Microwave reflectometer for density profile and turbulence measurements on the COMPASS tokamak.

The fast microwave reflectometer system on the COMPASS tokamak consists of an O-mode polarized K-band (18 GHz-26 GHz), Ka-band (26 GHz-40 GHz), and a part of U-band (40 GHz-54 GHz). The plasma density profile from the edge plasma area is measured using a fast sweeping rate up of to 6 µs of the probing wave. The processing of the reflected signal is realized by the heterodyne detection configuration based on the I/Q modulator. Two different methods of dynamic calibration of the required linear sweep frequency, together with static frequency and dispersion calibration, were used. The electron density profile was reconstructed by a spectrogram-based method with four sweeps on average. The system has the capability to measure the mid-plane low-field side electron density profile in the density range from 4 × 1018 m-3 to 3.6 × 1019 m-3. Experimental results obtained on COMPASS discharges are presented to demonstrate the performance of the diagnostics.

Radiometry for the vertical electron cyclotron emission from the runaway electrons at the COMPASS tokamak.

Due to an increased interest in runaway electron (RE) phenomena in tokamak research, the need for diagnostics of runaway electron population in plasma has emerged. A novel diagnostic of the nonthermal electron cyclotron emission from runaway electrons can be utilized for this purpose. It was designed and installed at the COMPASS tokamak based on the available heterodyne radiometer. The vertical ECE (V-ECE) system uses a 16-channel heterodyne radiometer with a vertically placed E2-band horn antenna with a 76.5-90 GHz frequency range front-end. Simulations with the ray-tracing SPECE code have shown a measurement feasibility of the runaway electrons with energies up to 1 MeV. Due to a low optical depth of the plasma in COMPASS during RE discharges, reflected waves from the tokamak wall can be detected as well. First results show strong connection with other RE diagnostics at COMPASS. The V-ECE can obtain important information about RE population evolution and primary generation mechanism.

On the three-finger protein domain fold and CD59-like proteins in Schistosoma mansoni.

BACKGROUND: It is believed that schistosomes evade complement-mediated killing by expressing regulatory proteins on their surface. Recently, six homologues of human CD59, an important inhibitor of the complement system membrane attack complex, were identified in the schistosome genome. Therefore, it is important to investigate whether these molecules could act as CD59-like complement inhibitors in schistosomes as part of an immune evasion strategy. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we describe the molecular characterization of seven putative SmCD59-like genes and attempt to address the putative biological function of two isoforms. Superimposition analysis of the 3D structure of hCD59 and schistosome sequences revealed that they contain the three-fingered protein domain (TFPD). However, the conserved amino acid residues involved in complement recognition in mammals could not be identified. Real-time RT-PCR and Western blot analysis determined that most of these genes are up-regulated in the transition from free-living cercaria to adult worm stage. Immunolocalization experiments and tegument preparations confirm that at least some of the SmCD59-like proteins are surface-localized; however, significant expression was also detected in internal tissues of adult worms. Finally, the involvement of two SmCD59 proteins in complement inhibition was evaluated by three different approaches: (i) a hemolytic assay using recombinant soluble forms expressed in Pichia pastoris and E. coli; (ii) complement-resistance of CHO cells expressing the respective membrane-anchored proteins; and (iii) the complement killing of schistosomula after gene suppression by RNAi. Our data indicated that these proteins are not involved in the regulation of complement activation. CONCLUSIONS: Our results suggest that this group of proteins belongs to the TFPD superfamily. Their expression is associated to intra-host stages, present in the tegument surface, and also in intra-parasite tissues. Three distinct approaches using SmCD59 proteins to inhibit complement strongly suggested that these proteins are not complement inhibitors and their function in schistosomes remains to be determined.

Immunization with tegument nucleotidases associated with a subcurative praziquantel treatment reduces worm burden following Schistosoma mansoni challenge.

Schistosomiasis is a debilitating disease caused by flatworm parasites of the Schistosoma genus and remains a high public health impact disease around the world, although effective treatment with Praziquantel (PZQ) has been available since the 1970s. Control of this disease would be greatly improved by the development of a vaccine, which could be combined with chemotherapy. The sequencing of the Schistosoma mansoni transcriptome and genome identified a range of potential vaccine antigens. Among these, three nucleotidases from the tegument of the parasite, presumably involved in purinergic signaling and nucleotide metabolism, were proposed as promising vaccine candidates: an alkaline phosphatase (SmAP), a phosphodiesterase (SmNPP-5) and a diphosphohydrolase (SmNTPDase). Herein, we evaluate the potential of these enzymes as vaccine antigens, with or without subcurative PZQ treatment. Immunization of mice with the recombinant proteins alone or in combination demonstrated that SmAP is the most immunogenic of the three. It induced the highest antibody levels, particularly IgG1, associated with an inflammatory cellular immune response characterized by high TNF-α and a Th17 response, with high IL-17 expression levels. Despite the specific immune response induced, immunization with the isolated or combined proteins did not reduce the worm burden of challenged mice. Nonetheless, immunization with SmAP alone or with the three proteins combined, together with subcurative PZQ chemotherapy was able to reduce the worm burden by around 40%. The immunogenicity and relative exposure of SmAP to the host immune system are discussed, as key factors involved in the apparently synergistic effect of SmAP immunization and subcurative PZQ treatment.

Schistosoma mansoni Stomatin like protein-2 is located in the tegument and induces partial protection against challenge infection.

BACKGROUND: Schistosomiasis affects more than 200 million individuals worldwide, with a further 650 million living at risk of infection, constituting a severe health problem in developing countries. Even though an effective treatment exists, it does not prevent re-infection, and the development of an effective vaccine still remains the most desirable means of control for this disease. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we report the cloning and characterization of a S. mansoni Stomatin-like protein 2 (SmStoLP-2). In silico analysis predicts three putative sites for palmitoylation (Cys11, Cys61 and Cys330), which could contribute to protein membrane association; and a putative mitochondrial targeting sequence, similar to that described for human Stomatin-like protein 2 (HuSLP-2). The protein was detected by Western blot with comparable levels in all stages across the parasite life cycle. Fractionation by differential centrifugation of schistosome tegument suggested that SmStoLP-2 displays a dual targeting to the tegument membranes and mitochondria; additionally, immunolocalization experiments confirm its localization in the tegument of the adult worms and, more importantly, in 7-day-old schistosomula. Analysis of the antibody isotype profile to rSmStoLP-2 in the sera of patients living in endemic areas for schistosomiasis revealed that IgG1, IgG2, IgG3 and IgA antibodies were predominant in sera of individuals resistant to reinfection as compared to those susceptible. Next, immunization of mice with rSmStoLP-2 engendered a 30%-32% reduction in adult worm burden. Protective immunity in mice was associated with specific anti-rSmStoLP-2 IgG1 and IgG2a antibodies and elevated production of IFN-gamma and TNF-alpha, while no IL-4 production was detected, suggesting a Th1-predominant immune response. CONCLUSIONS/SIGNIFICANCE: Data presented here demonstrate that SmStoLP-2 is a novel tegument protein located in the host-parasite interface. It is recognized by different subclasses of antibodies in patients resistant and susceptible to reinfection and, based on the data from murine studies, shows protective potential against schistosomiasis. These results indicate that SmStoLP-2 could be useful in a combination vaccine.