Nox2-deficient Tregs improve heart transplant outcomes via their increased graft recruitment and enhanced potency

Nox2 is a ROS-generating enzyme, deficiency of which increases suppression by Tregs in vitro and in an in vivo model of cardiac remodelling. Since Tregs have emerged as a candidate therapy in autoimmunity and transplantation, we hypothesised that Nox2 deficiency in Tregs in recipient mice may improve outcomes in a heart transplant model. A novel B6129 mouse model with Treg-targeted Nox2 deletion (Nox2ᶠˡ/ᶠˡFoxP3Cre⁺) was generated and transplanted with hearts from CB6F1 donors. As compared to littermate controls, Nox2ᶠˡ/ᶠˡFoxP3Cre⁺ mice had lower plasma levels of alloantibodies and troponin-I, reduced levels of IFN-γ in heart allograft homogenates and diminished cardiomyocyte necrosis and allograft fibrosis. Single cell analyses of allografts revealed higher absolute numbers of Tregs and lower CD8⁺ T cell infiltration in Nox2-deficient recipients compared to Nox2-replete mice. Mechanistically, in addition to a greater suppression of CD8⁺CD25⁻ T effector cell proliferation and IFN-γ production, Nox2-deficient Tregs expressed higher levels of CCR4 and CCR8, driving cell migration to allografts; this was associated with increased expression of miR214-3p. These data indicate that Nox2 deletion in Tregs enhances their suppressive ability and migration to heart allografts. Therefore, Nox2 inhibition in Tregs may be a useful approach to improve their therapeutic efficacy

First-principle based multi-channel integrated modelling in support to the design of the Divertor Tokamak Test facility

An intensive integrated modelling work of main scenarios of the new tokamak DTT (Divertor Tokamak Test facility) with the Single Null divertor configuration has been performed using first-principle quasi-linear transport models, in support to the design of the device and to the definition of its scientific work-programme. First results of this integrated modelling work on DTT (R0= 2.14 m, a= 0.65 m) are presented here along with outcome of the gyrokinetic simulations used to validate the reduced models in the DTT range of parameters. As a result of this work, the heating mix was defined, the size of device was increased to R0= 2.19 m and a= 0.70 m, the use of pellets for fuelling has been advised and reference profiles for diagnostic design, estimates of neutron yields and fast particle losses have become available.</p

What you should know about Zika virus testing : for pregnant women who may have been exposed to Zika 2-12 weeks ago

If you or your sex partner live in or recently traveled to an area with Zika, you may have been exposed to Zika. You may havequestions about Zika and how to find out if you\ue2\u20ac\u2122ve been infected. Learn more about Zika virus testing for pregnant womenand what you might expect if you have Zika virus during pregnancy.CS272943Date printed on piece: December 20, 2016.Date from document properties: modified 1/4/2017igm.pd

Curvature of Double-Membrane Organelles Generated by Changes in Membrane Size and Composition

Transient double-membrane organelles are key players in cellular processes such as autophagy, reproduction, and viral infection. These organelles are formed by the bending and closure of flat, double-membrane sheets. Proteins are believed to be important in these morphological transitions but the underlying mechanism of curvature generation is poorly understood. Here, we describe a novel mechanism for this curvature generation which depends primarily on three membrane properties: the lateral size of the double-membrane sheets, the molecular composition of their highly curved rims, and a possible asymmetry between the two flat faces of the sheets. This mechanism is evolutionary advantageous since it does not require active processes and is readily available even when resources within the cell are restricted as during starvation, which can induce autophagy and sporulation. We identify pathways for protein-assisted regulation of curvature generation, organelle size, direction of bending, and morphology. Our theory also provides a mechanism for the stabilization of large double-membrane sheet-like structures found in the endoplasmic reticulum and in the Golgi cisternae