E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family.

E2F transcription factors are central regulators of cell division and cell fate decisions. E2F4 often represents the predominant E2F activity in cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the expression of cell cycle genes. This role for E2F4 is independent of the RB family. Furthermore, E2F4 functionally interacts with chromatin regulators associated with gene activation and we observed decreased histone acetylation at the promoters of cell cycle genes and E2F targets upon loss of E2F4 in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that provide insights into the biology of rapidly dividing cells

Psychological factors associated with uptake of the childhood influenza vaccine and perception of post-vaccination side-effects : a cross-sectional survey in England

Objectives To identify predictors of: uptake of the childhood influenza vaccine in the 2015–2016 influenza season, parental perceptions of side-effects from the influenza vaccine and intention to vaccinate one's child for influenza in the 2016–2017 influenza season. Design Cross-sectional online survey. Setting Data were collected in England shortly after the end of the 2015–2016 immunization campaign. Participants 1001 parents or guardians of children aged between two and seven. Main outcome measures Self-reported uptake of the childhood influenza vaccine in the 2015–2016 influenza season, perception of side-effects from the influenza vaccine and intention to vaccinate one's child in the 2016–2017 influenza season. Results Self-reported uptake of the childhood influenza vaccine was 52.8%. Factors strongly positively associated with uptake included the child having previously been vaccinated against influenza, perceiving the vaccine to be effective and perceiving the child to be susceptible to flu. Factors strongly negatively associated with uptake included perceiving the vaccine to be unsafe, to cause short-term side-effects or long-term health problems and believing that yearly vaccination may overload the immune system. Predictors of intended vaccine uptake in 2016–2017 were similar. Participants who perceived side-effects after the 2015–2016 vaccination reported being less likely to vaccinate their child next year. Side-effects were more likely to be reported in first-born children, by participants who knew another child who had side-effects, those who thought that the vaccine would interact with medication that the child was currently taking, and those who believed the vaccine causes short-term side-effects. Conclusions Perceptions about the childhood influenza vaccine show strong associations with uptake, intended uptake and perception of side-effects. Attempts to improve uptake rates from their current low levels must address these perceptions

Intimate partner violence in South Asian communities:Exploring the notion of 'shame' to promote understandings of migrant women's experiences

The notion of 'shame' is increasingly being recognized as a tool with some explanatory power to help promote understandings about a range of social problems. Through an exploration of migrant South Asian women's experiences of domestic violence and help-seeking practices, this article considers the relevance of the notion of shame as a unit of analysis to help contribute to the growing theoretical and empirical literature. This article sheds light on the meanings, events, processes and structures in the lives of migrant South Asian women respondents living in Hong Kong. Within the framework of the discussion on shame and intimate partner violence(IPV), the article also identifies the implications for social work practice

Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay.

Sequencing of cell-free DNA (cfDNA) in cancer patients' plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with <10% tumor fractions when compared against an independent assay. Finally, we applied PCF_SELECT to serial plasma samples intensively collected from three patients previously characterized as harboring alterations involving DNA repair genes and consequently offered PARP inhibition. We identified more extensive pan-genome allelic imbalance than previously recognized in prostate cancer. We confirmed high sensitivity detection of BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. Overall, we present a framework for sensitive detection of allele-specific copy number changes in cfDNA

Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay

Sequencing of cell-free DNA (cfDNA) in cancer patients' plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with <10% tumor fractions when compared against an independent assay. Finally, we applied PCF_SELECT to serial plasma samples intensively collected from three patients previously characterized as harboring alterations involving DNA repair genes and consequently offered PARP inhibition. We identified more extensive pan-genome allelic imbalance than previously recognized in prostate cancer. We confirmed high sensitivity detection of BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. Overall, we present a framework for sensitive detection of allele-specific copy number changes in cfDNA

Drosophila Neurotrophins Reveal a Common Mechanism for Nervous System Formation

Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects.By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1 maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring cell death, and it enables targeting by motor neurons. We show that Spa¨ tzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases

Life-Span Perspective of Personality in Dementia

To propose an alternative view of personality change in dementia by presenting existing evidence for the continuity of personality. Significance : As the population continues to age, dementing illnesses will account for a greater proportion of morbidity and mortality; the care of these people will have a significant effect on the health care system. Organizing Framework : Life-span perspective of personality continuity. Scope, Method : Review of current literature on personality in dementia using Medline, 1980–1994; CINAHL, 1990–1994; and Psych Lit, 1980–1994. Findings : Although there are systematic shifts in personality with dementia, individuals tend to maintain their unique pattern of premorbid personality traits. Conclusions : The personalities of dementia patients seem to reflect adaptive patterns that served them in the past. Implications : Use of a life-span perspective can enhance individualized care for demented patients and advance theory development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73653/1/j.1547-5069.1996.tb00380.x.pd