Saline-treated mutants showed increased locomotion, more stereotypic behavior and a decrease in rearing compared to wild-type mice. This baseline level of activity was similar to behaviors observed in wild-type animals treated with high doses of psychostimulants. In mutants methylphenidate (5 or 30 mg/kg) or amphetamine (2 or 4 mg/kg) did not further increase activity or even caused a decrease of locomotor activity, in contrast to wildtype mice. Fluoxetine (5 or

10 mg/kg) reduced hyperactivity of mutants to levels observed in wild-types. Transmitter measurements, dopamine and serotonin transporter binding assays and autoradiography, indicated a subtle increase in striatal dopaminergic innervation and a marked general decrease of serotonergic innervation in mutants. Taken together, our data suggest that buy WZB117 mice with an aberrantly positioned mid-hindbrain organizer show altered sensitivity to psychostimulants and that an increase of serotonergic neurotransmission reverses their hyperactivity. We conclude that the mid-hindbrain organizer, by orchestrating the formation of dopaminergic and serotonergic neurons, is an essential developmental parameter of locomotor activity and psychostimulant response. (C) 2009 IBRO. MX69 ic50 Published by Elsevier Ltd. All rights reserved.”
“Runt-related transcription factor 1 (RUNX1) is essential for normal hematopoiesis.

RUNX1 mutations have rarely been reported in chronic myelomonocytic leukemia (CMML). We examined RUNX1 mutations in 81 patients with CMML at initial diagnosis. Mutational analysis was performed on bone marrow samples by direct sequencing of all reverse transcription PCR

products amplified with three primer pairs that cover the entire coding sequences of RUNX1b. Thirty-two RUNX1 mutations were detected in 30 patients (37%); 23 mutants were located in the N-terminal part and 9 in the C-terminal region. The mutations consisted of 9 missense, 1 silent, 7 nonsense and 15 frameshift mutations. Two patients had biallelic heterozygous mutations. There was no difference in overall survival between patients with and without RUNX1 mutations, but a trend of higher risk of acute myeloid leukemia (AML) progression was observed in mutation-positive patients (16/30 vs 17/51, P = 0.102), especially in patients however with C-terminal mutations (P = 0.023). The median time to AML progression was 6.8 months in patients with C-terminal mutations compared with 28.3 months in those without mutations (P = 0.022). This study showed for the first time a high frequency of RUNX1 mutations in CMML. C-terminal mutations might be associated with a more frequent and rapid AML transformation. Leukemia (2009) 23, 1426-1431; doi:10.1038/leu.2009.48; published online 19 March 2009″
“Adult hippocampal cell proliferation (HCP) has been associated with psychopathology, especially depression.