PUCHI regulates very long chain fatty acid biosynthesis during lateral root and callus formation

© 2019 National Academy of Sciences. All rights reserved. Lateral root organogenesis plays an essential role in elaborating plant root system architecture. In Arabidopsis, the AP2 family transcription factor PUCHI controls cell proliferation in lateral root primordia. To identify potential targets of PUCHI, we analyzed a time course transcriptomic dataset of lateral root formation. We report that multiple genes coding for very long chain fatty acid (VLCFA) biosynthesis enzymes are induced during lateral root development in a PUCHI-dependent manner. Significantly, several mutants perturbed in VLCFA biosynthesis show similar lateral root developmental defects as puchi-1. Moreover, puchi-1 roots display the same disorganized callus formation phenotype as VLCFA biosynthesis-deficient mutants when grown on auxin-rich callus-inducing medium. Lipidomic profiling of puchi-1 roots revealed reduced VLCFA content compared with WT. We conclude that PUCHI-regulated VLCFA biosynthesis is part of a pathway controlling cell proliferation during lateral root and callus formation

Effects of water scarcity awareness and climate change belief on recycled water usage willingness: Evidence from New Mexico, United States

The global water crisis is being exacerbated by climate change, even in the United States. Recycled water is a feasible alternative to alleviate the water shortage, but it is constrained by humans’ perceptions. The current study examines how residents’ water scarcity awareness and climate change belief influence their willingness to use recycled water directly and indirectly. Bayesian Mindsponge Framework (BMF) analytics was employed on a dataset of 1831 residents in Albuquerque, New Mexico, an arid inland region in the US. We discovered that residents’ willingness to use direct recycled potable water is positively affected by their awareness of water scarcity, but the effect is conditional on their belief in the impacts of climate change on the water cycle. Meanwhile, the willingness to use indirect recycled potable water is influenced by water scarcity awareness, and the belief in climate change further enhances this effect. These findings implicate that fighting climate change denialism and informing the public of the water scarcity situation in the region can contribute to the effectiveness and sustainability of long-term water conservation and climate change alleviation efforts

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Propriétés du réseau de gènes contrôlant l'organisation du primordium de racine latérale chez Arabidopsis thaliana

Post-embryonic lateral root organogenesis plays an essential role in defining plant root system architecture, and therefore plant growth and fitness. The aim of the thesis is to elucidate the gene regulatory network regulating lateral root development and de novo root meristem formation during root branching in the model plant Arabidopsis thaliana by combining a system-biology based analysis of lateral root primordium transcritome dynamics with the functional characterization of genes possibly involved in regulating lateral root organogenesis.The first part of the thesis deals with the identification the target genes of PUCHI, an AP2/EREBP transcription factor that is involved in controlling cell proliferation and differentiation during lateral root formation. We showed that loss of PUCHI function leads to defects lateral root initiation and primordium growth and organisation. We found that several genes coding for proteins of the very long chain fatty acid (VLCFA) biosynthesis machinery are transiently induced in a PUCHI-dependent manner during lateral root development. Moreover, a mutant perturbed in VLCFA biosynthesis (kcs1-5) displays similar lateral root development defects as does puchi-1. In addition, puchi-1 loss of function mutant roots show enhanced and continuous callus formation in auxin-rich callus induction medium, consistent with the recently reported role of VLCFAs in organizing separated callus proliferation on this inductive growing medium. Thus, our results show that PUCHI positively regulates the expression of VLCFA biosynthesis genes during lateral root development, and further support the hypothesis that lateral