A Unique Voltage Sensor Sensitizes the Potassium Channel AKT2 to Phosphoregulation

Among all voltage-gated K+ channels from the model plant Arabidopsis thaliana, the weakly rectifying K+ channel (Kweak channel) AKT2 displays unique gating properties. AKT2 is exceptionally regulated by phosphorylation: when nonphosphorylated AKT2 behaves as an inward-rectifying potassium channel; phosphorylation of AKT2 abolishes inward rectification by shifting its activation threshold far positive (>200 mV) so that it closes only at voltages positive of +100 mV. In its phosphorylated form, AKT2 is thus locked in the open state in the entire physiological voltage range. To understand the molecular grounds of this unique gating behavior, we generated chimeras between AKT2 and the conventional inward-rectifying channel KAT1. The transfer of the pore from KAT1 to AKT2 altered the permeation properties of the channel. However, the gating properties were unaffected, suggesting that the pore region of AKT2 is not responsible for the unique Kweak gating. Instead, a lysine residue in S4, highly conserved among all Kweak channels but absent from other plant K+ channels, was pinpointed in a site-directed mutagenesis approach. Substitution of the lysine by serine or aspartate abolished the “open-lock” characteristic and converted AKT2 into an inward-rectifying channel. Interestingly, phosphoregulation of the mutant AKT2-K197S appeared to be similar to that of the Kin channel KAT1: as suggested by mimicking the phosphorylated and dephosphorylated states, phosphorylation induced a shift of the activation threshold of AKT2-K197S by about +50 mV. We conclude that the lysine residue K197 sensitizes AKT2 to phosphoregulation. The phosphorylation-induced reduction of the activation energy in AKT2 is ∼6 kT larger than in the K197S mutant. It is discussed that this hypersensitive response of AKT2 to phosphorylation equips a cell with the versatility to establish a potassium gradient and to make efficient use of it

WAT1 (WALLS ARE THIN1) defines a novel auxin transporter in plants and integrates auxin signaling in secondary wall formation in Arabidopsis fibers

International audienceWAT1 (WALLS ARE THIN1) defines a novel auxin transporter in plants and integrates auxin signaling in secondary wall formation in Arabidopsis fibers. IUFRO Tree Biotechnology Conference 2011: From Genomes to Integration and Deliver

De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits:report of 25 new individuals and review of the literature

TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands

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/)

PROPAGATION DE LA LUMIERE EN MILIEU ALEATOIRE (FONDEMENTS ET LIMITES DE LA DESCRIPTION RADIOMETRIQUE ; APPLICATION A L'IMAGERIE)

CE MEMOIRE PORTE SUR LA MODELISATION DE LA PROPAGATION DU RAYONNEMENT ELECTROMAGNETIQUE DANS DES MILIEUX AL'EATOIRES, QUI PERMETTENT NOTAMMENT DE MODELISER LES PROPRIETES OPTIQUES DE TISSUS BIOLOGIQUES, DE PEINTURES, D'EMULSIONS, ETC. LA RADIOMETRIE DONNE UNE DESCRIPTION INCOHERENTE DE LA PROPAGATION, FONDEE SUR LA NOTION DE LUMINANCE ET SUR L'EQUATION DU TRANSFERT RADIATIF (ETR), QUI EST COURAMMENT ASSOCIEE A L'HYPOTHESE DE DIFFUSION INDEPENDANTE. UNE COMPARAISON DES SOLUTIONS NUMERIQUES DONNEES AU PROBLEME COMPLET DE LA REFLEXION ET DE LA TRANSMISSION PAR UN TEL MILIEU, PAR UNE SIMULATION ELECTROMAGNETIQUE RIGOUREUSE FONDEE SUR DES EQUATIONS INTEGRALES DE SURFACE D'UNE PART, ET PAR UNE RESOLUTION DE L'E.T.R. D'AUTRE PART, EST EFFECTUEE. CETTE COMPARAISON DEMONTRE LA VALIDITE DE L'E.T.R. POUR UN SYSTEME D'EPAISSEUR COMPARABLE A LA LONGUEUR D'ONDE. ELLE MONTRE AUSSI QUE L'ETR COMPORTE DES LIMITES LIEES A L'HYPOTHESE DE DIFFUSION INDEPENDANTE, AINSI QU'A D'AUTRES PHENOMENES COHERENTS : UN TROU DANS L'INCOHERENT VERS L'AVANT DU A LA DIFFUSION SIMPLE, ET UN PIC DE RETRODIFFUSION COHERENTE DU A LA DIFFUSION MULTIPLE. LA RETRODIFFUSION COHERENTE EST INTEGREE ORIGINALEMENT DANS LE MODELE RADIOMETRIQUE PAR L'INTERMEDIAIRE DE LA BRDF GENERALISEE DU SYSTEME, A LAQUELLE LA PROPRIETE DE RECIPROCITE EST CONFEREE PAR L'INTERMEDIAIRE DE LA MATRICE DE DIFFUSION. CETTE APPROCHE GENERALISE AUX SYSTEMES MINCES ET SOUS INCIDENCE OBLIQUE UN RESULTAT PRECEDENT ETABLI DANS L'APPROXIMATION DE LA DIFFUSION. UNE METHODE NUMERIQUE FONDEE SUR DES EQUATIONS INTEGRALES DE SURFACE EST ENFIN PROPOSEE POUR RESOUDRE, DANS CETTE APPROXIMATION, LE PROBLEME DIRECT DE LA DETECTION D'UN OBJET DANS UN MILIEU FORTEMENT DIFFUSANT. CETTE METHODE EST EXPOSEE POUR LE PROBLEME ANALOGUE DE L'IMAGERIE PHOTOTHERMIQUE.CHATENAY MALABRY-Ecole centrale (920192301) / SudocSudocFranceF