308 research outputs found

    Promoting emotional health, well-being, and resilience in primary schools

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    • This report synthesises evidence on promoting emotional health, well-being, and resilience in primary schools. We argue that: a) both universal support for all pupils and targeted work for specific groups and individuals can be very effective, and b) connected school systems help to translate the research evidence into sustained positive impacts. • We focus on preventing or reducing problems such as emotional difficulties and aggressive behaviour, as well as efforts to promote emotional health more broadly and to address the underlying social and emotional skills. Reported activities involve specific teaching curricula and the use of specialist staff or services, but also encompass broader school systems and climate, as well as pedagogical approaches to teaching and learning. • Therapeutic approaches to remediating or preventing emotional difficulties can be successful in schools, but effects are variable and may not be sustained over time. • Whole-school approaches to supporting mental health are encouraged, but evidence suggests that the implementation of such approaches is challenging. • Specialist school-based staff and services with dedicated responsibilities in this area have an important role to play, but the evidence base for their impacts is not sufficiently developed, and the way in which their activities can be integrated with other school systems needs close attention. • There is a compelling evidence base regarding the potential impacts of school-based strategies that are designed to promote social and emotional learning, including both enhancement of a variety of skills and positive attributes and reduction of emotional and behavioural difficulties. • Even where social and emotional learning programmes have a very strong evidence base, there is no guarantee of success, as there are significant challenges in terms of both implementing the programme activities and embedding them in broader school systems and everyday interactions. • Research on anti-bullying programmes provides a good illustration of how effective work in this area needs to permeate the school climate. • Overall, we recommend a carefully planned and well-supported programme of work on social and emotional learning that is rooted in, and reinforced by, connections with school systems and all stakeholders, and integration with broader pedagogical approaches to good teaching and learning throughout the revised Welsh curriculum

    Coping with stigma and discrimination: evidence from mental health service users in England

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    Mental health stigma and discrimination are significant problems. Common coping orientations include: concealing mental health problems, challenging others and educating others. We describe the use of common stigma coping orientations and explain variations within a sample of English mental health service users. Cross-sectional survey data were collected as part of the Viewpoint survey of mental health service users’ experiences of discrimination (n = 3005). Linear regression analyses were carried out to identify factors associated with the three stigma coping orientations. The most common coping orientation was to conceal mental health problems (73%), which was strongly associated with anticipated discrimination. Only 51% ever challenged others because of discriminating behaviour, this being related to experienced discrimination, but also to higher confidence to tackle stigma. Although stigma coping orientations vary by context, individuals often choose to conceal problems, which is associated with greater anticipated and experienced discrimination and less confidence to challenge stigma. The direction of this association requires further investigation

    Core human mitochondrial transcription apparatus is a regulated two-component system in vitro

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    The core human mitochondrial transcription apparatus is currently regarded as an obligate three-component system comprising the bacteriophage T7-related mitochondrial RNA polymerase, the rRNA methyltransferase-related transcription factor, h-mtTFB2, and the high mobility group box transcription/DNA-packaging factor, h-mtTFA/TFAM. Using a faithful recombinant human mitochondrial transcription system from Escherichia coli, we demonstrate that specific initiation from the mtDNA promoters, LSP and HSP1, only requires mitochondrial RNA polymerase and h-mtTFB2 in vitro. When h-mtTFA is added to these basal components, LSP exhibits a much lower threshold for activation and a larger amplitude response than HSP1. In addition, when LSP and HSP1 are together on the same transcription template, h-mtTFA-independent transcription from HSP1 and h-mtTFA-dependent transcription from both promoters is enhanced and a higher concentration of h-mtTFA is required to stimulate HSP1. Promoter competition experiments revealed that, in addition to LSP competing transcription components away from HSP1, additional cis-acting signals are involved in these aspects of promoter regulation. Based on these results, we speculate that the human mitochondrial transcription system may have evolved to differentially regulate transcription initiation and transcription-primed mtDNA replication in response to the amount of h-mtTFA associated with nucleoids, which could begin to explain the heterogeneity of nucleoid structure and activity in vivo. Furthermore, this study sheds new light on the evolution of mitochondrial transcription components by showing that the human system is a regulated two-component system in vitro, and thus more akin to that of budding yeast than thought previously

    Mitochondrial Stress Engages E2F1 Apoptotic Signaling to Cause Deafness

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    SummaryMitochondrial dysfunction causes poorly understood tissue-specific pathology stemming from primary defects in respiration, coupled with altered reactive oxygen species (ROS), metabolic signaling, and apoptosis. The A1555G mtDNA mutation that causes maternally inherited deafness disrupts mitochondrial ribosome function, in part, via increased methylation of the mitochondrial 12S rRNA by the methyltransferase mtTFB1. In patient-derived A1555G cells, we show that 12S rRNA hypermethylation causes ROS-dependent activation of AMP kinase and the proapoptotic nuclear transcription factor E2F1. This retrograde mitochondrial-stress relay is operative in vivo, as transgenic-mtTFB1 mice exhibit enhanced 12S rRNA methylation in multiple tissues, increased E2F1 and apoptosis in the stria vascularis and spiral ganglion neurons of the inner ear, and progressive E2F1-dependent hearing loss. This mouse mitochondrial disease model provides a robust platform for deciphering the complex tissue specificity of human mitochondrial-based disorders, as well as the precise pathogenic mechanism of maternally inherited deafness and its exacerbation by environmental factors.PaperFlic

    Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression

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    Human mitochondrial transcription requires the bacteriophage-related RNA polymerase, POLRMT, the mtDNA-binding protein, h-mtTFA/TFAM, and two transcription factors/rRNA methyltransferases, h-mtTFB1 and h-mtTFB2. Here, we determined the steady-state levels of these core transcription components and examined the consequences of purposeful elevation of h-mtTFB1 or h-mtTFB2 in HeLa cells. On a per molecule basis, we find an ∼6-fold excess of POLRMT to mtDNA and ∼3-fold more h-mtTFB2 than h-mtTFB1. We also estimate h-mtTFA at ∼50 molecules/mtDNA, a ratio predicted to support robust transcription, but not to coat mtDNA. Consistent with a role for h-mtTFB2 in transcription and transcription-primed replication, increased mitochondrial DNA and transcripts result from its over-expression. This is accompanied by increased translation rates of most, but not all mtDNA-encoded proteins. Over-expression of h-mtTFB1 did not significantly influence these parameters, but did result in increased mitochondrial biogenesis. Furthermore, h-mtTFB1 mRNA and protein are elevated in response to h-mtTFB2 over-expression, suggesting the existence of a retrograde signal to the nucleus to coordinately regulate expression of these related factors. Altogether, our results provide a framework for understanding the regulation of human mitochondrial transcription in vivo and define distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression that together likely fine-tune mitochondrial function
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