Barbuise, La Saulsotte – Ferme de Frécul

Identifiant de l'opération archéologique : 4847 Date de l'opération : 2004 (PC) Néolithique Sandrine Bonnardin a étudié la parure des sépultures RRBP et VSG. S.92.31 : sépulture d’enfant, une parure composée de 20 perles trapézoïdales en coquille de Cardiidés et 2 perles en dentale. S.92.32 : sépulture d’adulte, une parure constituée de 162 perles circulaires en coquille de Cardiidés. S.94.113 : sépulture multiple (4 corps plus ou moins complets) comprenant 1 perle circulaire en coquille d..

The Acidic Amino-Terminal Region of Varicella-Zoster Virus Open Reading Frame 4 Protein Is Required for Transactivation and Can Functionally Replace the Corresponding Region of Herpes Simplex Virus ICP27

AbstractBoth varicella-zoster virus open reading frame 4 (ORF4) protein and its herpes simplex virus type 1 homolog ICP27 have highly acidic amino-terminal regions and cysteine-rich carboxy-terminal regions. To investigate the functional domains of these proteins, mutants were constructed and their transregulatory functions were tested in transient expression assays using two reporter plasmids, pTK-CAT-SV40A and pTK-CAT-synA, containing the same promoter sequences but different mRNA processing signals. ORF4 transactivates both pTK-CAT-SV40A and pTK-CAT-synA, while ICP27 transrepresses pTKCAT-SV40A and transactivates pTK-CAT-synA. Deletion of the ORF4 amino-terminal region abolished most of the transactivating activity for pTK-CAT-synA but retained most of the transactivating activity for pTK-CAT-SV40A. Construction of chimeric ORF4-ICP27 molecules indicated that the ORF4 amino-terminal region was able to replace the corresponding region of ICP27 which is required for both transrepression of pTK-CAT-SV40A and transactivation of pTK-CAT-synA. Similarly, the ICP27 amino-terminal region was able to partially replace the corresponding region of ORF4 which is required for transactivation of pTK-CAT-synA. Thus, while ORF4 and ICP27 have different properties in transient expression assays, the aminoterminal regions of ORF4 and ICP27 are functionally homologous to each other and are important in regulating gene expression

Varicella-zoster virus IE63 protein phosphorylation by roscovitine-sensitive cyclin-dependent kinases modulates its cellular localization and activity.

peer reviewedDuring the first stage of Varicella-Zoster virus (VZV) infection, IE63 (immediate early 63 protein) is mostly expressed in the nucleus and also slightly in the cytoplasm, and during latency, IE63 localizes in the cytoplasm quite exclusively. Because phosphorylation is known to regulate various cellular mechanisms, we investigated the impact of phosphorylation by roscovitine-sensitive cyclin-dependent kinase (RSC) on the localization and functional properties of IE63. We demonstrated first that IE63 was phosphorylated on Ser-224 in vitro by CDK1 and CDK5 but not by CDK2, CDK7, or CDK9. Furthermore, by using roscovitine and CDK1 inhibitor III (CiIII), we showed that CDK1 phosphorylated IE63 on Ser-224 in vivo. By mutagenesis and the use of inhibitors, we demonstrated that phosphorylation on Ser-224 was important for the correct localization of the protein. Indeed, the substitution of these residues by alanine led to an exclusive nuclear localization of the protein, whereas mutations into glutamic acid did not modify its subcellular distribution. When transfected or VZV-infected cells were treated with roscovitine or CiIII, an exclusive nuclear localization of IE63 was also observed. By using a transfection assay, we also showed that phosphorylation on Ser-224 and Thr-222 was essential for the down-regulation of the basal activity of the VZV DNA polymerase gene promoter. Similarly, roscovitine and CiIII impaired these properties of the wild-type form of IE63. These observations clearly demonstrated the importance of CDK1-mediated IE63 phosphorylation for a correct distribution of IE63 between both cellular compartments and for its repressive activity toward the promoter tested

Geldanamycin inhibits tyrosine phosphorylation-dependent NF-kB activation

peer reviewedHsp90 is a protein chaperone regulating the stability and activity of many signalling molecules. The requirement of Hsp90 activity in the NF-κB pathway has been recently reported by several authors using the Hsp90 ATPase inhibitor Geldanamycin (GA), an anti-tumour drug. Hsp90 inhibition blocks the synthesis and activation of the IKK complex, the major kinases complex responsible for IκBα phosphorylation on serine 32 and 36, a key step for its degradation and the nuclear translocation of NF-κB. However, the effect of GA on other IκBα kinases, including tyrosine kinases, is unknown. In the present study, we investigated the effect of GA on NF-κB activation induced by sodium pervanadate (PV), a tyrosine phosphatase inhibitor triggering c-Src-mediated tyrosine phosphorylation of IκBα. We reporte for the first time that GA inhibits PV-induced IκBα tyrosine phosphorylation and degradation. Using an in vitro kinase assay, we demonstrated that GA inhibits the activity of c-Src as an IκBα tyrosine kinase, but not its cellular expression. As a result, GA blocked PV-induced NF-κB DNA binding activity on an exogenous κB element and on the endogenous iκbα promoter, thereby inhibiting IκBα transcription. Finally, we demonstrated that, despite NF-κB inhibition, pre-treatment with GA does not potentiate PV-induced apoptosis. We conclude that c-Src requires Hsp90 for its tyrosine kinase activity, and its inhibition by GA blocks c-Src-dependent signalling pathways, such as NF-κB activation induced by sodium pervanadate. The effect of GA on PV-induced apoptosis is discussed in the light of recent publications in the literature

Long term aging effect on the creep strength of the T92 steel

International audienceCreep strength loss of T92 steel after long-term creep exposure at 600°C and 650°C is partially due to a thermal aging of the steel during the first part of the test. In order to quantify the effect of long-term aging on the creep strength loss, creep tests were conducted at 600 and 650°C on T92 steel thermally aged for 10,000h at the same temperature and on as-received T92 steel. Laves phases precipitates were found after thermal aging at 600°C and 650°C with an average equivalent diameter of about 200nm and of about 350nm, respectively. No significant change in hardness and in the matrix substructure as revealed by electron backscatter diffraction occurred during aging. For stresses higher than 170MPa at 600°C and higher than 110MPa at 650°C the time to rupture is four times lower in the aged steels compared to the as-received steel, this is correlated to a secondary creep rate four times higher for the aged specimens compared to that of the as-received steel. Creep tests conducted at 650°C under lower stresses revealed a creep lifetime only twice lower after aging