609 research outputs found

    'We’re just gonna scribble it': The affective and social work of destruction in children’s art-making with different semiotic resources

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    In this paper I explore children’s destruction of their artwork as it occurs on paper or digitally via the interactive whiteboard (IWB). Social semiotics offers a theoretical lens for understanding children’s acts of destruction as meaningful and how different semiotic resources shape the meaning-making involved in destruction differently. To explore this further, I consider two episodes of art-making: firstly, an episode of child-parent art-making that ended in the five year old child scribbling over a drawing on paper with a black crayon, and secondly, an episode of a five year old child using touch to cover over the drawing she had made on the classroom IWB during free-flow activity time. A comparison between these two episodes is used to explore how digital and paper-based semiotic resources may impact differently on the experience of destruction and the affective and relational work that it can achieve

    Highly Differentiated Human Fetal RPE Cultures Are Resistant to the Accumulation and Toxicity of Lipofuscin-Like Material

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    PURPOSE. The accumulation of undigestible autofluorescent material (UAM), termed lipofuscin in vivo, is a hallmark of aged RPE. Lipofuscin derives, in part, from the incomplete degradation of phagocytized photoreceptor outer segments (OS). Whether this accumulated waste is toxic is unclear. We therefore investigated the effects of UAM in highly differentiated human fetal RPE (hfRPE) cultures. METHODS. Unmodified and photo-oxidized OS were fed daily to confluent cultures of ARPE-19 RPE or hfRPE. The emission spectrum, composition, and morphology of resulting UAM were measured and compared to in vivo lipofuscin. Effects of UAM on multiple RPE phenotypes were assessed. RESULTS. Compared to ARPE-19, hfRPE were markedly less susceptible to UAM buildup. Accumulated UAM in hfRPE initially resembled the morphology of lipofuscin from AMD eyes, but compacted and shifted spectrum over time to resemble lipofuscin from healthy aged human RPE. UAM accumulation mildly reduced transepithelial electrical resistance, ketogenesis, certain RPE differentiation markers, and phagocytosis efficiency, while inducing senescence and rare, focal pockets of epithelial-mesenchymal transition. However, it had no effects on mitochondrial oxygen consumption rate, certain other RPE differentiation markers, secretion of drusen components or polarity markers, nor cell death. CONCLUSIONS. hfRPE demonstrates a remarkable resistance to UAM accumulation, suggesting mechanisms for efficient OS processing that may be lost in other RPE culture models. Furthermore, while UAM alters hfRPE phenotype, the effects are modest, consistent with conflicting reports in the literature on the toxicity of lipofuscin. Our results suggest that healthy RPE may adequately adapt to and tolerate lipofuscin accumulation

    Fibroid explants reveal a higher sensitivity against MDM2-inhibitor nutlin-3 than matching myometrium

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    <p>Abstract</p> <p>Background</p> <p>Spontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also to identify novel therapeutic targets.</p> <p>Methods</p> <p>We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14<sup>Arf </sup>and used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. For these studies quantitative real-time RT-PCR, Western blots, and immunohistochemistry were used. Statistical analyses were performed using the student's <it>t </it>test.</p> <p>Results</p> <p>An in depth analysis of 52 fibroids along with matching myometrium from 31 patients revealed in almost all cases a higher expression of p14<sup>Arf </sup>in the tumors than in the matching normal tissue. In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of <it>BAX </it>as well as of <it>p21</it>, respectively. Simultaneously, the expression of the proliferation marker Ki-67 drastically decreased. Western-blot analysis identified an increase of the p53 level as the most likely reason for the increased activity of its downstream markers <it>BAX </it>and <it>p21</it>. Because as a rule fibroids express much higher levels of p14<sup>Arf</sup>, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium. We were able to show that in most fibroids analyzed a higher sensibility than that of matching myometrium was noted with a corresponding increase of the p53 immunopositivity of the fibroid samples compared to those from myometrium.</p> <p>Conclusions</p> <p>The results show that uterine fibroids represent a cell population of advanced cellular age compared to matching myometrium. Moreover, the data point to members of the p53-network as to potential novel therapeutic targets for the treatment of uterine fibroids.</p

    Parents' assessment of parent-child interaction interventions – a longitudinal study in 101 families

