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.     

The Glucose-Related Decrease in Polar Auxin Transport During Ripening and its Possible Role in Grapevine Berry Coloring

Journal of Plant Growth Regulation - Auxin is a hormone that delays ripening in part by reducing anthocyanin content and impairing color development. Auxin content declines during the ripening...     

Discrete modeling for integration and analysis of large-scale signaling networks

Most biological processes are orchestrated by large-scale molecular networks which are described in large-scale model repositories and whose dynamics are extremely complex. An observed phenotype is a state of this system that results from control mechanisms whose identification is key to its understanding. The Biological Pathway Exchange (BioPAX) format is widely used to standardize the biological information relative to regulatory processes. However, few modeling approaches developed so far enable for computing the events that control a phenotype in large-scale networks.Here we developed an integrated approach to build large-scale dynamic networks from BioPAX knowledge databases in order to analyse trajectories and to identify sets of biological entities that control a phenotype. The Cadbiom approach relies on the guarded transitions formalism, a discrete modeling approach which models a system dynamics by taking into account competition and cooperation events in chains of reactions. The method can be applied to every BioPAX (large-scale) model thanks to a specific package which automatically generates Cadbiom models from BioPAX files.The Cadbiom framework was applied to the BioPAX version of two resources (PID, KEGG) of the Pathway Commons database and to the Atlas of Cancer Signalling Network (ACSN). As a case-study, it was used to characterize sets of biological entities implicated in the epithelial-mesenchymal transition. Our results highlight the similarities between the PID and ACSN resources in terms of biological content, and underline the heterogeneity of usage of the BioPAX semantics limiting the fusion of models that require curation. Causality analyses demonstrate the smart complementarity of the databases in terms of combinatorics of controllers that explain a phenotype. From a biological perspective, our results show the specificity of controllers for epithelial and mesenchymal phenotypes that are consistent with the literature and identify a novel signature for intermediate states.     

Timing and abundance as key mechanisms affecting trophic interactions in variable environments

Climatic changes are disrupting otherwise tight trophic interactions between predator and prey. Most of the earlier studies have primarily focused on the temporal dimension of the relationship in the framework of the match–mismatch hypothesis. This hypothesis predicts that predator's recruitment will be high if the peak of the prey availability temporally matches the most energy‐demanding period of the predators breeding phenology. However, the match–mismatch hypothesis ignores the level of food abundance while this can compensate small mismatches. Using a novel time‐series model explicitly quantifying both the timing and the abundance component for trophic relationships, we here show that timing and abundance of food affect recruitment differently in a marine (cod/zooplankton), a marine–terrestrial (puffin/herring) and a terrestrial (sheep/vegetation) ecosystem. The quantification of the combined effect of abundance and timing of prey on predator dynamics enables us to come closer to the mechanisms by which environment variability may affect ecological systems.     

Large-scale production of a therapeutic protein in transgenic tobacco plants: effect of subcellular targeting on quality of a recombinant dog gastric lipase

A recombinant dog gastric lipase with therapeutic potential for the treatment of exocrine pancreatic insufficiency was expressed in transgenic tobacco plants. We targeted the protein using two different signal sequences for either vacuolar retention or secretion. In both cases, an active glycosylated recombinant protein was obtained. The recombinant enzymes and the native enzyme displayed similar properties including acid resistance and acidic optimum pH. The proteolytic maturation and the specific activity of the recombinant proteins, however, were found to be dependent on subcellular compartmentalization. Expression levels of recombinant dog gastric lipase were about 5% and 7% of acid extractable plant proteins for vacuolar retention and secretion respectively. This expression system already has allowed the production of tens of grams of purified lipase through open-field culture of transgenic tobacco plants.     

Role of RYR3 splice variants in calcium signaling in mouse nonpregnant and pregnant myometrium

Alternative splicing of ryanodine receptor subtype 3 (RYR3) may generate a short isoform (RYR3S) without channel function and a functional full-length isoform (RYR3L). The RYR3S isoform has been shown to negatively regulate the native RYR2 subtype in smooth muscle cells as well as the RYR3L isoform when both isoforms were coexpressed in HEK-293 cells. Mouse myometrium expresses only the RYR3 subtype, but the role of RYR3 isoforms obtained by alternative splicing and their activation by cADP-ribose during pregnancy have never been investigated. Here, we show that both RYR3S and RYR3L isoforms are differentially expressed in nonpregnant and pregnant mouse myometrium. The use of antisense oligonucleotides directed against each isoform indicated that only RYR3L was activated by caffeine and cADP-ribose in nonpregnant myometrium. These RYR3L-mediated Ca²⁺ releases were negatively regulated by RYR3S expression. At the end of pregnancy, the relative expression of RYR3L versus RYR3S and its ability to respond to cADP-ribose were increased. Therefore, our results suggest that physiological regulation of RYR3 alternative splicing may play an essential role at the end of pregnancy. ryanodine receptor; smooth muscle; alternative splicing     

Alpha6beta1 integrin expressed by sperm is determinant in mouse fertilization

Background  

Based on inhibition tests, the alpha6beta1 integrin was suggested to be a sperm receptor, but further experiments using gene deletion techniques have shown that neither oocyte alpha6, nor beta1 integrin subunits were essential for mouse fertilization.