LHC and lepton flavour violation phenomenology of a left-right extension of the MSSM

We study the phenomenology of a supersymmetric left-right model, assuming minimal supergravity boundary conditions. Both left-right and (B-L) symmetries are broken at an energy scale close to, but significantly below the GUT scale. Neutrino data is explained via a seesaw mechanism. We calculate the RGEs for superpotential and soft parameters complete at 2-loop order. At low energies lepton flavour violation (LFV) and small, but potentially measurable mass splittings in the charged scalar lepton sector appear, due to the RGE running. Different from the supersymmetric 'pure seesaw' models, both, LFV and slepton mass splittings, occur not only in the left- but also in the right slepton sector. Especially, ratios of LFV slepton decays, such as Br(${\tilde\tau}_R \to \mu \chi^0_1$)/Br(${\tilde\tau}_L \to \mu \chi^0_1$) are sensitive to the ratio of (B-L) and left-right symmetry breaking scales. Also the model predicts a polarization asymmetry of the outgoing positrons in the decay $\mu^+ \to e^+ \gamma$, A ~ [0,1], which differs from the pure seesaw 'prediction' A=1$. Observation of any of these signals allows to distinguish this model from any of the three standard, pure (mSugra) seesaw setups.Comment: 43 pages, 17 figure

Interplay of LFV and slepton mass splittings at the LHC as a probe of the SUSY seesaw

We study the impact of a type-I SUSY seesaw concerning lepton flavour violation (LFV) both at low-energies and at the LHC. The study of the di-lepton invariant mass distribution at the LHC allows to reconstruct some of the masses of the different sparticles involved in a decay chain. In particular, the combination with other observables renders feasible the reconstruction of the masses of the intermediate sleptons involved in $\chi_2^0\to \tilde \ell \,\ell \to \ell \,\ell\,\chi_1^0$ decays. Slepton mass splittings can be either interpreted as a signal of non-universality in the SUSY soft breaking-terms (signalling a deviation from constrained scenarios as the cMSSM) or as being due to the violation of lepton flavour. In the latter case, in addition to these high-energy processes, one expects further low-energy manifestations of LFV such as radiative and three-body lepton decays. Under the assumption of a type-I seesaw as the source of neutrino masses and mixings, all these LFV observables are related. Working in the framework of the cMSSM extended by three right-handed neutrino superfields, we conduct a systematic analysis addressing the simultaneous implications of the SUSY seesaw for both high- and low-energy lepton flavour violation. We discuss how the confrontation of slepton mass splittings as observed at the LHC and low-energy LFV observables may provide important information about the underlying mechanism of LFV.Comment: 50 pages, 42 eps Figures, typos correcte

Monitoring Toxicity Associated with Parenteral Sodium Stibogluconate in the Day-Case Management of Returned Travellers with New World Cutaneous Leishmaniasi

Sodium stibogluconate (SbV), a pentavalent antimonial, administered parenterally, is the recommended treatment for South American cutaneous leishmaniasis, caused by Leishmania Viannia, which is a neglected disease that affects many people resident in Central and South America, as well as travellers to the areas. Antimonials have been used for the treatment of leishmaniasis since the 1930s. We report the toxicity experienced by a series of NWCL patients receiving SbV in a resource-rich setting. This study also evaluates administration of the drug to patients without admitting them to hospital. The administration of parenteral SbV was associated with myelosuppression, derangement of markers of liver function and prolongation of the QT interval on electrocardiography, although these effects were not found to be associated with adverse clinical events, and the majority of doses of SbV were administered without cause for hospital admission. Our data shows that parenteral SbV treatment may be provided with reduced monitoring for toxicity than is currently done, and on an outpatient-basis, without endangering safety. Such practice, with reduced demands on local finances and the healthcare workforce, would be desirable in more resource-limited settings

Plasmodium vivax Adherence to Placental Glycosaminoglycans

BACKGROUND: Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear. METHODOLOGY: The adherence properties of P. vivax infected red blood cells (PvIRBC) were evaluated under static and flow conditions. PRINCIPAL FINDINGS: P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA) and hyaluronic acid (HA), the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5). Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD) shear stress reducing maximum attachment by 50% was 0.06 (0.02) Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours. SIGNIFICANCE: Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation

Serologically defined variations in malaria endemicity in Pará state, Brazil

BACKGROUND: Measurement of malaria endemicity is typically based on vector or parasite measures. A complementary approach is the detection of parasite specific IgG antibodies. We determined the antibody levels and seroconversion rates to both P. vivax and P. falciparum merozoite antigens in individuals living in areas of varying P. vivax endemicity in Pará state, Brazilian Amazon region. METHODOLOGY/PRINCIPAL FINDINGS: The prevalence of antibodies to recombinant antigens from P. vivax and P. falciparum was determined in 1,330 individuals. Cross sectional surveys were conducted in the north of Brazil in Anajás, Belém, Goianésia do Pará, Jacareacanga, Itaituba, Trairão, all in the Pará state, and Sucuriju, a free-malaria site in the neighboring state Amapá. Seroprevalence to any P. vivax antigens (MSP1 or AMA-1) was 52.5%, whereas 24.7% of the individuals were seropositive to any P. falciparum antigens (MSP1 or AMA-1). For P. vivax antigens, the seroconversion rates (SCR) ranged from 0.005 (Sucuriju) to 0.201 (Goianésia do Pará), and are strongly correlated to the corresponding Annual Parasite Index (API). We detected two sites with distinct characteristics: Goianésia do Pará where seroprevalence curve does not change with age, and Sucuriju where seroprevalence curve is better described by a model with two SCRs compatible with a decrease in force of infection occurred 14 years ago (from 0.069 to 0.005). For P. falciparum antigens, current SCR estimates varied from 0.002 (Belém) to 0.018 (Goianésia do Pará). We also detected a putative decrease in disease transmission occurred ∼29 years ago in Anajás, Goianésia do Pará, Itaituba, Jacareacanga, and Trairão. CONCLUSIONS: We observed heterogeneity of serological indices across study sites with different endemicity levels and temporal changes in the force of infection in some of the sites. Our study provides further evidence that serology can be used to measure and monitor transmission of both major species of malaria parasite

