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Accueil > Publications > Recherche par années > Années 2000 > 2005

2005

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A comparison of the ability of DMXAA and xanthenone analogues to activate NF-kappa B in murine and human cell lines

DMXAA (5,6-dimethylxanthenone-4-acetic acid), the most potent of a series of xanthenone (XAA) analogues developed in this laboratory, is currently undergoing combination clinical trials as an antivascular agent for cancer treatment. XAAs have a complex mode of action, and in vitro assays that are predictive of in vivo antitumor activity have been difficult to develop. In this study, we have utilized a series including XAA, DMXAA, and mono-substituted XAA derivatives to determine firstly whether in vitro NF-kappa B activation of mouse cell lines predicts for the in vivo antitumor potential of this class of agents, and secondly whether the relative activity of these analogues is similar in murine and human cell lines.

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A paediatric vaccination vector based on live attenuated measles vaccine

Live attenuated RNA viruses make highly efficient vaccines. Among them, measles virus (MV) vaccine has been given to a very large number of children and shown to be highly effective and safe. MV vaccine induces a life-long immunity after a single or two low-dose injections. It is easily produced on a large scale in most countries and can be distributed at low cost. Reversion to pathogenicity has never been observed with this vaccine. Because of all these characteristics, MV vaccine might be a very promising vector to immunise children against both measles and other infectious agents, such as HIV or flaviviruses, in the developing world. In this article, we describe recent data that we obtained showing the capacity of recombinant Schwarz MVs to express proteins from human immunodeficiency or West Nile viruses, and to induce specific immune responses able, in the case of West Nile virus, to protect from an experimental challenge.

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Adhesion properties of adhesion-regulating molecule 1 protein on endothelial cells

Numerous adhesion molecules have been described, and the molecular mechanisms of lymphocyte trafficking across the endothelium is starting to be elucidated. Identification of the molecules involved in the organoselectivity of this process would help in the targeting of drug therapy to specific tissues. Adhesion-regulating molecule-1 (ARM-1) is an adhesion-regulating molecule previously identified on T cells. It does not belong to any known families of adhesion molecules. In this study, we show the presence of ARM-1 in endothelial cells, the adhesion partners of lymphocytes.

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Atypical recognition of particular DNA sequences by the archaeal chromosomal MC1 protein

The MC1 protein is a chromosomal protein likely involved in the DNA compaction of some methanogenic archaea. This small and monomeric protein, structurally unrelated to other DNA binding proteins, bends DNA sharply. By studying the protein binding to various kinds of kinked DNA, we have previously shown that MC1 is able to discriminate between different deformations of the DNA helix. Here we investigate its capacity to recognize particular DNA sequences by using a SELEX procedure. We find that MC1 is able to preferentially bind to a 15 base pair motif [AAAAACACAC(A/C)CCCC]. The structural parameters of this sequence are characterized by molecular dynamics simulation experiments, and the binding mode of the protein to the DNA is studied by footprinting experiments. Our results strongly suggest that the protein realizes an indirect readout of the DNA sequence by binding to the DNA minor groove.

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Bone geometry in response to long-term tennis playing and its relationship with muscle volume : A quantitative magnetic resonance imaging study in tennis players

The benefit of impact-loading activity for bone strength depends on whether the additional bone mineral content (BMC) accrued at loaded sites is due to an increased bone size, volumetric bone mineral density (vBMD) or both. Using magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA), the airn of this study was to characterize the geometric changes of the dominant radius in response to long-term tennis playing and to assess the influence of muscle forces on bone tissue by investigating the muscle-bone relationship. Twenty tennis players (10 men and 10 women, mean age : 23.1 +/- 4.7 years, with 14.3 +/- 3.4 years of playing) were recruited. The total bone volume, cortical volume, sub-cortical volume and muscle volume were measured at both distal radii by MRI. BMC was assessed by DXA and was divided by the total bone volume to derive vBMD.

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Characterization of a TET-like aminopeptidase complex from the hyperthermophilic archaeon Pyrococcus horikoshii

Pyrococcus horikoshii open reading frame PH1527 encodes a 39014 Da protein that shares about 30% identity with endoglucanases and members of the M42 peptidase family. Analytical ultracentrifugation and electron microscopy studies showed that the purified recombinant protein forms stable, large dodecameric complexes with a tetrahedral shape similar to the one described for DAP, a deblocking aminopeptidase that was characterized in the same organism. The two related proteins were named PhTET1 (for DAP) and PhTET2 (for PH1527).

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