Antibody deficiency due to a missense mutation in CD19 demonstrates the importance of the conserved tryptophan 41 in immunoglobulin superfamily domain formation.

Immunoglobulin superfamily (IgSF) domains are conserved structures present in many proteins in eukaryotes and prokaryotes. These domains are well-capable of facilitating sequence variation, which is most clearly illustrated by the variable regions in immunoglobulins (Igs) and T cell receptors (TRs). We studied an antibody-deficient patient suffering from recurrent respiratory infections and with impaired antibody responses to vaccinations. Patient's B cells showed impaired Ca(2+) influx upon stimulation with anti-IgM and lacked detectable CD19 membrane expression. CD19 sequence analysis revealed a homozygous missense mutation resulting in a tryptophan to cystein (W52C) amino acid change. The affected tryptophan is CONSERVED-TRP 41 located on the C-strand of the first extracellular IgSF domain of CD19 and was found to be highly conserved, not only in mammalian CD19 proteins, but in nearly all characterized IgSF domains. Furthermore, the tryptophan is present in all variable domains in Ig and TR and was not mutated in 117 Ig class-switched transcripts of B cells from controls, despite an overall 10% amino acid change frequency. In vitro complementation studies and CD19 western blotting of patient's B cells demonstrated that the mutated protein remained immaturely glycosylated. This first missense mutation resulting in a CD19 deficiency demonstrates the crucial role of a highly conserved tryptophan in proper folding or stability of IgSF domains.

La formation discursive eurorégionale. Articulation et approche sémantique d’un corpus multilingue

L’objectif de cet article est double :il s’agit, d’une part, de présenter un nouveau corpus permettant d’envisager le phénomène émergent de la communication transfrontalière en Europe et, d’autre part, de formuler trois questionnements utiles au cadrage de son analyse sémantique. À partir du corpus eurorégional – multilingue et multigenre - nous posons les questions de la dispersion des discours en ligne, de l’hétérogénéité des données et de la contextualisation de l’analyse. Notre démarche consiste à construire progressivement un modèle d’analyse adapté à l’appréhension, tantôt automatique et tantôt manuelle, de la diversité des textes. Enfin, nous proposons d’illustrer la démarche en l’appliquant à la mobilité, observable récurrent du corpus.

Properties of the protein matrix revealed by the free energy of cavity formation.

The classical picture of the hydrophobic stabilization of proteins invokes a resemblance between the protein interior and nonpolar solvents, but the extent to which this is the case has often been questioned. The protein interior is believed to be at least as tightly packed as organic crystals, and was shown to have very low compressibility. There is also evidence that these properties are not uniform throughout the protein, and conflicting views exist on the nature of sidechain packing and on its influence on the properties of the protein.