A Concerted Kinase Interplay Identifies PPARγ as a Molecular Target of Ghrelin Signaling in Macrophages

The peroxisome proliferator-activator receptor PPARγ plays an essential role in vascular biology, modulating macrophage function and atherosclerosis progression. Recently, we have described the beneficial effect of combined activation of the ghrelin/GHS-R1a receptor and the scavenger receptor CD36 to induce macrophage cholesterol release through transcriptional activation of PPARγ. Although the interplay between CD36 and PPARγ in atherogenesis is well recognized, the contribution of the ghrelin receptor to regulate PPARγ remains unknown. Here, we demonstrate that ghrelin triggers PPARγ activation through a concerted signaling cascade involving Erk1/2 and Akt kinases, resulting in enhanced expression of downstream effectors LXRα and ABC sterol transporters in human macrophages. These effects were associated with enhanced PPARγ phosphorylation independently of the inhibitory conserved serine-84. Src tyrosine kinase Fyn was identified as being recruited to GHS-R1a in response to ghrelin, but failure of activated Fyn to enhance PPARγ Ser-84 specific phosphorylation relied on the concomitant recruitment of docking protein Dok-1, which prevented optimal activation of the Erk1/2 pathway. Also, substitution of Ser-84 preserved the ghrelin-induced PPARγ activity and responsiveness to Src inhibition, supporting a mechanism independent of Ser-84 in PPARγ response to ghrelin. Consistent with this, we found that ghrelin promoted the PI3-K/Akt pathway in a Gαq-dependent manner, resulting in Akt recruitment to PPARγ, enhanced PPARγ phosphorylation and activation independently of Ser-84, and increased expression of LXRα and ABCA1/G1. Collectively, these results illustrate a complex interplay involving Fyn/Dok-1/Erk and Gαq/PI3-K/Akt pathways to transduce in a concerted manner responsiveness of PPARγ to ghrelin in macrophages

Transitive projective planes

A long-standing conjecture is that any transitive finite projective plane is Desarguesian. We make a contribution towards a proof of this conjecture by showing that a group acting transitively on the the points of a non-Desarguesian projective plane must not contain any components

Analysis and investigation of the degree of moment rigidity of steel beam-to-column connections

In the conventional structural analysis of frames, it is assumed that beam-to-column connections behave perfectly rigid. However, this assumption fails to consider the actual behavior of beam-to-column connections. Knowing the actual rotational behavior of these connections and including the rotational spring stiffness in the model will allow for a more accurate analysis of frame structures. The study investigated five types of steel beam-to-column connections. The rotational spring stiffness values of these connections were determined through laboratory testing. The rotational spring stiffness is a quantity that represents the rotational behavior of the connections. The rotational spring stiffness values of the connections were used in the semi-rigid structural analysis using two types of spring models. Model 1 has rotational springs located at the intersections of beam and column, whereas model 2 has rotational springs located at the ends of the beam element. The test specimens were analyzed theoretically and their deflections were calculated. The theoretical deflections were compared with the experimental deflections and the results indicated that the semi-rigid structural analysis using spring model 2 predicts the actual deflection of the specimen during its linear elastic behavior. Therefore the study concluded that the rotational spring stiffness values obtained experimentally are accurate representations of the degree of moment rigidity of the connections

Finite groups with four conjugacy class sizes

This is an author's accepted manuscript of an article published in the Communications in Algebra: Volume 39, Issue 4, 2011: copyright Taylor & Francis. Available online at: http://www.tandfonline.com/doi/abs/10.1080/00927871003645417We determine the structure of all finite groups with four class sizes when two of them are coprime numbers larger than 1. We prove that such groups are solvable and that the set of class sizes is exactly {1, m, n, mk}, where m, n > 1 are coprime numbers and k > 1 is a divisor of n.We would like to thank the referee for all his comments and suggestions, and we are also truly grateful to Professor Kazarin for the detailed information he provided us on his article [19]. This work was partially supported by Proyecto MTM2007-68010-C03-03, by Proyecto MTM2010-19938-C03-02 and by Proyecto GV-2009-021 MTM2007-68010-C03-03 and the first author is also supported by grant Fundacio Caixa-Castello P11B2008-09.Beltrán, A.; Felipe Román, MJ. (2011). Finite groups with four conjugacy class sizes. Communications in Algebra. 39(4):1260-1272. https://doi.org/10.1080/00927871003645417S1260127239