Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets

<p>Abstract</p> <p>Background</p> <p>Flavonoids, a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. Quercetin, the most abundant of plant flavonoids, exerts a modulatory action at nanomolar concentrations on human basophils. As this mechanism needs to be elucidated, in this study we focused the possible signal transduction pathways which may be affected by this compound. Methods: K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE, fMLP, the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or CD203c-PE were used to produce dose response curves. The same population was assayed for histamine release.</p> <p>Results</p> <p>Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the anti-IgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA. The specific phosphoinositide-3 kinase (PI3K) inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation, thus suggesting a role for PI3K involvement in the priming mechanism.</p> <p>Conclusions</p> <p>These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin, while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.</p

Data Fairy in Engineering Land: The Magic of Data Analysis as a Sociotechnical Process in Engineering Companies

In the era of digitalization, manufacturing companies expect their growing access to data to lead to improvements and innovations. Manufacturing engineers will have to collaborate with data scientists to analyse the ever-increasing volume of data. This process of adopting data science techniques into an engineering organisation is a sociotechnical process fraught with challenges. This paper uses a participant observation case study to to investigate and discuss the sociotechnical nature of the adoption data science technology into an engineering organisation. In the case study, a young data scientist / statistician interacted with experienced production engineers in a global automotive organisation to mutual satisfaction. However, the case study highlights the mis-aligned expectations between engineers and data scientists and knowledge in what is necessary to successfully benefit from manufacturing process data. The results reveal that the engineers had an initially romantic and idealistic view on how data scientists can bring value out of dispersed and complex information residing in the multi-site manufacturing organisation’s datasets in a “magic” way. Conversely, the data scientist had not enough engineering and contextual understanding to ask the right questions. The case reveals important shortcomings in the sociotechnical processes that undergo changes as digitalisation is brought into mature engineering organisations and points to a lack of knowledge on multiple levels of the data analysis process and the ethical implications this could have

Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children and Adolescents

Treatment for emotional disorders in children and adolescents is increasingly being applied in a transdiagnostic manner to address the need for more broadly applicable, yet mechanism-focused psychotherapy. The Unified Protocols for Transdiagnostic Treatment of Emotional Disorders in Children and Adolescents (UP-C/A) are modular, flexible, evidence-based treatment manuals that utilize empirically supported, largely cognitive and behavioral strategies to treat anxiety, mood, and other emotional disorders. In this chapter, we describe the rationale and empirical support for the use of the UP-C/A, provide a pragmatic overview of its contents, and briefly discuss application of core intervention components