56 research outputs found

    The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin.

    Get PDF
    International audienceMannan-binding lectin (MBL), ficolins and collectin-11 are known to associate with three homologous modular proteases, the MBL-Associated Serine Proteases (MASPs). The crystal structures of the catalytic domains of MASP-1 and MASP-2 have been solved, but the structure of the corresponding domain of MASP-3 remains unknown. A link between mutations in the MASP1/3 gene and the rare autosomal recessive 3MC (Mingarelli, Malpuech, Michels and Carnevale,) syndrome, characterized by various developmental disorders, was discovered recently, revealing an unexpected important role of MASP-3 in early developmental processes. To gain a first insight into the enzymatic and structural properties of MASP-3, a recombinant form of its serine protease (SP) domain was produced and characterized. The amidolytic activity of this domain on fluorescent peptidyl-aminomethylcoumarin substrates was shown to be considerably lower than that of other members of the C1r/C1s/MASP family. The E. coli protease inhibitor ecotin bound to the SP domains of MASP-3 and MASP-2, whereas no significant interaction was detected with MASP-1, C1r and C1s. A tetrameric complex comprising an ecotin dimer and two MASP-3 SP domains was isolated and its crystal structure was solved and refined to 3.2 Å. Analysis of the ecotin/MASP-3 interfaces allows a better understanding of the differential reactivity of the C1r/C1s/MASP protease family members towards ecotin, and comparison of the MASP-3 SP domain structure with those of other trypsin-like proteases yields novel hypotheses accounting for its zymogen-like properties in vitro

    Novel immunomodulators from hard ticks selectively reprogramme human dendritic cell responses

    Get PDF
    Hard ticks subvert the immune responses of their vertebrate hosts in order to feed for much longer periods than other blood-feeding ectoparasites; this may be one reason why they transmit perhaps the greatest diversity of pathogens of any arthropod vector. Tick-induced immunomodulation is mediated by salivary components, some of which neutralise elements of innate immunity or inhibit the development of adaptive immunity. As dendritic cells (DC) trigger and help to regulate adaptive immunity, they are an ideal target for immunomodulation. However, previously described immunoactive components of tick saliva are either highly promiscuous in their cellular and molecular targets or have limited effects on DC. Here we address the question of whether the largest and globally most important group of ticks (the ixodid metastriates) produce salivary molecules that specifically modulate DC activity. We used chromatography to isolate a salivary gland protein (Japanin) from Rhipicephalus appendiculatus ticks. Japanin was cloned, and recombinant protein was produced in a baculoviral expression system. We found that Japanin specifically reprogrammes DC responses to a wide variety of stimuli in vitro, radically altering their expression of co-stimulatory and co-inhibitory transmembrane molecules (measured by flow cytometry) and their secretion of pro-inflammatory, anti-inflammatory and T cell polarising cytokines (assessed by Luminex multiplex assays); it also inhibits the differentiation of DC from monocytes. Sequence alignments and enzymatic deglycosylation revealed Japanin to be a 17.7 kDa, N-glycosylated lipocalin. Using molecular cloning and database searches, we have identified a group of homologous proteins in R. appendiculatus and related species, three of which we have expressed and shown to possess DC-modulatory activity. All data were obtained using DC generated from at least four human blood donors, with rigorous statistical analysis. Our results suggest a previously unknown mechanism for parasite-induced subversion of adaptive immunity, one which may also facilitate pathogen transmission

    Role of instabilities in the survival of quantum correlations

    No full text
    Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)This article surveys quantum correlations dynamics, in the Markovian and non-Markovian regimes, in a system of two harmonic oscillators connected by a time-dependent coupling and in contact with a common heat bath. The results show the survival of the quantum correlations, including entanglement, even at very high temperatures, as well as a remarkable relation between entanglement and the instability of the system. The results also show that the indirect interaction of the oscillators via a bath significantly enhances the quantum correlations and that quantum correlations are much more sensitive to the parameters of the oscillators than the temperature of the bath.883Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2011/04521-0

    QUANTUM SUPERPOSITIONS OF BINOMIAL STATES OF LIGHT

    No full text
    We introduce new kinds of states of electromagnetic field, which are quantum superpositions of binomial states. They not only exhibit remarkable non-classical properties but can also interpolate between the 'Schrodinger cat' type of states and the number states in a particularly interesting way. We basically discuss some of their main statistical properties, as well as schemes for their generation. We also employ quasiprobability distributions in phase space.42122475249

    Quantum state transfer between atoms located in coupled optical cavities

    No full text
    We investigated the interaction between two coupled cavities, each one of them interacting with a two-level atom in its interior. We observed that if one of the atoms is in a superposition state and the other parts of the system are in their fundamental states, it is possible to transfer this state to the atom in the other cavity through the temporal evolution of the system. The time-evolution behaviour of the system during this transfer was studied and we observed its dependence with the frequency of the atom and the coupling constant between the atom and its respective cavity.5481139114
    corecore