A new gene coding for an antigen recognized by autologous cytolytic T lymphocytes on a human renal carcinoma

Previous reports have described antigens that are recognized on human melanoma cells by autologous cytolytic T lymphocytes (CTL). The genes coding for a number of these antigens have been identified. Here we report the cloning of a gene that codes for an antigen recognized by autologous CTL on a human renal carcinoma cell line. This antigen is presented byHLA-B7 and is encoded by a new gene that we have namedRAGE1. No expression ofRAGE1 was found in normal tissues other than retina. RAGE1 expression was found in only one of 57 renal cell carcinoma samples, and also in some sarcomas, infiltrating bladder carcinomas, and melanomas. This represents the first identification of an antigen recognized by autologous CTL on a renal tumor.     

Crystal structure of a prokaryotic aspartyl tRNA-synthetase.

The crystal structure of Thermus thermophilus aspartyl tRNA-synthetase (AspRS) refined at 2.5 A resolution is described. This molecular structure is a textbook illustration of the modular organization of aminoacyl-tRNA synthetases. In addition to the three domains found in yeast AspRS, each monomer exhibits a module specific to prokaryotic enzymes, which corresponds to a helix-turn-helix motif in yeast AspRS, a domain implicated in the stabilization of the complex with tRNA. Its topology matches that of the histidine-containing phosphocarrier HPr which has been linked recently to another group of proteins containing the ferredoxin fold. We propose a more extensive alignment of these folds, which involves a circular permutation of the sequences and changes the point of entry of the whole domain. The C-terminal extension, another prokaryotic characteristic, leads to a significant increase in the network of interaction at the dimer interface. Some potential communication pathways suggest how a transfer of information between the two active sites of the homodimer might occur. Most of the residues involved belong to the class II-specific motifs in correlation with the dimeric state of nearly all class II enzymes. The T. thermophilus enzyme exhibits some features not found in any of the six other known AspRSs from mesophilic organisms.     

Unexpected inactivation of acceptor consensus splice sequence by a −3 C to T transition in intron 2 of the CFTR gene

Human Genetics - Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Analysis of DNA from a pancreatic sufficient patient by means of...     

Tum—mutation P35B generates the MHC-binding site of a new antigenic peptide

Immunogenic tumor cell variant P35 was obtained by mutagen treatment of mouse mastocytoma P815. It express a potent new antigen recognized by syngeneic cytolytic T lymphocytes (CTL). This antigen is the result of a point mutation in a gene that is expressed by most healthy cells. A decapeptide encoded by the region spanning the mutation sensitized P815 cells to the relevant CTL, whereas the homologous decapeptide corresponding to the normal sequence did not. Only the mutant decapeptide was capable of enhancing the expression of the D^d-presenting molecule at the cell surface, indicating that the mutation generates a motif which enables the antigenic peptide to bind to D^d. Correspondence to: T. Boon.     

Bioguided Fractionation and Isolation of an Antiplasmodial Saponin from the Roots of Nauclea xanthoxylon (A.Chev.) Aubrév. (Rubiaceae)

The root extract of Nauclea xanthoxylon (A.Chev.) Aubrév. displayed significant 50 % inhibition concentration (IC₅₀s) of 0.57 and 1.26 μg/mL against chloroquine resistant and sensitive Plasmodium falciparum (Pf) Dd2 and 3D7 strains, respectively. Bio-guided fractionation led to an ethyl acetate fraction with IC₅₀s of 2.68 and 1.85 μg/mL and subsequently, to the new quinovic acid saponin named xanthoxyloside ( 1 ) with IC₅₀s of 0.33 and 1.30 μM, respectively against the tested strains. Further compounds obtained from ethyl acetate and hexane fractions were the known clethric acid ( 2 ), ursolic acid ( 3 ), quafrinoic acid ( 4 ), quinovic acid ( 5 ), quinovic acid 3-O-β-D-fucopyranoside ( 6 ), oleanolic acid ( 7 ), oleanolic acid 3-acetate ( 8 ), friedelin ( 9 ), β-sitosterol ( 10a ), stigmasterol ( 10b ) and stigmasterol 3-O-β-D-glucopyranoside ( 11 ). Their structures were characterised with the aid of comprehensive spectroscopic methods (1 and 2D NMR, Mass). Bio-assays were performed using nucleic acid gel stain (SYBR green I)-based fluorescence assay with chloroquine as reference. Extracts and compounds exhibited good selectivity indices (SIs) of >10. Significant antiplasmodial activities measured for the crude extract, the ethyl acetate fraction and xanthoxyloside ( 1 ) from that fraction can justify the use of the root of N. xanthoxylon in ethnomedicine to treat malaria.     

What generates the diversity of Wolbachia—arthropod interactions?

Wolbachia are strictly endocellular, vertically transmitted bacteria associated with insects and crustaceans. This group of parasites modify their hosts' reproduction so as to increase their own fitness. This paper reviews the variability of these parasitic alterations and their consequences for host biology and populations. Wolbachia induce cytoplasmic incompatibility (a characteristic apparently specific to Wolbachia) in several insects and one isopod crustacean; parthenogenesis (thelytoky) in haplo-diploid insects; feminization in various isopods. The consequences of these phenomena on speciation, population dynamics and genetic polymorphism are discussed. The variability of the mechanisms of host sex determination is one important factor responsible for the diversity of Wolbachia-host interactions. However, parasite characteristics, such as the capacity to disturb host mitosis, and the ability to be horizontally transferred between hosts, also appear to play a role in this diversity.     

Further progress towards a catalogue of all Arabidopsis genes: analysis of a set of 5000 non-redundant ESTs

Nearly 7000 Arabidopsis thaliana -expressed sequence tags (ESTs) from 10 cDNA libraries have been sequenced, of which almost 5000 non-redundant tags have been submitted to the EMBL data bank. The quality of the cDNA libraries used is analysed. Similarity searches in international protein data banks have allowed the detection of significant similarities to a wide range of proteins from many organisms. Alignment with ESTs from the rice systematic sequencing project has allowed the detection of amino acid motifs which are conserved between the two organisms, thus identifying tags to genes encoding highly conserved proteins. These genes are candidates for a common framework in genome mapping projects in different plants.