The monomorphic type was the most common, with diffuse large B-cell lymphoma as the origin. The most frequent presentation was fever. Four in five patients had Epstein-Barr related PTLD. All patients received various regimens FK228 in vitro of immunosuppression reduction (IR), with 4 converting CNI to mTOR inhibitor (imTOR). Subsequent treatment (when needed) was chemotherapy, radiotherapy, and surgery. The maximum follow-up time was 6.7 years, with a 50% mortality rate that occurred at a median time of 3.5 months (2 died with functioning kidney). All 4 patients who were in remission
at the end of follow-up had CNI conversion to imTOR, and none lost the allograft. Conclusions. Despite the small number of cases, our results confirm the high PTLD impact in overall and allograft survival. Our PTLD type distribution is in accord with the literature. First-line PTLD treatment is IR, but the best method is still unknown; our results may suggest a beneficial effect of CNI conversion to imTOR.”
“Cell-to-cell communication, or quorum sensing (QS), enables cell CA4P datasheet density-dependent regulation of bacterial gene expression which can be exploited for the autonomous-signal-guided expression of recombinant proteins (C. Y. Tsao, S. Hooshangi, H.
C. Wu, J. J. Valdes, and W. E. Bentley, Metab. Eng. 12:291-297, 2010). Earlier observations that the metabolic potential of Escherichia coli is conveyed via the QS signaling molecule autoinducer-2 (AI-2) suggested that the capacity for protein synthesis could also be affected by AI-2 signaling (M. P. DeLisa, J. J. Valdes, and W. E. Bentley, J. Bacteriol. 183:2918-2928, 2001). In this work, we found that simply adding conditioned medium containing high levels of GSK J4 concentration AI-2 at the same time as inducing the synthesis of recombinant proteins doubled the yield of active product. We have hypothesized that AI-2 signaling “conditions” cells as a natural consequence of cell-to-cell communication and that this could tweak the signal transduction
cascade to alter the protein synthesis landscape. We inserted luxS (AI-2 synthase) into vectors which cosynthesized proteins of interest (organophosphorus hydrolase [OPH], chloramphenicol acetyltransferase [CAT], or UV-variant green fluorescent protein [GFPuv]) and evaluated the protein expression in luxS-deficient hosts. In this way, we altered the level of luxS in the cells in order to “tune” the synthesis of AI-2. We found conditions in which the protein yield was dramatically increased. Further studies demonstrated coincident upregulation of the chaperone GroEL, which may have facilitated higher yields and is shown for the first time to be positively regulated at the posttranscriptional level by AI-2. This report is the first to demonstrate that the protein synthesis capacity of E. coli can be altered by rewiring quorum sensing circuitry.