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    <p>Abstract</p> <p>Background</p> <p>The aim of the study was to describe families with small children who participated in parent-child interaction interventions at four centres in Sweden, and to examine long term and short term changes regarding the parents' experience of parental stress, parental attachment patterns, the parents' mental health and life satisfaction, the parents' social support and the children's problems.</p> <p>Methods</p> <p>In this longitudinal study a consecutive sample of 101 families (94 mothers and 54 fathers) with 118 children (median age 3 years) was assessed, using self-reports, at the outset of the treatment (T1), six months later (T2) and 18 months after the beginning of treatment (T3). Analysis of the observed differences was carried out using Wilcoxon's Signed-Rank test and Cohen's d.</p> <p>Results</p> <p>The results from commencement of treatment showed that the parents had considerable problems in all areas examined. At the outset of treatment (T1) the mothers showed a higher level of problem load than the fathers on almost all scales. In the families where the children's problems have also been measured (children from the age of four) it appeared that they had problems of a nature and degree otherwise found in psychiatric populations. We found a clear general trend towards a positive development from T1 to T2 and this development was also reinforced from T2 to T3. Aggression in the child was one of the most common causes for contact. There were few undesired or unplanned interruptions of the treatment, and the attrition from the study was low.</p> <p>Conclusion</p> <p>This study has shown that it is possible to reach mothers as well as fathers with parenting problems and to create an intervention program with very low dropout levels – which is of special importance for families with small children displaying aggressive behaviour. The parents taking part in this study showed clear improvement trends after six months and this development was reinforced a year later. This study suggests the necessity of clinical development and future research concerning the role of fathers in parent-child interaction interventions.</p

    Relational agency: Relational sociology, agency and interaction

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    yesThis article explores how the concept of agency in social theory changes when it is conceptualised as a relational rather than an individual phenomenon. I begin with a critique of the structure/agency debate, particularly of how this emerges in the critical realist approach to agency typified by Margaret Archer. It is argued that this approach, and the critical realist version of relational sociology that has grown from it, reifies social relations as a third entity to which agents have a cognitive, reflexive relation, playing down the importance of interaction. This upholds the Western moral and political view of agents as autonomous, independent, and reflexive individuals. Instead of this I consider agency from a different theoretical tradition in relational sociology in which agents are always located in manifold social relations. From this I create an understanding of agents as interactants, ones who are interdependent, vulnerable, intermittently reflexive, possessors of capacities that can only be practiced in joint actions, and capable of sensitive responses to others and to the situations of interaction. Instead of agency resting on the reflexive monitoring of action or the reflexive deliberation on structurally defined choices, agency emerges from our emotional relatedness to others as social relations unfold across time and space

    Family coordination in families who have a child with autism spectrum disorder

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    Little is known about the interactions of families where there is a child with autism spectrum disorder (ASD). The present study applies the Lausanne Trilogue Play (LTP) to explore both its applicability to this population as well as to assess resources and areas of deficit in these families. The sample consisted of 68 families with a child with ASD, and 43 families with a typically developing (TD) child. With respect to the global score for family coordination there were several negative correlations: the more severe the symptoms (based on the child’s ADOS score), the more family coordination was dysfunctional. This correlation was particularly high when parents had to play together with the child. In the parts in which only one of the parents played actively with the child, while the other was simply present, some families did achieve scores in the functional range, despite the child’s symptom severity. The outcomes are discussed in terms of their clinical implications both for assessment and for interventio

    Regulation of Ubx Expression by Epigenetic Enhancer Silencing in Response to Ubx Levels and Genetic Variation

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    For gene products that must be present in cells at defined concentrations, expression levels must be tightly controlled to ensure robustness against environmental, genetic, and developmental noise. By studying the regulation of the concentration-sensitive Drosophila melanogaster Hox gene Ultrabithorax (Ubx), we found that Ubx enhancer activities respond to both increases in Ubx levels and genetic background. Large, transient increases in Ubx levels are capable of silencing all enhancer input into Ubx transcription, resulting in the complete silencing of this gene. Small increases in Ubx levels, brought about by duplications of the Ubx locus, cause sporadic silencing of subsets of Ubx enhancers. Ubx enhancer silencing can also be induced by outcrossing laboratory stocks to D. melanogaster strains established from wild flies from around the world. These results suggest that enhancer activities are not rigidly determined, but instead are sensitive to genetic background. Together, these findings suggest that enhancer silencing may be used to maintain gene product levels within the correct range in response to natural genetic variation
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