184 research outputs found

    Pathways of Superoxide (O2-) decay in the Eastern Tropical North Atlantic

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    Superoxide (O2-: IUPAC name dioxide (•1−)) is an important transient reactive oxygen species (ROS) in the ocean formed as an intermediate in the redox transformation of oxygen (O2) into hydrogen peroxide (H2O2) and vice versa. This highly reactive and very short-lived radical anion can be produced both via photochemical and biological processes in the ocean. In this paper we examine the decomposition rate of O2- throughout the water column, using new data collected in the Eastern Tropical North Atlantic (ETNA) Ocean. For this approach we applied a semi factorial experimental design, to identify and quantify the pathways of the major identified sinks in the ocean. In this work we occupied 6 stations, 2 on the West African continental shelf and 4 open ocean stations, including the CVOO time series site adjacent to Cape Verde. Our results indicate that in the surface ocean, impacted by Saharan aerosols and sediment resuspension, the main decay pathways for superoxide is via reactions with Mn(II) and organic matter

    Peroxiredoxin II Regulates Effector and Secondary Memory CD8+ T cell Responses

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    Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in cellular responses. However, the effect of increased H2O2on an antigen-specific CD8+ T cell response was unknown. Following T cell receptor (TCR) stimulation, the expression and oxidation of peroxiredoxin II (PrdxII), a critical antioxidant enzyme, increased in CD8+ T cells. Deletion of PrdxII increased ROI, S phase entry, division, and death during in vitro division. During primary acute viral and bacterial infection, the number of effector CD8+ T cells in PrdxII-deficient mice was increased, while the number of memory cells were similar to those of the wild-type cells. Adoptive transfer of P14 TCR transgenic cells demonstrated that the increased expansion of effector cells was T cell autonomous. After rechallenge, effector CD8+ T cells in mutant animals were more skewed to memory phenotype than cells from wild-type mice, resulting in a larger secondary memory CD8+ T cell pool. During chronic viral infection, increased antigen-specific CD8+ T cells accumulated in the spleens of PrdxII mutant mice, causing mortality. These results demonstrate that PrdxII controls effector CD8+ T cell expansion, secondary memory generation, and immunopathology

    Isolation and Characterization of a Mn(II)-Oxidizing Bacillus Strain from the Demosponge Suberites domuncula

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    In this study we demonstrate that the demosponge Suberites domuncula harbors a Mn(II)-oxidizing bacterium, a Bacillus strain, termed BAC-SubDo-03. Our studies showed that Mn(II) stimulates bacterial growth and induces sporulation. Moreover, we show that these bacteria immobilize manganese on their cell surface. Comparison of the 16S rDNA sequence allowed the grouping of BAC-SubDo-03 to the Mn-precipitating bacteria. Analysis of the spore cell wall revealed that it contains an Mn(II)-oxidizing enzyme. Co-incubation studies of BAC-SubDo-03 with 100 μM MnCl2 and >1 μM of CuCl2 showed an increase in their Mn(II)-oxidizing capacity. In order to prove that a multicopper oxidase-like enzyme(s) (MCO) exists in the cell wall of the S. domuncula-associated BAC-SubDo-03 Bacillus strain, the gene encoding this enzyme was cloned (mnxG-SubDo-03). Sequence alignment of the deduced MCO protein (MnxG-SubDo-03) revealed that the sponge bacterium clusters together with known Mn(II)-oxidizing bacteria. The expression of the mnxG-SubDo-03 gene is under strong control of extracellular Mn(II). Based on these findings, we assume that BAC-SubDo-03 might serve as a Mn reserve in the sponge providing the animal with the capacity to detoxify Mn in the environment. Applying the in vitro primmorph cell culture system we could demonstrate that sponge cells, that were co-incubated with BAC-SubDo-03 in the presence of Mn(II), show an increased proliferation potential

    Polymorphisms of CD16A and CD32 Fcγ receptors and circulating immune complexes in Ménière's disease: a case-control study

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    <p>Abstract</p> <p>Background</p> <p>Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC.</p> <p>Methods</p> <p>The functional CD16A (FcγRIIIa*559A > C, rs396991) and CD32A (FcγRIIa*519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ<sup>2 </sup>with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC.</p> <p>Results</p> <p>Elevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10<sup>-4 </sup>for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11).</p> <p>Conclusions</p> <p>Elevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.</p

    Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis

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    Phosphoenol pyruvate is the highest-energy phosphate found in living organisms and is one of the most versatile molecules in metabolism. Consequently, it is an essential intermediate in a wide variety of biochemical pathways, including carbon fixation, the shikimate pathway, substrate-level phosphorylation, gluconeogenesis and glycolysis. Triose glycolysis (generation of ATP from glyceraldehyde 3-phosphate via phosphoenol pyruvate) is among the most central and highly conserved pathways in metabolism. Here, we demonstrate the efficient and robust synthesis of phosphoenol pyruvate from prebiotic nucleotide precursors, glycolaldehyde and glyceraldehyde. Furthermore, phosphoenol pyruvate is derived within an α-phosphorylation controlled reaction network that gives access to glyceric acid 2-phosphate, glyceric acid 3-phosphate, phosphoserine and pyruvate. Our results demonstrate that the key components of a core metabolic pathway central to energy transduction and amino acid, sugar, nucleotide and lipid biosyntheses can be reconstituted in high yield under mild, prebiotically plausible conditions

    Differential Recognition of P. falciparum VAR2CSA Domains by Naturally Acquired Antibodies in Pregnant Women from a Malaria Endemic Area

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    Plasmodium falciparum infected red blood cells (iRBC) express variant surface antigens (VSA) of which VAR2CSA is involved in placental sequestration and causes pregnancy-associated malaria (PAM). Primigravidae are most susceptible to PAM whereas antibodies associated with protection are often present at higher levels in multigravid women. However, HIV co-infection with malaria has been shown to alter this parity-dependent acquisition of immunity, with more severe symptoms as well as more malaria episodes in HIV positive women versus HIV negative women of a similar parity.Using VAR2CSA DBL-domains expressed on the surface of CHO-745 cells we quantified levels of DBL-domain specific IgG in sera from pregnant Malawian women by flow cytometry. Dissociations constants of DBL5epsilon specific antibodies were determined using a surface plasmon resonance technique, as an indication of antibody affinities.VAR2CSA DBL5epsilon was recognized in a gender and parity-dependent manner with anti-DBL5epsilon IgG correlating significantly with IgG levels to VSA-PAM on the iRBC surface. HIV positive women had lower levels of anti-DBL5epsilon IgG than HIV negative women of similar parity. In primigravidae, antibodies in HIV positive women also showed significantly lower affinity to VAR2CSA DBL5epsilon.Pregnant women from a malaria-endemic area had increased levels of anti-DBL5epsilon IgG by parity, indicating this domain of VAR2CSA to be a promising vaccine candidate against PAM. However, it is important to consider co-infection with HIV, as this seems to change the properties of antibody response against malaria. Understanding the characteristics of antibody response against VAR2CSA is undoubtedly imperative in order to design a functional and efficient vaccine against PAM

    Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study.

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    OBJECTIVE: A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. METHODS: In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. RESULTS: In the initial study (n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed (k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study (n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed (k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p < 0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. CONCLUSIONS: IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.info:eu-repo/semantics/publishedVersio
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