root and callus formation share common genetic regulatory mechanisms.A second part of the thesis specifically addresses the issue of identifying key regulators of root meristem organization in the developing lateral root primordium. Material enabling the tracking of meristem cell identity establishment in developing primordia with live confocal microscopy was generated. A gene network inference was run to predict potential regulatory relationships between genes of interest during the time course of lateral root development. It identified potential regulators of quiescent center formation, a key step in functional organization of the lateral root primordia into a new root apical meristem. The characterization of some of these candidate genes was initiated.Altogether, this work participated in deciphering the genetic regulation of lateral root formation in Arabidopsis thaliana .L’organogenèse post-embryonnaire des racines latérales joue un rôle essentiel dans l’établissement de l’architecture du système racinaire des plantes, et donc dans leur croissance et leur performance. L’objectif de cette thèse est de caractériser le réseau de gènes régulant le développement des racines latérales et en particulier, l’organisation fonctionnelle du primordium de racine latérale, formant un nouveau méristème racinaire, chez la plante modèleArabidopsis thaliana en combinant des études de biologie des systèmes appliquées à la dynamique du transcriptome lors de la formation des racines latérales avec la caractérisation fonctionnelle de gènes candidats pour la régulation de ce phénomène d’organogenèse.La première partie de la thèse concerne l’identification des cibles de PUCHI, un facteur de transcription de type AP2/EREBP impliqué dans le contrôle de la prolifération et de la différentiation cellulaire dans le primordium de racine latérale. Le phénotype liés à la parte de fonction de PUCHI a été caractérisé en détail et à mis en évidence un rôle de ce facteur de transcription dans l'initiation des racines latérales et le développement et l'organisation des primordia. Par l’analyse de profils spatiaux et temporels d’expression de gènes, nous avons pu mettre en évidence que l’expression de gènes codant des protéines impliquées dans la biosynthèse des acides gras à très longues chaînes (VLCFA) est transitoirement activée durant la formation de la racine latérale et que cette dynamique est dépendante de PUCHI. De plus, le mutant kcs1-5, perturbé dans la biosynthèse de VLCFAs, présente un phénotype de développement des racines latérales similaire à celui de puchi-1. Par ailleurs, la perte de fonction puchi-1 augmente fortement la formation de cals continus dans des racines cultivées sur milieu inducteur riche en auxine, ce qui est cohérent avec le rôle récemment décrit des VLCFA racinaires dans la formation et l’organisation de cals distincts lorsque la racine est cultivé sur milieu inducteur de cals. L'ensemble de nos résultats démontre que PUCHI régule positivement l’expression de gènes de biosynthèse de VLCFAs lors de la formation de racines latérales et la callogenèse. Nos résultats confortent également l’hypothèse selon laquelle la formation des racines latérales et celle de cals racinaires partagent des mécanismes de régulation communs.La seconde partie de la thèse s’intéresse à l’identification de facteurs régulateurs clés dans l’organisation fonctionnelle du primordium de racine latérale et particulièrement, l’organisation d’un nouveau méristème racinaire. J’ai contribué à produire de nouvelles lignées de plantes permettant de suivre en temps réel par microscopie confocale la mise en place des identités cellulaires caractéristiques d’un méristème racinaire dans le primordium de racine latérale en développement. En utilisant un algorithme d’inférence de réseau de gènes, j’ai produit puis analysé les relations prédites de régulation entre gènes d’intérêt, afin d’identifier des gènes candidats potentiellement impliqués dans la formation du centre quiescent, un élément clé dans l’organisation du primordium et la mise en place du nouveau méristème racinaire. La caractérisation fonctionnelle de certains de ces gènes candidats a été initiée.Ces travaux de thèse ont donc contribué à mieux comprendre les mécanismes de régulation de la formation des racines latérales chez Arabidopsis thaliana

