The cerebellar transcriptome during postnatal development of the Ts1Cje mouse, a segmental trisomy model for Down syndrome

The central nervous system of persons with Down syndrome presents cytoarchitectural abnormalities that likely result from gene-dosage effects affecting the expression of key developmental genes. To test this hypothesis, we have investigated the transcriptome of the cerebellum of the Ts1Cje mouse model of Down syndrome during postnatal development using microarrays and quantitative PCR (qPCR). Genes present in three copies were consistently overexpressed, with a mean ratio relative to euploid of 1.52 as determined by qPCR. Out of 63 three-copy genes tested, only five, nine and seven genes had ratios >2 or <1.2 at postnatal days 0 (P0), P15 and P30, respectively. This gene-dosage effect was associated with a dysregulation of the expression of some two-copy genes. Out of 8258 genes examined, the Ts1Cje/euploid ratios differed significantly from 1.0 for 406 (80 and 154 with ratios above 1.5 and below 0.7, respectively), 333 (11 above 1.5 and 55 below 0.7) and 246 genes (59 above 1.5 and 69 below 0.7) at P0, P15 and P30, respectively. Among the two-copy genes differentially expressed in the trisomic cerebellum, six homeobox genes, two belonging to the Notch pathway, were severely repressed. Overall, at P0, transcripts involved in cell differentiation and development were over-represented among the dysregulated genes, suggesting that cell differentiation and migration might be more altered than cell proliferation. Finally, global gene profiling revealed that transcription in Ts1Cje mice is more affected by the developmental changes than by the trisomic state, and that there is no apparent detectable delay in the postnatal development of the cerebellum of Ts1Cje mic

Phylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa

Background: Phylostratigraphy is a method used to correlate the evolutionary origin of founder genes (that is, functional founder protein domains) of gene families with particular macroevolutionary transitions. It is based on a model of genome evolution that suggests that the origin of complex phenotypic innovations will be accompanied by the emergence of such founder genes, the descendants of which can still be traced in extant organisms. The origin of multicellularity can be considered to be a macroevolutionary transition, for which new gene functions would have been required. Cancer should be tightly connected to multicellular life since it can be viewed as a malfunction of interaction between cells in a multicellular organism. A phylostratigraphic tracking of the origin of cancer genes should, therefore, also provide insights into the origin of multicellularity. Results: We find two strong peaks of the emergence of cancer related protein domains, one at the time of the origin of the first cell and the other around the time of the evolution of the multicellular metazoan organisms. These peaks correlate with two major classes of cancer genes, the 'caretakers', which are involved in general functions that support genome stability and the 'gatekeepers', which are involved in cellular signalling and growth processes. Interestingly, this phylogenetic succession mirrors the ontogenetic succession of tumour progression, where mutations in caretakers are thought to precede mutations in gatekeepers. Conclusions: A link between multicellularity and formation of cancer has often been predicted. However, this has not so far been explicitly tested. Although we find that a significant number of protein domains involved in cancer predate the origin of multicellularity, the second peak of cancer protein domain emergence is, indeed, connected to a phylogenetic level where multicellular animals have emerged. The fact that we can find a strong and consistent signal for this second peak in the phylostratigraphic map implies that a complex multi-level selection process has driven the transition to multicellularity

Identification And Validation Of A Neural Network Estimating The Fluxes Of An Induction Machine.

: In the frame of a study on real-time emulators of electromechanical systems, we have built a neural model of an induction machine. An original methodology is used to design the neural network architecture, as well as training sequences allowing a proper identification of the induction machine behavior in its whole operating range. In the same spirit, exhaustive test sequences are built in order to obtain an accurate estimate of the neural model performance. 1.- INTRODUCTION The present paper deals with the modeling of electromechanical systems using neural networks. In the frame of a study on emulators of {static converters / electrical machines / sensors} associations [2], our aim is to simulate complex electromechanical systems in real-time. The ability to parsimoniously approximate nonlinear mappings [3], as well as the possibility of parallel computing, make neural networks efficient in terms both of accuracy and computation time. The use of feedback (dynamic) neural networks [..

Combined XRD, EXAFS, and mossbauer studies of the reduction by lithium of alpha-Fe2O3 with various particle size.

International audienceThe electrochemical reduction of hematite with various particle sizes by metallic lithium has been studied by means of X-ray diffraction (XRD) Mössbauer and extended X-ray absorption fine structure (EXAFS) spectroscopy. Previous in situ XRD analysis coupled with electrochemical data showed that lithium can be inserted in the nanosized sample up to 1 Li per Fe2O3 whereas bulk material undergoes an irreversible Li-driven transformation from an hexagonal anionic packing to a close cubic packed framework as soon as 0.03 Li is inserted in the corundum structure. The present data show that only 0.6 Li per formula unit are actually inserted in the structure of small particles. The remaining lithium (0.4) is engaged in irreversible reduction of surface groups, or capacitive behavior. Beyond the solid solution domains, both samples are multiphase, and consist of Li2Fe2O3, Fe0 clusters (10-15 Å) and inserted -Fe2O3, which proportions are used to calculate the mean iron oxidation state in the electrode as the reaction proceeds. From these data, we found that electrolyte decomposition can occur at very different steps of the reduction depending on the texture of the active materials. In addition, during the reduction process, we evidenced a reaction of disproportionation (3Fe2+2Fe3+ + Fe0), an intense electrochemical grinding of the hematite particles and the formation of extremely fine metallic surface clusters. For the first time, the EXAFS/X-ray absorption near-edge structure signature of the divalent intermediate Li2Fe2O3 phase is obtained

Combined XRD, EXAFS, and Mössbauer studies of the reduction by lithium of α-Fe2O3 with various particle sizes

The electrochemical reduction of hematite with various particle sizes by metallic lithium has been studied by means of X-ray diffraction (XRD) Mössbauer and extended X-ray absorption fine structure (EXAFS) spectroscopy. Previous in situ XRD analysis coupled with electrochemical data showed that lithium can be inserted in the nanosized sample up to 1 Li per Fe2O3 whereas bulk material undergoes an irreversible Li-driven transformation from an hexagonal anionic packing to a close cubic packed framework as soon as 0.03 Li is inserted in the corundum structure. The present data show that only 0.6 Li per formula unit are actually inserted in the structure of small particles. The remaining lithium (0.4) is engaged in irreversible reduction of surface groups, or capacitive behavior. Beyond the solid solution domains, both samples are multiphase, and consist of Li2Fe2O3, Fe0 clusters (10-15 Å) and inserted α-Fe2O3, which proportions are used to calculate the mean iron oxidation state in the electrode as the reaction proceeds. From these data, we found that electrolyte decomposition can occur at very different steps of the reduction depending on the texture of the active materials. In addition, during the reduction process, we evidenced a reaction of disproportionation (3Fe2+ → 2Fe3 + Fe0), an intense electrochemical grinding of the hematite particles and the formation of extremely fine metallic surface clusters. For the first time, the EXAFS/X-ray absorption near-edge structure signature of the divalent intermediate Li2Fe2O3 phase is obtained