Charting the NF-κB Pathway Interactome Map

Inflammation is part of a complex physiological response to harmful stimuli and pathogenic stress. The five components of the Nuclear Factor κB (NF-κB) family are prominent mediators of inflammation, acting as key transcriptional regulators of hundreds of genes. Several signaling pathways activated by diverse stimuli converge on NF-κB activation, resulting in a regulatory system characterized by high complexity. It is increasingly recognized that the number of components that impinges upon phenotypic outcomes of signal transduction pathways may be higher than those taken into consideration from canonical pathway representations. Scope of the present analysis is to provide a wider, systemic picture of the NF-κB signaling system. Data from different sources such as literature, functional enrichment web resources, protein-protein interaction and pathway databases have been gathered, curated, integrated and analyzed in order to reconstruct a single, comprehensive picture of the proteins that interact with, and participate to the NF-κB activation system. Such a reconstruction shows that the NF-κB interactome is substantially different in quantity and quality of components with respect to canonical representations. The analysis highlights that several neglected but topologically central proteins may play a role in the activation of NF-κB mediated responses. Moreover the interactome structure fits with the characteristics of a bow tie architecture. This interactome is intended as an open network resource available for further development, refinement and analysis

Vascularized osteochondral graft from the medial femoral trochlea: anatomical study and clinical perspectives

PURPOSE: Few donor sites for vascularized reconstruction of convex joint surfaces have been described. We studied the feasibility of a convex vascularized osteochondral graft harvested from the medial femoral condyle and trochlea, on an anatomical and practical point of view. METHODS: An injection-corrosion technique was used on 16 fresh cadaver specimens, and completed by a modified Spalteholz clearing. The extra- and intraosseous vascularization of the medial femoral condyle was systematized and the luminal diameter of the arteries was microscopically measured. Radii of curvature of the medial trochlea and of the carpal bones were measured on arthro-CT-scanner reconstructed images. RESULTS: The periosteal vessels of the medial condyle are responsible for the whole peripheral intraosseous vascularization, without any watershed region. They are fed by the articular branch of the descending genicular artery and/or the superomedial genicular artery. Several constant vascular axes can be found, and may serve as a pedicle for a vascularized osteochondral graft from the medial femoral trochlea. The radii of curvature of this graft do fit those of the proximal carpal row. A simple surgical approach is suggested. CONCLUSIONS: A vascularized graft harvested on the medial femoral trochlea is a technically feasible procedure that could represent a new reconstructive tool for convex joint surfaces. Osteonecrosis of the proximal pole of the scaphoid or Kienböck's disease are among several situation