Amplification of the Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 lytic origin of DNA replication is dependent upon a cis-acting AT-rich region and an ORF50 response element and the trans-acting factors ORF50 (K-Rta) and K8 (K-bZIP)

AbstractKaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), has significant sequence homology to Epstein–Barr virus (EBV). In cell culture, HHV8 is primarily latent, and viral genes associated with lytic replication are not expressed. Two lytic origins of DNA replication (oriLyt) are present within the HHV8 genome and are composed of an AT-rich region adjacent to GC-rich DNA sequences. We have now identified essential cis- and trans-acting elements required for oriLyt-dependent DNA replication. The transient replication assay was used to show that two AT-rich elements, three consensus AP1 transcription factor-binding sites, an ORF50 response element (RE), and a consensus TATA box motif are essential for efficient origin-dependent DNA replication. Transient transfection of luciferase reporter constructs indicated that the downstream region of the HHV8 oriLyt responds to ORF50 and suggests that part of the oriLyt may be an enhancer/promoter. In addition, a transient cotransfection–replication assay elucidated the set of trans-acting factors required for lytic DNA replication. These factors consist of homologues to the core replication proteins: ORF6 (ssDNA binding protein), ORF9 (DNA polymerase), ORF40-41 (primase-associated factor), ORF44 (helicase), ORF56 (primase), and ORF59 (polymerase processivity factor) common to all herpesviruses along with ORF50 (K-Rta) and K8 (K-bZIP)

Materialities and imaginaries of home: geographies of British returnees in later life

This article explores home materialities and home imaginaries in later life, to provide insight into the dialectical relation between the spatial processes of ageing and migration. The article draws on empirical research with British return migrants in older age. The analysis purposively selects four participants from among a wider sample of interviewees to highlight some of the diversity among British returnees and their varied experiences of remaking home upon return. The article explores both the privilege and vulnerabilities of all British returnees as the meaning of home transforms in later life

Sober social networks: the role of online support groups in recovery from alcohol addiction

In the context of addiction research, positive recovery outcomes are affected by the quality of people's social interactions and perhaps to an even greater extent, by the defining norms of the groups they identify with—that is, using versus recovery groups. Here, we examine the role of online supportive networks in the process of recovery from alcohol addiction. We analyse the relationship between negative and positive aspects of recovery capital (i.e., self‐stigma, and respectively, positive recovery identity and self‐efficacy) as they relate to well‐being outcomes among alcohol users in an online recovery support group. Based on a computerised linguistic analysis of the naturally occurring data extracted from an online recovery support group (i.e., 257 posts made by 237 group members), we found that self‐stigma negatively predicts self‐efficacy and well‐being, and social identification with a recovery identity mediates these relationships. Overall, these findings highlight that positive engagement with supportive recovery networks is central to an effective and sustainable recovery

Exploring the lived experience of gay men with prostate cancer: A phenomenological study

Purpose: Gay men with prostate cancer are an ‘invisible species’ in the research literature despite concerns that the impact of treatment may be more profound and in some ways unique compared to heterosexual men. The aim of this research is to explore the lived experience of gay men with prostate cancer. Method: In-depth interviews were recorded and transcribed verbatim from a purposive sample of eight gay men treated for prostate cancer in Ireland. A qualitative methodological approach employing Giorgi's descriptive phenomenological method was used to collect and analyse data. Findings: Three key aspects emerged representing the essence of the participants lived experience; The experience of diagnosis, treatment decision making, and the impact of treatment, with sub-themes of shock of diagnosis, the generalist nature of information, sexual side effects and incontinence, and masculinity and gay identity. Secondly, the experience of the healthcare service with sub-themes of sexual orientation disclosure and communication with the healthcare team; and thirdly, sources of support and means of coping which included significant others, family & friends, cancer support groups, and gay resources and support services. Conclusion: Gay men with prostate cancer have unmet information and supportive care needs throughout their prostate cancer journey, especially related to the impact of sexual dysfunction and associated rehabilitation, negatively impacting their quality of life. Issues associated with heteronormativity, minority stress, and stigma may influence how gay men interact with the health service, or how they perceive the delivery of care. Healthcare education providers should update prostate cancer education programmes accordingly

It's political: How the salience of one's political identity changes climate change beliefs and policy support

Previous research has demonstrated a striking difference in climate change beliefs and policy support between people who identify with the right-wing of politics and with the left-wing of politics. But are we destined to continue with this divergence? We suggest that there is movement around these differences based on the politicization of climate change and we conducted two experimental studies with 126 and 646 people, respectively, to examine this effect. We found that those people whose political identity was made salient were less likely to believe in an anthropogenic cause of climate change and less likely to support government climate change policies than those whose identity was not made salient; particularly when those people were aligned with the right-wing of politics. The results demonstrate the importance of the salience of one's political identity in determining attitudes and beliefs even for scientific facts such as climate change. Our research also identifies some ways forward in dealing with climate change-based on depoliticizing the issue

Seven features of safety in maternity units: a framework based on multisite ethnography and stakeholder consultation

Background: Reducing avoidable harm in maternity services is a priority globally. As well as learning from mistakes, it is important to produce rigorous descriptions of ‘what good looks like’. Objective: We aimed to characterise features of safety in maternity units and to generate a plain language framework that could be used to guide learning and improvement. Methods: We conducted a multisite ethnography involving 401 hours of non-participant observations 33 semistructured interviews with staff across six maternity units, and a stakeholder consultation involving 65 semistructured telephone interviews and one focus group. Results: We identified seven features of safety in maternity units and summarised them into a framework, named For Us (For Unit Safety). The features include: (1) commitment to safety and improvement at all levels, with everyone involved; (2) technical competence, supported by formal training and informal learning; (3) teamwork, cooperation and positive working relationships; (4) constant reinforcing of safe, ethical and respectful behaviours; (5) multiple problem-sensing systems, used as basis of action; (6) systems and processes designed for safety, and regularly reviewed and optimised; (7) effective coordination and ability to mobilise quickly. These features appear to have a synergistic character, such that each feature is necessary but not sufficient on its own: the features operate in concert through multiple forms of feedback and amplification. Conclusions: This large qualitative study has enabled the generation of a new plain language framework—For Us—that identifies the behaviours and practices that appear to be features of safe care in hospital-based maternity units