Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor

Negative selection eliminates thymocytes bearing autoreactive T cell receptors (TCR) via an apoptotic mechanism. We have cloned an inhibitor of NF-kappa B, I kappa BNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death. The predicted protein contains seven ankyrin repeats and is homologous to I kappa B family members. In class I and class II MHC-restricted TCR transgenic mice, transcription of I kappa BNS is stimulated by peptides that trigger negative selection but not by those inducing positive selection (i.e., survival) or nonselecting peptides. I kappa BNS blocks transcription from NF-kappa B reporters, alters NF-kappa B electrophoretic mobility shifts, and interacts with NF-kappa B proteins in thymic nuclear lysates following TCR stimulation. Retroviral transduction of I kappa BNS in fetal thymic organ culture enhances TCR-triggered cell death consistent with its function in selection

Modelling fungal colonies and communities:challenges and opportunities

This contribution, based on a Special Interest Group session held during IMC9, focuses on physiological based models of filamentous fungal colony growth and interactions. Fungi are known to be an important component of ecosystems, in terms of colony dynamics and interactions within and between trophic levels. We outline some of the essential components necessary to develop a fungal ecology: a mechanistic model of fungal colony growth and interactions, where observed behaviour can be linked to underlying function; a model of how fungi can cooperate at larger scales; and novel techniques for both exploring quantitatively the scales at which fungi operate; and addressing the computational challenges arising from this highly detailed quantification. We also propose a novel application area for fungi which may provide alternate routes for supporting scientific study of colony behaviour. This synthesis offers new potential to explore fungal community dynamics and the impact on ecosystem functioning

Hercynian Metamorphism in the Catalonian Coastel Ranges

Paleozoic rocks in the Catalonian Coastal Ranges are in their largest part affectedby alow- tovery-low grade Hercynian metamorphism. Amphibolite facies conditions are only found in restricted areas such as the southwestern part of the Guilleries massif where upper amphibolite facies conditions are reached. Metamorphic grade increases from top to bottom of the Paleozoic stratigraphic sequence and the metamorphic peak is diachronous, being progressively older in the lower grade metamorphic zones. The isograd pattern, mineral assemblages, mineral chemistry and preserved reaction textures are consistent with a low pressure metamorphism possibly evolving from a previous Barrovian type event. The metamorphic climax in the high grade zone was reached after the seconddeformational phase. Calculatedpeak P-Tconditions are 620-640 OC and around 3.5 Kb . A latter episode of decompression from the maximum conditions to 1-2 Kb, with an associated temperature decrease to 530-550 OC, is recognized. The intrusion of late Hercynian granitoids produced contact metamorphic aureoles where the pyroxene-hornfels facies is locally reached

Prediction of MHC-peptide binding: a systematic and comprehensive overview

T cell immune responses are driven by the recognition of peptide antigens (T cell epitopes) that are bound to major histocompatibility complex (MHC) molecules. T cell epitope immunogenicity is thus contingent on several events, including appropriate and effective processing of the peptide from its protein source, stable peptide binding to the MHC molecule, and recognition of the MHC-bound peptide by the T cell receptor. Of these three hallmarks, MHC-peptide binding is the most selective event that determines T cell epitopes. Therefore, prediction of MHC-peptide binding constitutes the principal basis for anticipating potential T cell epitopes. The tremendous relevance of epitope identification in vaccine design and in the monitoring of T cell responses has spurred the development of many computational methods for predicting MHC-peptide binding that improve the efficiency and economics of T cell epitope identification. In this report, we will systematically examine the available methods for predicting MHC-peptide binding and discuss their most relevant advantages and drawbacks

Discovery of conserved epitopes through sequence variability analyses

Depto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEpu