Thirteen patients (15%) carried TET2 mutations Patients with mut

Thirteen patients (15%) carried TET2 mutations. Patients with mutated and wild-type (WT) TET2 had mostly comparable pretreatment

characteristics, except for lower hemoglobin, better cytogenetic risk and longer MDS duration before AZA in TET2 mutated patients (P = 0.03, P = 0.047 and P = 0.048, respectively). The response rate (including hematological improvement) was 82% in MUT versus 45% in WT patients (P = 0.007). Mutated TET2 (P = 0.04) and favorable cytogenetic risk (intermediate risk: P = 0.04, poor risk: P = 0.048 compared with good risk) independently predicted a higher response rate. Response duration and overall survival were, however, comparable in the MUT and WT groups. In higher risk MDS and AML with low blast count, TET2 status may be a genetic predictor of response to AZA, independently of karyotype. Leukemia (2011) 25, 1147-1152; doi:10.1038/leu.2011.71; Blasticidin S published online selleck chemical 15 April 2011″
“How transforming growth factor-beta (TGF-beta) signaling elicits diverse cell responses remains elusive, despite the major molecular components of the pathway being known. We contend that understanding TGF-beta biology requires mathematical models to decipher the quantitative nature of TGF-beta/Smad signaling and to account for its complexity.

Here, we review mathematical models of TGF-beta superfamily signaling that predict how robustness is achieved in bone-morphogenetic-protein signaling in the Drosophila embryo, how changes in receptor-trafficking dynamics can be exploited by cancer cells and how the basic mechanisms of TGF-beta/Smad signaling conspire to promote 3-Methyladenine price Smad accumulation in the nucleus. These studies demonstrate the power of mathematical modeling for understanding TGF-beta biology.”
“Ether-a-go-go (ERG) K+ channel

is a channel of potassium inward rectification. ERG channelopathy may be a cause of sudden unwanted death. The purpose of our study is to assess the effect of antiepileptic drugs on the expression of ERG K+ channel in the hippocampus using seizure resistant (SR) and seizure sensitive (SS) gerbils. As compared to controls, in principal neuron of hippocampus ERG immunoreactivity was significantly decreased after administration of AEDs in SS and SR gerbils. In addition, population spike in response to the second stimulus disappeared, thus population spike amplitude ratio was significantly reduced to zero. These findings indicate that AEDs reduce the expression of ERG channel in the hippocampus of the SR and SS gerbils accompanied by the enhancement of paired-pulse inhibition. In addition, the influence of AEDs on ERG expression in the brain may not be relevant to sudden unexpected death in epilepsy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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