Pour une démocratie socio-environnementale : cadre pour une plate-forme participative « transition écologique »

Contribution publiée in Penser une démocratie alimentaire Volume II – Proposition Lascaux entre ressources naturelles et besoins fondamentaux, F. Collart Dutilleul et T. Bréger (dir), Inida, San José, 2014, pp. 87-111.International audienceL’anthropocène triomphant actuel, avec ses forçages environnementaux et sociaux, est à l’origine de l’accélération des dégradations des milieux de vie sur Terre et de l’accentuation des tensions sociales et géopolitiques. Passer à un anthropocène de gestion équitable, informé et sobre vis-à-vis de toutes les ressources et dans tous les secteurs d’activité (slow anthropocene), impose une analyse préalable sur l’ensemble des activités et des rapports humains. Cette transition dite « écologique », mais en réalité à la fois sociétale et écologique, est tout sauf un ajustement technique de secteurs dits prioritaires et technocratiques. Elle est avant tout culturelle, politique et philosophique au sens propre du terme. Elle est un horizon pour des trajectoires de développement humain, pour des constructions sociales et économiques, censées redéfinir socialement richesse, bien-être, travail etc. La dénomination « transition écologique » est largement véhiculée, mais ses bases conceptuelles ne sont pas entièrement acquises ni même élaborées. Dans ce contexte, les étudiants en première année de Master BioSciences à l’Ecole Normale Supérieure (ENS) de Lyon ont préparé une première étude analytique de ce changement radical et global de société pour mieux comprendre dans quelle société ils souhaitent vivre, en donnant du sens aux activités humaines présentes et à venir. Une trentaine de dossiers sur divers secteurs d’activités et acteurs de la société ont été produits et ont servis de support à cette synthèse. Plus largement, le but est de construire un socle conceptuel et une plate-forme de travail sur lesquels les questions de fond, mais aussi opérationnelles, peuvent être posées et étudiées en permanence. Cette démarche participative est ouverte à la collectivité sur le site http://institutmichelserres.ens-lyon.fr/

A phosphoinositide map at the shoot apical meristem in Arabidopsis thaliana

International audienceBackground: In plants, the shoot apical meristem (SAM) has two main functions, involving the production of all aerial organs on the one hand and self-maintenance on the other, allowing the production of organs during the entire post-embryonic life of the plant. Transcription factors, microRNA, hormones, peptides and forces have been involved in meristem function. Whereas phosphatidylinositol phosphates (PIPs) have been involved in almost all biological functions, including stem cell maintenance and organogenesis in animals, the processes in meristem biology to which PIPs contribute still need to be delineated.Results: Using biosensors for PI4P and PI(4,5)P 2 , the two most abundant PIPs at the plasma membrane, we reveal that meristem functions are associated with a stereotypical PIP tissue-scale pattern, with PI(4,5)P 2 always displaying a more clear-cut pattern than PI4P. Using clavata3 and pin-formed1 mutants, we show that stem cell maintenance is associated with reduced levels of PIPs. In contrast, high PIP levels are signatures for organ-meristem boundaries. Interestingly, this pattern echoes that of cortical microtubules and stress anisotropy at the meristem. Using ablations and pharmacological approaches, we further show that PIP levels can be increased when the tensile stress pattern is altered. Conversely, we find that katanin mutant meristems, with increased isotropy of microtubule arrays and slower response to mechanical perturbations, exhibit reduced PIP gradients within the SAM. Comparable PIP pattern defects were observed in phospholipase A3β overexpressor lines, which largely phenocopy katanin mutants at the whole plant level.Conclusions: Using phospholipid biosensors, we identified a stereotypical PIP accumulation pattern in the SAM that negatively correlates with stem cell maintenance and positively correlates with organ-boundary establishment. While other cues are very likely to contribute to the final PIP pattern, we provide evidence that the patterns of PIP, cortical microtubules and mechanical stress are positively correlated, suggesting that the PIP pattern, and its reproducibility, relies at least in part on the mechanical status of the SAM

Chimeric identities and reduced stiffness characterise the shoot apex of Arabidopsis stem cell mutants

Abstract Stem cell homeostasis in the shoot apical meristem involves a core regulatory feedback loop between the signalling peptide CLAVATA3, produced in stem cells, and the transcription factor WUSCHEL, expressed in the underlying organising centre. Compromised CLAVATA activity leads to massive meristem overgrowth, which is thought to be caused by stem cell overproliferation. However, it is unknown how uncontrolled stem cell divisions lead to the specific changes observed in clavata mutants. Here we first quantitatively characterise these mutants, to reveal underlying tissue curvature defects. We use analytical models to show how perturbed mechanical properties and/or growth rates may contribute to altered meristem morphology. Indeed, we find that clavata meristems are softer than the wild type, and that stereotypical meristem organisation is lost, with cells instead simultaneously expressing multiple domain markers. Furthermore, we show that mutant meristematic cells are auxin-responsive, suggesting that they are functionally different from wild-type stem cells. We propose that the clavata phenotype is not caused by stem cell overproliferation, but rather by the disruption of a more complex regulatory framework that is key to maintaining distinct genetic and functional domains at the shoot apex. Summary statement Mechanical, genetic and functional evidence supported by theoretical models call into question the current definition of stem cells in the shoot apex

Heterogeneous identity, stiffness and growth characterise the shoot apex of Arabidopsis stem cell mutants

International audienceABSTRACT Stem cell homeostasis in the shoot apical meristem involves a core regulatory feedback loop between the signalling peptide CLAVATA3 (CLV3), produced in stem cells, and the transcription factor WUSCHEL, expressed in the underlying organising centre. clv3 mutant meristems display massive overgrowth, which is thought to be caused by stem cell overproliferation, although it is unknown how uncontrolled stem cell divisions lead to this altered morphology. Here, we reveal local buckling defects in mutant meristems, and use analytical models to show how mechanical properties and growth rates may contribute to the phenotype. Indeed, clv3 mutant meristems are mechanically more heterogeneous than the wild type, and also display regional growth heterogeneities. Furthermore, stereotypical wild-type meristem organisation, in which cells simultaneously express distinct fate markers, is lost in mutants. Finally, cells in mutant meristems are auxin responsive, suggesting that they are functionally distinguishable from wild-type stem cells. Thus, all benchmarks show that clv3 mutant meristem cells are different from wild-type stem cells, suggesting that overgrowth is caused by the disruption of a more complex regulatory framework that maintains distinct genetic and functional domains in the meristem

Additional file 4: Figure S2. of A phosphoinositide map at the shoot apical meristem in Arabidopsis thaliana

Variable auxin pattern in NPA-treated plants expressing DII-Venus. Shoot apical meristems from seedlings grown on NPA-containing medium from germination. At t = 0 h, plants were taken off the drug. Scale bar, 20 μm. (JPG 1268 kb

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old