Rôle des Strigolactones dans la Symbiose Mycorhizienne à Arbuscules

La symbiose mycorhizienne à arbuscules (MA) est une association entre les champignons du groupe des Gloméromycètes et les racines de la plupart des plantes terrestres. Cette symbiose améliore la santé et la nutrition hydrique et minérale des plantes. Des travaux antérieurs ont montré qu'une famille de molécules, les strigolactones, secrétées par les racines des plantes, étaient capables de stimuler fortement la croissance pré-symbiotique des champignons MA. Ces molécules, initialement caractérisées comme étant inductrices de la germination des graines des plantes parasites Striga et Orobanche, sont peu stables dans le sol, produites à l'état de traces, et actives sur les plantes parasites et les champignons MA à de très faibles concentrations. Afin de préciser l'importance des strigolactones dans la symbiose MA, nous avons tout d'abord étudié des plantes de maïs (Zea mays) bloquées dans les étapes précoces de la synthèse des caroténoïdes (précurseurs hypothétiques des strigolactones). Les plantes mutées (mutant y9) ou traitées à la fluridone présentent une diminution de leur taux de mycorhization, et ce phénotype a été restauré par l'ajout exogène de GR24, une strigolactone synthétique. Ensuite, l'analyse de mutants de Pois (Pisum sativum) rms1 et rms5, affectés dans le clivage des caroténoïdes (enzymes CCD8 et CCD7, respectivement) par des techniques de spectrométrie de masse a révélé que le Pois sauvage produisait deux strigolactones, l'orobanchyl acétate et une autre strigolactone incomplètement identifiée, mais que les mutants rms1 et rms5 ne produisaient aucune des deux. Les exsudats des mutants étaient aussi moins actifs sur les champignons MA et sur la germination des graines de plantes parasites. De plus, le mutant rms1 était moins mycorhizé et l'application exogène de GR24 permettait de restaurer le taux normal de mycorhization. Ces résultats ont permis de démontrer l'importance des deux enzymes CCD8 et CCD7 dans la synthèse des strigolactones et leur importance pour l'établissement de la symbiose MA. Les mutants rms1 et rms5 (avec des tiges hyper ramifiées) ont permis ces dernières années de révéler l'existence d'une nouvelle hormone végétale (appelée SMS, pour Shoot Multiplication Signal) de structure chimique inconnue et contrôlant la croissance des bourgeons axillaires. En collaboration avec d'autres équipes il a été montré que l'application de GR24 sur les bourgeons axillaires des mutants rms1 et rms5 permettait de restaurer le phénotype sauvage (inhibition de la croissance des bourgeons). Le mutant rms4, bloqué dans la perception du SMS et non dans sa synthèse, produit des strigolactones et est insensible à l'application de GR24. Ces résultats confirment l'intervention des strigolactones comme signal hormonal dans la voie SMS. Ces résultats ont été confirmés chez Arabidopsis avec les mutants max. Nous avons révélé la nature multi signalétique des strigolactones dans trois processus biologiques distincts : la stimulation de la germination des graines des plantes parasites, la mise en place de la symbiose MA et le contrôle hormonal de la croissance des bourgeons axillaires chez les plantes. Ces résultats ouvrent de nombreuses perspectives de recherche fondamentale et appliquée sur l'origine évolutive des strigolactones, leurs mécanismes d'action, leur rôle écologique, et sur leur potentiel d'exploitation agronomique.The Arbuscular Mycorrhizal (AM) symbiosis is a mutualistic association between fungi to the group of Glomeromycota and the roots of most land plants. This symbiosis helps to improve plant health as well as water and mineral nutrition. Previous work has shown that a family of molecules called strigolactones, secreted by plant roots, are able to stimulate pre-symbiotic growth of AM fungi. These molecules initially characterize as seed germination stimulants for the parasitic plants Striga and Orobanche, are very unstable in the soil, produced in trace amounts, and active on parasitic plants and AM fungi at very low concentrations. To investigate the importance of strigolactones in the AM symbiosis, we first studied maize (Zea mays) plants affected at early stages of carotenoid synthesis, because carotenoids are hypothetical precursors of strigolactones. Mutant (y9) and fluridone-treated plants exhibit a decreased mycorrhization rate and this phenotype can be rescued by treatment with the synthetic strigolactone GR24. We then analysed rms1 and rms5 garden pea (Pisum sativum) mutants affected in carotenoid cleavage enzymes CCD8 and CCD7, respectively. Using mass spectrometry techniques we showed that root exudates of wild-type pea plants contain orobanchyl acetate and another incompletely identified strigolactone while rms1 and rms5 produce neither of these two strigolactones. Mutant exudates are also less active on AM fungi and on Orobanche seed germination. Furthermore, rms1 mutants are less mycorrhized than the wild type and exogenous treatment with GR24 can restore a normal mycorrhization rate. Together, these results demonstrate the importance of two enzymes, CCD8 and CCD7, in the synthesis of strigolactones and show that these compounds are important for the etablishment of AM symbiosis. Pea rms1 and rms5 mutants (with an increased shoot branching phenotype) have been used to reveale the existence of a new plant hormone called SMS, for Shoot Multiplication Signal. This hormone inhibits lateral bud outgrowth, and its chemical structure has long remained unknown. In collaboration with other research groups, we showed that the application of GR24 on axillary buds of rms1 and rms5 mutants can restore the wild-type phenotype (inhibition of bud outgrowth). The rms4 mutant, blocked in the perception of SMS and not in its synthesis, produces strigolactones and is insensitive to the application of GR24. These results confirm the involvement of strigolactones as hormonal signals in the SMS pathway. Similar experiments carried out on max mutants confirmed our findings in Arabidopsis. Our work shows that strigolactones act as signals in three distinct biological processes: the stimulation of parasitic plant seed germination, the establishment of AM symbiosis and the hormonal control of lateral bud growth in plants. Our results open up many opportunities for basic and applied research into the evolutionary origin of strigolactones, their mechanisms of action, their ecological role and their potential use in agriculture