Gene regulatory network for lateral root formation in Arabidopsis thaliana

L’organogenèse post-embryonnaire des racines latérales joue un rôle essentiel dans l’établissement de l’architecture du système racinaire des plantes, et donc dans leur croissance et leur performance. L’objectif de cette thèse est de caractériser le réseau de gènes régulant le développement des racines latérales et en particulier, l’organisation fonctionnelle du primordium de racine latérale, formant un nouveau méristème racinaire, chez la plante modèleArabidopsis thaliana en combinant des études de biologie des systèmes appliquées à la dynamique du transcriptome lors de la formation des racines latérales avec la caractérisation fonctionnelle de gènes candidats pour la régulation de ce phénomène d’organogenèse.La première partie de la thèse concerne l’identification des cibles de PUCHI, un facteur de transcription de type AP2/EREBP impliqué dans le contrôle de la prolifération et de la différentiation cellulaire dans le primordium de racine latérale. Le phénotype liés à la parte de fonction de PUCHI a été caractérisé en détail et à mis en évidence un rôle de ce facteur de transcription dans l'initiation des racines latérales et le développement et l'organisation des primordia. Par l’analyse de profils spatiaux et temporels d’expression de gènes, nous avons pu mettre en évidence que l’expression de gènes codant des protéines impliquées dans la biosynthèse des acides gras à très longues chaînes (VLCFA) est transitoirement activée durant la formation de la racine latérale et que cette dynamique est dépendante de PUCHI. De plus, le mutant kcs1-5, perturbé dans la biosynthèse de VLCFAs, présente un phénotype de développement des racines latérales similaire à celui de puchi-1. Par ailleurs, la perte de fonction puchi-1 augmente fortement la formation de cals continus dans des racines cultivées sur milieu inducteur riche en auxine, ce qui est cohérent avec le rôle récemment décrit des VLCFA racinaires dans la formation et l’organisation de cals distincts lorsque la racine est cultivé sur milieu inducteur de cals. L'ensemble de nos résultats démontre que PUCHI régule positivement l’expression de gènes de biosynthèse de VLCFAs lors de la formation de racines latérales et la callogenèse. Nos résultats confortent également l’hypothèse selon laquelle la formation des racines latérales et celle de cals racinaires partagent des mécanismes de régulation communs.La seconde partie de la thèse s’intéresse à l’identification de facteurs régulateurs clés dans l’organisation fonctionnelle du primordium de racine latérale et particulièrement, l’organisation d’un nouveau méristème racinaire. J’ai contribué à produire de nouvelles lignées de plantes permettant de suivre en temps réel par microscopie confocale la mise en place des identités cellulaires caractéristiques d’un méristème racinaire dans le primordium de racine latérale en développement. En utilisant un algorithme d’inférence de réseau de gènes, j’ai produit puis analysé les relations prédites de régulation entre gènes d’intérêt, afin d’identifier des gènes candidats potentiellement impliqués dans la formation du centre quiescent, un élément clé dans l’organisation du primordium et la mise en place du nouveau méristème racinaire. La caractérisation fonctionnelle de certains de ces gènes candidats a été initiée.Ces travaux de thèse ont donc contribué à mieux comprendre les mécanismes de régulation de la formation des racines latérales chez Arabidopsis thaliana.Post-embryonic lateral root organogenesis plays an essential role in defining plant root system architecture, and therefore plant growth and fitness. The aim of the thesis is to elucidate the gene regulatory network regulating lateral root development and de novo root meristem formation during root branching in the model plant Arabidopsis thaliana by combining a system-biology based analysis of lateral root primordium transcritome dynamics with the functional characterization of genes possibly involved in regulating lateral root organogenesis.The first part of the thesis deals with the identification the target genes of PUCHI, an AP2/EREBP transcription factor that is involved in controlling cell proliferation and differentiation during lateral root formation. We showed that loss of PUCHI function leads to defects lateral root initiation and primordium growth and organisation. We found that several genes coding for proteins of the very long chain fatty acid (VLCFA) biosynthesis machinery are transiently induced in a PUCHI-dependent manner during lateral root development. Moreover, a mutant perturbed in VLCFA biosynthesis (kcs1-5) displays similar lateral root development defects as does puchi-1. In addition, puchi-1 loss of function mutant roots show enhanced and continuous callus formation in auxin-rich callus induction medium, consistent with the recently reported role of VLCFAs in organizing separated callus proliferation on this inductive growing medium. Thus, our results show that PUCHI positively regulates the expression of VLCFA biosynthesis genes during lateral root development, and further support the hypothesis that lateral root and callus formation share common genetic regulatory mechanisms.A second part of the thesis specifically addresses the issue of identifying key regulators of root meristem organization in the developing lateral root primordium. Material enabling the tracking of meristem cell identity establishment in developing primordia with live confocal microscopy was generated. A gene network inference was run to predict potential regulatory relationships between genes of interest during the time course of lateral root development. It identified potential regulators of quiescent center formation, a key step in functional organization of the lateral root primordia into a new root apical meristem. The characterization of some of these candidate genes was initiated.Altogether, this work participated in deciphering the genetic regulation of lateral root formation in Arabidopsis thaliana

Lateral Root Formation: Building a Meristem de novo

International audienceThe complex and adaptable architecture of the plant root system in soil is of paramount importance for crop growth and performance. Root growth depends on the activity of the root apical meristem, an organized population of proliferating progenitor cells continuously replenished from a stem cell niche. Root branching, which greatly contributes to root system architecture in most dicot species, consists in de novoformation of new root meristems in existing root tissues. This phenomenon illustrates the ability of plants to repeatedly generate new tissues specialized in post-embryonic continuous growth and greatly impacts the elaboration of the root system architecture and its adaptation to environmental constraints. Here, we review the recent findings and models related to lateral root organogenesis in the dicot species Arabidopsis thaliana, with emphasis on the mechanisms controlling de novoroot meristem formation. Experimental evidence suggests that critical regulatory modules are common between embryonic and post-embryonic root meristem organogenesis, and that the lateral root formation molecular pathway is in part common with organ regeneration from callus

Sepal shape variability is robust to cell size heterogeneity in Arabidopsis

International audienceHow organisms produce organs with robust shapes and sizes is still an open question. In recent years, the Arabidopsis sepal has been used as a model system to study this question because of its highly reproducible shape and size. One interesting aspect of the sepal is that its epidermis contains cells of very different sizes. Previous reports have qualitatively shown that sepals with more or less giant cells exhibit comparable final size and shape. Here, we investigate this question using quantitative approaches. We find that a mixed population of cell size modestly contribute to the normal width of the sepal but is not essential for its shape robustness. Furthermore, in a mutant with increased cell and organ growth variability, the change in final sepal shape caused by giant cells is exaggerated but the shape robustness is not affected. This formally demonstrates that sepal shape variability is robust to cell size heterogeneity

Sepal shape variability is robust to cell size heterogeneity in Arabidopsis

Assess the impacts of uniform cell types on organ shape robustness using Arabidopsis sepal as the mode