Decreased CD127 expression has been associated with persistent

Decreased CD127 expression has been associated with persistent click here viral infections (e.g. HIV, HCV) and cancer. Many IL-2R gamma-sharing (gamma(C)) cytokines decrease CD127 expression on CD4(+) and CD8(+) T cells in mice (IL-2, IL-4, IL-7, IL-15) and in humans (IL-2, IL-7), suggesting a common function. IL-4 is of particular interest as it is upregulated in HIV infection and in thyroid and colon cancers. The role of IL-4 in regulating CD127 expression and IL-7 activity in human thymocytes and mature CD8(+) T cells is unknown and was therefore investigated. IL-4 decreased CD127 expression on all thymocyte subsets tested and only on naive (CD45RA) CD8(+) T cells,

without altering membrane-bound CD127 mRNA expression. Pre-treatment of thymocytes or CD8(+) T cells with IL-4 inhibited IL-7-mediated phosphorylation of STAT5 and decreased proliferation of CD8(+) T cells. By downregulating CD127 expression and signaling on developing thymocytes and CD8(+) T cells, IL-4 is a potential contributor to impaired CD8(+) T-cell function in some anti-viral and anti-tumor responses. These findings are of particular consequence to diseases such as HIV, HCV, RSV, measles and cancer, in which CD127 expression is decreased, IL-7 activity is impaired and IL-4 concentrations are elevated.”
“Triptolide,

a traditional anti-inflammatory and anti-immunodepressive www.selleckchem.com/products/10058-f4.html agent, has been reported to exert antineoplastic activity AZD2014 mw on several human tumor cell lines. This study investigates the pro-apoptotic function and the functional mechanism of triptolide on anaplastic thyroid carcinoma (ATC) cells. Experiments presented here demonstrated that triptolide had dose-dependent effects on cell viability of human ATC cell line TA-K cells through inducing cell apoptosis. In the molecular level, triptolide did not successfully initiate p53 signaling pathway, but downregulated the nuclear factor kappa B (NF-kappa B) pathway. Our studies suggest that triptolide functions as an effective apoptotic inducer in a p53-independent, but NF-kappa B-dependent mechanism, thus providing a promising

agent for tumor types with p53 mutation/deletion.”
“The replica exchange statistical temperature Monte Carlo algorithm (RESTMC) is presented, extending the single-replica STMC algorithm [J. Kim, J. E. Straub, and T. Keyes, Phys. Rev. Lett. 97, 050601 (2006)] to alleviate the slow convergence of the conventional temperature replica exchange method (t-REM) with increasing system size. In contrast to the Gibbs-Boltzmann sampling at a specific temperature characteristic of the standard t-REM, RESTMC samples a range of temperatures in each replica and achieves a flat energy sampling employing the generalized sampling weight, which is automatically determined via the dynamic modification of the replica-dependent statistical temperature.

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