Apoptosis of peritoneal leucocytes during early stages of Fasciola hepatica infections in sheep

Several immunomodulatory properties have been described in Fasciola hepatica infections. Apoptosis has been shown to be an effective mechanism to avoid the immune response in helminth infections. The aim of the present work was to study apoptosis in peritoneal leucocytes of sheep experimentally infected with F. hepatica during the early stages of infection. Five groups (n = 5) of sheep were used. Groups 2–5 were orally infected with 200 metacercariae (mc) and sacrificed at 1, 3, 9 and 18 days post-infection (dpi), respectively. Group 1 was used as the uninfected control (UC). Apoptosis was detected using three different methods 1) immunocytochemistry (ICC) with a polyclonal antibody anti-active caspase-3; 2) an annexin V flow cytometry assay using the Annexin V-FITC/propidium iodide (PI); and 3) transmission electron microscopy (TEM). The differential leucocyte count revealed that the majority of peritoneal granulocytes were eosinophils, which increased significantly at 9 and 18 dpi with respect to the uninfected controls. The ICC study revealed that the percentage of caspase-3+ apoptotic peritoneal leucocytes increased significantly from 3 dpi onwards with respect to the uninfected controls. The flow cytometry annexin V assay detected a very significant (P < 0.001) increase of apoptotic peritoneal macrophages, lymphocytes and granulocytes, which remained higher than in the UC until 18 dpi. Transmission electron microscopy studies also confirmed the presence of apoptosis in peritoneal eosinophils at 18 dpi. This is the first report of apoptosis induced by F. hepatica in the peritoneal leucocytes of sheep in vivo. The results of this work suggest the importance of apoptosis induction for the survival of the juvenile parasites in the peritoneal migratory stages of infection.This work was supported by EU grants (H2020-635408-PARAGONE) and the Spanish Ministry of Science grant AGL2015-67023-C2-1-R. The TEM studies were carried out by the Central Research Services (SCAI) of the University of CórdobaAccepted manuscriptVeterinari

Comparative dynamics of peritoneal cell immunophenotypes in sheep during the early and late stages of the infection with Fasciola hepatica by flow cytometric analysis

Background: The peritoneal cell populations (PCP) are thought to play a crucial role during the early immune response in Fasciola hepatica infection while newly excysted juveniles (NEJ) are migrating in the peritoneal cavity (PC) towards the liver. In this study, we aimed to determine the immunophenotypes of the PCP and to analyse the dynamics of the recruitment of the PCP during the early and late stage of the infection in sheep infected with F. hepatica. Methods: Thirty-seven sheep were divided into three groups: Group 1 (n = 20) and 2 (n = 10) were challenged with F. hepatica, Group 3 (n = 7) was not infected and remained as uninfected control (UC). After the slaughtering, peritoneal lavages were carried out to isolate peritoneal cell populations at 1, 3, 9 and 18 days post-infection (dpi) for Group 1 and at 14 weeks post-infection (wpi) for Group 2 and 3. Flow cytometry was conducted to assess the dynamics of peritoneal cavity cell populations. Results: TCD4 cells showed a significant decrease at 1 and 18 dpi when compared to UC; no statistical differences were detected for TCD8 and WC1+ γδ during the early stage of the infection with respect to the UC. CD14 cells exhibited a decreasing trend, with a significant decrease at 9 and 18 dpi when compared to the UC. The dynamics of MHCII and CD83 cells showed a similar increasing pattern from 3 to 18 dpi. During the chronic stage, both TCD4 and TCD8 cells showed no significant differences when compared to the UC, although a slight but statistically significant higher level of WC1+ γδ cells was observed. A lower percentage of antigen-presenting cells (APCs) was detected with respect to the UC. Conclusions: The recruitment of the lymphocytes subsets did not show a significant increase during the course of the infection and only WC1+ γδ cells displayed a significant increase at the chronic stage. For the CD14, a decreasing trend was observed during the early stage, which was statistically significant at the chronic stage of the infection. Peritoneal CD83 and MHCII cells developed an increasing trend during the early stage of infection, and showed a significant decrease at the late stage of the infection.This study was funded by the European Union Grant H2020-635408- PARAGONE and by National Grant AGL2015-67023-C2-1-R. RPC was supported by an FPU grant of the Spanish Ministry of Education, Culture and Sport. Funding bodies were neither involved in the design of the study nor in analysis and interpretation of the dataVeterinari

