Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1
ABSTRACT Development of immunoglobulin-secreting plasma cells from B cells is a tightly regulated process controlled by the action of a number of transcription factors. In particular, the transcription factor Blimp-1 is a key positive regulator of plasmacytic differentiation via its ability to suppress expression of genes involved in the mature B cell program. The transcription factor Ets-1 is a negative regulator of plasmacytic differentiation, as indicated by the development of increased numbers of IgM-secreting plasma cells in Ets-1 knock-out mice. We have previously shown that Ets-1-deficient B cells undergo enhanced differentiation into IgM-secreting plasma cells in response to Toll-like receptor 9 (TLR9) signaling. We now explore the mechanism by which Ets-1 limits differentiation downstream of TLR9. Our results indicate that Ets-1 physically interacts with Blimp-1, which leads to a block in Blimp-1 DNA binding activity and a reduction in the ability of Blimp-1 to repress target genes without interfering with Blimp-1 protein levels. In addition, we show that Ets-1 induces the expression of several target genes that are repressed by Blimp-1, including Pax-5. These results reveal a previously unknown mechanism for the control of Blimp-1 activity by Ets-1 and suggest that expression of Ets-1 must be down-regulated before plasmacytic differentiation can occur.
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ABSTRACT: Endothelial cells play essential roles in maintenance of vascular integrity, angiogenesis, and wound repair. We show that an endothelial cell-restricted microRNA (miR-126) mediates developmental angiogenesis in vivo. Targeted deletion of miR-126 in mice causes leaky vessels, hemorrhaging, and partial embryonic lethality, due to a loss of vascular integrity and defects in endothelial cell proliferation, migration, and angiogenesis. The subset of mutant animals that survives displays defective cardiac neovascularization following myocardial infarction. The vascular abnormalities of miR-126 mutant mice resemble the consequences of diminished signaling by angiogenic growth factors, such as VEGF and FGF. Accordingly, miR-126 enhances the proangiogenic actions of VEGF and FGF and promotes blood vessel formation by repressing the expression of Spred-1, an intracellular inhibitor of angiogenic signaling. These findings have important therapeutic implications for a variety of disorders involving abnormal angiogenesis and vascular leakage.Developmental Cell 09/2008; 15(2):261-71. DOI:10.1016/j.devcel.2008.07.002 · 10.37 Impact Factor
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ABSTRACT: We present contributions to improve a previously published approach for the segmentation of magnetic resonance images of the human brain, based on an unsupervised Hopfield neural network. We formulate the segmentation problem as the minimization of an energy function constructed with two terms, the cost-term as a sum of squared errors, and the second term temporary noise added to the cost-term as an excitation to the network to escape certain local minima with the result of being closer to the global minimum. Also, to ensure the convergence of the network and its utilisation in the clinic with useful results, the minimization is achieved with a step function which permits the network to reach stability corresponding to a local minimum close to the global minimum in a prespecified period of time. We present segmentation results of our approach for data of patient diagnosed with a metastatic tumor in the brain, and we compare them to those obtained from, previous work using Hopfield neural networks, the Boltzmann machine and the conventional ISODATA clustering techniquePattern Recognition, 1996., Proceedings of the 13th International Conference on; 09/1996
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ABSTRACT: Advances of computer and network technology have expanded multimedia applications to very broad ranges. An operating system that supports not only generic best effort applications but also multimedia real-time applications is required. But there is no operating system to support various types of applications in a system. The proposed algorithm supports several scheduling methods under an operating system. The algorithm groups applications into several classes, partitions CPU bandwidth, and assigns a portion of CPU bandwidth according to the class of applications. Depending upon the applications, the algorithm allocates a proper scheduler for each application. And a two-level scheduler is deployed to schedule each class and task. The first-level scheduler selects a class by the rate and passes a time quantum to the second-level scheduler. The second-level scheduler schedules tasks by a conventional scheduling algorithm such as RR(round-robin) or EDF. Under overloaded condition, the algorithm does not affect other classes of applications. By using static rate for an application class, the algorithm not only prevents starvation for best effort applications but also guarantees the minimal execution of applications.Communications, Computers and signal Processing, 2003. PACRIM. 2003 IEEE Pacific Rim Conference on; 09/2003