1,706 research outputs found

    Immunization with rP22 induces protective immunity against Schistosoma mansoni: Effects on granuloma down-modulation and cytokine production

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    AbstractSchistosomiasis remains a significant public health problem in tropical countries and it is recognized as the most important human helminth infection in terms of morbidity and mortality. Although the existing antischistosomal drugs are highly effective, they do not prevent against reinfection or granuloma formation. Therefore, vaccine strategies are essential for the control of schistosomiasis. Our group recently identified the recombinant (r) P22 protein, a component of the adult worm protein fraction PIII that has been shown to engender protective and immunomodulatory effects on murine schistosomiasis. A cDNA clone encoding rP22 was isolated from a Schistosoma mansoni adult worm cDNA library using anti-PIII rabbit serum; it exhibited complete identity with S. mansoni Sm21.7 EF-hand antigen. Confocal microscopy revealed that rP22 is a tegument protein localized on the surface of S. mansoni miracidia and adult worms. Mice immunized with rP22 exhibited a 51% and 22.5% decrease in adult worm burden and in hepatic eggs, respectively. Additionally, rP22 vaccine produced a reduction in 60% of liver granuloma size and 71% of fibrosis in mice, suggesting that rP22 might contribute to down-modulate granulomatous hypersensitivity to S. mansoni eggs. Protective immunity in mice was associated with high titers of rP22-specific IgG antibodies; elevated production of IFN-γ, TNF-α and IL-10; and a reduced level of IL-4. In conclusion, these findings indicate that rP22-based vaccines could be useful to elicit protection and reduce pathology associated to schistosomiasis

    The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis.

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    Inherited retinal diseases (IRDs) are a group of ocular conditions characterized by an elevated genetic and clinical heterogeneity. They are transmitted almost invariantly as monogenic traits. However, with more than 280 disease genes identified so far, association of clinical phenotypes with genotypes can be very challenging, and molecular diagnosis is essential for genetic counseling and correct management of the disease. In addition, the prevalence and the assortment of IRD mutations are often population-specific. In this work, we examined 230 families from Portugal, with individuals suffering from a variety of IRD diagnostic classes (270 subjects in total). Overall, we identified 157 unique mutations (34 previously unreported) in 57 distinct genes, with a diagnostic rate of 76%. The IRD mutational landscape was, to some extent, different from those reported in other European populations, including Spanish cohorts. For instance, the EYS gene appeared to be the most frequently mutated, with a prevalence of 10% among all IRD cases. This was, in part, due to the presence of a recurrent and seemingly founder mutation involving the deletion of exons 13 and 14 of this gene. Moreover, our analysis highlighted that as many as 51% of our cases had mutations in a homozygous state. To our knowledge, this is the first study assessing a cross-sectional genotype-phenotype landscape of IRDs in Portugal. Our data reveal a rather unique distribution of mutations, possibly shaped by a small number of rare ancestral events that have now become prevalent alleles in patients

    Metabolic oscillations on the circadian time scale in <i>Drosophila</i> cells lacking clock genes.

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    Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 h. Current models propose that transcriptional feedback loops are the primary mechanism for the generation of circadian oscillations. Within this framework, &lt;i&gt;Drosophila&lt;/i&gt; S2 cells are regarded as "non-rhythmic" cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery that &lt;i&gt;Drosophila&lt;/i&gt; S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products, and in particular metabolic enzymes, are rhythmically expressed in a 24-h cycle. Metabolomics analyses extended these findings and demonstrate that central carbon metabolism and amino acid metabolism are core metabolic pathways driven by protein rhythms. We thus demonstrate that 24-h metabolic oscillations, coupled to gene and protein cycles, take place in nucleated cells without the contribution of any known circadian regulators. These results therefore suggest a reconsideration of existing models of the clockwork in &lt;i&gt;Drosophila&lt;/i&gt; and other eukaryotic systems

    Nonlinear atom optics and bright gap soliton generation in finite optical lattices