Control of anthocyanin and non-flavonoid compounds by anthocyanin-regulating MYB and bHLH transcription factors in Nicotiana benthamiana leaves

Coloration of plant organs such as fruit, leaves and flowers through anthocyanin production is governed by a combination of MYB and bHLH type transcription factors (TFs). In this study we introduced Rosea1 (ROS1, a MYB type) and Delila (DEL, a bHLH type), into Nicotiana benthamiana leaves by agroinfiltration. ROS1 and DEL form a pair of well-characterized TFs from Snapdragon (Antirrhinum majus), which specifically induce anthocyanin accumulation when expressed in tomato fruit. In N. benthamiana, robust induction of a single anthocyanin, delphinidin-3-rutinoside (D3R) was observed after expression of both ROS1 and DEL. Surprisingly in addition to D3R, a range of additional metabolites were also strongly and specifically up-regulated upon expression of ROS1 and DEL. Except for the D3R, these induced compounds were not derived from the flavonoid pathway. Most notable among these are nornicotine conjugates with butanoyl, hexanoyl, and octanoyl hydrophobic moieties, and phenylpropanoid-polyamine conjugates such as caffeoyl putrescine. The defensive properties of the induced molecules were addressed in bioassays using the tobacco specialist lepidopteran insect Manduca sexta. Our study showed that the effect of ROS1 and DEL expression in N. benthamiana leaves extends beyond the flavonoid pathway. Apparently the same transcription factor may regulate different secondary metabolite pathways in different plant species

Strigolactones Stimulate Arbuscular Mycorrhizal Fungi by Activating Mitochondria

The association of arbuscular mycorrhizal (AM) fungi with plant roots is the oldest and ecologically most important symbiotic relationship between higher plants and microorganisms, yet the mechanism by which these fungi detect the presence of a plant host is poorly understood. Previous studies have shown that roots secrete a branching factor (BF) that strongly stimulates branching of hyphae during germination of the spores of AM fungi. In the BF of Lotus, a strigolactone was found to be the active molecule. Strigolactones are known as germination stimulants of the parasitic plants Striga and Orobanche. In this paper, we show that the BF of a monocotyledonous plant, Sorghum, also contains a strigolactone. Strigolactones strongly and rapidly stimulated cell proliferation of the AM fungus Gigaspora rosea at concentrations as low as 10 (−13) M. This effect was not found with other sesquiterperne lactones known as germination stimulants of parasitic weeds. Within 1 h of treatment, the density of mitochondria in the fungal cells increased, and their shape and movement changed dramatically. Strigolactones stimulated spore germination of two other phylogenetically distant AM fungi, Glomus intraradices and Gl. claroideum. This was also associated with a rapid increase of mitochondrial density and respiration as shown with Gl. intraradices. We conclude that strigolactones are important rhizospheric plant signals involved in stimulating both the pre-symbiotic growth of AM fungi and the germination of parasitic plants

Diverse values of nature for sustainability

Twenty-five years since foundational publications on valuing ecosystem services for human well-being(1,2), addressing the global biodiversity crisis(3) still implies confronting barriers to incorporating nature's diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever(4). Notwithstanding agreements to incorporate nature's values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)(5) and the UN Sustainable Development Goals(6), predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature(7). Arguably, a 'values crisis' underpins the intertwined crises of biodiversity loss and climate change(8), pandemic emergence(9) and socio-environmental injustices(10). On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature's diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions(7,11). Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures

