Effect of the Purinergic Inhibitor Oxidized ATP in a Model of Islet Allograft Rejection

The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R+CD4+ T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function

Effect of the Purinergic Inhibitor Oxidized ATP in a Model of Islet Allograft Rejection

The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R+CD4+ T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function

Sequential capillarity-assisted particle assembly in a microfluidic channel

The authors acknowledge support from an ETH Research Grant ETH-15 17-1 (R. S.), from an ETH Postdoctoral Fellowship FEL-21 15-2 and SNSF PRIMA Grant 179834 (E. S.), from a Postdoctoral fellowships programme “Beatriu de Pinós”, funded by the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 programme of research and innovation of the European Union under the Marie Sklodwoska-Curie grant agreement no. 801370 (Grant 2018 BP 00029) (M. A. F. R.) and from a Gordon and Betty Moore Foundation Investigator Award on Aquatic Microbial Symbiosis (grant GBMF9197) (R. S.). The authors thank Dr. Heiko Wolf at IBM Research Zurich for insightful discussions.Colloidal patterning enables the placement of a wide range of materials into prescribed spatial arrangements, as required in a variety of applications, including micro- and nano-electronics, sensing, and plasmonics. Directed colloidal assembly methods, which exploit external forces to place particles with high yield and great accuracy, are particularly powerful. However, currently available techniques require specialized equipment, which limits their applicability. Here, we present a microfluidic platform to produce versatile colloidal patterns within a microchannel, based on sequential capillarity-assisted particle assembly (sCAPA). This new microfluidic technology exploits the capillary forces resulting from the controlled motion of an evaporating droplet inside a microfluidic channel to deposit individual particles in an array of traps microfabricated onto a substrate. Sequential depositions allow the generation of a desired spatial layout of colloidal particles of single or multiple types, dictated solely by the geometry of the traps and the filling sequence. We show that the platform can be used to create a variety of patterns and that the microfluidic channel easily allows surface functionalization of trapped particles. By enabling colloidal patterning to be carried out in a controlled environment, exploiting equipment routinely used in microfluidics, we demonstrate an easy-to-build platform that can be implemented in microfluidics labs.ETH Research Grant ETH-15 17-1ETH Postdoctoral Fellowship FEL-21 15-2SNSF PRIMA Grant 179834Postdoctoral fellowships programme "Beatriu de Pinos" - Government of CataloniaHorizon 2020 programme of research and innovation of the European Union under the Marie Sklodwoska-Curie grant 801370 2018 BP 00029Gordon and Betty Moore Foundation Investigator Award on Aquatic Microbial Symbiosis GBMF919

Mixed Finite Elements for spatial regression with PDE penalization

We study a class of models at the interface between statistics and numerical analysis. Specifically, we consider nonparametric regression models for the estimation of spatial fields from pointwise and noisy observations, which account for problem-specific prior information, described in terms of a partial differential equation governing the phenomenon under study. The prior information is incorporated in the model via a roughness term using a penalized regression framework. We prove the well-posedness of the estimation problem, and we resort to a mixed equal order finite element method for its discretization. Moreover, we prove the well-posedness and the optimal convergence rate of the proposed discretization method. Finally the smoothing technique is extended to the case of areal data, particularly interesting in many applications