Performance of the ATLAS Electromagnetic Calorimeter End-cap Module 0

The construction and beam test results of the ATLAS electromagnetic end-cap calorimeter pre-production module 0 are presented. The stochastic term of the energy resolution is between 10% GeV^1/2 and 12.5% GeV^1/2 over the full pseudorapidity range. Position and angular resolutions are found to be in agreement with simulation. A global constant term of 0.6% is obtained in the pseudorapidity range 2.5 < eta < 3.2 (inner wheel)

60S ribosomal subunit assembly dynamics defined by semi-quantitative mass spectrometry of purified complexes

During the highly conserved process of eukaryotic ribosome formation, RNA follows a maturation path with well-defined, successive intermediates that dynamically associate with many pre-ribosomal proteins. A comprehensive description of the assembly process is still lacking. To obtain data on the timing and order of association of the different pre-ribosomal factors, a strategy consists in the use of pre-ribsomal particles isolated from mutants that block ribosome formation at different steps. Immunoblots, inherently limited to only a few factors, have been applied to evaluate the accumulation or decrease of pre-ribosomal intermediates under mutant conditions. For a global protein-level description of different 60S ribosomal subunit maturation intermediates in yeast, we have adapted a method of in vivo isotopic labelling and mass spectrometry to study pre-60S complexes isolated from strains in which rRNA processing was affected by individual depletion of five factors: Ebp2, Nog1, Nsa2, Nog2 or Pop3. We obtained quantitative data for 45 distinct pre-60S proteins and detected coordinated changes for over 30 pre-60S factors in the analysed mutants. These results led to the characterisation of the composition of early, intermediate and late pre-ribosomal complexes, specific for crucial maturation steps during 60S assembly in eukaryotes

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Ecm1 is a new pre-ribosomal factor involved in pre-60S particle export

International audienceIn eukaryotes, ribosome biogenesis is a highly conserved process that starts in the nucleus and ends in the cytoplasm. In actively growing yeast cells, it is estimated that each nuclear pore complex (NPC) contributes to the export of about 25 pre-ribosomal particles per minute. Such an extremely active process requires several redundant export receptors for the pre-60S particles. Here, we report the identification of a novel pre-60S factor, Ecm1, which partially acts like Arx1 and becomes essential when the NPC function is affected. Ecm1 depletion, combined with the deletion of NPC components led to pre-60S retention in the nucleus. Functional links that we identified between Ecm1, 60S biogenesis, pre-60S export, and the NPC were correlated with physical interactions of Ecm1 with pre-60S particles and nucleoporins. These results support that Ecm1 is an additional factor involved in pre-60S export. While Ecm1 and Arx1 have redundant functions, overproduction of either one could not complement the absence of the other, whereas overproduction of Mex67 was able to partially restore the growth defect resulting from the absence of Ecm1 or Arx1. These data highlight the involvement of many factors acting together to export pre-60S particles

The p21-activated protein kinase inhibitor Skb15 and its budding yeast homologue are 60S ribosome assembly factors.

International audienceRibosome biogenesis is driven by a large number of preribosomal factors that associate with and dissociate from the preribosomal particles along the maturation pathway. We have previously shown that budding yeast Mak11, whose homologues in other eukaryotes were described as modulating a p21-activated protein kinase function, accumulates in Rlp24-associated pre-60S complexes when their maturation is impeded in Saccharomyces cerevisiae. The functional inactivation of WD40 repeat protein Mak11 interfered with the 60S rRNA maturation, led to a cell cycle delay in G(1), and blocked green fluorescent protein-tagged Rpl25 in the nucleoli of yeast cells, indicating an early role of Mak11 in ribosome assembly. Surprisingly, Mak11 inactivation also led to a dramatic destabilization of Rlp24. The suppression of the thermosensitive phenotype of a mak11 mutant by RLP24 overexpression and a direct in vitro interaction between Rlp24 and Mak11 suggest that Mak11 acts as an Rlp24 cofactor during early steps of 60S ribosomal subunit assembly. Moreover, we found that Skb15, the Mak11 homologue in Schizosaccharomyces pombe, also associated with preribosomes and affected 60S biogenesis in fission yeast. It is thus likely that the previously observed phenotypes for MAK11 homologues in other eukaryotes are secondary to the main function of these proteins in ribosome formation

Fibrillation atriale de novo chez les patients en choc septique

Une fibrillation atriale de novo (FAN)survient chez 4,5 à 11% des patients admis en réanimation et peut atteindre 46% chez des patients en choc septique. Si la morbidité associée à la FAN semble acquise (instabilité hémodynamique, accident vasculaire cérébral, allongement de la durée de séjour), les données de la littérature concernant l’association d’une FAN à la mortalité restent débattues. Les recommandations actuelles émanant des sociétés internationales de rythmologie sont plutôt en faveur d’un contrôle de la fréquence cardiaque en cas de retentissement hémodynamique plutôt qu’un contrôle du rythme cardiaque. Dans ce dernier cas, on pourrait proposer un bétabloquant de durée d’action courte pour bloquer l’activation sympathique présente en phase aiguë du choc septique. Il faut, quelle que soit la stratégie adoptée, identifier et contrôler les facteurs de risques de FAN, notamment les troubles hydro-électrolytiques. L'anticoagulation se discute en cas de retour en rythme sinusal et pourrait dépendre des scores de risques thrombo-emboliques (CHA2DS2VASc) et hémorragiques (HAS-BLED) mais aussi du risque individuel du patient. Le risque d’AVC à moyen et long terme de ces patients même après un retour en rythme sinusal reste présent et nécessite sans doute un suivi régulier pour traquer les FA silencieuses.</jats:p