Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution

Viral genomes have high gene densities and complex transcription strategies rendering transcriptome analysis through short-read RNA-seq approaches problematic. Adenovirus transcription and splicing is especially complex. We used long-read direct RNA sequencing to study adenovirus transcription and splicing during infection. This revealed a previously unappreciated complexity of alternative splicing and potential for secondary initiating codon usage. Moreover, we find that most viral transcripts tend to shorten polyadenylation lengths as infection progresses. Development of an open reading frame centric bioinformatics analysis pipeline provided a deeper quantitative and qualitative understanding of adenovirus’s genetic potential. Across the viral genome adenovirus makes multiple distinctly spliced transcripts that code for the same protein. Over 11,000 different splicing patterns were recorded across the viral genome, most occurring at low levels. This low-level use of alternative splicing patterns potentially enables the virus to maximise its coding potential over evolutionary timescales

Positive practices : solution-focused and narrative therapeutic techniques with children with sexually harmful behaviours

This article explores the use of solution-focused and Narrative Therapeutic approaches with a boy who had sexually harmful behaviours. The paper will highlight the practical challenges of working with someone who is 'problem-saturated' through institutionalisation and who is also subjected to powerful discourses claiming the 'truth' about him. The use of solution-focused and Narrative Therapeutic principles and approaches will be demonstrated in the work described, in a way that allows the reader to reflect on how these may differ from modernist understandings and responses to this behaviour

Aboriginal Practitioners Speak Out: Contextualising Child Protection Interventions

One month before the June 2007 Federal Government Emergency Intervention in the Northern Territory some 55 West Australian Aboriginal child protection workers attended a 3-day summit in Fremantle. Their purpose as front-line practitioners from across the State was to identify how more nurturing and healing communities could be developed and supported in a climate of despair. This paper reports on how the summit was designed and on some of the ideas and concerns that emerged within this dialogical space of cooperative inquiry. The project was a partnership between Aboriginal and non-Aboriginal representatives of university, government, and community-service bodies. Aboriginal practitioners identified the complexity of what was happening in their experience and where changes were needed. Integral to this participation and coproduction of knowledge by Aboriginal child protection workers was the provision of a safe space for the articulation of reflected experience. Implications for policy, practice, and curriculum of both process and outcome dimensions to considering Aboriginal views on this contentious issue are discussed

Roles for the coactivators CBP and p300 and the APC/C E3 ubiquitin ligase in E1A-dependent cell transformation

Adenovirus early region 1A (E1A) possesses potent transforming activity when expressed in concert with activated ras or E1B genes in in vitro tissue culture systems such as embryonic human retinal neuroepithelial cells or embryonic rodent epithelial and fibroblast cells. Early region 1A has thus been used extensively and very effectively as a tool to determine the molecular mechanisms that underlie the basis of cellular transformation. In this regard, roles for the E1A-binding proteins pRb, p107, p130, cyclic AMP response element-binding protein (CBP)/p300, p400, TRRAP and CtBP in cellular transformation have been established. However, the mechanisms by which E1A promotes transformation through interaction with these partner proteins are not fully delineated. In this review, we focus on recent advances in our understanding of CBP/p300 function, particularly with regard to its relationship to the anaphase-promoting complex/cyclosome E3 ubiquitin ligase, which has recently been shown to interact and affect the activity of CBP/p300 through interaction domains that are evolutionarily conserved in E1A

The Trouble With Fathers: The Impact of Time and Gendered-Thinking on Working Relationships Between Fathers and Social Workers in Child Protection Practice in England

The lives of families entering the child protection arena may be shaped by a range of troubles, including material deprivation, physical and mental health problems, and substance misuse or domestic abuse. Despite the interest in whole family approaches, the issue of how professionals fail to work effectively with fathers is long-standing and resistant to change. This article illustrates challenges in building working relationships with men, including the challenge of avoiding binary thinking in the assessment of fathers as “risk” or “resource.” Drawing on our qualitative longitudinal study of men’s experiences of child protection in England, we highlight how both organizational (clashing time perspectives) and cultural (gendered-thinking) factors can trouble the potential relationship between social workers and fathers. We argue for a more gender sensitive approach to social work practice, which can respond more fully and effectively to the experiences of fathers and mothers

