Platelet-activating factor downregulates the expression of liver X receptor-α and its target genes in human neutrophils

Liver X receptors (LXRs) are ligand-activated members of the nuclear receptor superfamily that regulate the expression of genes involved in lipid metabolism and inflammation, although their role in inflammation and immunity is less well known. It has been reported that oxysterols/LXRs may act as anti-inflammatory molecules, although opposite actions have also been reported. In this study, we investigated the effect of platelet-activating factor (PAF), a proinflammatory molecule, on LXRα signalling in human neutrophils. We found that PAF exerted an inhibitory effect on mRNA expression of TO901317-induced LXRα, ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and sterol response element binding protein 1c. This negative action was mediated by the PAF receptor, and was dependent on the release of reactive oxygen species elicited by PAF, as it was enhanced by pro-oxidant treatment and reversed by antioxidants. Current data also support the idea that PAF induces phosphorylation of the LXRα molecule in an extracellular signal-regulated kinase 1/2-mediated fashion. These results suggest that a possible mechanism by which PAF exerts its proinflammatory effect is through the downregulation of LXRα and its related genes, which supports the notion that LXRα ligands exert a modulatory role in the neutrophil-mediated inflammatory response.

Industry-specific effect of CSR initiatives: hotels and airlines

Purpose – This study aims to examine the relationships between a firm's corporate social responsibility (CSR) activities and its performance and risk. The authors hypothesize that industry-level effects are highly determinant of the sign and magnitude of these relationships to establish a ranking of industries to identify the position of the most prominent tourism-related industries: hotels and airlines. Based on the cybernetic model of decision making and the heuristics thereof, shareholders base their investment decisions derived from CSR announcements on the idea that the industries behave differently; their fixed costs being a relevant factor. Design/methodology/approach – The authors estimate the industry-specific effects of CSR initiatives on firms' performance and risk using a sample of 583 announcements from the Spanish Stock Market. Findings – The results show that while CSR announcements have a positive effect on performance when the authors do not account for industry-specific factors, once the authors incorporate these factors into the analysis, the authors find that firm performance and risk vary quite substantially as a function of the industry to which the firm belongs. Interestingly, while the hotel industry presents an average behavior (standing at 9th position in returns, 15th in terms of risk, and 8th according to the ratio returns/volatility), the airline industry presents the worst situation of all industries: last in performance and last in risk. Practical implications – The results help managers assess their decisions and allocate CSR resources optimally. Originality/value – This article is the first attempt to empirically test and comprehensively detect the different relationships between CSR and firm performance across industries.

Revisiting the effect of foundation embedment on elastic settlement: A new approach

The effect of foundation embedment on settlement calculation is a widely researched topic in which there is no scientific consensus regarding the magnitude of settlement reduction. In this paper, a non-linear three dimensional Finite Element analysis has been performed with the aim of evaluating the aforementioned effect. For this purpose, 1800 models were run considering different variables, such as the depth and dimensions of the foundation and the Young’s modulus and Poisson’s ratio of the soil. The settlements from models with foundations at surface level and at depth were then compared and the relationship between them established. The statistical analysis of this data allowed two new expressions, with a mean maximum error of 1.80%, for the embedment influence factor of a foundation to be proposed and these to be compared with commonly used corrections. The proposed equations were validated by comparing the settlements calculated with the proposed influence factors and the true settlements measured in several real foundations. From the comprehensive study of all modelled cases, an improved approach, when compared to those proposed by other authors, for the calculation of the true elastic settlements of an embedded foundation is proposed.

The activating role of phospho-(Tyr)-calmodulin on the epidermal growth factor receptor

The activity of calmodulin (CaM) is modulated not only by oscillations in the cytosolic concentration of free Ca2+, but also by its phosphorylation status. In the present study, the role of tyrosine-phosphorylated CaM [P-(Tyr)-CaM] on the regulation of the epidermal growth factor receptor (EGFR) has been examined using in vitro assay systems. We show that phosphorylation of CaM by rat liver solubilized EGFR leads to a dramatic increase in the subsequent phosphorylation of poly-L-(Glu:Tyr) (PGT) by the receptor in the presence of ligand, both in the absence and in the presence of Ca2+. This occurred in contrast with assays where P-(Tyr)-CaM accumulation was prevented by the presence of Ca2+, absence of a basic cofactor required for CaM phosphorylation and/or absence of CaM itself. Moreover, an antibody against CaM, which inhibits its phosphorylation, prevented the extra ligand-dependent EGFR activation. Addition of purified P-(Tyr)-CaM, phosphorylated by recombinant c-Src (cellular sarcoma kinase) and free of non-phosphorylated CaM, obtained by affinity-chromatography using an immobilized anti-phospho-(Tyr)-antibody, also increased the ligand-dependent tyrosine kinase activity of the isolated EGFR toward PGT. Also a CaM(Y99D/Y138D) mutant mimicked the effect of P-(Tyr)-CaM on ligand-dependent EGFR activation. Finally, we demonstrate that P-(Tyr)-CaM binds to the same site (645R-R-R-H-I-V-R-K-R-T-L-R-R-L-L-Q660) as non-phosphorylated CaM, located at the cytosolic juxtamembrane region of the EGFR. These results show that P-(Tyr)-CaM is an activator of the EGFR and suggest that it could contribute to the CaM-mediated ligand-dependent activation of the receptor that we previously reported in living cells.

Algunas consideraciones sobre el valor intrínseco del factor de impacto de las revistas científicas

Se analiza el porqué de las citaciones de los artículos. Se realizan también algunas consideraciones sobre el factor de impacto de las revistas, sus ventajas y sus posibles defectos. El factor de impacto de las revistas, desde su popularización por el Institute for Scientific Information, ha tomado una gran importancia como parámetro objetivo de evaluación de las revistas científicas y, por extensión, de todo lo que las rodea. No hay correlación con el desfase en factores de impacto de algunas revistas anglosajonas y el de las revistas escritas en otros idiomas. Probablemente se benefician de publicar en inglés y del llamado “efecto Mateo”, según el cual los investigadores científicos eminentes cosechan aplausos mucho más nutridos que otros investigadores, menos conocidos, por contribuciones equivalentes. Es paradójico también que los grandes descubrimientos de nuestra época no figuren entre los 100 artículos más citados. No hay tampoco una correlación entre todos los artículos aparecidos en una publicación y su factor de impacto; la mitad de los artículos de una revista son citados diez veces más que la otra mitad. Los artículos citados 0 veces reciben el mérito de los mejores. Lo ortodoxo sería utilizar en cada artículo el número de citas que recibe, que sería su propio factor de impacto y, para los autores, el índice H.