3,121 research outputs found

    Mind the Gap? : An Intensive Longitudinal Study of Between-Person and Within-Person Intention-Behavior Relations

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    Acknowledgments This work was supported by the University of Konstanz, Germany. The first author was supported by a fellowship of the Swiss National Science Foundation (Fellowship P2ZHP1_155103).Peer reviewedPostprin

    Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels

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    Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology

    Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

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    The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserve

    Investigating mechanisms of social support effectiveness: The case of locomotion motivation

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    Although social support can entail costs, individuals with a higher locomotion orientation, who are motivated to move and take action, benefit from support. In two dyadic studies, we tested whether perceived movement towards important goals would mediate the effect of recipients’ locomotion motivation on positive outcomes in support contexts. In Study 1, couples completed a 10-day diary and then recalled support interactions with their partner after the diary period. In Study 2, couples engaged in laboratory support interactions for important goals. Perceived goal movement mediated the effect of higher (vs. lower) locomotion on self-reported ratings and coder ratings of support outcomes. Higher locomotion recipients may benefit in support contexts because they perceive they can move smoothly towards their goals

    Rapid screening of environmental chemicals for estrogen receptor binding capacity.

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    Over the last few years, an increased awareness of endocrine disrupting chemicals (EDCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity in a wide range of environmental and industrial chemicals. While it is clear that in vivo methods will be required to identify adverse effects produced by these chemicals, in vitro assays can define particular mechanisms of action and have the potential to be employed as rapid and low-cost screens for use in large scale EDC screening programs. Traditional estrogen receptor (ER) binding assays are useful for characterizing a chemical's potential to be an estrogen-acting EDC, but they involve displacement of a radioactive ligand from crude receptor preparations at low temperatures. The usefulness of these assays for realistically determining the ER binding interactions of weakly estrogenic environmental and industrial compounds that have low aqueous solubility is unclear. In this report, we present a novel fluorescence polarization (FP) method that measures the capacity of a competitor chemical to displace a high affinity fluorescent ligand from purified, recombinant human ER-[alpha] at room temperature. The ER-[alpha] binding interactions generated for 15 natural and synthetic compounds were found to be similar to those determined with traditional receptor binding assays. We also discuss the potential to employ this FP technology to binding studies involving ER-ss and other receptors. Thus, the assay introduced in this study is a nonradioactive receptor binding method that shows promise as a high throughput screening method for large-scale testing of environmental and industrial chemicals for ER binding interactions

    Understanding how institutions may support the development of transdisciplinary approaches to sustainability research

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    This article analyses the approaches of academics seeking to engage with private, public and community-based stakeholders through transdisciplinary research about pressing sustainability challenges and, in particular, climate change; it outlines aspects of the institutional factors which influence transdisciplinary research. A qualitative approach was employed in conducting 10 semi-structured interviews to analyse the challenges and motivations of academic researchers when working with a range of other stakeholders through transdisciplinary practice. Two key contributions are made through this work. First, this article adds to the existing literature on motivations and challenges for undertaking research with private, public and community stakeholders in a cross-disciplinary manner. Second, the current institutional circumstances influencing such research practices are outlined, alongside potential ways forward. The research presented here has been undertaken in light of the experiences of the two lead co-authors as early career researchers coming from the disciplines of sociology and energy engineering, engaging in transdisciplinary research within a local community context in relation to a regional energy transition project

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72954/1/j.1523-1739.1988.tb00160.x.pd

    Global levels of fundamental motor skills in children : a systematic review

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    Competence in fundamental motor skills (FMS) facilitates physical activity participation and is important for children’s holistic development. This study aimed to systematically review the FMS levels of children worldwide, using the Test of Gross Motor Development-2 (TGMD-2). In accordance with PRISMA guidelines, studies were identified from searches across 7 databases. Studies were required to: (i) include typically developing children (3–10 years), (ii) be published in English, (iii) have been published between 2004 and 2019 and, (iv) report ≄1 TGMD-2 outcome scores. Extracted data were evaluated based on importance of determinants, strength of evidence, and methodological quality. Data from 64 articles were included. Weighted mean (and standard deviation) scores were calculated for each FMS outcome score. Analyses revealed FMS competence increases across age during childhood, with greater proficiency in locomotor skills than object control skills. Additionally, boys exhibit higher object control skill proficiency than girls. Compared to TGMD-2 normative data, children demonstrate “below average” to “average” FMS levels. This review highlights the scope for FMS development among children worldwide. These findings reinforce the necessity for FMS interventions in early educational settings, as FMS competence is positively associated with physical activity and other health outcomes

    Mental Health of Parents and Life Satisfaction of Children: A Within-Family Analysis of Intergenerational Transmission of Well-Being

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    This paper addresses the extent to which there is an intergenerational transmission of mental health and subjective well-being within families. Specifically it asks whether parents’ own mental distress influences their child’s life satisfaction, and vice versa. Whilst the evidence on daily contagion of stress and strain between members of the same family is substantial, the evidence on the transmission between parental distress and children’s well-being over a longer period of time is sparse. We tested this idea by examining the within-family transmission of mental distress from parent to child’s life satisfaction, and vice versa, using rich longitudinal data on 1,175 British youths. Results show that parental distress at year t-1 is an important determinant of child’s life satisfaction in the current year. This is true for boys and girls, although boys do not appear to be affected by maternal distress levels. The results also indicated that the child’s own life satisfaction is related with their father’s distress levels in the following year, regardless of the gender of the child. Finally, we examined whether the underlying transmission correlation is due to shared social environment, empathic reactions, or transmission via parent-child interaction
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