Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks

DNA double-strand break (DSB) repair via the homologous recombination pathway is a multi-stage process, which results in repair of the DSB without loss of genetic information or fidelity. One essential step in this process is the generation of extended single-stranded DNA (ssDNA) regions at the break site. This ssDNA serves to induce cell cycle checkpoints and is required for Rad51 mediated strand invasion of the sister chromatid. Here, we show that human Exonuclease 1 (Exo1) is required for the normal repair of DSBs by HR. Cells depleted of Exo1 show chromosomal instability and hypersensitivity to ionising radiation (IR) exposure. We find that Exo1 accumulates rapidly at DSBs and is required for the recruitment of RPA and Rad51 to sites of DSBs, suggesting a role for Exo1 in ssDNA generation. Interestingly, the phosphorylation of Exo1 by ATM appears to regulate the activity of Exo1 following resection, allowing optimal Rad51 loading and the completion of HR repair. These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the maintenance of genomic stability.

Children re-read and re-write their neighborhoods : critical literacies and identity work

This chapter considers the complex literate repertoires of 21st century children in multicultural primary classrooms in Adelaide South Australia. It draws on the curricular and pedagogical work of two experienced primary school teachers who explore culture, race and class, by positioning children as textual producers across a variety of media. In particular we discuss two child-authored texts – A is for Arndale – a local alphabet book co-authored by children aged between eight and ten, and – Cooking Afghani Style - a magazine style film produced by a multi-aged class of children (aged eight to thirteen) recently arrived in Australia. In the process of making these texts, primary children engaged in reading as a cultural practice – re-reading and re-writing their neighbourhoods and identities (both individual and collective). This involved frequent excursions to local key sites, both familiar and unfamiliar to the children. They investigated how diverse children experienced and lived their lives in particular places within changing communities.

Trans digital storytelling : everyday activism, mutable identity and the problem of visibility

Mainstream representations of trans people typically run the gamut from victim to mentally ill and are almost always articulated by non-trans voices. The era of user-generated digital content and participatory culture has heralded unprecedented opportunities for trans people who wish to speak their own stories in public spaces. Digital Storytelling, as an easy accessible autobiographic audio-visual form, offers scope to play with multi-dimensional and ambiguous representations of identity that contest mainstream assumptions of what it is to be ‘male’ or ‘female’. Also, unlike mainstream media forms, online and viral distribution of Digital Stories offer potential to reach a wide range of audiences, which is appealing to activist oriented storytellers who wish to confront social prejudices. However, with these newfound possibilities come concerns regarding visibility and privacy, especially for storytellers who are all too aware of the risks of being ‘out’ as trans. This paper explores these issues from the perspective of three trans storytellers, with reference to the Digital Stories they have created and shared online and on DVD. These examplars are contextualised with some popular and scholarly perspectives on trans representation, in particular embodied and performed identity. It is contended that trans Digital Stories, while appearing in some ways to be quite conventional, actually challenge common notions of gender identity in ways that are both radical and transformative.

Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid

To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro. Methods. Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and 3 H-proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated 3 H-proline. Results. Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly. Conclusion. These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.

Role demands and work-family balance experience in Malaysia : the different moderating effects of collectivism and gender role identity among diverse ethnic groups

The purpose of this thesis is to examine the influence of ethnic cultural values on the relationship of role demands and the work-family balance (WFB) experience. Past studies have found that the demands from work and family roles have a different impact on the work-family experience in people of different ethnicity. Researchers attribute these results to the cultural differences across the groups. However, there has been no empirical support for these assumptions because most past studies did not explicitly measure the cultural dimension in their design. Therefore, although studies have found ethnic differences in work-family experience, as cultural variables were not measured, it cannot be determined whether these differences were due to the differing ethnic groups’ cultural styles. The present thesis is set up to address this limitation in the literature, employing the Malay and Chinese ethnic groups in Malaysia as the study samples. The investigation consisted of pilot interviews and two survey studies. The interviews were carried out to establish the perception of WFB by target participants of a non-western nation. The first survey served to identify whether the Malay and Chinese ethnic groups residing under the same economic and social systems vary in their perceptions of work and family roles. The second survey tests the research model empirically, that is, whether cultural values moderate the relationship between role demands and WFB and if these moderation effects vary across ethnic groups. From the interviews, the results indicated that work-family experience is not a universal experience, but is partly culture-specific. Specifically, in the case of Malaysia, WFB is very much observed from the role obligation perspective. In particular, balance is perceived when work duties and household affairs are both adequately fulfilled. On the other hand, the conceptualisation of WFB in terms of role satisfaction and role interference also emerged in the interviews, suggesting the universality of these constructs across cultures. The findings from Survey One indicated that participants of different ethnicities in this study do not differ greatly in their perceptions regarding their participation in work and family roles. Generally, these participants revealed the less traditional attitudes towards women’s participation in work and family roles. However, variations were observed between the two groups in terms of reasons for working, spouses’ preferences towards their employment, and the extent to which their work role is perceived to impede their normative role performance in the household. Despite these differences, the Malay and Chinese ethnic groups showed more similarities than differences in their perceptions of work and family. The findings from Survey Two, which tested the research model, produced mixed results. On the whole, the results showed that the cultural dimensions examined in this study (i.e. collectivism, work identity and family identity) did influence the relationship between role demands and WFB experience, thus providing empirical evidence for the assumption in the literature that the relationship between role demand and work-family experience is moderated by cultural values. Most importantly, support was found for the proposition that these moderation effects vary between the Malay and Chinese ethnic groups. Moreover, this study also found evidence that Malays and Chinese differ significantly on collectivism and work identity cultural dimensions where Malays are found to be more collectivist than the Chinese, while work identity is stronger in the Chinese than in the Malays. There is no difference in the levels of family identity between the two groups. Of all the three moderators, work identity was deemed the most important because many of the supported hypotheses pertained to the work identity moderating effects. In contrast, family identity does not seem to have much moderating influence on role demand-WFB relationships, while the results for the collectivism moderator are mixed. As such, although not conclusive, it can be deduced that variations in the effects of role demand on work-family experience across ethnicity are a result of the groups’ cultural differences, thereby supporting the assumption in the literature.