Importantly, we showed that the downregulation of these specific miRNAs and the upregulation of their targets also occur simultaneously in primary cases of h-MM. These data provide further evidence on the unifying role of cyclin D pathways deregulation as the key mechanism involved in the development of both groups of MM. Finally, they establish the importance Romidepsin order of miRNA deregulation in the context of MM, thereby opening up the potential for future therapeutic approaches
based on this molecular mechanism. Leukemia (2013) 27, 925-931; doi:10.1038/leu.2012.302″
“Background. As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent check details models for studying the neurobiology of addiction, without the confounding deleterious brain effects which may occur from chronic substance abuse.
Method. A community sample of individuals aged
18-65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded.
Results. A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median ‘go’ trial response latency) Diflunisal and cognitive flexibility [total intra-dimensional/extra-dimensional (IDED) errors] versus controls. The finding of impaired impulse control and cognitive flexibility
was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance.
Conclusions. Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.”
“THOC5 is a member of the THO complex that is involved in processing and transport of mRNA. We have shown previously that hematopoietic stem cells have an absolute requirement for THOC5 for survival and that THOC5 is phosphorylated on tyrosine 225 as a consequence of leukemogenic protein tyrosine kinase (PTK) action. We have investigated pathways for THOC5 phosphorylation to develop an understanding of THO complex modulation by tyrosine kinase (TK) oncogenes in leukemias.