344 research outputs found
Thrombotic risk assessment in antiphospholipid syndrome: The role of new antibody specificities and thrombin generation assay
Antiphospholipid syndrome (APS) is an autoimmune condition characterized by the presence of antiphospholipid antibodies (aPL) in subjects presenting with thrombosis and/or pregnancy loss. The currently used classification criteria were updated in the international consensus held in Sidney in 2005. Vascular events seem to result of local procoagulative alterations upon triggers influence (the so called “second-hit theory”), while placental thrombosis and complement activation seem to lead to pregnancy morbidity. The laboratory tests suggested by the current classification criteria include lupus anticoagulant, a functional coagulation assay, and anticardiolipin and anti-β2-glycoprotein-I antibodies, generally detected by solid phase enzyme-linked immunosorbent assay. The real challenge for treating physicians is understanding what is the actual weight of aPL in provoking clinical manifestations in each case. As thrombosis has a multi-factorial cause, each patient needs a risk-stratified approach. In this review we discuss the role of thrombotic risk assessment in primary and secondary prevention of venous and arterial thromboembolic disease in patients with APS, focusing on new antibody specificities, available risk scoring models and new coagulation assays
IRS4, a novel modulator of BMP/Smad and Akt signalling during early muscle differentiation
Elaborate regulatory networks of the Bone Morphogenetic Protein (BMP) pathways
ensure precise signalling outcome during cell differentiation and tissue
homeostasis. Here, we identified IRS4 as a novel regulator of BMP signal
transduction and provide molecular insights how it integrates into the
signalling pathway. We found that IRS4 interacts with the BMP receptor BMPRII
and specifically targets Smad1 for proteasomal degradation consequently
leading to repressed BMP/Smad signalling in C2C12 myoblasts while
concomitantly activating the PI3K/Akt axis. IRS4 is present in human and
primary mouse myoblasts, the expression increases during myogenic
differentiation but is downregulated upon final commitment coinciding with
Myogenin expression. Functionally, IRS4 promotes myogenesis in C2C12 cells,
while IRS4 knockdown inhibits differentiation of myoblasts. We propose that
IRS4 is particularly critical in the myoblast stage to serve as a molecular
switch between BMP/Smad and Akt signalling and to thereby control cell
commitment. These findings provide profound understanding of the role of BMP
signalling in early myogenic differentiation and open new ways for targeting
the BMP pathway in muscle regeneration
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