Cytosolic Guanine Nucledotide Binding Deficient Form of Transglutaminase 2 (R580a) Potentiates Cell Death in Oxygen Glucose Deprivation

Transglutaminase 2 (TG2) is a hypoxia-responsive protein that is a calcium-activated transamidating enzyme, a GTPase and a scaffolding/linker protein. Upon activation TG2 undergoes a large conformational change, which likely affects not only its enzymatic activities but its non-catalytic functions as well. The focus of this study was on the role of transamidating activity, conformation and localization of TG2 in ischemic cell death. Cells expressing a GTP binding deficient form of TG2 (TG2-R580A) with high basal transamidation activity and a more extended conformation showed significantly increased cell death in response to oxygen-glucose deprivation; however, targeting TG2-R580A to the nucleus abrogated its detrimental role in oxygen-glucose deprivation. Treatment of cells expressing wild type TG2, TG2-C277S (a transamidating inactive mutant) and TG2-R580A with Cp4d, a reversible TG2 inhibitor, did not affect cell death in response to oxygen-glucose deprivation. These findings indicate that the pro-cell death effects of TG2 are dependent on its localization to the cytosol and independent of its transamidation activity. Further, the conformational state of TG2 is likely an important determinant in cell survival and the prominent function of TG2 in ischemic cell death is as a scaffold to modulate cellular processes

Horizon 2020 EuPRAXIA design study

The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020

EuPRAXIA - A compact, cost-efficient particle and radiation source

Plasma accelerators present one of the most suitable candidates for the development of more compact particle acceleration technologies, yet they still lag behind radiofrequency (RF)-based devices when it comes to beam quality, control, stability and power efficiency. The Horizon 2020-funded project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") aims to overcome the first three of these hurdles by developing a conceptual design for a first international user facility based on plasma acceleration. In this paper we report on the main features, simulation studies and potential applications of this future research infrastructure

EuPRAXIA - A Compact, Cost-Efficient Particle and Radiation Source

Plasma accelerators present one of the most suitable candidates for the development of more compact particle acceleration technologies, yet they still lag behind radiofrequency (RF)-based devices when it comes to beam quality, control, stability and power efficiency. The Horizon 2020-funded project EuPRAXIA (“European Plasma Research Accelerator with eXcellence In Applications”) aims to overcome the first three of these hurdles by developing a conceptual design for a first international user facility based on plasma acceleration. In this paper we report on the main features, simulation studies and potential applications of this future research infrastructure

Les paysages du Parc National Tursujuq dans le regard de ses habitants Inuit et Cris

International audienceLes parcs nationaux du Québec, en plus de leurs mandats d’éducation et d’accessibilité, jouent un rôle essentiel pour la conservation : ils permettent de préserver un territoire représentatif d’une région naturelle. Dans les parcs nationaux du Nunavik, la conservation du patrimoine culturel prend tout son sens. En effet, le Nunavik englobe un vaste territoire où les peuples autochtones se rencontrent avec un bagage culturel inestimable. En 2009, un projet de recueil photographique a débuté dans la communauté d’Umiujaq pour être ensuite transposé dans les communautés de Kuujjuarapik et de Whapmagoostui, qui fréquentent aussi le territoire du parc national Tursujuq ( Figure 1 ). Les Inuits et les Cris de ces communautés ont été appelés à fournir des photographies de paysages dans le cadre d’un concours. Ces images ont été choisies par leurs auteurs pour leur beauté, les souvenirs qu’elles évoquaient ou le lieu qu’elles suggéraient. Chacune d’entre elles était commentée par son auteur

Rh-RhAG/ankyrin-R, a new interaction site between the membrane bilayer and the red cell skeleton, is impaired by Rh(null)-associated mutation.

Several studies suggest that the Rh complex represents a major interaction site between the membrane lipid bilayer and the red cell skeleton, but little is known about the molecular basis of this interaction. We report here that ankyrin-R is capable of interacting directly with the C-terminal cytoplasmic domain of Rh and RhAG polypeptides. We first show that the primary defect of ankyrin-R in normoblastosis (nb/nb) spherocytosis mutant mice is associated with a sharp reduction of RhAG and Rh polypeptides. Secondly, our flow cytometric analysis of the Triton X-100 extractability of recombinant fusion proteins expressed in erythroleukemic cell lines suggests that the C-terminal cytoplasmic domains of Rh and RhAG are sufficient to mediate interaction with the erythroid membrane skeleton. Using the yeast two-hybrid system, we demonstrate a direct interaction between the cytoplasmic tails of Rh and RhAG and the second repeat domain (D2) of ankyrin-R. This finding is supported by the demonstration that the substitution of Asp-399 in the cytoplasmic tail of RhAG, a mutation associated with the deficiency of the Rh complex in one Rhnull patient, totally impaired interaction with domain D2 of ankyrin-R. These results identify the Rh/RhAG-ankyrin complex as a new interaction site between the red cell membrane and the spectrin-based skeleton, the disruption of which might result in the stomato-spherocytosis typical of Rhnull red cells

Evidence that the red cell skeleton protein 4.2 interacts with the Rh membrane complex member CD47.

Rh(null) red cells are characteristically stomato-spherocytic. This and other evidence suggest that the Rh complex represents a major attachment site between the membrane lipid bilayer and the erythroid skeleton. As an attempt to identify the linking protein(s) between the red cell skeleton and the Rh complex, we analyzed the expression of Rh, RhAG, CD47, LW, and glycophorin B proteins in red cells from patients with hereditary spherocytosis associated with complete protein 4.2 deficiency but normal band 3 (4.2(-)HS). Flow cytometric and immunoblotting analysis revealed a severe reduction of CD47 (up to 80%) and a slower mobility of RhAG on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, possibly reflecting an overglycosylation state. Unexpectedly, 4.2(-/-) mice, which are anemic, displayed a normal red cell expression of CD47 and RhAG. These results suggest that human protein 4.2, through interaction with CD47, is involved in the skeleton linkage and/or membrane translocation of the Rh complex. However, these potential role(s) of protein 4.2 might be not conserved across species. Finally, the absence or low expression of red cell CD47 in CD47(-/-) mice and in some humans carrying RHCE gene variants (D--, D., and R(N)), respectively, had no detectable effect on protein 4.2 and RhAG expression. Since these cells are morphologically normal with no sign of hemolysis, it is assumed that CD47 deficiency per se is not responsible for the cell shape abnormalities and for the compensated hemolytic anemia typical of 4.2(-) and Rh(null) red cells