Duffy Negative Antigen Is No Longer a Barrier to Plasmodium vivax – Molecular Evidences from the African West Coast (Angola and Equatorial Guinea)

Recent reports of Plasmodium vivax infections, the most widely distributed species of human malaria, show that this parasite is evolving and adapting, becoming not only more aggressive but also more frequent in countries where it was not present in the past, becoming, therefore, a major source of concern. Thus, it is extremely important to perform new studies of its distribution in West and Central Africa, where there are few reports of its presence, due to the high prevalence of Duffy-negative individuals. The aim of this study was to investigate the presence of P. vivax in Angola and in Equatorial Guinea, using blood samples and mosquitoes. The results showed that P. vivax seems to be able to invade erythrocytes using receptors other than Duffy, and this new capacity is not exclusive to one strain of P. vivax, since we have found samples infected with two different strains: VK247 and classic. Additionally we demonstrated that the parasite has a greater distribution than previously thought, calling for a reevaluation of its worldwide distribution

UHPLC-ESI/TOFMS Determination of Salicylate-like Phenolic Gycosides in Populus tremula Leaves

Associations of salicylate-like phenolic glycosides (PGs) with biological activity have been reported in Salix and Populus trees, but only for a few compounds, and in relation to a limited number of herbivores. By considering the full diversity of PGs, we may improve our ability to recognize genotypes or chemotype groups and enhance our understanding of their ecological function. Here, we present a fast and efficient general method for salicylate determination in leaves of Eurasian aspen that uses ultra-high performance liquid chromatography-electrospray ionization/time-of-flight mass spectrometry (UHPLC-ESI/TOFMS). The time required for the liquid chromatography separations was 13.5 min per sample, compared to around 60 min per sample for most HPLC protocols. In leaf samples from identical P. tremula genotypes with diverse propagation and treatment histories, we identified nine PGs. We found the compound-specific mass chromatograms to be more informative than the UV-visible chromatograms for compound identification and when quantitating samples with large variability in PG content. Signature compounds previously reported for P. tremoloides (tremulacin, tremuloidin, salicin, and salicortin) always were present, and five PGs (2'-O-cinnamoyl-salicortin, 2'-O-acetyl-salicortin, 2'-O-acetyl-salicin, acetyl-tremulacin, and salicyloyl-salicin) were detected for the first time in P. tremula. By using information about the formic acid adduct that appeared for PGs in the LTQ-Orbitrap MS environment, novel compounds like acetyl-tremulacin could be tentatively identified without the use of standards. The novel PGs were consistently either present in genotypes regardless of propagation and damage treatment or were not detectable. In some genotypes, concentrations of 2'-O-acetyl-salicortin and 2'-O-cinnamoyl-salicortin were similar to levels of biologically active PGs in other Salicaceous trees. Our study suggests that we may expect a wide variation in PG content in aspen populations which is of interest both for studies of interactions with herbivores and for mapping population structure

Worldwide Genetic Variability of the Duffy Binding Protein: Insights into Plasmodium vivax Vaccine Development

The dependence of Plasmodium vivax on invasion mediated by Duffy binding protein (DBP) makes this protein a prime candidate for development of a vaccine. However, the development of a DBP-based vaccine might be hampered by the high variability of the protein ligand (DBPII), known to bias the immune response toward a specific DBP variant. Here, the hypothesis being investigated is that the analysis of the worldwide DBPII sequences will allow us to determine the minimum number of haplotypes (MNH) to be included in a DBP-based vaccine of broad coverage. For that, all DBPII sequences available were compiled and MNH was based on the most frequent nonsynonymous single nucleotide polymorphisms, the majority mapped on B and T cell epitopes. A preliminary analysis of DBPII genetic diversity from eight malaria-endemic countries estimated that a number between two to six DBP haplotypes (17 in total) would target at least 50% of parasite population circulating in each endemic region. Aiming to avoid region-specific haplotypes, we next analyzed the MNH that broadly cover worldwide parasite population. The results demonstrated that seven haplotypes would be required to cover around 60% of DBPII sequences available. Trying to validate these selected haplotypes per country, we found that five out of the eight countries will be covered by the MNH (67% of parasite populations, range 48–84%). In addition, to identify related subgroups of DBPII sequences we used a Bayesian clustering algorithm. The algorithm grouped all DBPII sequences in six populations that were independent of geographic origin, with ancestral populations present in different proportions in each country. In conclusion, in this first attempt to undertake a global analysis about DBPII variability, the results suggest that the development of DBP-based vaccine should consider multi-haplotype strategies; otherwise a putative P. vivax vaccine may not target some parasite populations