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71.
Recent experiments have implicated intracellular events in the formation of the MHC class II-peptide complexes recognized by CD4-positive T cells. These data raise the possibility that the intracellular association of class II with the non-polymorphic glycoprotein, invariant chain (Ii), may regulate the interaction between processed antigen and MHC class II molecules. To address this possibility, we have generated a series of transfected fibroblast cell lines that express class II with and without Ii. Although the presence of Ii does not seem to affect the ability of the cells to process and present intact antigen, Ii-negative cells express an altered form of class II at the cell surface. This modified conformation of class II in Ii-negative cells is detectable by an increase in the ability to present antigenic peptides to T cells and a decrease in the binding of several class II-specific monoclonal antibodies. 相似文献
72.
A transgene containing lacZ inserted into the dystonia locus is expressed in neural tube 总被引:12,自引:0,他引:12
The site of integration of transgenes in the host genome can affect levels of expression and occasionally confer ectopic patterns of expression on otherwise tissue-specific genes. We describe here a line of mice in which an hsp68-lacZ transgene is expressed in unstressed developing neural tissue and where the transgene insertion has caused a mutation of a neural tissue-specific gene, dystonia musculorum (dt). This coincidence suggests that expression of the hsp68-lacZ construct may be controlled directly by cis-acting regulatory sequences that normally control the developmental expression of the dt gene. Such constructs may serve as useful tools for identifying new tissue-specific enhancers and their associated genes. 相似文献
73.
Philippe H Brinkmann H Copley RR Moroz LL Nakano H Poustka AJ Wallberg A Peterson KJ Telford MJ 《Nature》2011,470(7333):255-258
Xenoturbellida and Acoelomorpha are marine worms with contentious ancestry. Both were originally associated with the flatworms (Platyhelminthes), but molecular data have revised their phylogenetic positions, generally linking Xenoturbellida to the deuterostomes and positioning the Acoelomorpha as the most basally branching bilaterian group(s). Recent phylogenomic data suggested that Xenoturbellida and Acoelomorpha are sister taxa and together constitute an early branch of Bilateria. Here we assemble three independent data sets-mitochondrial genes, a phylogenomic data set of 38,330 amino-acid positions and new microRNA (miRNA) complements-and show that the position of Acoelomorpha is strongly affected by a long-branch attraction (LBA) artefact. When we minimize LBA we find consistent support for a position of both acoelomorphs and Xenoturbella within the deuterostomes. The most likely phylogeny links Xenoturbella and Acoelomorpha in a clade we call Xenacoelomorpha. The Xenacoelomorpha is the sister group of the Ambulacraria (hemichordates and echinoderms). We show that analyses of miRNA complements have been affected by character loss in the acoels and that both groups possess one miRNA and the gene Rsb66 otherwise specific to deuterostomes. In addition, Xenoturbella shares one miRNA with the ambulacrarians, and two with the acoels. This phylogeny makes sense of the shared characteristics of Xenoturbellida and Acoelomorpha, such as ciliary ultrastructure and diffuse nervous system, and implies the loss of various deuterostome characters in the Xenacoelomorpha including coelomic cavities, through gut and gill slits. 相似文献
74.
Hansj?rg Rindt Pei-Fen Yen Christina N. Thebeau Troy S. Peterson Gary A. Weisman Christian L. Lorson 《Cellular and molecular life sciences : CMLS》2012,69(24):4191-4204
Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder caused by polyglutamine expansion in the amino-terminus of huntingtin (HTT). HD offers unique opportunities for promising RNA-based therapeutic approaches aimed at reducing mutant HTT expression, since the HD mutation is considered to be a “gain-of-function” mutation. Allele-specific strategies that preserve expression from the wild-type allele and reduce the levels of mutant protein would be of particular interest. Here, we have conducted proof-of-concept studies to demonstrate that spliceosome-mediated trans-splicing is a viable molecular strategy to specifically repair the HTT allele. We employed a dual plasmid transfection system consisting of a pre-mRNA trans-splicing module (PTM) containing HTT exon 1 and a HTT minigene to demonstrate that HTT exon 1 can be replaced in trans. We detected the presence of the trans-spliced RNA in which PTM exon 1 was correctly joined to minigene exons 2 and 3. Furthermore, exon 1 from the PTM was trans-spliced to the endogenous HTT pre-mRNA in cultured cells as well as disease-relevant models, including HD patient fibroblasts and primary neurons from a previously described HD mouse model. These results suggest that the repeat expansion of HTT can be repaired successfully not only in the context of synthetic minigenes but also within the context of HD neurons. Therefore, pre-mRNA trans-splicing may be a promising approach for the treatment of HD and other dominant genetic disorders. 相似文献
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Recent evidence suggests a role for eosinophil granule proteins in contact-dependent antibody-mediated cytotoxicity. Cytolysis may involve a secretory phenomenon whereby granule proteins are released at the site of contact between eosinophil and target cells. Several basic proteins have been isolated from eosinophil granules, including the major basic protein, eosinophil cationic protein, eosinophil protein-X and eosinophil peroxidase. One of the major granule proteins of human eosinophils is the eosinophil cationic protein (ECP) which has been shown to damage schistosomula of Schistosoma mansoni at concentrations as low as 10(-7). Here, we describe the formation of functional channels by purified human ECP. The transmembrane pores formed by ECP are relatively voltage-insensitive and non-ion-selective, suggesting a role for channel formation by ECP in target cell damage mediated by eosinophils. Channel formation by granule proteins of immune effector cells may represent a general and effective mechanism of target cell killing. 相似文献
80.
L. Giacometti E. N. Peterson R. E. Behrmann 《Cellular and molecular life sciences : CMLS》1972,28(3):358-359
Zusammenfassung Die Durchblutung der Haut von Rhesus-Affen (Macaca mulatta) wurde mittels Verteilung radioaktiver Kügelchen gemessen und beträgt etwa 7% des HerzMinutenvolumens. 相似文献