We have identified in and around the immunoglobulin heavy-chain enhancer two apparently distinct negative regulatory elements which repress immunoglobulin H enhancer, simian virus 40 enhancer, and heterologous promoter activity in fibroblasts but not in myeloma cells. We propose that in nonlymphoid cells, negative regulatory elements prevent activation of the immunoglobulin H enhancer by ubiquitous stimulatory trans-acting factors.Enhancers are eucaryotic promoter sequences which activate transcription over large distances. They stimulate transcription in cis and in an orientation-independent manner from both homologous and heterologous promoter elements. Specific trans-acting factors interact with defined sequence motifs in enhancers and modulate their activity. Several genes which are specifically expressed in differentiated cells have been shown to contain tissue-specific enhancers. An important aim is to identify the factors which control the tissue specificity of these enhancers (5,6,11,19,28,34,41,44,(47)(48)(49)55).Immunoglobulin heavy-chain (IgH) gene expression is controlled by three different tissue-specific regulatory elements, the enhancer (2, 18, 32, 33), promoter (30), and intragenic sequences (23). We have dissected the IgH enhancer and studied its activity in fibroblasts, in which the IgH gene is inactive, and in myelomas, in which the gene is active. We previously showed that a central sequence in the IgH enhancer stimulates transcription in both fibroblasts and myelomas, whereas flanking sequences on either side stimulate transcription specifically in myeloma cells (53), suggesting that cells which do not express the IgH gene contain positive factors which can interact with the IgH enhancer and that myeloma cells contain additional specific positive factors. We now show that negative control of IgH enhancer activity in fibroblasts also contributes to the regulation of its tissue specificity. We suggest that these negative regulatory elements prevent interaction of the IgH enhancer with ubiquitous stimulatory trans-acting factors.MATERIALS AND METHODS Recombinants. Standard recombinant DNA techniques were used as described previously (29). pGlMX and pGlMIX contain the XbaI fragment (nucleotides 1 to 992) encompassing the IgH enhancer inserted in both orientations in the XbaI site of pGl (53). A deletion mutants were constructed from pGlMIX as previously described (53

Dystrophin is a very large muscle protein (approximately 400 kd) the deficiency of which is responsible for Duchenne muscular dystrophy. Its function is unknown at present. In order to know whether different domains of the protein are differentially conserved during evolution, we have cloned and sequenced the chicken dystrophin cDNA. The protein coding sequence has almost the same size as in man. The N‐terminal region that resembles the actin binding domain of alpha actinin, as well as the large spectrin like domain show 80% and 75% conservation respectively between chicken and man. In contrast, the C‐terminal region shows 95% identity over 627 aa suggesting that it is an important region of interaction with other proteins. Comparison of the amino acid sequence of this C‐terminal region to other protein sequences shows only marginally significant similarities. Finally we have found a striking conservation of three segments of the 3′ untranslated sequence (85% homology over a total of 920 nt) between chicken and man. These also appear to be conserved in other mammals. This high conservation is not linked to open reading frames.

Using the severe combined immunodeficiency (SCID) mouse model, we investigated the requirement of the immune system for the development of scrapie after peripheral inoculation. A total of 33% of SCID mice, all but one immunologically reconstituted SCID mice (93%), and all CB17 control mice developed the disease. PrPres was detectable in the brains of all diseased animals and in the spleens of reconstituted SCID and CB17 control mice but not of the diseased non-immunologically reconstituted SCID mice. The immune system appears to be a primary target in the pathogenesis of scrapie, but direct spread to the central nervous system from the peritoneum via visceral nerve fibers can probably also occur.

Cette étude caractérise la structure de population de Mya arenaria d'une baie de l'estuaire du Saint-Laurent et dégage certains facteurs biotiques et abiotiques agissant sur les stratégies et les tactiques de croissance et de reproduction. En 1985, la population avait une classe d'âge modale de 10 ans résultant d'un recrutement massif en 1975. La distribution spatiale est contagieuse avec une moyenne de 177 individus/m2. La croissance linéaire annuelle varie selon les années. Le sex-ratio de la population n'est pas différent de 1:1 et la croissance pondérale et la reproduction sont indépendantes du sexe. Bien qu'une deuxième gamétogénèse ait lieu à l'automne, il n'y a qu'une seule ponte par année. Les indices gonado-somatiques sont plus grands pour les individus du bas de plage. Pour un même âge, les individus du bas de plage ont une fécondité plus grande. Par contre, pour une même longueur, il n'y a pas de différence de fécondité entre les niveaux altimétriques. Mya arenaria investit donc préférentiellement dans sa croissance, ce qui assure une reproduction plus jeune. La masse fraîche somatique et celle des gonades sont plus élevées chez les individus de bas de plage. Les myes de bas de plage semblent réagir rapidement aux variations des conditions du milieu et présentent une tactique d'opportunistes. La tactique des myes de haut de plage est de répondre aux conditions minimales du milieu sans chercher à exploiter des conditions plus favorables mais de courte durée. Une expérience in situ montre que, dans des conditions favorables, M. arenaria investit plus dans la reproduction que dans la croissance.