The Hexapeptide and Linker Regions of the AbdA Hox Protein Regulate Its Activating and Repressive Functions

AbstractThe Hox family transcription factors control diversified morphogenesis during development and evolution. They function in concert with Pbc cofactor proteins. Pbc proteins bind the Hox hexapeptide (HX) motif and are thereby thought to confer DNA binding specificity. Here we report that mutation of the AbdA HX motif does not alter its binding site selection but does modify its transregulatory properties in a gene-specific manner in vivo. We also show that a short, evolutionarily conserved motif, PFER, in the homeodomain-HX linker region acts together with the HX to control an AbdA activation/repression switch. Our in vivo data thus reveal functions not previously anticipated from in vitro analyses for the hexapeptide motif in the regulation of Hox activity

Mener un projet international

Internet, construction européenne, mondialisation… : notre horizon ne s'arrête plus à nos frontières. Du jumelage à la coopération décentralisée, les municipalités demandent à leurs services de participer à des projets à dimension internationale. Processus de Bologne, formation tout au long de la vie, internationalisation des études, les universités font elles aussi appel à leurs services pour les accompagner dans ces évolutions. C'est dans ce contexte que s'inscrit ce volume, avec l'ambition de fournir à tous les professionnels des bibliothèques des clés de compréhension de ces nouveaux enjeux ainsi que des exemples concrets d'actions de coopération soutenus par des apports méthodologiques. Comment travailler et partager avec des partenaires étrangers ? Quelles sont les étapes fondamentales d'une coopération : de la convention à l'évaluation ? Qui sont nos relais en France et à l'étranger pour de tels projets ? C'est à travers ces questions que s'organise l'ouvrage, en proposant des éléments de préparation pratiques pour mener ces actions internationales et les pérenniser. Coordonné par Raphaëlle Bats, conservateur chargée des relations internationales à l'enssib, et écrit par différents acteurs du terrain, l'ouvrage traite également de la mobilité des professionnels et des voyages d'étude, du bibliothécaire-formateur ou expert, d'action culturelle et de politique documentaire (du don des documents à l'avenir du patrimoine en Europe en passant par la lecture pour les enfants)

Squalamine: An Appropriate Strategy against the Emergence of Multidrug Resistant Gram-Negative Bacteria?

We reported that squalamine is a membrane-active molecule that targets the membrane integrity as demonstrated by the ATP release and dye entry. In this context, its activity may depend on the membrane lipid composition. This molecule shows a preserved activity against bacterial pathogens presenting a noticeable multi-resistance phenotype against antibiotics such as polymyxin B. In this context and because of its structure, action and its relative insensitivity to efflux resistance mechanisms, we have demonstrated that squalamine appears as an alternate way to combat MDR pathogens and by pass the gap regarding the failure of new active antibacterial molecules

Insights into Hox Protein Function from a Large Scale Combinatorial Analysis of Protein Domains

Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences

The MYST-Containing Protein Chameau Is Required for Proper Sensory Organ Specification during Drosophila Thorax Morphogenesis

The adult thorax of Drosophila melanogaster is covered by a stereotyped pattern of mechanosensory bristles called macrochaetes. Here, we report that the MYST containing protein Chameau (Chm) contributes to the establishment of this pattern in the most dorsal part of the thorax. Chm mutant pupae present extra-dorsocentral (DC) and scutellar (SC) macrochaetes, but a normal number of the other macrochaetes. We provide evidences that chm restricts the singling out of sensory organ precursors from proneural clusters and genetically interacts with transcriptional regulators involved in the regulation of achaete and scute in the DC and SC proneural cluster. This function of chm likely relies on chromatin structure regulation since a protein with a mutation in the conserved catalytic site fails to rescue the formation of supernumerary DC and SC bristles in chm mutant flies. This is further supported by the finding that mutations in genes encoding chromatin modifiers and remodeling factors, including Polycomb group (PcG) and Trithorax group (TrxG) members, dominantly modulate the penetrance of chm extra bristle phenotype. These data support a critical role for chromatin structure modulation in the establishment of the stereotyped sensory bristle pattern in the fly thorax

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/)

Radioactivité et repères naturels

La radioactivité est omniprésente dans notre environnement, et jusque dans notre propre corps. Nous allons tenter dans cet article de répondre à quelques-unes des questions les plus fréquemment posées sur les faibles doses de radioactivité d'origine humaine (ou liées aux comportements de l'homme) en les comparant aux radioactivités d'origine naturelle de niveau souvent comparables, voire supérieures. Bien que, sur un plan strictement scientifique, il faudrait disposer d'études épidémiologiques approfondies pour conclure de façon définitive, ces comparaisons nous amèneront à suggérer qu'il n'y a vraisemblablement aucun effet sur la santé lorsque les doses d'origine humaine sont inférieures aux variations courantes d'un point à un autre de la radioactivité naturelle