FGB1 and WSC3 are in planta-induced beta-glucan-binding fungal lectins with different functions

In the root endophyte Serendipita indica, several lectin-like members of the expanded multigene family of WSC proteins are transcriptionally induced in planta and are potentially involved in beta-glucan remodeling at the fungal cell wall. Using biochemical and cytological approaches we show that one of these lectins, SiWSC3 with three WSC domains, is an integral fungal cell wall component that binds to long-chain beta 1-3-glucan but has no affinity for shorter beta 1-3- or beta 1-6-linked glucose oligomers. Comparative analysis with the previously identified beta-glucan-binding lectin SiFGB1 demonstrated that whereas SiWSC3 does not require beta 1-6-linked glucose for efficient binding to branched beta 1-3-glucan, SiFGB1 does. In contrast to SiFGB1, the multivalent SiWSC3 lectin can efficiently agglutinate fungal cells and is additionally induced during fungus-fungus confrontation, suggesting different functions for these two beta-glucan-binding lectins. Our results highlight the importance of the beta-glucan cell wall component in plant-fungus interactions and the potential of beta-glucan-binding lectins as specific detection tools for fungi in vivo

Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical status

Blood samples were collected from controls and P. falciparum-infected patients before treatment on the day of hospitalization (day 0) in India and, in addition, on days 7 and 30 after treatment in Gabon. Total IgE levels were determined by ELISA and functional P. falciparum-specific IgE were estimated using a mast cell line RBL-2H3 transfected with a human Fcε RI α-chain that triggers degranulation upon human IgE cross-linking. Mann Whitney and Kruskall Wallis tests were used to compare groups and the Spearman test was used for correlations. Total IgE levels were confirmed to increase upon infection and differ with level of transmission and age but were not directly related to the disease phenotype. All studied groups exhibited functional parasite-specific IgEs able to induce mast cell degranulation in vitro in the presence of P. falciparum antigens. Plasma IgE levels correlated with those of IL-10 in uncomplicated malaria patients from Gabon. In Indian patients, plasma IFN-γ , TNF and IL-10 levels were significantly correlated with IgE concentrations in all groups

Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3

Background Mechanisms of acquired protection to malaria in asymptomatic Plasmodium falciparum carriers are only partially understood. Among them, the role plays by the self-reactive antibodies has not been clarified yet. In this study, the relationship between repertoires of circulating self-reactive and parasite-specific immunoglobulin G (IgG), their correlation with cytokine levels, and their association with protection against malaria was investigated in asymptomatic Plasmodium falciparum-infected Gabonese children. Methods The diversity of P. falciparum-specific antibody repertoire was analysed using a protein micro-array immunoassay, the total auto-antibody repertoire by quantitative immunoblotting and circulating cytokine levels were measured by ELISA in endemic controls (EC) and P. falciparum-infected children from Gabon with asymptomatic (AM) or mild malaria (MM). The association of self- and parasite-specific antibody repertoires with circulating cytokines was evaluated using single linkage hierarchical clustering, Kruskal – Wallis tests and Spearman’s rank correlation. Results Children with AM exhibited an IgG response to merozoite surface protein 3 (MSP3) but not to MSP1-19, although their levels of total P. falciparum-specific IgG were similar to those in the MM group. Moreover, the asymptomatic children had increased levels of autoantibodies recognising brain antigens. In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children. These two groups also exhibited significant correlations between plasma levels of IL-10 and IFN-γ with age and with total plasma IgG levels. IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM. Conclusions Altogether, these results indicate that a self-reactive polyclonal response associated with increased IgG to MSP3 and high plasma levels of IL-10 and IFN-γ may contribute to protective immune mechanisms triggered in asymptomatic P. falciparum infection in Gabonese children

Active regulatory T-cells contribute to broadened T-cell repertoire diversity in ivIg-treated SLE patients

Octapharma

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.National Institutes of Health grants: (UL1RR025741, K24AR002138, P602AR30692, P01AR49084, UL1TR000165, P01AI083194, RO1AR43814, P60AR053308, UL1TR000004, AR43727, R21AI070304, RO1AR057172, UL1RR025014, R01AR051545-03, UL1RR029882, P60AR062755, P30AR53483, U19AI082714, P30GM103510, U01AI101934, AI063274, AR056360, AI083194, R37AI024717, P01083194, P01AR049084, PR094002); Northwestern University Feinberg School of Medicine; University of Alabama Birmingham; National Institute of Arthritis and Musculoskeletal and Skin Diseases; University of California Los Angeles; University of California San Francisco; Hopkins University; University of Colorado School of Medicine; University of Southern California; Seattle Children's Research Institute Arthritis Foundation; Medical University of South Carolina; Oklahoma Medical Research Foundation; Cincinnati Children's Hospital Medical Center; US Departments of Defense grant: (PR094002); Veterans Affairs; Alliance for Lupus Research; Kirkland Scholar Award; Korea Healthcare technology R & D project: (A121983); Ministry for Health and Welfare; Republic of Korea; Swedish Research Council; Instituto de Salud Carlos III grant: (PS09/00129); European Union FEDER funds; Fundação para a Ciência e Tecnologia fellowships: (SFRH/BPD/29354/2006, SFRH/BPD/34648/2007)

