choice not to wait. The next day, children were faced with the same choice again. Children who regretted choosing the short delay on Day 1 were more likely to delay gratification on Day 2 than children who had not regretted their previous choice. In a second study, we replicated this finding while controlling for intellectual ability and children's preference for four candies over two candies. This suggests that experiencing regret about a choice not to wait assists children in delaying gratification when faced with the same choice again.

Knowing when to hold 'em: regret and the relation between missed opportunities and risk taking in children, adolescents and adults.

Regret over missed opportunities leads adults to take more risks. Given recent evidence that the ability to experience regret impacts decisions made by 6-year-olds, and pronounced interest in the antecedents to risk taking in adolescence, we investigated the age at which a relationship between missed opportunities and risky decision-making emerges, and whether that relationship changes at different points in development. Six- and 8-year-olds, adolescents and adults completed a sequential risky decision-making task on which information about missed opportunities was available. Children also completed a task designed to measure their ability to report regret when explicitly prompted to do so. The relationship between missed opportunities and risky decision-making did not emerge until 8 years, at which age it was associated with the ability to explicitly report regret, and was stronger in adults than in adolescents. These novel results highlight the potential importance of the ability to experience regret in children and adolescents' risky decision-making.

The development of regret and relief about the outcomes of risky decisions.

Although a number of studies have examined the developmental emergence of counterfactual emotions of regret and relief, none of these has used tasks that resemble those used with adolescents and adults, which typically involve risky decision making. We examined the development of the counterfactual emotions of regret and relief in two experiments using a task in which children chose between one of two gambles that varied in risk. In regret trials they always received the best prize from that gamble but were then shown that they would have obtained a better prize had they chosen the alternative gamble, whereas in relief trials the other prize was worse. We compared two methods of measuring regret and relief based on children's reported emotion on discovering the outcome of the alternative gamble: one in which children judged whether they now felt the same, happier, or sadder on seeing the other prize and one in which children made emotion ratings on a 7-point scale after the other prize was revealed. On both of these methods, we found that 6- and 7-year-olds' and 8- and 9-year-olds' emotions varied appropriately depending on whether the alternative outcome was better or worse than the prize they had actually obtained, although the former method was more sensitive. Our findings indicate that by at least 6 or 7years children experience the same sorts of counterfactual emotions as adults in risky decision-making tasks, and they also suggest that such emotions are best measured by asking children to make comparative emotion judgments.

Regret and adaptive decision making in young children.

In line with the claim that regret plays a role in decision making, O'Connor, McCormack, and Feeney (Child Development, 85 (2014) 1995-2010) found that children who reported feeling sadder on discovering they had made a non-optimal choice were more likely to make a different choice the next time around. We examined two issues of interpretation regarding this finding: whether the emotion measured was indeed regret and whether it was the experience of this emotion, rather than the ability to anticipate it, that affected decision making. To address the first issue, we varied the degree to which children aged 6 or 7 years were responsible for an outcome, assuming that responsibility is a necessary condition for regret. The second issue was addressed by examining whether children could accurately anticipate that they would feel worse on discovering they had made a non-optimal choice. Children were more likely to feel sad if they were responsible for the outcome; however, even if they were not responsible, children were more likely than chance to report feeling sadder. Moreover, across all conditions, feeling sadder was associated with making a better subsequent choice. In a separate task, we demonstrated that children of this age cannot accurately anticipate feeling sadder on discovering that they had not made the best choice. These findings suggest that although children may feel regret following a non-optimal choice, even if they were not responsible for an outcome, they may experience another negative emotion such as frustration. Experiencing either of these emotions seems to be sufficient to support better decision making.

Do children who experience regret make better decisions? A developmental study of the behavioral consequences of regret.

Although regret is assumed to facilitate good decision making, there is little research directly addressing this assumption. Four experiments (N = 326) examined the relation between children's ability to experience regret and the quality of their subsequent decision making. In Experiment 1 regret and adaptive decision making showed the same developmental profile, with both first appearing at about 7 years. In Experiments 2a and 2b, children aged 6-7 who experienced regret decided adaptively more often than children who did not experience regret, and this held even when controlling for age and verbal ability. Experiment 3 ruled out a memory-based interpretation of these findings. These findings suggest that the experience of regret facilitates children's ability to learn rapidly from bad outcomes.

The development of regret.

In two experiments, 4- to 9-year-olds played a game in which they selected one of two boxes to win a prize. On regret trials the unchosen box contained a better prize than the prize children actually won, and on baseline trials the other box contained a prize of the same value. Children rated their feelings about their prize before and after seeing what they could have won if they had chosen the other box and were asked to provide an explanation if their feelings had changed. Patterns of responding suggested that regret was experienced by 6 or 7 years of age; children of this age could also explain why they felt worse in regret trials by referring to the counterfactual situation in which the prize was better. No evidence of regret was found in 4- and 5-year-olds. Additional findings suggested that by 6 or 7 years, children's emotions were determined by a consideration of two different counterfactual scenarios.