Crystal Structure of Saccharomyces cerevisiae ECM4, a Xi-Class Glutathione Transferase that Reacts with Glutathionyl-(hydro)quinones

International audienceGlutathionyl-hydroquinone reductases (GHRs) belong to the recently characterized Xi-class of glutathione transferases (GSTXs) according to unique structural properties and are present in all but animal kingdoms. The GHR ScECM4 from the yeast Saccharomyces cerevisiae has been studied since 1997 when it was found to be potentially involved in cell-wall biosyn-thesis. Up to now and in spite of biological studies made on this enzyme, its physiological role remains challenging. The work here reports its crystallographic study. In addition to exhibiting the general GSTX structural features, ScECM4 shows extensions including a huge loop which contributes to the quaternary assembly. These structural extensions are probably specific to Saccharomycetaceae. Soaking of ScECM4 crystals with GS-menadione results in a structure where glutathione forms a mixed disulfide bond with the cysteine 46. Solution studies confirm that ScECM4 has reductase activity for GS-menadione in presence of glutathione. Moreover, the high resolution structures allowed us to propose new roles of conserved residues of the active site to assist the cysteine 46 during the catalytic act

Micromachine d'essais mécaniques de type traction et compression ayant une accessibilité optimisée

L'invention concerne une micromachine de traction destinée à être utilisée dans une enceinte de microscope électronique à balayage ou avec un appareil de diffraction, comportant deux mors (1) portés par deux supports, chaque mors (1) étant destiné à recevoir une extrémité d'une éprouvette mécanique (4), et des moyens pour exercer sur les supports des efforts tendant à les écarter l'un de l'autre ou à les rapprocher l'un de l'autre selon une direction longitudinale (AL), chaque mors (1) comprenant une embase (2) et une bride (3) pour fixer une extrémité (21) d'éprouvette (4) au mors (1) en l'enserrant entre la bride (3) et l'embase (2) au moyen d'au moins deux vis (12-15 ) traversant chacune la bride (3) et au moins une partie de l'embase (2), ces deux vis (12-15) étant situées de part et d'autre de l'extrémité d'éprouvette (21)

Micromachine d'essais mécaniques de type traction et compression ayant une accessibilité optimisée

L'invention concerne une micromachine de traction destinée à être utilisée dans une enceinte de microscope électronique à balayage ou avec un appareil de diffraction, comportant deux mors (1) portés par deux supports, chaque mors (1) étant destiné à recevoir une extrémité d'une éprouvette mécanique (4), et des moyens pour exercer sur les supports des efforts tendant à les écarter l'un de l'autre ou à les rapprocher l'un de l'autre selon une direction longitudinale (AL), chaque mors (1) comprenant une embase (2) et une bride (3) pour fixer une extrémité (21) d'éprouvette (4) au mors (1) en l'enserrant entre la bride (3) et l'embase (2) au moyen d'au moins deux vis (12-15 ) traversant chacune la bride (3) et au moins une partie de l'embase (2), ces deux vis (12-15) étant situées de part et d'autre de l'extrémité d'éprouvette (21)

Effect of extracranial lesion severity on outcome of endovascular thrombectomy in patients with anterior circulation tandem occlusion: analysis of the TITAN registry

Introduction Endovascular treatment (EVT) for tandem occlusion (TO) of the anterior circulation is complex but effective. The effect of extracranial internal carotid artery (EICA) lesion severity on the outcomes of EVT is unknown. In this study we investigated the effect of EICA lesion severity on the outcomes of tandem occlusion EVT. Methods A multicenter retrospective TITAN (Thrombectomy In TANdem lesions) study that included 18 international endovascular capable centers was performed. Patients who received EVT for atherosclerotic TO with or without EICA lesion intervention were included. Patients were divided into two groups based on the EICA lesion severity (high-grade stenosis (>= 90% North American Symptomatic Carotid Endarterectomy Trial) vs complete occlusion). Outcome measures included the 90-day clinical outcome (modified Rankin Scale score (mRS)), angiographic reperfusion (modified Thrombolysis In Cerebral Ischemia (mTICI) at the end of the procedure), procedural complications, and intracranial hemorrhage at 24 hours follow-up. Results A total of 305 patients were included in the study, of whom 135 had complete EICA occlusion and 170 had severe EICA stenosis. The EICA occlusion group had shorter mean onset-to-groin time (259 +/- 120 min vs 305 +/- 202 min;p=0.037), more patients with diabetes, and fewer with hyperlipidemia. With respect to the outcome, mTICI 2b-3 reperfusion was lower in the EICA occlusion group (70% vs 81%;p=0.03). The favorable outcome (90-day mRS 0-2), intracerebral hemorrhage and procedural complications were similar in both groups. Conclusion Atherosclerotic occlusion of the EICA in acute tandem strokes was associated with a lower rate of mTICI 2b-3 reperfusion but similar functional and safety outcomes when compared with high-grade EICA stenosis

