“
“Mutations in the gene encoding adenosine deaminase (ADA), a purine salvage enzyme, lead to immunodeficiency in humans. Although ADA deficiency has been analyzed in cell culture and murine models, information is lacking

concerning its impact on the development of human thymocytes. We have used chimeric human/mouse fetal thymic organ culture to study ADA-deficient human thymocyte development in an “in vivo-like” environment where toxic metabolites accumulate in situ. Inhibition Poziotinib of ADA during human thymocyte development resulted in a severe reduction in cellular expansion as well as impaired differentiation, largely affecting mature thymocyte populations. Thymocyte differentiation was not blocked at a discrete stage; rather, the paucity of mature thymocytes was due to the induction of apoptosis as evidenced by activation of caspases and was accompanied by the accumulation of intracellular dATP. Inhibition of adenosine kinase and deoxycytidine kinase

prevented the accumulation of dATP and restored thymocyte differentiation and proliferation. Our work reveals that multiple deoxynucleoside kinases are involved in the phosphorylation of deoxyadenosine when ADA is absent, and Z-IETD-FMK cost suggests an alternate therapeutic strategy for treatment of ADA-deficient patients. The Journal of Immunology, 2008, 181: 8153-8161.”
“Alexithymia is found in up to 10% of the general population and is associated with lower quality of life. Alexithymia is a major risk factor for a range of medical and psychiatric problems. Although a deficit involving the anterior cingulate cortex (ACC) deficit is thought

LY333531 nmr to offer the most promising neurobiological model of alexithymia, current studies have yielded inconsistent findings. In this study, neural activity was investigated in well-controlled alexithymic individuals subjected to emotional stimuli. Fifteen individuals with high Toronto Alexithymia Scale (TAS-20) scores (high-alexithymic group) and 15 individuals with low TAS-20 scores (low-alexithymic group) were screened from 432 female college students. Depressive and anxious behaviors were scored using self-rating depression scale (SDS) and self-rating anxiety scale (SAS) questionnaires, respectively. Emotional stimuli consisted of pictures with positive, negative, or neutral pleasantness and high or low arousal of emotional intensity. Regional cerebral activation was measured by functional magnetic resonance imaging (fMRI). The anterior cingulate, mediofrontal cortices, insula and temporal lobe were significantly activated by intense emotional stimuli (negative or positive pictures) in high-alexithymic individuals compared to low-alexithymic individuals. Conversely, high-alexithymic and low-alexithymic individuals showed similar brain activity when subjected to neutral stimuli. Alexithymia is associated with activation in anterior cingulate and mediofrontal cortices during emotional stimuli processing.