Reducing recurrent care proceedings: initial evidence from new interventions

The English family justice system faces a crisis of recurrence. As many as one in four birth mothers involved in public law care proceedings in English family courts are likely to reappear in a subsequent set of proceedings within seven years. These mothers are involved in up to one-third of total care applications, as they are – by definition – linked to more than one child . Few birth mothers experiencing the removal of a child to care are offered any follow-up support, despite often facing multiple challenges including poverty, addiction, domestic violence and mental health problems. Since 2011, however, a number of new services have been established to begin to address their unmet needs. This article summarises the findings of the first academic-led evaluation of two of these initiatives. Presenting evidence from a mixed-methods evaluative study, it concludes that the new services were able to foster relationships that ‘worked’ in reducing recurrent proceedings. None of the women engaging with the services went on to experience what could be described as a ‘rapid repeat pregnancy’ within the evaluation window. Just as significantly, a number of clients reported some improvement in their psychological functioning, and the practitioners involved reported positively on their experience of delivering and managing innovative services. The article closes with a discussion of the challenges of evaluating personalised, strengths-based interventions and the possibilities of evidencing empowerment in these cases

The PTTG1-binding factor (PBF/PTTG1IP) regulates p53 activity in thyroid cells

The PTTG1-Binding Factor (PBF/PTTG1IP) has an emerging repertoire of roles, especially in thyroid biology, and functions as a proto-oncogene. High PBF expression is independently associated with poor prognosis and lower disease-specific survival in human thyroid cancer. However, the precise role of PBF in thyroid tumorigenesis is unclear. Here, we present extensive evidence demonstrating that PBF is a novel regulator of p53, a tumor suppressor protein with a key role in maintaining genetic stability, which is infrequently mutated in differentiated thyroid cancer. By coimmunoprecipitation and proximity ligation assays, we show that PBF binds specifically to p53 in thyroid cells, and significantly represses transactivation of responsive promoters. Further, we identify that PBF decreases p53 stability by enhancing ubiquitination, which appears dependent on the E3 ligase activity of Mdm2. Impaired p53 function was evident in a transgenic mouse model with thyroid-specific PBF over-expression (PBF-Tg), which had significantly increased genetic instability as indicated by FISSR-PCR analysis. Consistent with this, ~40% of all DNA repair genes examined were repressed in PBF-Tg primary cultures, including genes with critical roles in maintaining genomic integrity such as Mgmt, Rad51 and Xrcc3. Our data also revealed that PBF induction resulted in upregulation of the E2 enzyme Rad6 in murine thyrocytes, and was associated with Rad6 expression in human thyroid tumors. Overall, this work provides novel insights into the role of the proto-oncogene PBF as a negative regulator of p53 function in thyroid tumorigenesis, where PBF is generally over-expressed and p53 mutations are rare compared to other tumor types

From Aristotle to Arendt : a phenomenological exploration of forms of knowledge and practice in the context of child protection social work in the UK

This paper attempts to explore the relationship between different forms of knowledge and the kinds of activity that arise from them within child protection social work practice. The argument that social work is more than either ‘science’ or ‘art’ but distinctly ‘practice’ is put through a historical description of the development of Aristotle’s views of the forms of knowledge and Hannah Arendt’s later conceptualisations as detailed in The Human Condition (1958). The paper supports Arendt’s privileging of Praxis over Theoria within social work and further draws upon Arendt’s distinctions between Labour, Work and Action to delineate between different forms of social work activity. The author highlights dangers in social work relying too heavily on technical knowledge and the use of theory as a tool in seeking to understand and engage with the people it serves and stresses the importance of a phenomenological approach to research and practice as a valid, embodied form of knowledge. The argument further explores the constructions of service users that potentially arise from different forms of social work activity and cautions against over-prescriptive use of ‘outcomes’ based practice that may reduce the people who use services to products or consumables. The author concludes that social work action inevitably involves trying to understand humans in a complex and dynamic way that requires engagement and to seek new meanings for individual humans