Dopamine receptor D5 signaling plays a dual role in experimental autoimmune encephalomyelitis potentiating Th17-mediated immunity and favoring suppressive activity of regulatory T-cells

Indexación: Scopus.This work was supported by grants FONDECYT-1170093 (to RP) and FONDECYT-3160383 (to CP) from ‘‘Fondo Nacional de Desarrollo Científico y Tecnológico de Chile’’, AFB170004 (to RP) from ‘‘Comisión Nacional de Investigación Científica y Tecnológica de Chile (CONICYT)’’ and DI-1224-16/R (to RP) from Universidad Andres Bello.A number of studies have shown pharmacologic evidence indicating that stimulation of type I dopamine receptor (DR), favors T-helper-17 (Th17)-mediated immunity involved in experimental autoimmune encephalomyelitis (EAE) and in some other inflammatory disorders. Nevertheless, the lack of drugs that might discriminate between DRD1 and DRD5 has made the pharmacological distinction between the two receptors difficult. We have previously shown genetic evidence demonstrating a relevant role of DRD5-signaling in dendritic cells (DCs) favoring the CD4+ T-cell-driven inflammation in EAE. However, the role of DRD5-signaling confined to CD4+ T-cells in the development of EAE is still unknown. Here, we analyzed the functional role of DRD5-signaling in CD4+ T-cell-mediated responses and its relevance in EAE by using a genetic approach. Our results show that DRD5-signaling confined to naive CD4+ T-cells exerts a pro-inflammatory effect promoting the development of EAE with a stronger disease severity. This pro-inflammatory effect observed for DRD5-signaling in naive CD4+ T-cells was related with an exacerbated proliferation in response to T-cell activation and to an increased ability to differentiate toward the Th17 inflammatory phenotype. On the other hand, quite unexpected, our results show that DRD5-signaling confined to Tregs strengthens their suppressive activity, thereby dampening the development of EAE manifestation. This anti-inflammatory effect of DRD5-signaling in Tregs was associated with a selective increase in the expression of glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), which has been described to play a critical role in the expansion of Tregs. Our findings here indicate a complex role for DRD5-signaling in CD4+ T-cells-driven responses potentiating early inflammation mediated by effector T-cells in EAE, but exacerbating suppressive activity in Tregs and thereby dampening disease manifestation in late EAE stages. © 2018 Osorio-Barrios, Prado, Contreras and Pacheco.https://www.frontiersin.org/articles/10.3389/fncel.2018.00192/ful

Roman Legal Tradition and the Mismanagement of Hunting Resources

Hunting and game-preservation are interrelated: hunting must respect the intentions of game-preservation, and game-preservation must rely on hunting as one method to achieve its intentions. HASENKAMP (1995) applied the Economic Theory of Common Resources to the problem to provide conclusions about the management and conservation of hunting resources. These conclusions are reflected in the existing relevant legal hunting setting in Germany. German Law contains legal principles that confronts the hunter with the objectives of hunting preservation and held him the responsibility for pursuing these goals. In our paper, we derive a model of hunting management, adapting the GORDON/SCHAEFER fisheries model. The conclusions of the model, similar with those of Hasenkamp, are confronted with Portuguese hunting regulation. We conclude that Portugal has a Roman legal tradition with respect to hunting propertyrights. To the Roman conception, the wild animals constitute res nullius (things without owner) that all men can appropriate by ocupatio. The classification of free land implicates the idea that the hunter has the freedom of access to hunt in other’s land, although respecting imposed norms. This tradition of open access is the root-cause of hunting depletion. But, at the same time, the legislator sees it as a form of giving the hunters without land, the possibility of enjoying this activity. This is compatible with the Portuguese tradition, which almost attributes a personality right to the right of hunting.

Second-order variational equations for spatial point processes with a view to pair correlation function estimation

Second-order variational type equations for spatial point processes are established. In case of log linear parametric models for pair correlation functions, it is demonstrated that the variational equations can be applied to construct estimating equations with closed form solutions for the parameter estimates. This result is used to fit orthogonal series expansions of log pair correlation functions of general form

Probable presencia de sedimentos secundarios y paleógenos sobre la plataforma continental de Galicia

Kn el toii~o 61 del Boletín de la Real Sociedad ISspaFiola de Historia Ilatural, aparecido en 1963, di a conocer un trabajo titulado "Probable orla mesozoica-terciaria submarina en el XW de la Península Hispánica". Se indica en el mismo que la recogida de fondos nlarinos frente a la costa de las Rías Bajas de Galicia, con ocasión de las campañas del "Xauen" de 1949-1950, permitieron al especialista G. Coloril reconocer algunas especies de rnicrofauna fósil pertenecientes al Eoceno y en especial de algunos iitimmulites y entre ellos el Nummulites cf. preswichianus R. Jon típico del Eoceno.Tal hecho planteó el problema de la posible esistencia de restos de depósitos rocosos de edad eocena, según opinión de G. Colom, que descansasen sobre el borde de la plataforma continental y a profundidades ya pertenecientes al talud, teniendo en cuenta In hondura a que fueron retiradas las muestras, cuestión ésta que debiera ser aclarada mediante investigaciones en tales parajes marinos

Probable presencia de sedimentos secundarios y paleógenos sobre la plataforma continental de Galicia

Kn el toii~o 61 del Boletín de la Real Sociedad ISspaFiola de Historia Ilatural, aparecido en 1963, di a conocer un trabajo titulado "Probable orla mesozoica-terciaria submarina en el XW de la Península Hispánica". Se indica en el mismo que la recogida de fondos nlarinos frente a la costa de las Rías Bajas de Galicia, con ocasión de las campañas del "Xauen" de 1949-1950, permitieron al especialista G. Coloril reconocer algunas especies de rnicrofauna fósil pertenecientes al Eoceno y en especial de algunos iitimmulites y entre ellos el Nummulites cf. preswichianus R. Jon típico del Eoceno.Tal hecho planteó el problema de la posible esistencia de restos de depósitos rocosos de edad eocena, según opinión de G. Colom, que descansasen sobre el borde de la plataforma continental y a profundidades ya pertenecientes al talud, teniendo en cuenta In hondura a que fueron retiradas las muestras, cuestión ésta que debiera ser aclarada mediante investigaciones en tales parajes marinos

Regularized estimation for highly multivariate log Gaussian Cox processes

Statistical inference for highly multivariate point pattern data is challenging due to complex models with large numbers of parameters. In this paper, we develop numerically stable and efficient parameter estimation and model selection algorithms for a class of multivariate log Gaussian Cox processes. The methodology is applied to a highly multivariate point pattern data set from tropical rain forest ecology