Extreme Starbursts in the Local Universe

The "Extreme starbursts in the local universe" workshop was held at the Insituto de Astrofisica de Andalucia in Granada, Spain on 21-25 June 2010. Bearing in mind the advent of a new generation of facilities such as JWST, Herschel, ALMA, eVLA and eMerlin, the aim of the workshop was to bring together observers and theorists to review the latest results. The purpose of the workshop was to address the following issues: what are the main modes of triggering extreme starbursts in the local Universe? How efficiently are stars formed in extreme starbursts? What are the star formation histories of local starburst galaxies? How well do the theoretical simulations model the observations? What can we learn about starbursts in the distant Universe through studies of their local counterparts? How important is the role of extreme starbursts in the hierarchical assembly of galaxies? How are extreme starbursts related to the triggering of AGN in the nuclei of galaxies? Overall, 41 talks and 4 posters with their corresponding 10 minutes short talks were presented during the workshop. In addition, the workshop was designed with emphasis on discussions, and therefore, there were 6 discussion sessions of up to one hour during the workshop. Here is presented a summary of the purposes of the workshop as well as a compilation of the abstracts corresponding to each of the presentations. The summary and conclusions of the workshop along with a description of the future prospects by Sylvain Veilleux can be found in the last section of this document. A photo of the assistants is included.Comment: worksho

Total Absorption Spectroscopy Study of 92^{92}Rb Decay: A Major Contributor to Reactor Antineutrino Spectrum Shape

The antineutrino spectra measured in recent experiments at reactors are inconsistent with calculations based on the conversion of integral beta spectra recorded at the ILL reactor. $^{92}$Rb makes the dominant contribution to the reactor spectrum in the 5-8 MeV range but its decay properties are in question. We have studied $^{92}$Rb decay with total absorption spectroscopy. Previously unobserved beta feeding was seen in the 4.5-5.5 region and the GS to GS feeding was found to be 87.5(25)%. The impact on the reactor antineutrino spectra calculated with the summation method is shown and discussed.Comment: 6 pages, 3 figure

Linfoma de Hodgkin refractario con afectación ósea y esplénica con rápida y completa respuesta a Nivolumab

Abstract [PB-062] Introducción: En el linfoma de Hodgkin (LH) las alteraciones genéticas del cromosoma 9p24.1 de la célula de Reed-Sternberg, causan una sobreexpresión del ligando 1 de muerte programada (PDL-1), que conducen a una evasión del sistema inmune y resistencia terapéutica. Para pacientes que recaen después de un trasplante autólogo y de tratamiento con Brentuxumab, existen pocas posibilidades. Basándose en la sobreexpresión del PDL-1, los inhibidores de PD1/PDL1 son una opción. Nivolumab (anti PD1) ha demostrado eficacia en LH recaído/refractario (R/R). Presentamos un caso con respuesta clínica completa rápida en un LH refractario a Brentuximab y con gran afectación extranodal (ósea y esplénica). Paciente y Métodos: Varón de 55 años diagnosticado de LH celularidad mixta estadio IIIA en Junio de 2005. 1ª línea: ABVDx6 y radioterapia mediastínica con RC. 2ª línea (Enero 2009) por recidiva cervical: Ifosfamida, Vinorelbina y Prednisona con RC. 3ª línea (Junio 2009) con afectación cervical y retoperitoneal: cisplatino, citarabina y dexametasona más radioterapia cervical con RC. 4ª línea (Enero 2011): MOPPx4 y Rituximab Gemcitabina con RC. Pasa a Hematología y se realiza autotrasplante en Noviembre de 2011 con RC. 5ª línea (Noviembre 2016) por afectación cervical, retroperitoneal, esplénica e iliaco: Brentuximabx4 y por mala respuesta se añade Bendamustinax3 con RC. Tras finalizar se realiza PET/TAC (Junio 2017) siendo negativo. En Agosto de 2017 importante clínica con síntomas constitucionales, pérdida de 10 Kg de peso en un mes. Analítica: Hb: 11, 5 g/dl, leucocitos: 2x109/l, plaquetas: 57x109/l. VSG: 120, PCR: 14 mg/dl, metabolismo hierro de proceso crónico. TAC: no adenopatías, esplenomegalia con lesiones. Biopsia de MO: afectación hodgkiniana. Se solicita Nivolumab. Mientras autorización se instaura Gemcitabina-Oxaliplatinox4 con mejoría clínica. Se realiza PET/TAC previo Nivolumab (Noviembre 2017): extensa afectación ósea esqueleto axial y huesos largos y afectación esplénica. Se inicia Nivolumab (16 Noviembre) a 3 mg/kg/ 14 días. Respuesta clínica óptima. No efectos secundarios, ni clínicos, ni analíticos. Tras 9 ciclos se realiza PET/TAC de control con RC. Por edad, hipertratado y deseo del paciente se descarta trasplante alogénico. Continúa tratamiento con Nivolumab, sin ningún efecto adverso y estando previsto discontinuar al año. Conclusiones: Nivolumab es un fármaco que puede rescatar a pacientes con LH R/R a las terapias disponibles (trasplante y Brentuximab), donde las opciones son escasas. Puede servir como tratamiento puente para un trasplante alogénico y en pacientes no candidatos, como nuestro caso, su administración continua puede deparar en un aumento de la supervivencia libre de progresión y supervivencia global. Se necesita más investigación y seguimiento para valorar la duración de la respuesta y el tiempo o secuencia de administración

Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

Mujer joven con poliadenopatías y anasarca. ¿Es siempre neoplásico?

