Peritoneal fluid modifies the response of human spermatozoa to follicular fluid

The aim of this study was to elucidate the mechanism involved in the acrosome reaction (AR) induced by follicular fluid (FF) in spermatozoa previously exposed to peritoneal fluid (PF). The influence of progesterone was also investigated. Semen samples were from 18 normozoospermic donors. PF samples were from 13 women with unexplained infertility and from a woman treated with synthetic progestagen. FF samples were collected from six women undergoing IVF/embryo transfer and pooled. Motile spermatozoa were capacitated overnight and a kinetic and inhibition study on the FF-induced AR was performed. Spermatozoa pretreated with PF were challenged with either FF or progesterone. The ability of progesterone- and progestagen-supplemented PF to induce AR was analysed. Enzyme-digested PF was also tested. Pre-incubation with PF for 60 min completely prevented the FF-induced AR; spermatozoa treated with PF were unable to respond to FF or progesterone and this effect was not reversible. Progesterone- and progestagen-supplemented PF stimulated the AR relative to controls. Enzyme-digested PF did not have an inhibitory capacity. These data strongly suggest that there are one or more inhibitory proteins in PF that interact with spermatozoa so as to prevent access of progesterone to its receptor and thus inhibit the occurrence of the AR. The oviduct, or Fallopian tube, provides a place for spermatozoa and egg transport and storage, fertilization and early embryo development. If ovulation has not occurred, spermatozoa may reside in the oviduct for several hours or even a few days, awaiting oocyte arrival. It is assumed that fluids present in the female genital tract may have a role in synchronizing the timing required to guarantee the success of fertilization. We previously observed that the peritoneal fluid that bathes the peritoneal cavity is a suitable medium for sperm survival and we also reported that this fluid could stabilize spermatozoa. In this study we show further evidence that the exposure to peritoneal fluid modifies the response of spermatozoa to oocyte signals.Fil: Caille, Adriana M.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Berta, Cesar L.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Munuce, María J.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentin

Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis

Introduction: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. Methods: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. Results: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. Conclusion: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes

Uncovering Ecosystem Service Bundles through Social Preferences

Ecosystem service assessments have increasingly been used to support environmental management policies, mainly based on biophysical and economic indicators. However, few studies have coped with the social-cultural dimension of ecosystem services, despite being considered a research priority. We examined how ecosystem service bundles and trade-offs emerge from diverging social preferences toward ecosystem services delivered by various types of ecosystems in Spain. We conducted 3,379 direct face-to-face questionnaires in eight different case study sites from 2007 to 2011. Overall, 90.5% of the sampled population recognized the ecosystem’s capacity to deliver services. Formal studies, environmental behavior, and gender variables influenced the probability of people recognizing the ecosystem’s capacity to provide services. The ecosystem services most frequently perceived by people were regulating services; of those, air purification held the greatest importance. However, statistical analysis showed that socio-cultural factors and the conservation management strategy of ecosystems (i.e., National Park, Natural Park, or a non-protected area) have an effect on social preferences toward ecosystem services. Ecosystem service trade-offs and bundles were identified by analyzing social preferences through multivariate analysis (redundancy analysis and hierarchical cluster analysis). We found a clear trade-off among provisioning services (and recreational hunting) versus regulating services and almost all cultural services. We identified three ecosystem service bundles associated with the conservation management strategy and the rural-urban gradient. We conclude that socio-cultural preferences toward ecosystem services can serve as a tool to identify relevant services for people, the factors underlying these social preferences, and emerging ecosystem service bundles and trade-offs

Póster: Escala 1-1. trayectos experimentales en el proceso proyectual.

Esta ponencia refiere a un proyecto de investigación donde se exploran las posibilidades pedagógicas y disciplinares de la introducción ejercitaciones a escala real como dispositivos de interfaz entre sucesivas instancias de trans-formación en el proceso la determinación de la arquitectura en los tres primeros años de la carrera de Arquitectura. El mismo consiste en una secuencia didáctica de ejercitaciones trans-formativas encadenadas a escala 1:1, tendientes a producir proyectos de arquitectura sensibles con el paisaje. Esta secuencia supone que la consistencia material de la arquitectura puede ser determinada a partir de la observación, captura y traducción de las preexistencias físicas, imaginarias, naturales y artificiales en un diálogo constante con el paisaje. El proyecto de investigación desarrollado durante los años 2013-2017 (PID SCYT Arq.135) Y Su continuación durante los años 2017-2019 (PID SCYT Arq. 195) consolidaron una didáctica para el proceso proyectual como una sucesión de trans-formaciones encadenadas que fue incorporando progresivamente trayectos experimentales a escala 1:1 en una apuesta hacia el aprendizaje situado, la participación corporal en la lectura de los territorios y el vínculo con la práctica artesanal. La experiencia contribuyó sustancialmente a la capacidad perceptiva del espacio, el manejo de la performatividad de los materiales y sus técnicas constructivas. Durante el desarrollo del proyecto PID 195, a través de la evaluación de los resultados y encuestas a los estudiantes se ha identificado una discontinuidad entre las fases 1 (contextualización) y 2 (descontextualización o laboratorio), es decir en el momento entre el cual los estudiantes traducen la información recogida del lugar en la materialización de un artefacto. Cuando la información recogida no está debidamente instruida, recolectada o sistematizada, se producen artefactos de dificultosa re-contextualización, impactando negativamente en la posibilidad de fusión del objeto arquitectónico con el paisaje. A partir de estos últimos resultados, se introdujeron ejercitaciones experimentales en cada una de las fases del proceso de trans-formación, avanzando no solo en la estimulación de los aspectos perceptivos y performativos de la construcción 1:1, sino también en la capacidad de interrelación con el paisaje en sus materiales físicos y simbólicos. Actualmente se trabaja con una secuencia didáctica de contextualización-descontextualización-recontextualización, que incluye una parametrización del proceso de determinación a partir de “tipos” elaborados en una articulación entre el estudio del proceso de formación y transformación del territorio con los patrones de organización espacial del programa específico en cada caso. Asimismo se están elaborando ejercitaciones intermedias en los momentos de interfase para reducir las posibilidades de desvinculación del objeto arquitectónico con el paisaje. El proyecto de investigación obtuvo el Premio Barbieri de la Bienal de Arquitectura Argentina 2018 y la Beca a la Producción 2018 del Fondo Nacional de las Artes.Fil: Valderrama, Ana - Universidad Nacional de Rosario. Facultad de Arquitectura, Planeamiento y Diseño; Argentina

Breed concept van deelname met smalle strafschaal

status: publishe

Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA

Objectives Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association. Methods Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR. Results The strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10-4, OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10-7, OR 0.71; case-only pmeta=1.9×10-4, OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR. Conclusions These data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications

Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE