Apoptosis and failure of checkpoint kinase 1 activation in human induced pluripotent stem cells under replication stress

Background: Human induced pluripotent stem (hiPS) cells have the ability to undergo self-renewal and differentiation similarly to human embryonic stem (hES) cells. We have recently shown that hES cells under replication stress fail to activate checkpoint kinase 1 (CHK1). They instead commit to apoptosis, which appears to be a primary defense mechanism against genomic instability. It is not known whether the failure of CHK1 activation and activation of apoptosis under replication stress is solely a feature of hES cells, or if it is a feature that can be extended to hiPS cells. Methods: Here we generated integration-free hiPS cell lines by mRNA transfection, and characterised the cell lines. To investigate the mechanism of S phase checkpoint activation, we have induced replication stress by adding excess thymidine to the cell culture medium, and performed DNA content analysis, apoptosis assays and immunoblottings. Results: We are showing that hiPS cells similarly to hES cells, fail to activate CHK1 when exposed to DNA replication inhibitors and commit to apoptosis instead. Our findings also suggest the Ataxia Telangiectasia Mutated pathway might be responding to DNA replication stress, resulting in apoptosis. Conclusion: Together, these data suggest that the apoptotic response was properly restored during reprogramming with mRNA, and that apoptosis is an important mechanism shared by hiPS and hES cells to maintain their genomic integrity when a replication stress occurs

Interpersonal effects of parents and adolescents on each other’s health behaviours: a dyadic extension of the theory of planned behaviour

Objective: Interpersonal relationships are important predictors of health outcomes and interpersonal influences on behaviours may be key mechanisms underlying such effects. Most health behaviour theories focus on intrapersonal factors and may not adequately account for interpersonal influences. We evaluate a dyadic extension of the Theory of Planned Behaviour by examining whether parent and adolescent characteristics (attitudes, subjective norms, perceived behavioural control and intentions) are associated with not only their own but also each other’s intentions/behaviours. Design: Using the Actor-Partner Interdependence Model, we analyse responses from 1717 parent-adolescent dyads from the Family Life, Activity, Sun, Health, and Eating study. Main Outcome Measures: Adolescents/parents completed self-reports of their fruit and vegetable consumption, junk food and sugary drinks consumption, engagement in physical activity, and engagement in screen time sedentary behaviours. Results: Parent/adolescent characteristics are associated with each other’s health-relevant intentions/behaviours above the effects of individuals’ own characteristics on their own behaviours. Parent/adolescent characteristics covary with each other’s outcomes with similar strength, but parent characteristics more strongly relate to adolescent intentions, whereas adolescent characteristics more strongly relate to parent behaviours. Conclusions: Parents and adolescents may bidirectionally influence each other’s health intentions/behaviours. This highlights the importance of dyadic models of health behaviour and suggests intervention targets

The Dyadic Health Influence Model

Relationship partners affect one another’s health outcomes through their health behaviors, yet how this occurs is not well understood. To fill this gap, we present the Dyadic Health Influence Model (DHIM). The DHIM identifies three routes through which a person (the agent) can impact the health beliefs and behavior of their partner (the target). An agent may (a) model health behaviors and shape the shared environment, (b) enact behaviors that promote their relationship, and/or (c) employ strategies to intentionally influence the target’s health behavior. A central premise of the DHIM is that agents act based on their beliefs about their partner’s health and their relationship. In turn, their actions have consequences not only for targets’ health behavior but also for their relationship. We review theoretical and empirical research that provides onitial support for the routes and offer testable predictions at the intersection of health behavior change research and relationship science

Parenting styles moderate how parent and adolescent beliefs shape each other's eating and physical activity: Dyadic evidence from a cross-sectional, U.S. National Survey

Psychological theories of health behavior focus on intrapersonal influences on behavior. Greater attention to interpersonal effects and the relational contexts that regulate them has the potential to improve theory, and offer innovative strategies for intervention. This research takes a dyadic approach to understanding how parent and adolescent beliefs influence each other's health behaviors, and how the relationship context of parent-adolescent dyads moderates these effects. Using the Family Life, Activity, Sun, Health, and Eating study (FLASHE), we analyze responses from 1717 parent-adolescent dyads from across the U.S., and explore a dyadic extension to the Theory of Planned Behavior (TPB). We evaluate how parenting styles that characterize each parent-adolescent dyad moderate the degree to which parents’ and adolescents’ own attitudes, subjective norms, and perceived behavioral control are associated with the other person's behaviors across four domains: fruit and vegetable consumption, junk food and sugary drinks consumption, engagement in physical activity, and engagement in screen time sedentary behaviors. We find that the association between parents’ attitudes, social norms, and perceived behavioral control and their adolescent's eating behavior tends to be stronger when parents have an authoritative parenting style. However, we also find that the association between adolescents’ attitudes, social norms, and perceived behavioral control and their parent's eating behavior tends to be stronger when parents have an authoritative parenting style. These findings show the importance of context in evaluating interpersonal influence, and hold implications for health-relevant interventions

Comparing Student Models in Different Formalisms by Predicting their Impact on Help Success

Session: Student Modeling & PersonalizationInternational audienceWe describe a method to evaluate how student models affect ITS decision quality - their raison d'être. Given logs of randomized tutorial decisions and ensuing student performance, we train a classifier to predict tutor decision outcomes (success or failure) based on situation features, such as student and task. We define a decision policy that selects whichever tutor action the trained classifier predicts in the current situation is likeliest to lead to a successful outcome. The ideal but costly way to evaluate such a policy is to implement it in the tutor and collect new data, which may require months of tutor use by hundreds of students. Instead, we use historical data to simulate a policy by extrapolating its effects from the subset of randomized decisions that happened to follow the policy. We then compare policies based on alternative student models by their simulated impact on the success rate of tutorial decisions. We test the method on data logged by Project LISTEN's Reading Tutor, which chooses randomly which type of help to give on a word. We report the cross-validated accuracy of predictions based on four types of student models, and compare the resulting policies' expected success and coverage. The method provides a utility-relevant metric to compare student models expressed in different formalisms