Gravity and antimatter: The AEgIS experiment at CERN

open62siFrom the experimental point of view, very little is known about the gravitational interaction between matter and antimatter. In particular, the Weak Equivalence Principle, which is of paramount importance for the General Relativity, has not yet been directly probed with antimatter. The main goal of the AEgIS experiment at CERN is to perform a direct measurement of the gravitational force on antimatter. The idea is to measure the vertical displacement of a beam of cold antihydrogen atoms, traveling in the gravitational field of the Earth, by the means of a moiré deflectometer. An overview of the physics goals of the experiment, of its apparatus and of the first results is presented.openPagano D.; Aghion S.; Amsler C.; Bonomi G.; Brusa R.S.; Caccia M.; Caravita R.; Castelli F.; Cerchiari G.; Comparat D.; Consolati G.; Demetrio A.; Noto L.D.; Doser M.; Evans A.; Fani M.; Ferragut R.; Fesel J.; Fontana A.; Gerber S.; Giammarchi M.; Gligorova A.; Guatieri F.; Haider S.; Hinterberger A.; Holmestad H.; Kellerbauer A.; Khalidova O.; Krasnicky D.; Lagomarsino V.; Lansonneur P.; Lebrun P.; Malbrunot C.; Mariazzi S.; Marton J.; Matveev V.; Mazzotta Z.; Muller S.R.; Nebbia G.; Nedelec P.; Oberthaler M.; Pacifico N.; Penasa L.; Petracek V.; Prelz F.; Prevedelli M.; Ravelli L.; Rienaecker B.; Robert J.; Rohne O.M.; Rotondi A.; Sandaker H.; Santoro R.; Smestad L.; Sorrentino F.; Testera G.; Tietje I.C.; Widmann E.; Yzombard P.; Zimmer C.; Zmeskal J.; Zurlo N.Pagano, D.; Aghion, S.; Amsler, C.; Bonomi, G.; Brusa, R. S.; Caccia, M.; Caravita, R.; Castelli, F.; Cerchiari, G.; Comparat, D.; Consolati, G.; Demetrio, A.; Noto, L. D.; Doser, M.; Evans, A.; Fani, M.; Ferragut, R.; Fesel, J.; Fontana, A.; Gerber, S.; Giammarchi, M.; Gligorova, A.; Guatieri, F.; Haider, S.; Hinterberger, A.; Holmestad, H.; Kellerbauer, A.; Khalidova, O.; Krasnicky, D.; Lagomarsino, V.; Lansonneur, P.; Lebrun, P.; Malbrunot, C.; Mariazzi, S.; Marton, J.; Matveev, V.; Mazzotta, Z.; Muller, S. R.; Nebbia, G.; Nedelec, P.; Oberthaler, M.; Pacifico, N.; Penasa, L.; Petracek, V.; Prelz, F.; Prevedelli, M.; Ravelli, L.; Rienaecker, B.; Robert, J.; Rohne, O. M.; Rotondi, A.; Sandaker, H.; Santoro, R.; Smestad, L.; Sorrentino, F.; Testera, G.; Tietje, I. C.; Widmann, E.; Yzombard, P.; Zimmer, C.; Zmeskal, J.; Zurlo, N

AEg̅IS latest results

The validity of the Weak Equivalence Principle (WEP) as predicted by General Relativity has been tested up to astounding precision using ordinary matter. The lack hitherto of a stable source of a probe being at the same time electrically neutral, cold and stable enough to be measured has prevented highaccuracy testing of the WEP on anti-matter. The AEg̅IS (Antimatter Experiment: Gravity, Interferometry, Spectroscopy) experiment located at CERN's AD (Antiproton Decelerator) facility aims at producing such a probe in the form of a pulsed beam of cold anti-hydrogen, and at measuring by means of a moiré deflectometer the gravitational force that Earth's mass exerts on it. Low temperature and abundance of the H̅ are paramount to attain a high precision measurement. A technique employing a charge-exchange reaction between antiprotons coming from the AD and excited positronium atoms is being developed at AEg̅IS and will be presented hereafter, alongside an overview of the experimental apparatus and the current status of the experimen

Laser excitation of the n=3 level of positronium for antihydrogen production

We demonstrate the laser excitation of the n = 3 state of positronium (Ps) in vacuum. A combination of a specially designed pulsed slow positron beam and a high-efficiency converter target was used to produce Ps. Its annihilation was recorded by single-shot positronium annihilation lifetime spectroscopy. Pulsed laser excitation of the n = 3 level at a wavelength lambda approximate to 205 nm was monitored via Ps photoionization induced by a second intense laser pulse at lambda = 1064 nm. About 15% of the overall positronium emitted into vacuum was excited to n = 3 and photoionized. Saturation of both the n = 3 excitation and the following photoionization was observed and explained by a simple rate equation model. The positronium's transverse temperature was extracted by measuring the width of the Doppler-broadened absorption line. Moreover, excitation to Rydberg states n = 15 and 16 using n = 3 as the intermediate level was observed, giving an independent confirmation of excitation to the 3 P-3 state

The AEgIS experiment at CERN: Measuring antihydrogen free-fall in earth's gravitational field to test WEP with antimatter

The AEgIS (Antimatter Experiment: Gravity, Interferometry, Spectroscopy) experiment is designed with the objective to test the weak equivalence principle with antimatter by studying the free fall of antihydrogen in the Earth's gravitational field. A pulsed cold beam of antihydrogen will be produced by charge exchange between cold Ps excited in Rydberg state and cold antiprotons. Finally the free fall will be measured by a classical moir\ue9 deflectometer. The apparatus being assembled at the Antiproton Decelerator at CERN will be described, then the advancements of the experiment will be reported: positrons and antiprotons trapping measurements, Ps two-step excitation and a test-measurement of antiprotons deflection with a small scale moir\ue9 deflectometer