Cloned HTLV-1+CD4+, but not CD8+, T-cells display an oncogenic miRNome

HTLV-1 persistence in vivo relies on the persistent clonal expansion of its host cells. These are CD4+ and CD8+ T cells, yet ATL is regularly CD4+. Accordingly, untransformed HTLV-1+CD4+ but not CD8+ T cells cloned from carriers cumulate the features of preleukemic cells, including multinuclearity, chromatin bridges, increased cell cycling and inappropriate telomerase activity. MicroRNAs (miR) modify the maturation of a plethora of T-cells RNA and their deregulation would therefore constitute an appropriate explanation for the Tax-dependent or -independent pleiotropic changes in the phenotype of HTLV-1+CD4+ T cells. As the miRNome of naturally infected untransformed cells has not been investigated to date, we assessed the miR expression profiling of T cells cloned from carriers. Microarray results, confirmed by quantitative RTPCR, showed that, upon infection, CD4+ and CD8+ clones yielded aberrant expression of 15 distinct miRs including miR-34b and miR-494 that were respectively over- and underexpressed in both compartments. The more prominent effect of the infection consisted in the CD4+-restricted overexpression of the cancer-related miRs miR-21, -27b and -23b associated with the CD4+-restricted downregulation of the proapoptotic miR-15 and -16. Data were extended by the analysis of 40 additional CD4+ clones (20 infected). Crossing the miRNome against the whole transcriptome data identified putative miR-targeted genes. In silico, those targeted by miR-23b and -27b defined 2 hitherto unknown pathways involving the cell cycle and genetic disorders. Therefore HTLV-1 triggers a phenotype-specific miR signature consistent with the preleukemic HTLV-1+CD4+ phenoty

Fibre reinforced refractory concrete as a tooling material for organic matrix composite processing routes

International audienc

Fibre reinforced refractory concrete as a tooling material for organic matrix composite processing routes

International audienc

Thermomechanical characterization of monolithic refractory castables

CIMTEC 2010 - 12th International ceramics congress, June 6-11, 2010, Montecatini Terme, ITALYInternational audienceThis paper deals with the characterization of the thermomechanical behavior of monolithic refractory castables in a wide temperature range, up to 1200°C. Different test types are considered: tensile tests, compression tests, bending tests and tests on more complex shapes and geometries. A particular attention is paid to the detailed characterization and interpretation of the non-linear behaviors of these materials. Monotonic, cyclic and creep tests are considered. In some cases, digital image correlation (DIC) methods can be coupled to mechanical tests to obtain strain fields. Such results are particularly interesting to observe and to understand damage processes. As damage is a major characteristic of the monolithic castable behaviors, links are established between the thermomechanical behavior and damage mechanisms. Two main scales are taken into account for damage characterization: the macroscopic and the microscopic ones. Main mechanisms that are considered deal with microcracking, macrocracking, debonding and cavitation. Two types of materials are considered: non-reinforced and fiber reinforced refractory castables

DEMONSTRATION OF THE APPLICATION OF SUPERPLASTIC FORMING USING INFRARED HEATING EMITTERS TO A PART OF STRUCTURE INCLUDING VARIOUS GEOMETRICAL SINGULARITIES

ArianeGroup and Aurock led a feasibility study through the realization of a scale 1 TA6V demonstrator, using superplastic forming (SPF). ArianeGroup designed the demonstrator according to its knowledge of representative structures, comprising singularities: welds, stiffeners and areas with important thicknesses variations. Aurock performed first numerical simulations of the complete process, putting in evidence the various difficulties to be solved. Then, the demonstrator was physically carried out. Once the demonstration was virtually obtained, each steps of the process were experimented: welding of thick plates with limited deformation, machining of flat panels, pre-forming by rolling and final SPF. For the SPF step, a heating cover and a reinforced refractory castable die were manufactured. Infrared emitters’ position and heating power regulation laws were carefully defined, for the panel to be kept at the correct temperature until being formed. The SPF step led to a successful demonstration of the representative structure. The experimental approach confirmed the process modelling predictability. Limited Scale 1 demonstration was necessary to ensure the process validity with real thicknesses and thickness variations, which are known to mask problems if scale reductions are used without precautions. This methodology can be transfer to a real structure only by tooling adaptations, without additional feasibility works

HTLV-1 bZIP Factor HBZ Promotes Cell Proliferation and Genetic Instability by Activating OncomiRs

International audienc

Occurrence of Stenotrophomonas maltophilia in agricultural soils and antibiotic resistance properties

The occurrence of Stenotrophomonas maltophilia was monitored in organic amendments and agricultural soils from various sites in France and Tunisia. S. maltophilia was detected in horse and bovine manures, and its abundance ranged from 0.294 (±0.509) × 103 to 880 (±33.4) × 103 CFU (g drywt)−1 of sample. S. maltophilia was recovered from most tested soil samples (104/124). Its abundance varied from 0.33 (±0.52) to 414 (±50) × 103 CFU (g drywt)−1 of soil and was not related to soil characteristics. Antibiotic resistance properties of a set of environmental strains were compared to a clinical set, and revealed a high diversity of antibiotic resistance profiles, given both the numbers of resistance and the phenotypes. Manure strains showed resistance phenotypes, with most of the strains resisting between 7 and 9 antibiotics. While French soil strains were sensitive to most antibiotics tested, some Tunisian strains displayed resistance phenotypes close to those of clinical French strains. Screening for metal resistance among 66 soil strains showed a positive relationship between antibiotic and metal resistance. However, the prevalence of antibiotic resistance phenotypes in the studied sites was not related to the metal content in soil samples

Rare Circulating Cells in Familial Waldenström Macroglobulinemia Displaying the MYD88 L265P Mutation Are Enriched by Epstein-Barr Virus Immortalization.

The MYD88 L265P is a recurrent somatic mutation in neoplastic cells from patients with Waldenström Macroglobulinemia (WM). We identified the MYD88 L265P mutation in three individuals from unrelated families, but its presence did not explain the disease segregation within these WM pedigrees. We observed the mutation in these three individuals at high allele fractions in DNA extracted from EBV-immortalized Lymphoblastoid cell lines established from peripheral blood (LCL), but at much lower allele fractions in DNA extracted directly from peripheral blood, suggesting that this mutation is present in a clonal cell subpopulation rather than of germ-line origin. Furthermore, we observed that the MYD88 L265P mutation is enriched in WM families, detected in 40.5% of patients with familial WM or MGUS (10/22 WM, 5/15 MGUS), compared to 3.5% of patients with familial MM or MGUS (0/72 MM, 4/41 MGUS) (p = 10-7). The mutant allele frequency increased with passages in vitro after immortalization with Epstein-Barr virus (EBV) consistent with the MYD88 L265P described gain-of-function proposed for this mutation. The MYD88 L265P mutation appears to be frequently present in circulating cells in patients with WM, and MGUS, and these cells are amenable to immortalization by EBV