Reciprocal regulation of PKA and rac signaling

Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial and temporal controlled kinase and GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein kinase A (PKA) is the prime example for compartmentalized signal transmission downstream of distinct GPCRs. A-kinase anchoring proteins tether PKA to specific intracellular sites to ensure precision and directionality of PKA phosphorylation events. Here, we show that the Rho-GTPase Rac contains A-kinase anchoring protein properties and forms a dynamic cellular protein complex with PKA. The formation of this transient core complex depends on binary interactions with PKA subunits, cAMP levels and cellular GTP-loading accounting for bidirectional consequences on PKA and Rac downstream signaling. We show that GTP-Rac stabilizes the inactive PKA holoenzyme. However, β-adrenergic receptor-mediated activation of GTP-Rac–bound PKA routes signals to the Raf-Mek-Erk cascade, which is critically implicated in cell proliferation. We describe a further mechanism of how cAMP enhances nuclear Erk1/2 signaling: It emanates from transphosphorylation of p21-activated kinases in their evolutionary conserved kinase-activation loop through GTP-Rac compartmentalized PKA activities. Sole transphosphorylation of p21-activated kinases is not sufficient to activate Erk1/2. It requires complex formation of both kinases with GTP-Rac1 to unleash cAMP-PKA–boosted activation of Raf-Mek-Erk. Consequently GTP-Rac functions as a dual kinase-tuning scaffold that favors the PKA holoenzyme and contributes to potentiate Erk1/2 signaling. Our findings offer additional mechanistic insights how β-adrenergic receptor-controlled PKA activities enhance GTP-Rac–mediated activation of nuclear Erk1/2 signaling

The development and validation of a general measure of well-being: the BBC well-being scale

Purpose: The concept of maximising well-being, as opposed to merely treating mental disorder, is a powerful current theme in the area of mental health. Clearly this emphasises the need for appropriate valid and reliable measures of general well-being. This paper examines the appropriateness of a number of measures in this area and concludes that existing assessment tools fail to address the full range of aspects of personal well-being. This paper therefore presents the psychometric properties, validity and reliability of a new measure of well-being-the BBC Well-being Scale. Methods: A total of 1,940 participants completed the new measure, the Goldberg scales of anxiety and depression, the 'List of Threatening Experiences' life events scale, a modified version of the Response Styles Questionnaire and a modified version of the Internal, Personal and Situational Attributions Questionnaire presented via the internet. Results: Exploratory factor-analysis suggested a three-factor solution including themes of psychological well-being, physical health and well-being and relationships. The total 24-item scale had good internal consistency (α = .935) and correlated significantly with key demographic variables and measures of concurrent validity. Conclusions: The new measure-the BBC Well-being Scale-is recommended for research and clinical purposes. © 2011 Springer Science+Business Media B.V

Understood at Last?: A Memetic Analysis of Beethoven’s ‘Bloody Fist’

As a singular moment in the western canon, the opening of the recapitulation in the first movement of Beethoven’s Ninth Symphony has prompted a variety of structural and expressive readings. This paper explores its intertextual connections with Mozart’s Don Giovanni from a memetic perspective, outlining certain extra musical interpretations, including some related to Susan McClary’s controversial reading of the passage, one might infer from the strong musical connections

Synthesising Corporate Responsibility on Organisational and Societal Levels of Analysis: An Integrative Perspective

This article develops an integrative perspective on corporate responsibility by synthesising competing perspectives on the responsibility of the corporation at the organisational and societal levels of analysis. We review three major corporate responsibility perspectives, which we refer to as economic, critical, and politico-ethical. We analyse the major potential uses and pitfalls of the perspectives, and integrate the debate on these two levels. Our synthesis concludes that when a society has a robust division of moral labour in place, the responsibility of a corporation may be economic (as suggested under the economic perspective) without jeopardising democracy and sustainability (as reported under the critical perspective). Moreover, the economic role of corporations neither signifies the absence of deliberative democratic mechanisms nor business practices extending beyond compliance (as called for under the politico-ethical perspective). The study underscores the value of integrating different perspectives and multiple levels of analysis to present comprehensive descriptions and prescriptions of the responsibility phenomenon

