Parent-perceived isolation and barriers to psychosocial support: A qualitative study to investigate how peer support might help parents of burn-injured children

Introduction: Burn injuries can be traumatic and distressing for the affected child and family, with a prolonged period of recovery. This research explores parents’ experiences of support following their child’s injury and their thoughts on peer support specifically.Methods: Thirteen semi-structured interviews were conducted with parents/caregivers, a mean of three years after their child’s injury, either face-to-face or remotely. Responses were analysed using thematic analysis.Results: Analysis produced four themes and 11 sub-themes. These described parents’ experiences of loss, change, isolation and access to psychosocial support. This paper focuses on themes of isolation and parents’ access to psychosocial support.Discussion: Findings indicate that parents access psychosocial support following their child’s injury and often find it helpful; however, there is a prevailing sense of isolation. Parents often seek information online and find that this is lacking. Many parents reported that peer support would be valuable to them, particularly the sharing of experiential knowledge.Conclusion: An online resource may be beneficial for parents, but further research is needed to confirm the exploratory data gained to date, ensuring that any resource developed would meet the identified needs of parents

PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts

Stalled replication forks can be restarted and repaired by RAD51-mediated homologous recombination (HR), but HR can also perform post-replicative repair after bypass of the obstacle. Bulky DNA adducts are important replication-blocking lesions, but it is unknown whether they activate HR at stalled forks or behind ongoing forks. Using mainly BPDE-DNA adducts as model lesions, we show that HR induced by bulky adducts in mammalian cells predominantly occurs at post-replicative gaps formed by the DNA/RNA primase PrimPol. RAD51 recruitment under these conditions does not result from fork stalling, but rather occurs at gaps formed by PrimPol re-priming and resection by MRE11 and EXO1. In contrast, RAD51 loading at double-strand breaks does not require PrimPol. At bulky adducts, PrimPol promotes sister chromatid exchange and genetic recombination. Our data support that HR at bulky adducts in mammalian cells involves post-replicative gap repair and define a role for PrimPol in HR-mediated DNA damage tolerance

Expression and targeting of transcription factor ATF5 in dog gliomas

BackgroundActivating transcription factor 5 (ATF5) is a transcription factor that is highly expressed in undifferentiated neural progenitor/stem cells as well as a variety of human cancers including gliomas.AimsIn this study, we examined the expression and localization of ATF5 protein in canine gliomas, and targeting of ATF5 function in canine glioma cell lines.Materials and methodsParaffin-embedded canine brain glioma tissue sections and western blots of tumours and glioma cells were immunoassayed with anti-ATF5 antibody. Viability of glioma cells was tested with a synthetic cell-penetrating ATF5 peptide (CP-d/n ATF5) ATF5 antagonist.ResultsATF5 protein expression was in the nucleus and cytoplasm and was present in normal adult brain and tumour samples, with significantly higher expression in tumours as shown by western immunoblotting. CP-d/n ATF5 was found to decrease cell viability in canine glioma cell lines in vitro in a dose-dependent manner.ConclusionSimilarities in expression of ATF5 in rodent, dog and human tumours, and cross species efficacy of the CP-d/n ATF5 peptide support the development of this ATF5-targeting approach as a novel and translational therapy in dog gliomas

Signalling of the BCR is regulated by a lipid rafts-localised transcription factor, Bright

Regulation of BCR signalling strength is crucial for B-cell development and function. Bright is a B-cell-restricted factor that complexes with Bruton's tyrosine kinase (Btk) and its substrate, transcription initiation factor-I (TFII-I), to activate immunoglobulin heavy chain gene transcription in the nucleus. Here we show that a palmitoylated pool of Bright is diverted to lipid rafts of resting B cells where it associates with signalosome components. After BCR ligation, Bright transiently interacts with sumoylation enzymes, blocks calcium flux and phosphorylation of Btk and TFII-I and is then discharged from lipid rafts as a Sumo-I-modified form. The resulting lipid raft concentration of Bright contributes to the signalling threshold of B cells, as their sensitivity to BCR stimulation decreases as the levels of Bright increase. Bright regulates signalling independent of its role in IgH transcription, as shown by specific dominant-negative titration of rafts-specific forms. This study identifies a BCR tuning mechanism in lipid rafts that is regulated by differential post-translational modification of a transcription factor with implications for B-cell tolerance and autoimmunity