PB-122 Introducción: La enfermedad de Castleman (EC) es una entidad linfoproliferativa, descrita por primera vez en 1954. Tiene dos formas de presentación: unicéntrica, con afectación de un único ganglio linfático y multicéntrica (ECM), con afectación de múltiples nódulos y presentación clínica en forma de linfadenopatías, fiebre, pérdida de peso, disnea, edemas, anemia e hipoalbuminemia. En la patogenia de la enfermedad hay una sobreproducción de IL6, que induce un síndrome proinflamatorio, responsable de los síntomas clínicos. ECM puede ser secundaria a infección por virus VIH y VHH8. En pacientes que no se demuestra causa etiológica se denomina ECM idiopática (ECMi), dentro de la cual se diferencian dos subtipos clínicos ECMi-TAFRO (trombocitopenia, anasarca, fiebre, fibrosis reticulínica/disfunción renal y organomegalia), o ECMi-NOS (not otherwise specified). ^ Métodos: se presenta el caso de una paciente con enfermedad de Castleman multicéntrica idiopática. Resultados: El caso corresponde a una mujer de 53 años, sin antecedentes patológicos de interés, que en junio 2018, ingresa en el servicio de Medicina Interna de nuestro centro, por cuadro de fiebre, ascitis, derrame pleural y síndrome poliadenopático sin filiar. Durante ingreso presenta una evolución tórpida, objetivándose a la exploración esplenomegalia y cuadro de anasarca. Analíticamente destacan hipoalbuminemia (1, 1 g/dl), insuficiencia renal (creatinina 1, 88 mg/dl, FGE 36 mil/min), anemia (Hb 10, 3 g/dl), trombocitopenia (123000/mm3) y elevación de reactantes de fase aguda (PCR 36 mg/dl, ferritina 1063 ng/ml, fibrinógeno 1000 mg/dl). En PET/TC se observa un patron poliadenopático discretamente hipermetabólico supra e infradiafragmático, con incremento de captación difuso del radiotrazador en bazo (SUV máx ..

The Mass-Metallicity relation explored with CALIFA: I. Is there a dependence on the star formation rate?

We present the results on the study of the global and local M-Z relation based on the first data available from the CALIFA survey (150 galaxies). This survey provides integral field spectroscopy of the complete optical extent of each galaxy (up to 2-3 effective radii), with enough resolution to separate individual HII regions and/or aggregations. Nearly $\sim$3000 individual HII regions have been detected. The spectra cover the wavelength range between [OII]3727 and [SII]6731, with a sufficient signal-to-noise to derive the oxygen abundance and star-formation rate associated with each region. In addition, we have computed the integrated and spatially resolved stellar masses (and surface densities), based on SDSS photometric data. We explore the relations between the stellar mass, oxygen abundance and star-formation rate using this dataset. We derive a tight relation between the integrated stellar mass and the gas-phase abundance, with a dispersion smaller than the one already reported in the literature ($\sigma_{\Delta{\rm log(O/H)}}=$0.07 dex). Indeed, this dispersion is only slightly larger than the typical error derived for our oxygen abundances. However, we do not find any secondary relation with the star-formation rate, other than the one induced due to the primary relation of this quantity with the stellar mass. We confirm the result using the $\sim$3000 individual HII regions, for the corresponding local relations. Our results agree with the scenario in which gas recycling in galaxies, both locally and globally, is much faster than other typical timescales, like that of gas accretion by inflow and/or metal loss due to outflows. In essence, late-type/disk dominated galaxies seem to be in a quasi-steady situation, with a behavior similar to the one expected from an instantaneous recycling/closed-box model.Comment: 19 Pages, 8 figures, Accepted for Publishing in Astronomy and Astrophysics (A&A

The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR

Comprehensive Comparison of Various Techniques for the Analysis of Elemental Distributions in Thin Films

The present work shows results on elemental distribution analyses in Cu(In,Ga)Se2 thin films for solar cells performed by use of wavelength-dispersive and energy-dispersive X-ray spectrometry (EDX) in a scanning electron microscope, EDX in a transmission electron microscope, X-ray photoelectron, angle-dependent soft X-ray emission, secondary ion-mass (SIMS), time-of-flight SIMS, sputtered neutral mass, glow-discharge optical emission and glow-discharge mass, Auger electron, and Rutherford backscattering spectrometry, by use of scanning Auger electron microscopy, Raman depth profiling, and Raman mapping, as well as by use of elastic recoil detection analysis, grazing-incidence X-ray and electron backscatter diffraction, and grazing-incidence X-ray fluorescence analysis. The Cu(In,Ga)Se2 thin films used for the present comparison were produced during the same identical deposition run and exhibit thicknesses of about 2 μm. The analysis techniques were compared with respect to their spatial and depth resolutions, measuring speeds, availabilities, and detection limit