946 resultados para Moreau, Jean-Michel


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Paris

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The Ets transcription factors of the PEA3 group - E1AF/PEA3, ETV1/ER81 and ERM - are almost identical in the ETS DNA-binding and the transcriptional acidic domains. To accelerate our understanding of the molecular basis of putative diseases linked to ETV1 such as Ewing's sarcoma we characterized the human ETV1 and the mouse ER81 genes. We showed that these genes are both encoded by 13 exons in more than 90 kbp genomic DNA, and that the classical acceptor and donor splicing sites are present in each junction except for the 5' donor site of intron 9 where GT is replaced by TT. The genomic organization of the ETS and acidic domains in the human ETV1 and mouse ER81 (localized to chromosome 12) genes is similar to that observed in human ERM and human E1AF/PEA3 genes. Moreover, as in human ERM and human E1AF/PEA3 genes, a first untranslated exon is upstream from the first methionine, and the mouse ER81 gene transcription is regulated by a 1.8 kbp of genomic DNA upstream from this exon. In human, the alternative splicing of the ETV1 gene leads to the presence (ETV1α) or the absence (ETV1β) of exon 5 encoding the C-terminal part of the transcriptional acidic domain, but without affecting the alpha helix previously described as crucial for transactivation. We demonstrated here that the truncated isoform (human ETV1β) and the full-length isoform (human ETV1α) bind similarly specific DNA Ets binding sites. Moreover, they both activate transcription similarly through the PKA-transduction pathway, so suggesting that this alternative splicing is not crucial for the function of this protein as a transcription factor. The comparison of human ETV1α and human ETV1β expression in the same tissues, such as the adrenal gland or the bladder, showed no clear-cut differences. Altogether, these data open a new avenue of investigation leading to a better understanding of the functional role of this transcription factor.

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Few studies have analysed the antibody response during intravesical BCG immunotherapy for superficial bladder cancer. We have examined the evolution in serum antibody response against several heat shock proteins (hsp), including the recombinant mycobacterial hsp65 and the native protein P64 from BCG, GroEL from Escherichia coli (hsp60 family), recombinant mycobacterial hsp70 and the E. coli DnaK (hsp70 family), against purified protein derivative of tuberculin (PPD) and the AG85 complex of Mycobacterium bovis BCG, as well as against tetanus toxoid in 42 patients with a superficial bladder tumour, 28 treated with six intravesical BCG instillations and 14 patients used as controls. We also analysed the lymphoproliferative response of peripheral blood mononuclear cells against PPD in this population. Data of antibody responses at 6 weeks post BCG were available in all 28 patients, and at 4 month follow up in 17 patients. All patients who demonstrated a significant increase in IgC antibodies against PPD at 4 months follow up had a significant increase already at 6 weeks of follow up. In contrast, IgG antibodies against hsp increased significantly from 6 weeks to 4 months post- treatment. A significant increase in IgG antibodies against PPD, hsp65, P64, GroEL, and hsp70 at 4 months follow up was observed in 10/17, 8/17, 10/17, 4/17 and 8/17 patients. Native P64 protein elicited a higher antibody response than recombinant mycobacterial hsp65. No increase in antibody response was observed against Dnak from E. coli, against AG85 or tetanus toxoid after BCG therapy. An increase in IgG antibodies against P64 at 4 months follow up compared with pretreatment values was found to be a significant predictor of tumour recurrence (P < 0.01). Further studies with a larger number of patients are needed to confirm the value of the antibody response against P64 as a clinical independent prognostic factor.

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New theoretical and experimental results on the acetylene-Ar van der Waals complex are presented and the literature is reviewed. New ab initio calculations at the MP2 level were performed using large basis sets with diffuse functions and taking into account the basis set superposition error. It was found that the structure of acetylene is not significantly altered by the complexation and that its vibrational frequencies are only slightly lowered. Finally, it was observed that the calculated properties of the complex (structure, vibrational spectrum, bond dissociation energy) are not sensitive to the structure imposed on acetylene. Experimentally, acetylene-Ar was produced in a supersonic expansion under experimental conditions corresponding to 9 K rotational temperature. Thanks to the performances of CW-CRDS detection, the Ka = 0 ← 1, 1 ← 0, and 2 ← 1 sub- bands of the v1 + v3 band could be recorded and resolved and most of their lines assigned. Upper-state rotational constants were fitted, however not including the upper Ka = 2 state, which shows K-doubling the opposite of the expected. The Lorentzian width of most line profiles sets the mean lifetime to some 7.5 ns. Local perturbations affecting line positions and/or line widths are demonstrated. Additional series of lines tentatively attributed to acetylene-Ar are discussed.© 2009 American Chemical Society.

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Accurate ab initio intermolecular potential energy surfaces (IPES) have been obtained for the first time for the ground electronic state of the C 2H2-Kr and C2H2-Xe van der Waals complexes. Extensive tests, including complete basis set and all-electron scalar relativistic results, support their calculation at the CCSD(T) level of theory, using small-core relativistic pseudopotentials for the rare-gas atoms and aug-cc-pVQZ basis sets extended with a set of 3s3p2d1f1g mid-bond functions. All results are corrected for the basis set superposition error. The importance of the scalar relativistic and rare-gas outer-core (n.1)d correlation effects is investigated. The calculated IPES, adjusted to analytical functions, are characterized by global minima corresponding to skew T-shaped geometries, in which the Jacobi vector positioning the rare-gas atom with respect to the center of mass of the C2H2 moiety corresponds to distances of 4.064 and 4.229Å, and angles of 65.22° and 68.67° for C 2H2-Kr and C2H2-Xe, respectively. The interaction energy of both complexes is estimated to be -151.88 (1.817 kJ mol-1) and -182.76 cm-1 (2.186 kJ mol-1), respectively. The evolution of the topology of the IPES as a function of the rare-gas atom, from He to Xe, is also discussed. © 2012 Taylor and Francis.

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The equilibrium structure of acetylene (also named ethyne) has been reinvestigated to resolve the small discrepancies noted between different determinations. The size of the system as well as the large amount of available experimental data provides the quite unique opportunity to check the magnitude and relevance of various contributions to equilibrium structure as well as to verify the accuracy of experimental results. With respect to pure theoretical investigation, quantum-chemical calculations at the coupled-cluster level have been employed together with extrapolation to the basis set limit, consideration of higher excitations in the cluster operator, inclusion of core correlation effects as well as relativistic and diagonal Born-Oppenheimer corrections. In particular, it is found that the extrapolation to the complete basis set limit, the inclusion of higher excitations in the electronic-correlation treatment and the relativistic corrections are of the same order of magnitude. It also appears that a basis set as large as a core-valence quintuple-zeta set is required for accurately accounting for the inner-shell correlation contribution. From a pure experimental point of view, the equilibrium structure has been determined using very accurate rotational constants recently obtained by a global analysis (that is to say that all non-negligible interactions are explicitely included in the Hamiltonian matrix) of rovibrational spectra. Finally, a semi-experimental equilibrium structure (where the equilibrium rotational constants are obtained from the experimental ground state rotational constants and computed rovibrational corrections) has been obtained from the available experimental ground-state rotational constants for ten isotopic species corrected for computed vibrational corrections. Such a determination led to the revision of the ground-state rotational constants of two isotopologues, thus showing that structural determination is a good method to identify errors in experimental rotational constants. The three structures are found in a very good agreement, and our recommended values are rCC 120.2958(7) pm and rCH 106.164(1) pm. © 2011 American Institute of Physics.

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