Respuesta immune humoral asociada a las vacunas contra SARS-CoV-2 en pacientes con artritis reumatoidea: datos del registro SAR-CoVAC

Introducción: la artritis reumatoidea (AR) y los tratamientos indicados para su manejo pueden afectar la respuesta a la vacuna para SARS-CoV-2. Sin embargo, aún no se cuenta con datos locales. Objetivos: evaluar la respuesta humoral de la vacuna para SARS-CoV-2 y su seguridad en esta población. Materiales y métodos: estudio observacional. Se incluyeron pacientes ≥18 años, con AR ACR/EULAR 2010 que recibieron la vacunación para SARS-CoV-2

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Diverse values of nature for sustainability

Twenty-five years since foundational publications on valuing ecosystem services for human well-being, addressing the global biodiversity crisis still implies confronting barriers to incorporating nature’s diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever. Notwithstanding agreements to incorporate nature’s values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF) and the UN Sustainable Development Goals, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature. Arguably, a ‘values crisis’ underpins the intertwined crises of biodiversity loss and climate change, pandemic emergence and socio-environmental injustices. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature’s diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Rôle des Strigolactones dans la symbiose mycorhizienne à arbuscules

La symbiose mycorhizienne à arbuscules (MA) est une association entre les champignons du groupe des Gloméromycètes et les racines de la plupart des plantes terrestres. Cette symbiose améliore la santé et la nutrition hydrique et minérale des plantes. Des travaux antérieurs ont montré qu'une famille de molécules, les strigolactones, secrétées par les racines des plantes, étaient capables de stimuler fortement la croissance pré-symbiotique des champignons MA. Ces molécules, initialement caractérisées comme étant inductrices de la germination des graines des plantes parasites Striga et Orobanche, sont peu stables dans le sol, produites à l'état de traces, et actives sur les plantes parasites et les champignons MA à de très faibles concentrations. Afin de préciser l'importance des strigolactones dans la symbiose MA, nous avons tout d'abord étudié des plantes de maïs (Zea mays) bloquées dans les étapes précoces de la synthèse des caroténoïdes (précurseurs hypothétiques des strigolactones). Les plantes mutées (mutant y9) ou traitées à la fluridone présentent une diminution de leur taux de mycorhization, et ce phénotype a été restauré par l'ajout exogène de GR24, une strigolactone synthétique. Ensuite, l'analyse de mutants de Pois (Pisum sativum) rms1 et rms5, affectés dans le clivage des caroténoïdes (enzymes CCD8 et CCD7, respectivement) par des techniques de spectrométrie de masse a révélé que le Pois sauvage produisait deux strigolactones, l'orobanchyl acétate et une autre strigolactone incomplètement identifiée, mais que les mutants rms1 et rms5 ne produisaient aucune des deux. Les exsudats des mutants étaient aussi moins actifs sur les champignons MA et sur la germination des graines de plantes parasites. De plus, le mutant rms1 était moins mycorhizé et l'application...The Arbuscular Mycorrhizal (AM) symbiosis is a mutualistic association between fungi to the group of Glomeromycota and the roots of most land plants. This symbiosis helps to improve plant health as well as water and mineral nutrition. Previous work has shown that a family of molecules called strigolactones, secreted by plant roots, are able to stimulate pre-symbiotic growth of AM fungi. These molecules initially characterize as seed germination stimulants for the parasitic plants Striga and Orobanche, are very unstable in the soil, produced in trace amounts, and active on parasitic plants and AM fungi at very low concentrations. To investigate the importance of strigolactones in the AM symbiosis, we first studied maize (Zea mays) plants affected at early stages of carotenoid synthesis, because carotenoids are hypothetical precursors of strigolactones. Mutant (y9) and fluridone-treated plants exhibit a decreased mycorrhization rate and this phenotype can be rescued by treatment with the synthetic strigolactone GR24. We then analysed rms1 and rms5 garden pea (Pisum sativum) mutants affected in carotenoid cleavage enzymes CCD8 and CCD7, respectively. Using mass spectrometry techniques we showed that root exudates of wild-type pea plants contain orobanchyl acetate and another incompletely identified strigolactone while rms1 and rms5 produce neither of these two strigolactones. Mutant exudates are also less active on AM fungi and on Orobanche seed germination. Furthermore, rms1 mutants are less mycorrhized than the wild type and exogenous treatment with GR24 can restore a normal mycorrhization rate...TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF