Hyperproliferation and Dysregulation ofIL-4 Expression in NF-ATp-Deficient Mice

AbstractNF-ATp is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In this study, we show that mice with a null mutation in the NF-ATp gene have splenomegaly with hyperproliferation of both B and T cells. They also display early defects in the transcription of multiple genes encoding cytokines and cell surface receptors, including CD40L and FasL. A striking defect in early IL-4 production was observed after ligation of the TCR complex by treatment with anti-CD3 in vivo. The transcription of other cytokines including IL-13, GM–CSF, and TNFα was also affected, though to a lesser degree. Interestingly, the cytokines IL-2 and IFNγ were minimally affected. Despite this early defect in IL-4 transcription, Th2 development was actually enhanced at later timepoints as evidenced by increased IL-4 production and IgE levels in situations that favor the formation of Th2 cells both in vitro and in vivo. These data suggest that NF-ATp may be involved in cell growth, and that it is important for the balanced transcription of the IL-4 gene during the course of an immune response.BDY

Visualizing the Needle in the Haystack: In Situ Hybridization With Fluorescent Dendrimers

In situ hybridization with 3DNA™ dendrimers is a novel tool for detecting low levels of mRNA in tissue sections and whole embryos. Fluorescently labeled dendrimers were used to identify cells that express mRNA for the skeletal muscle transcription factor MyoD in the early chick embryo. A small population of MyoD mRNA positive cells was found in the epiblast prior to the initiation of gastrulation, two days earlier than previously detected using enzymatic or radiolabeled probes for mRNA. When isolated from the epiblast and placed in culture, the MyoD mRNA positive cells were able to differentiate into skeletal muscle cells. These results demonstrate that DNA dendrimers are sensitive and precise tools for identifying low levels of mRNA in single cells and tissues

DNA Dendrimers Localize Myod mRNA in Presomitic Tissues of the Chick Embryo

MyoD expression is thought to be induced in somites in response to factors released by surrounding tissues; however, reverse transcription-PCR and cell culture analyses indicate that myogenic cells are present in the embryo before somite formation. Fluorescently labeled DNA dendrimers were used to identify MyoD expressing cells in presomitic tissues in vivo. Subpopulations of MyoD positive cells were found in the segmental plate, epiblast, mesoderm, and hypoblast. Directly after laying, the epiblast of the two layered embryo contained ∼20 MyoD positive cells. These results demonstrate that dendrimers are precise and sensitive reagents for localizing low levels of mRNA in tissue sections and whole embryos, and that cells with myogenic potential are present in the embryo before the initiation of gastrulation

Predicting Recovery Rates of Defaulted Bonds Using a Neural Network

In this study we implement a neural network to forecast recovery rates of defaulted bonds using bond-specific, firm-specific and macroeconomic variables. We benchmark the model with a simple linear regression and a random forest. The network is composed of one hidden layer and a sigmoid activation function to guarantee a prediction in the unit interval. The relative importance of the network's inputs is computed using Garson's and Olden's algorithm. The performance of each model is assessed with and without overestimation penalties. The results suggest that neural networks do not have better predictive abilities given the data and the parameters. Finally, we compare the impact of each model on the Value-at-Risk by simulating 20,000 portfolios. The results show the linear regression computes the highest VaR, followed by the neural network and the random forest.Master [120] en Ingénieur de gestion, Université catholique de Louvain, 201