The role of CTLA-4 in regulatory T cell (Treg) function is not well understood. We have examined the role of CTLA-4 and its relationship with the transcription factor FoxP3 using a model of Treg induction in human peripheral blood. Activation of human CD4(+)CD25(-) T cells resulted in the appearance of a de novo population of FoxP3-expressing cells within 48 h. These cells expressed high levels...

Complex life has arisen through a series of 'major transitions' in which collectives of formerly autonomous individuals evolve into a single, integrated organism. A key step in this process is the origin of higher-level evolvability, but little is known about how higher-level entities originate and gain the capacity to evolve as an individual. Here we report a single mutation that not only crea...

In Saccharomyces cerevisiae the protein kinase Cbk1p is a member of the regulation of Ace2p and cellular morphogenesis (RAM) network that is involved in cell separation after cytokinesis, cell integrity, and cell polarity. In cell separation, the RAM network promotes the daughter cell-specific localization of the transcription factor Ace2p, resulting in the asymmetric transcription of genes who...

The development of high-throughput phenotyping tools is lagging far behind the rapid advances of genotype generation methods. To bridge this gap, we report a new strategy for design, construction, and fine-tuning of intracellular-metabolite-sensing/regulation gene circuits by repurposing bacterial transcription factors and eukaryotic promoters. As proof of concept, we systematically investigate...

Article history: Available online 15 May 2012

In Saccharomyces cerevisiae, mothers and daughters have distinct fates. We show that Cbk1 kinase and its interacting protein Mob2 regulate this asymmetry by inducing daughter-specific genetic programs. Daughter-specific expression is due to Cbk1/Mob2-dependent activation and localization of the Ace2 transcription factor to the daughter nucleus. Ectopic localization of active Ace2 to mother nucl...

How cultures of genetically identical cells bifurcate into distinct phenotypic subpopulations under uniform growth conditions is an important question in developmental biology of relevance even to relatively simple developmental systems, such as spore formation in bacteria. A growing Bacillus subtilis culture consists of either cells that are motile and can swim or cells that are non-motile and...

results age was selected as the important factor based on all 7 statistics. exclusion of age variable decreased c index from 0.75 to 0.68 and r square from 0.25 to 0.15. duration of hospitalization was important based on 4 statistics. exclusion of this variable decreased r square from 0.25 to 0.21. while gender was a useful variable in separation of patients into risk groups, its omission did n...