An E2F1-Mediated DNA Damage Response Contributes to the Replication of Human Cytomegalovirus

DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses (DDRs) centered on protein kinase signaling cascades. The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis. Many DNA viruses elicit host DDRs during infection and some viruses require the DDR for efficient replication. However, the mechanism by which DDRs are activated by viral infection is poorly understood. Human cytomegalovirus (HCMV) infection induces a DDR centered on the activation of ataxia telangiectasia mutated (ATM) protein kinase. Here we show that HCMV replication is compromised in cells with inactivated or depleted ATM and that ATM is essential for the host DDR early during infection. Likewise, a downstream target of ATM phosphorylation, H2AX, also contributes to viral replication. The ATM-dependent DDR is detected as discrete, nuclear γH2AX foci early in infection and can be activated by IE proteins. By 24 hpi, γH2AX is observed primarily in HCMV DNA replication compartments. We identified a role for the E2F1 transcription factor in mediating this DDR and viral replication. E2F1, but not E2F2 or E2F3, promotes the accumulation of γH2AX during HCMV infection or IE protein expression. Moreover, E2F1 expression, but not the expression of E2F2 or E2F3, is required for efficient HCMV replication. These results reveal a novel role for E2F1 in mediating an ATM-dependent DDR that contributes to viral replication. Given that E2F activity is often deregulated by infection with DNA viruses, these observations raise the possibility that an E2F1-mediated mechanism of DDR activation may be conserved among DNA viruses

Integrating Academic and Everyday Learning Through Technology: Issues and Challenges for Researchers, Policy Makers and Practitioners

This paper builds on work undertaken over a number of years by a group of international researchers with an interest in the potential of connecting academic and everyday practices and knowledge. Drawing extensively on literature and our own work, we first discuss the challenges around defining informal learning, concluding that learning is multidimensional and has varying combinations of formal and informal attributes. We then highlight the potential of technology for integrating formal and informal learning attributes and briefly provide some exemplars of good practice. We then discuss in depth the challenges and issues of this approach to supporting learning from the perspective of pedagogy, research, policy and technology. We also provide some recommendations of how these issues may be addressed. We argue that for the learner, integration of formal and informal learning attributes should be an empowering process, enabling the learner to be self-directed, creative and innovative, taking learning to a deeper level. Given the complexity of the learning ecosystem, this demands support from the teacher but also awareness and understanding from others such as parents, family, friends and community members. We present a conceptual model of such an ecosystem to help develop further discussions within and between communities of researchers, policy makers and practitioners

Parenting and globalization in western countries: explaining differences in parent–child interactions

We review research on intra-cultural differences in parenting, and the sources of those differences. Ethnic-minority parents differ from majority parents in parenting values, childrearing goals and resources-differences that affect parenting practices and children's development. Within-country comparisons indicate less sensitivity, more authoritarian discipline, less child-focused communications, and less engagement in learning activities in ethnic-minority compared to ethnic-majority parents, which help account for disparities in children. Despite group differences in parenting, associations between parenting and child development generalize across cultures, with rare exceptions. However, a focus on intracultural differences is based on comparisons of group 'averages', which masks the enormous variation within ethnic-minority samples. Within-group variation can be partly explained by stressors associated with low socioeconomic status (SES), acculturation and discrimination.</p