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    We theoretically investigate the transmission dynamics of coherent matter wave pulses across finite optical lattices in both the linear and the nonlinear regimes. The shape and the intensity of the transmitted pulse are found to strongly depend on the parameters of the incident pulse, in particular its velocity and density: a clear physical picture for the main features observed in the numerical simulations is given in terms of the atomic band dispersion in the periodic potential of the optical lattice. Signatures of nonlinear effects due the atom-atom interaction are discussed in detail, such as atom optical limiting and atom optical bistability. For positive scattering lengths, matter waves propagating close to the top of the valence band are shown to be subject to modulational instability. A new scheme for the experimental generation of narrow bright gap solitons from a wide Bose-Einstein condensate is proposed: the modulational instability is seeded in a controlled way starting from the strongly modulated density profile of a standing matter wave and the solitonic nature of the generated pulses is checked from their shape and their collisional properties

    PrevenBox: Evaluation of concomitant use of preventive medications with OnabotulinumtoxinA in migraine

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    P114 Background: OnabotulinumtoxinA is an effective, tolerable and safepreventive treatment for chronic migraine (CM). Other than a reduc-tion in headache frequency or disability, in CM the withdrawal ofconcomitant preventive medication indicates treatment effectivenessand quality of life improvement. Objective: To characterize the change in the use of oral preventivemedication after treatment with OnabotulinumtoxinA in patientswith migraine. Methods: This is a multicentre study. We consecutively included pa-tients with migraine (ICHD-3) that were on preventive treatment withOnabotulinumtoxinA. We retrospectively collected demographic data, diagnosis of migraine, frequency and intensity changes, number ofcycle and OnabotulinumtoxinA dose. In addition, we listed the initialand current preventive treatment (number of drugs and group) andthe number and cycle of medications withdrawn. We performed aunivariate and logistic regression analysis. Results: We included 542 patients: 87.6% women, mean age 47.6 ±11.7 years. A 89.3% had chronic migraine and 10.8% had high fre-quency episodic migraine. The mean reduction in frequency aftertreatment was 13.4±8.2 headache days/month. At baseline, a 91.3%took other preventives and during treatment with Onabotulinumtox-inA a 58.6% withdrew at least one drug, 25.8% stopped completelyall oral preventive drugs. Factors associated with withdrawal were:being male, having >50% response in frequency and intensity, thenumber of infiltrations and a shorter chronification period until thefirst OnabotulinumtoxinA administration (p <0.05). The multivariateanalysis showed that a better response in intensity (OR:1.8 [1.4-2.2], p<0.001), a greater number of infiltrations (OR:1.1 [1.0-1.2], p<0.001)and a shorter chronification period (OR:0.994 [0.992-0.997], p<0.001)were predictors of withdrawal. The ROC curve, showed that 6 Onabo-tulinumtoxinA cycles was the cut-off point that better predicted oralpreventive medication withdrawal (p <0.001). Conclusions: Treatment with OnabotulinumtoxinA reduces the use ofother preventive medications for migraine. The highest probability ofwithdrawal occurs after 6 cycles of treatment

    H^+ -> W^+ l_i^- l_j^+$ decay in the two Higgs doublet model

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    We study the lepton flavor violating H^+ -> W^+ l_i^- l_j^+ and the lepton flavor conserving $H^+ -> W^+ l_i^- l_i^+ (l_i=\tau, l_j=\mu) decays in the general 2HDM, so called model III. We estimate the decay width \Gamma for LFV (LFC) at the order of the magnitude of (10^{-11}-10^{-5}) GeV ((10^{-9}-10^{-4}) GeV), for 200 GeV\leq m_{H^\pm}\leq 400 GeV, and the intermediate values of the coupling \bar{\xi}^{E}_{N,\tau \mu}\sim 5 GeV (\bar{\xi}^{E}_{N,\tau \tau}\sim 30 GeV). We observe that the experimental result of the process under consideration can give comprehensive information about the physics beyond the standard model and the existing free parameters.Comment: 8 pages, 7 Figure

    Inelastic Scattering Time for Conductance Fluctuations

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    We revisit the problem of inelastic times governing the temperature behavior of the weak localization correction and mesoscopic fluctuations in one- and two-dimensional systems. It is shown that, for dephasing by the electron electron interaction, not only are those times identical but the scaling functions are also the same.Comment: 10 pages Revtex; 5 eps files include
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