20 research outputs found

    The Multi-Level Action of Fatty Acids on Adiponectin Production by Fat Cells

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    Current epidemics of diabetes mellitus is largely caused by wide spread obesity. The best-established connection between obesity and insulin resistance is the elevated and/or dysregulated levels of circulating free fatty acids that cause and aggravate insulin resistance, type 2 diabetes, cardiovascular disease and other hazardous metabolic conditions. Here, we investigated the effect of a major dietary saturated fatty acid, palmitate, on the insulin-sensitizing adipokine adiponectin produced by cultured adipocytes. We have found that palmitate rapidly inhibits transcription of the adiponectin gene and the release of adiponectin from adipocytes. Adiponectin gene expression is controlled primarily by PPARγ and C/EBPα. Using mouse embryonic fibroblasts from C/EBPα-null mice, we have determined that the latter transcription factor may not solely mediate the inhibitory effect of palmitate on adiponectin transcription leaving PPARγ as a likely target of palmitate. In agreement with this model, palmitate increases phosphorylation of PPARγ on Ser273, and substitution of PPARγ for the unphosphorylated mutant Ser273Ala blocks the effect of palmitate on adiponectin transcription. The inhibitory effect of palmitate on adiponectin gene expression requires its intracellular metabolism via the acyl-CoA synthetase 1-mediated pathway. In addition, we found that palmitate stimulates degradation of intracellular adiponectin by lysosomes, and the lysosomal inhibitor, chloroquine, suppressed the effect of palmitate on adiponectin release from adipocytes. We present evidence suggesting that the intracellular sorting receptor, sortilin, plays an important role in targeting of adiponectin to lysosomes. Thus, palmitate not only decreases adiponectin expression at the level of transcription but may also stimulate lysosomal degradation of newly synthesized adiponectin

    Why so serious? Theorising playful model-driven group decision support with situated affectivity

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    This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.An integrative approach to theorising behavioural, affective and cognitive processes in modeldriven group decision support (GDS) interventions is needed to gain insight into the (micro-)processes by which outcomes are accomplished. This paper proposes that the theoretical lens of situated affectivity, grounded in recent extensions of scaffolded mind models, is suitable to understand the performativity of affective micro-processes in model-driven GDS interventions. An illustrative vignette of a humorous micro-moment in a group decision workshop is presented to reveal the performativity of extended affective scaffolding processes for group decision development. The lens of situated affectivity constitutes a novel approach for the study of interventionist practice in the context of group decision making (and negotiation). An outlook with opportunities for future research is offered to facilitate an integrated approach to the study of cognitive-affective and behavioural micro-processes in model-driven GDS interventions.This work was supported in part by the EU FP7-ENERGY- SMARTCITIES-2012 (314277) project STEEP (Systems Thinking for Comprehensive City Efficient Energy Planning

    Negotiation processes, evolutionary systems design, and NEGOTIATOR

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    A negotiation accord is often the result of an intense, laborious, and evolutionary negotiation process. During this process, disputing parties are confronted with goal, judgment, and outcome conflict. This article demonstrates the utility of a conflict resolution framework-Evolutionary Systems Design (ESD)-by using a Negotiation Support System. ESD seeks to guide negotiators to move their individual goals and judgments in such a way as to enhance the chance of achieving a common solution. As illustrated by the use of NEGOTIATOR, a multiattribute utility negotiation support system, we argue that computer mediation can prove to be an effective means to implement the ESD framework

    Sustainability and Systems Thinking

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    Organizing for Commons-Enabling Decision-Making Under Conflicting Institutional Logics in Social Entrepreneurship

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    Abstract Social entrepreneurship develops innovative opportunities and solutions aimed to (re)generate the common good. This emerging organizational form poses unprecedented challenges to group decision and negotiation studies. This article lever- ages conceptual tools from the literature on the commons and institutional logics as it explores the organizational conditions of social entrepreneurship that trigger commons-enabling decision-making in its organizational field. Through an inductive analysis of a longitudinal case, this study proposes a model that highlights the critical role of the bridging organization that can be introduced by the social entrepreneur in a previously fragmented organizational field. This bridging organization is in the con- dition to develop an innovative co-creation logic that can serve as a common ground to enable collaboration between actors from diverse and even conflicting institutional logics. The proposed model suggests that a practice-driven path to the construction of such a common ground for decision-making is more effective than a disclosure-driven path, which is based on classical conflict analysis techniques. The ICT-enabled activ- ity system developed by the social entrepreneur injects transparency and traceability into a previously opaque field, thus creating the conditions for distributed, flexible, and complementary sense- and decision-making processes that develop and protect the commons
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