We show selleck chemicals llc that THOC5 phosphorylation is elevated in stem cells from patients with chronic myeloid leukemia (CML) and that this phosphorylation is sensitive to the frontline drugs used in CML treatment. Further we show that THOC5 Y225 phosphorylation governs mRNA binding. In addition, CXCL12 is shown to induce
THOC5 Y225 phosphorylation, and site-directed mutagenesis demonstrates that this modulates motile response. In conclusion, we delineate a signaling pathway stimulated by leukemogenic PTKs, chemokines and oxidative stress that can affect THO complex mediation of gene expression describing mechanisms for post-transcriptional regulation of protein levels. Leukemia (2013) 27, 932-940; doi:10.1038/leu.2012.283″
“Background. Cannabis use is considered a component cause of psychotic illness, interacting with genetic and other environmental risk factors. Little is known, however, about these putative interactions. The present study investigated whether an urban environment plays a role in moderating the effects of adolescent cannabis use on psychosis risk.
Method. Prospective data (n = 1923, aged 14-24 years at baseline) from the longitudinal population-based German Early Developmental Stages of Psychopathology cohort study were analysed. Urbanicity was assessed at baseline and defined as living in the city of Munich (1562 persons
per km(2); 4061 individuals per square mile) or in the rural LDC000067 mouse surroundings (213 persons per km(2); 553 individuals per square mile). Cannabis use and psychotic symptoms were Rho inhibitor assessed three times over a 10-year follow-up period using the Munich version of the Composite International Diagnostic Interview.
Results. Analyses revealed a significant interaction between cannabis and urbanicity [10.9% adjusted
difference in risk, 95% confidence interval (CI) 3.2-18.6, p = 0.005]. The effect of cannabis use on follow-up incident psychotic symptoms was much stronger in individuals who grew up in an urban environment (adjusted risk difference 6.8%, 95% CI 1.0-12.5, p = 0.021) compared with individuals from rural surroundings (adjusted risk difference -4.1%, 95% CI -9.8 to 1.6, p = 0.159). The statistical interaction was compatible with substantial underlying biological synergism.
Conclusions. Exposure to environmental influences associated with urban upbringing may increase vulnerability to the psychotomimetic effects of cannabis use later in life.”
“A markedly elevated serum free light chain (FLC) ratio may serve as a biomarker for malignant transformation in high-risk smoldering multiple myeloma (SMM) and identify patients who are at imminent risk of progression. We retrospectively studied the predictive value of the serum (FLC) assay in 586 patients with SMM diagnosed between 1970 to 2010.