“Several bacterial pathogens inject virulence proteins into host target cells that are substrates of eukaryotic tyrosine kinases. One of the key examples is the Helicobacter pylori CagA effector protein which is translocated by a type-IV secretion system. Injected CagA becomes tyrosine-phosphorylated on EPIYA sequence motifs by Src and Abl family kinases. CagA then binds to and activates/inactivates multiple signaling proteins in a phosphorylation-dependent and phosphorylation-independent manner. A recent proteomic screen systematically identified eukaryotic binding
partners of the EPIYA phosphorylation sites of CagA and similar sites in other bacterial effectors by high-resolution mass spectrometry. Individual phosphorylation sites recruited a surprisingly high number of interaction partners suggesting that each phosphorylation site can interfere with many downstream pathways. We now count 20 reported cellular binding partners of CagA, which represents the highest Apoptosis inhibitor quantitiy among all yet known virulence-associated effector proteins in the microbial world. This complexity generates a highly remarkable and puzzling scenario. In addition, the first crystal structure of CagA provided us with new information on the function of this important virulence determinant. Here we review the recent advances in characterizing the multiple
binding signaling activities of CagA. Injected CagA can act as a ‘master key’ that evolved the ability to highjack multiple host Navitoclax inhibitor cell signalling cascades, SHP099 which include the induction of membrane dynamics, actin-cytoskeletal rearrangements and the disruption of cell-to-cell junctions as well as
proliferative, pro-inflammatory and anti-apoptotic nuclear responses. The discovery that different pathogens use this common strategy to subvert host cell functions suggests that more examples will emerge soon.”
“Objective: To evaluate the capacity of fetal echocardiography for predicting the more likely surgical approach in new-borns with coarctation of the aorta (CoAo) (left thoracotomy vs. median sternotomy). Material and Methods: We selected all cases of suspected CoAo prenatally diagnosed in 2003-2012 (n = 95). 49/95 were considered at high-risk and 46/95 at low-risk of CoAo, and 38/49 and 7/46 were postnatally confirmed, respectively. We firstly evaluated in 40 cases of CoAo surgically repaired (24 thoracotomy, 16 sternotomy) whether there were differences in fetal echocardiographic parameters between both groups. Secondly, we assessed the performance of these parameters for predicting the surgical approach in fetuses at high risk of CoAo. Results: Sternotomy approach was associated with higher rate of postoperative complications and longer hospital stay compared with thoracotomy (81.3 vs. 41.7%, p = 0.014; 30.5 vs. 15.4 days, p = 0.0004, respectively). The Z-score of the aortic isthmus, measured in the sagittal plane, was significantly smaller in the sternotomy group.