El análisis proteómico del interactoma intracelular revela que las tetraspaninas modulan el repertorio de proteínas que forman parte de los exosomas de linfocitos T humanos

Comunicaciones a congreso

Local Skin Inflammation in Cutaneous Leishmaniasis as a Source of Variable Pharmacokinetics and Therapeutic Efficacy of Liposomal Amphotericin B.

Disfiguring skin lesions caused by several species of the Leishmania parasite characterize cutaneous leishmaniasis (CL). Successful treatment of CL with intravenous (i.v.) liposomal amphotericin B (LAmB) relies on the presence of adequate antibiotic concentrations at the dermal site of infection within the inflamed skin. Here, we have investigated the impact of the local skin inflammation on the pharmacokinetics (PK) and efficacy of LAmB in two murine models of localized CL (Leishmania major and Leishmania mexicana) at three different stages of disease (papule, initial nodule, and established nodule). Twenty-four hours after the administration of one 25 mg/kg of body weight LAmB (i.v.) dose to infected BALB/c mice (n = 5), drug accumulation in the skin was found to be dependent on the causative parasite species (L. major > L. mexicana) and the disease stage (papule > initial nodule > established nodule > healthy skin). Elevated tissue drug levels were associated with increased vascular permeability (Evans blue assay) and macrophage infiltration (histomorphometry) in the infected skin, two pathophysiological parameters linked to tissue inflammation. After identical treatment of CL in the two models with 5 × 25 mg/kg LAmB (i.v.), intralesional drug concentrations and reductions in lesion size and parasite load (quantitative PCR [qPCR]) were all ≥2-fold higher for L. major than for L. mexicana In conclusion, drug penetration of LAmB into CL skin lesions could depend on the disease stage and the causative Leishmania species due to the influence of local tissue inflammation

Recovering the nonlinear density field from the galaxy distribution with a Poisson-Lognormal filter

We present a general expression for a lognormal filter given an arbitrary nonlinear galaxy bias. We derive this filter as the maximum a posteriori solution assuming a lognormal prior distribution for the matter field with a given mean field and modeling the observed galaxy distribution by a Poissonian process. We have performed a three-dimensional implementation of this filter with a very efficient Newton-Krylov inversion scheme. Furthermore, we have tested it with a dark matter N-body simulation assuming a unit galaxy bias relation and compared the results with previous density field estimators like the inverse weighting scheme and Wiener filtering. Our results show good agreement with the underlying dark matter field for overdensities even above delta~1000 which exceeds by one order of magnitude the regime in which the lognormal is expected to be valid. The reason is that for our filter the lognormal assumption enters as a prior distribution function, but the maximum a posteriori solution is also conditioned on the data. We find that the lognormal filter is superior to the previous filtering schemes in terms of higher correlation coefficients and smaller Euclidean distances to the underlying matter field. We also show how it is able to recover the positive tail of the matter density field distribution for a unit bias relation down to scales of about >~2 Mpc/h.Comment: 17 pages, 9 figures, 1 tabl

Biological and functional analysis of interactions among tetraspanin-associated proteins in human T lymphocites by high-throuchput methods using second generation proteomics techniques

Comunicaciones a congreso

H2AK121ub in Arabidopsis associates with a less accessible chromatin state at transcriptional regulation hotspots

Although it is well established that the Polycomb Group (PcG) complexes maintain gene repression through the incorporation of H2AK121ub and H3K27me3, little is known about the effect of these modifications on chromatin accessibility, which is fundamental to understand PcG function. Here, by integrating chromatin accessibility, histone marks and expression analyses in different Arabidopsis PcG mutants, we show that PcG function regulates chromatin accessibility. We find that H2AK121ub is associated with a less accessible but still permissive chromatin at transcriptional regulation hotspots. Accessibility is further reduced by EMF1 acting in collaboration with PRC2 activity. Consequently, H2AK121ub/H3K27me3 marks are linked to inaccessible although responsive chromatin. In contrast, only-H3K27me3-marked chromatin is less responsive, indicating that H2AK121ub-marked hotspots are required for transcriptional responses. Nevertheless, despite the loss of PcG activities leads to increased chromatin accessibility, this is not necessarily accompanied by transcriptional activation, indicating that accessible chromatin is not always predictive of gene expression.National Natural Science Foundation of China 31970532Ministerio de Ciencia e Innovación BIO2016-76457-P, PID2019-106664GB-I00, BIO2017-84066-

The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry

Syntenin-1 is a cytosolic adaptor protein involved in several cellular processes requiring polarization. Human immunodeficiency virus type 1 (HIV-1) attachment to target CD4(+) T-cells induces polarization of the viral receptor and coreceptor, CD4/CXCR4, and cellular structures toward the virus contact area, and triggers local actin polymerization and phosphatidylinositol 4,5-bisphosphate (PIP(2)) production, which are needed for successful HIV infection. We show that syntenin-1 is recruited to the plasma membrane during HIV-1 attachment and associates with CD4, the main HIV-1 receptor. Syntenin-1 overexpression inhibits HIV-1 production and HIV-mediated cell fusion, while syntenin depletion specifically increases HIV-1 entry. Down-regulation of syntenin-1 expression reduces F-actin polymerization in response to HIV-1. Moreover, HIV-induced PIP(2) accumulation is increased in syntenin-1–depleted cells. Once the virus has entered the target cell, syntenin-1 polarization toward the viral nucleocapsid is lost, suggesting a spatiotemporal regulatory role of syntenin-1 in actin remodeling, PIP(2) production, and the dynamics of HIV-1 entry

The Kinematic Connection Between Galaxies and Dark Matter Haloes

Using estimates of dark halo masses from satellite kinematics, weak gravitational lensing, and halo abundance matching, combined with the Tully-Fisher and Faber-Jackson relations, we derive the mean relation between the optical, V_opt, and virial, V_200, circular velocities of early- and late-type galaxies at redshift z~0. For late-type galaxies V_opt ~ V_200 over the velocity range V_opt=90-260 km/s, and is consistent with V_opt = V_maxh (the maximum circular velocity of NFW dark matter haloes in the concordance LCDM cosmology). However, for early-type galaxies V_opt \ne V_200, with the exception of early-type galaxies with V_opt simeq 350 km/s. This is inconsistent with early-type galaxies being, in general, globally isothermal. For low mass (V_opt V_maxh, indicating that baryons have modified the potential well, while high mass (V_opt > 400 km/s) early-types have V_opt < V_maxh. Folding in measurements of the black hole mass - velocity dispersion relation, our results imply that the supermassive black hole - halo mass relation has a logarithmic slope which varies from ~1.4 at halo masses of ~10^{12} Msun/h to ~0.65 at halo masses of 10^{13.5} Msun/h. The values of V_opt/V_200 we infer for the Milky Way and M31 are lower than the values currently favored by direct observations and dynamical models. This offset is due to the fact that the Milky Way and M31 have higher V_opt and lower V_200 compared to typical late-type galaxies of the same stellar masses. We show that current high resolution cosmological hydrodynamical simulations are unable to form galaxies which simultaneously reproduce both the V_opt/V_200 ratio and the V_opt-M_star (Tully-Fisher/Faber-Jackson) relation.Comment: 17 pages, 7 figures, accepted to MNRA