GILZ inhibits the mTORC2/AKT pathway in BCR-ABL+ cells

The malignant phenotype of chronic myeloid leukemia (CML) is due to the abnormal tyrosine kinase activity of the BCR-ABL oncoprotein, which signals several downstream cell survival pathways, including phosphoinositide 3-kinase/AKT, signal transducer and activator of transcription 5 and extracellular signal-regulated kinase 1/2. In patients with CML, tyrosine kinase inhibitors (TKIs) are used to suppress the BCR-ABL tyrosine kinase, resulting in impressive response rates. However, resistance can occur, especially in acute-phase CML, through various mechanisms. Here, we show that the glucocorticoid-induced leucine zipper protein (GILZ) modulates imatinib and dasatinib resistance and suppresses tumor growth by inactivating the mammalian target of rapamycin complex-2 (mTORC2)/AKT signaling pathway. In mouse and human models, GILZ binds to mTORC2, but not to mTORC1, inhibiting phosphorylation of AKT (at Ser473) and activating FoxO3a-mediated transcription of the pro-apoptotic protein Bim; these results demonstrate that GILZ is a key inhibitor of the mTORC2 pathway. Furthermore, CD34+ stem cells isolated from relapsing CML patients underwent apoptosis and showed inhibition of mTORC2 after incubation with glucocorticoids and imatinib. Our findings provide new mechanistic insights into the role of mTORC2 in BCR-ABL+ cells and indicate that regulation by GILZ may influence TKI sensitivity

congenital deafness

Discordant Hirschsprung's disease in monozygotic twins is extremely rare. A pair of monozygotic twins with congenital deafness and discordant colonic aganglionosis is presented and genetic and prenatal environmental factors are discussed

Pollution Monitoring Using Mytilus galloprovincialis and Fishes: A Case Study on the Southern Black Sea Shelf

In this study, the heavy metal bioaccumulations in mussels (Mytilus galloprovincialis) and fishes (Merlangius merlangus euxinus) have been studied along the Southern Black Sea Shelf. Generally, Pb and Cd contents were higher than the critical limits set by the Turkish Ministry of Environment for Aquatic Products (1 mu g g(-1) wet wt. and 0.1 mu g g(-1) wet wt., respectively) and European countries (2.0 mu g g(-1) UNEP, 1985). They showed increases towards the eastern end of the shelf. As contents were observed higher than the critical limits set by the Turkish Ministry of Environment for Aquatic Products (1.0 mu g g(-1) wet wt.) at stations Terkos, Samsun and Ordu in 2009. In contrast, Hg levels were also higher than the critical limits set by the Turkish Ministry of Environment for Aquatic Products (0.5 mu g g(-1) wet wt.) in 2005 and the highest Hg concentrations were found in the west and middle of the shelf

Pollution Monitoring Using Mytilus galloprovincialis and Fishes: A Case Study on the Southern Black Sea Shelf

In this study, the heavy metal bioaccumulations in mussels (Mytilus galloprovincialis) and fishes (Merlangius merlangus euxinus) have been studied along the Southern Black Sea Shelf. Generally, Pb and Cd contents were higher than the critical limits set by the Turkish Ministry of Environment for Aquatic Products (1 mu g g(-1) wet wt. and 0.1 mu g g(-1) wet wt., respectively) and European countries (2.0 mu g g(-1) UNEP, 1985). They showed increases towards the eastern end of the shelf. As contents were observed higher than the critical limits set by the Turkish Ministry of Environment for Aquatic Products (1.0 mu g g(-1) wet wt.) at stations Terkos, Samsun and Ordu in 2009. In contrast, Hg levels were also higher than the critical limits set by the Turkish Ministry of Environment for Aquatic Products (0.5 mu g g(-1) wet wt.) in 2005 and the highest Hg concentrations were found in the west and middle of the shelf

An experimental study to demonstrate the influence of temporary and continuous jejunostomy feeding on guinea pigs

[No abstract available

Discordant Hirschsprung's disease in monozygotic twins with concordant congenital deafness

Discordant Hirschsprung's disease in monozygotic twins is extremely rare. A pair of monozygotic twins with congenital deafness and discordant colonic aganglionosis is presented and genetic and prenatal environmental factors are discussed

ANOMALOUS CONGENITAL BANDS CAUSING INTESTINAL-OBSTRUCTION IN CHILDREN

In this report the conceptual query language ConQuer-92 is introduced. Thisquery language serves as the backbone of InfoAssistant's query facilities.Furthermore, this language can also be used for the specification of derivationrules (e.g. subtype defining rules) and textual constraints in InfoModeler.This report is solely concerned with a formal definition, and the explanationthereof, of ConQuer-92. The implementation of ConQuer-92 in SQL-92 will betreated in a separate report

ADHESIVE SMALL-BOWEL OBSTRUCTION IN CHILDREN - THE PLACE AND PREDICTORS OF SUCCESS FOR CONSERVATIVE TREATMENT

A Comment on the paper "Conservative Quantum Computing" by M. Ozawa, Phys.Rev. Lett. 89, 057902 (2002). The author replies in Phys. Rev. Lett. 91, 089802(2003)