Prosociality in business: a human empowerment framework

This study introduces a human empowerment framework to better understand why some businesses are more socially oriented than others in their policies and activities. Building on Welzel’s theory of emancipation, we argue that human empowerment—comprised of four components: action resources, emancipative values, social movement activity, and civic entitlements—enables, motivates, and entitles individuals to pursue social goals for their businesses. Using a sample of over 15,000 entrepreneurs from 43 countries, we report strong empirical evidence for two ecological effects of the framework components on prosociality. We find that human empowerment (1) lifts entrepreneurs’ willingness to choose a social orientation for their business, and (2) reinforces the gender effect on prosociality in business activity. We discuss the human empowerment framework’s added value in understanding how modernization processes fully leverage the potential of social business activities for societies

Applying the theory of planned behaviour to understand mental health professionals’ intentions to work using a human rights-based approach in acute inpatient settings

Background: There has been a shift to implement human rights-based approaches in acute mental health care due to increasing concerns around quality of care. National Health Service (NHS) Trusts have a legal duty to uphold a person’s human rights, therefore it is important to understand what any barriers might be. Using psychological theory may help to develop this understanding. Aim: To test whether the theory of planned behaviour can be an effective model in understanding mental health professionals’ intentions to work using a human rights-based approach. Method: Participants were recruited from two NHS Trusts in the North West of England. A cross-sectional, survey design was used to examine mental health professionals’ intentions to use human rights-based approaches. Results: Multiple regression analyses were performed on the theory of planned behaviour constructs showing that attitude and subjective norm significantly predicted intention. Perceived behavioural control did not add any significant variance, nor any demographic variables. Conclusion: There could be factors outside of the individual clinician’s control to fully work within a human rights-based framework on acute mental health wards. The theory of planned behaviour offers some understanding, however further development work into measuring human rights outcomes on acute mental health wards is needed

The Finnish Think Tank Landscape : A Mixture of Consensualism and Adversity?

As a common feature of Nordic countries, the Finnish landscape of thinks tanks has been populated by large corporatist interest organisations and government-funded research organisations. In addition to this, since 2005, party-affiliated think tanks form a notable part of the picture. Recently, several small think tanks that are oriented towards specific themes, such as international relations, the environment and feminism, have been founded. This article examines Finnish developments in the field of think tanks with two objectives. First, it gives a general overview of the Finnish think tank landscape. Second, by using interview data and public mission statements of the most prominent think tanks, it explores how these organisations see their role in Finnish society. What is their relationship with media and the political machinery, and how does this relate to their position and activities as either consensual or adversarial actors? It is concluded that redeeming the place of think tanks in the Finnish polity is a continuing challenge, and resorting to adversarial tactics is not a favourable way to do so. This approach has mostly been attempted by neoliberal think tanks that, in the past, have also profited from corporatist structures to enhance their objectives.Peer reviewe

Identifying protein complexes directly from high-throughput TAP data with Markov random fields

<p>Abstract</p> <p>Background</p> <p>Predicting protein complexes from experimental data remains a challenge due to limited resolution and stochastic errors of high-throughput methods. Current algorithms to reconstruct the complexes typically rely on a two-step process. First, they construct an interaction graph from the data, predominantly using heuristics, and subsequently cluster its vertices to identify protein complexes.</p> <p>Results</p> <p>We propose a model-based identification of protein complexes directly from the experimental observations. Our model of protein complexes based on Markov random fields explicitly incorporates false negative and false positive errors and exhibits a high robustness to noise. A model-based quality score for the resulting clusters allows us to identify reliable predictions in the complete data set. Comparisons with prior work on reference data sets shows favorable results, particularly for larger unfiltered data sets. Additional information on predictions, including the source code under the GNU Public License can be found at http://algorithmics.molgen.mpg.de/Static/Supplements/ProteinComplexes.</p> <p>Conclusion</p> <p>We can identify complexes in the data obtained from high-throughput experiments without prior elimination of proteins or weak interactions. The few parameters of our model, which does not rely on heuristics, can be estimated using maximum likelihood without a reference data set. This is particularly important for protein complex studies in organisms that do not have an established reference frame of known protein complexes.</p