Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie最新文献

Functional magnetic resonance imaging (fMRI) has appeared as a new tool that is very powerful for cognitive neuroscience, offering the potential to look at the dynamics of cerebral processes underlying cognition, non-invasively and on an individual basis. Work remains to be done to optimize the technique and to better understand its basic mechanisms, but one may expect to build in a foreseeable future a functional list of the main brain cortical networks implicated in sensory-motor or cognitive processes. Still, the real understanding of brain function requires direct access to the functional unit consisting of the neuron, so that one may look at the transient temporal relationships that exist between largely distributed groups of hundreds or thousands of neurons. Furthermore, communication pathways between networks, which are carried by brain white matter, must be identified to establish connectivity maps at the individual scale, taking into account individual variability resulting from genetic factors and cerebral plasticity. In this respect, MRI of molecular diffusion is very sensitive to water molecular motion and, thus, to tissue dynamic microstructure, such as cell size and geometry. Preliminary data suggest that diffusion MRI visualizes dynamic tissue changes associated with large neuronal activation and space orientation of large bundles of myelinated axons in the white matter.

In order to characterize peptide binding motifs of MHC class II molecules HLA-DR3, we have sequenced pool or single peptides eluted from the binding groove. Anchor residues identified are in agreement with peptide binding and sequencing studies reported by different groups. Four positions seem to be dominant (i, i + 3, i + 5, i + 8) while 2 secondary positions (i + 1, i + 2) could cooperate to facilitate binding. According to all the criteria define here and the literature, we propose an anchor motif specific for DR3, which has been tested on the sequence of an antigen from Schistosoma mansoni. Three out of 6 putative epitopes identified share common sequences with immunodominant regions determined in humans and by experimental immunizations in animal models. Extended to other alleles, this approach could be suitable to define potentially immunodominant peptides useful for vaccines.

Devazepide (L-364718, a non-peptide antagonist of CCK-A receptors), inhibits the proliferation and induces morphologic changes in the mucous-secreting, autonomously proliferating human cancer colon cell line (HT29-S-B6. Addition of devazepide (10 microM) for at least 3 days in the exponential phase of growth enhanced the baseline production of gastric M1 mucins 2-3-fold and that of carcinoembryonic antigens 5-fold. Moreover, devazepide induced an increase in the amount of the MUC-5AC mRNA expressed by HT29-S-B6 cells. The increased in mucins secretion induced by devazepide was persistent after removal and independent of the presence of serum. In conclusion, devazepide-L-364718 behaves as a maturation agent in the cell clone HT29-S-B6.

The bacteriophage T3 promoter can be selectively transcribed by the corresponding RNA polymerase in eukaryotic cells. A toxic gene can in principle be linked to this promoter in a "dormant" and innocuous transgene in a transgenic animal. In this scheme, the activating strain expresses the RNA polymerase. When expression of the gene is needed in the progeny, the 2 lines are crossed. However, when a single molecule is sufficient to kill the cell--as with the diphtheria toxin--transcriptional "leakage" from the promoter may not be tolerated by the cell, even when extremely weak. Therefore, prior to more elaborate studies, diphtheria toxin, as a prototype of a gene toxic to the organism, has been linked to the bacteriophage T3 promoter in a T3-E-DTA construct. The T3-E-DTA plasmid has been transiently transfected into human embryonic kidney derived cells together with a lacZ plasmid. By co-transfection, the T3-E-DTA cells can be readily identified as lacZ positive, and their fate followed by the production of beta-galactosidase at the single cell or overall population level. In spite of the extreme toxicity of the toxin, the cells tolerate the presence of the T3-E-DTA construct, and are only killed--with a high efficiency--when the T3 RNA polymerase is present. Transactivation is usually restricted to the auxiliary factors of transcription. With this study, the promoter and the polymerase are revealed as potential and efficient inducible and activating elements of a very simple binary system.

Stimulation of the synthesis of type I and III collagens by 0.15 mM L-ascorbic acid (AA) was investigated in primary cultures of dermal fibroblasts form 30 females aged between 19 and 70 years. At this concentration allowing maximal stimulation, fibroblast cultures responded to this agent by an increase in collagen secretion, but to a lower extent for type III compared to type I, leading to an increase in the type I/III collagen ratio. We showed that AA stimulation of type I and III collagen secretion decreased in a statistically significant linear manner with donor age (slope = 1.9; p = 0.0014 and slope = -0.5; p = 0.0164, respectively). We also observed an age-related AA stimulation of the cell-associated collagen pool for type I collagen but not for type III (slope = 0.29; p = 0.015). This might indicate that a reduced ability of fibroblasts to secrete the newly synthesized type I collagen is involved in loss of the cellular response to AA stimulation. Analysis of AA stimulation as a function of body site showed that during aging, the loss of AA stimulation of type I and III collagen synthesis was more for periauricular (slope = 2.7; p = 0.0280 and slope = -0.8; p = 0.0309, respectively) than for mammary skin (slope = 2.1; p = 0.0071 and slope = 0.1; p = 0.7337, respectively). This led us to consider that UV-exposed cutaneous sites may accelerate cellular dermal aging in terms of response to AA, making this parameter a quantitative indicator of human dermal cell aging.

In Percoll purified Leydig cells from mature rat incubated for 24 h in Ham F12/DME medium, we demonstrated that the testosterone production (6 ng/10(6) Leydig cells/24 h) is increased 11 fold by a saturating amount of hCG whereas rat Leydig cells the basal output of testosterone is 4.5 ng and increased 2.5 fold by hCG. In the sulfate-free Ham F12/DME medium used for the proteoglycan (PG) studies, the productions of testosterone are lower but the cells remain sensitive to hCG. Whatever the age, the Leydig cells synthesize labeled PG after 24 h of incubation in the presence of [3H] glucosamine and [35S] sulfate. In immature rat, the quantity of synthesized PG is 20% higher than in mature animal; the secreted PG represented respectively 70 and 85% of the immature and mature Leydig cells PG outputs. In addition, the immature Leydig cell HSPG represents 15% of the secreted PG whereas it is 5% in mature rat; irrespective of the age the associated-HSPG account for 10% of the PG. The addition of hCG improves the production of HSPG especially in the immature Leydig cells. Therefore we evidenced a rat Leydig cell synthesis of PG, especially HSPG which are likely involved in the regulation of the Leydig cell function.