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Biochemical characterization of glutathione transferases potentially involved in the metabolism of coumarins in Arabidopsis thaliana during iron deficiency

International audienc

Sobre Simmel e a guerra: escritos na imprensa alemã

Neste artigo, discutimos três textos de Simmel escritos para a imprensa de Berlim, inspirados em suas angústias durante a Primeira Guerra Mundial: “A ideia de Europa”, publicado em 7 de março de 1915, no Berliner Tageblatt; “A Europa e a América: considerações sobre a história universal”, publicado em 4 de julho de 1915, no Berliner Tageblatt; e “Bergson e o ‘cinismo’ alemão”, publicado em 1 de novembro de 1914, no Internationale Wochenschrift für Wissenschaft, Kunst und Technik. Os textos de Simmel para a imprensa constituem-se em importante material de estudos em comunicação, devido à liberdade com que Simmel se expressa ao público em geral, sem abandonar os conceitos fundamentais de sua sociologia. Um dos resultados desta pesquisa aponta o conflito como um componente fundamental aos processos de comunicação, visto que o dissenso, a discórdia e o combate implicam a compreensão dos códigos de cada parte

Insights into ascorbate regeneration in plants: investigating the redox and structural properties of dehydroascorbate reductases from Populus trichocarpa.

International audienceDehydroascorbate reductases (DHARs), enzymes belonging to the GST superfamily, catalyse the GSH-dependent reduction of dehydroascorbate into ascorbate in plants. By maintaining a reduced ascorbate pool, they notably participate to H2O2 detoxification catalysed by ascorbate peroxidases (APXs). Despite this central role, the catalytic mechanism used by DHARs is still not well understood and there is no supportive 3D structure. In this context, we have performed a thorough biochemical and structural analysis of the three poplar DHARs and coupled this to the analysis of their transcript expression patterns and subcellular localizations. The transcripts for these genes are mainly detected in reproductive and green organs and the corresponding proteins are expressed in plastids, in the cytosol and in the nucleus, but not in mitochondria and peroxisomes where ascorbate regeneration is obviously necessary. Comparing the kinetic properties and the sensitivity to GSSG-mediated oxidation of DHAR2 and DHAR3A, exhibiting 1 or 3 cysteinyl residues respectively, we observed that the presence of additional cysteines in DHAR3A modifies the regeneration mechanism of the catalytic cysteine by forming different redox states. Finally, from the 3D structure of DHAR3A solved by NMR, we were able to map the residues important for the binding of both substrates (GSH and DHA), showing that DHAR active site is very selective for DHA recognition and providing further insights into the catalytic mechanism and the roles of the additional cysteines found in some DHARs

ScECM4 glutathione binding site.

<p>The catalytic cysteine C46, the residues involved in polar interactions with glutathione (GS) and the tyrosines Y224, Y301 and Y346 from the triad are represented as sticks. Polar interactions (yellow dashed lines) were observed between: E173 carboxylate group and GSH N-terminal amine group; NH of S174 and carboxylate group of GSH γ-glutamyl residue; S174 hydroxyl group and carboxylate group of GSH γ-glutamyl residue; R15 guanidinium group and carbonyl group of GSH γ-glutamyl residue; W79 indole group and carbonyl group of GSH cysteine; NHs and COs of V158 and of GSH cysteine; R155 guanidinium group and carboxylate group of GSH glycinyl residue.</p