Parasitic Plants Striga and Phelipanche Dependent upon Exogenous Strigolactones for Germination Have Retained Genes for Strigolactone Biosynthesis

Abstract Strigolactones are plant hormones with multiple functions, including regulating various aspects of plant architecture such as shoot branching, facilitating the colonization of plant roots by arbuscular mycorrhizal fungi, and acting as seed germination stimulants for certain parasitic plants of the family Orobanchaceae. The obligate parasitic species Phelipanche aegyptiaca and Striga hermonthica require strigolactones for germination, while the facultative parasite Triphysaria versicolor does not. It has been hypothesized that P. aegyptiaca and S. hermonthica would have undergone evolutionary loss of strigolactone biosynthesis as a part of their mechanism to enable specific detection of exogenous strigolactones. We analyzed the transcriptomes of P. aegyptiaca, S. hermonthica and T. versicolor and identified genes known to act in strigolactone synthesis (D27, CCD7, CCD8, and MAX1), perception (MAX2 and D14) and transport (PDR12). These genes were then analyzed to assess likelihood of function. Transcripts of all strigolactone-related genes were found M. Das et al. 1152 in P. aegyptiaca and S. hermonthica, and evidence points to their encoding functional proteins. Gene open reading frames were consistent with homologs from Arabidopsis and other strigolactone-producing plants, and all genes were expressed in parasite tissues. In general, the genes related to strigolactone synthesis and perception appeared to be evolving under codon-based selective constraints in strigolactone-dependent species. Bioassays of S. hermonthica root extracts indicated the presence of strigolactone class stimulants on germination of P. aegyptiaca seeds. Taken together, these results indicate that Phelipanche aegyptiaca and S. hermonthica have retained functional genes involved in strigolactone biosynthesis, suggesting that the parasites use both endogenous and exogenous strigolactones and have mechanisms to differentiate the two

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Contrôle des adventices parasites par les acides aminés : un éclairage de la littérature

Parasitic Plants Newsletter (ISSN 1944-6969

Allelopathy for Parasitic Plant Management

A number of parasitic plants have adapted to agricultural environments becoming weedy and posing a serious threat to important crops. Available control measures rely heavily on use of synthetic herbicides. The side effects on environmental pollution and food health of chemical control prompted studies to find alternative strategies based on the use of natural products. This article reviews plant and fungal metabolites with potential for the development of specific and efficient methods for the control of parasitic plants

Ryecyanatines A and B and ryecarbonitrilines A and B, substituted cyanatophenol, cyanatobenzo[1,3]dioxole, and benzo[1,3]dioxolecarbonitriles from rye (Secale cereale L.) root exudates: Novel metabolites with allelopathic activity on Orobanche seed germination and radicle growth

International audienceOrobanche and Phelipanche species (the broomrapes) are root parasitic plants, some of which represent serious weed problems causing heavy yield losses on important crops. Current control relies on the use of certain agronomic practices, resistant crop varieties, and herbicides, albeit success has been marginal. Agronomic practices such as the use of allelopathic species in intercropping or cover crops, or the use of direct seedling over residues of allelopathic species incorporate the principle of allelopathy exerted by molecules exuded from roots or released by crop residues to control broomrapes. In addition, the isolation of natural substances from root exudates of plants with potential to inhibit broomrape development opens the door to the design of new herbicides based on natural and benign sources. Ryecyanatines A and B and ryecarbonitrilines A and B, the first new substituted cyanatophenol, substituted cyanatobenzo[1,3]dioxole, and the latter two new substituted benzo[1,3]dioxolecarbonitriles were isolated from rye (Secale cereale L.) root exudates. They were characterized as 4-cyanato-2-methoxyphenol, 2-cyanato-benzo[1,3]dioxole, 2-methoxybenzo[1,3]dioxole-5-carbonitrile and benzo[1,3]dioxole-2-carbonitrile by spectroscopic (essentially NMR and HRESI MS spectra) methods. These compounds were investigated for allelopathic activity on Orobanche germination and development. Ryecarbonitriline A induced germination of Orobanche cumana seeds, and this germination can be considered as suicidal because O. cumana does not parasite rye roots and cannot survive without host resources beyond germination stage. In addition, ryecyanatine A promotes a rapid cessation of O. cumana, Orobanche crenata and Orobanche minor radicle growth with the promotion of a layer of papillae at the radicle tip in O. cumana and O. crenata hampering the contact of the parasite to the host. Ryecarbonitriline B also displayed the same activity although being less active than ryecyanatine A and mainly restricted to O. cumana

Response and effect traits of arable weeds in agro-ecosystems: a review of current knowledge.

25 pagesInternational audienceIntegrating principles of ecological intensification into weed management strategies requires an understanding of the many relationships among weeds, crops and other organisms of agro-ecosystems in a changing context. Extensively used during the last two decades in weed science, trait-based approaches have provided general insights into weed community response to agricultural practices, and recently to understanding the effect of weeds on agro-ecosystem functioning. In this review, we provide a holistic synthesis of the current knowledge on weed response and effect functional traits. Based on the literature and recent advances in weed science, we review current knowledge on (i) weed functional groups and ecological strategies, (ii) weed functional response traits to cropping systems and (iii) weed functional effect traits affecting agro-ecosystem functioning. For each functional trait, we explicitly present the assumptions and evidence on the linkage between trait values and ecological functions, in response to either management practices, for example tillage, sowing and herbicides, or biotic interactions, for example crop–weed competition and pollination. Finally, we address and discuss major research avenues that may significantly improve the use of traits and the knowledge of functional diversity in weed science for the future, especially to design and implement more environmentally sustainable weed management strategies

Response and effect traits of arable weeds in agro-ecosystems: a review of current knowledge.

25 pagesInternational audienceIntegrating principles of ecological intensification into weed management strategies requires an understanding of the many relationships among weeds, crops and other organisms of agro-ecosystems in a changing context. Extensively used during the last two decades in weed science, trait-based approaches have provided general insights into weed community response to agricultural practices, and recently to understanding the effect of weeds on agro-ecosystem functioning. In this review, we provide a holistic synthesis of the current knowledge on weed response and effect functional traits. Based on the literature and recent advances in weed science, we review current knowledge on (i) weed functional groups and ecological strategies, (ii) weed functional response traits to cropping systems and (iii) weed functional effect traits affecting agro-ecosystem functioning. For each functional trait, we explicitly present the assumptions and evidence on the linkage between trait values and ecological functions, in response to either management practices, for example tillage, sowing and herbicides, or biotic interactions, for example crop–weed competition and pollination. Finally, we address and discuss major research avenues that may significantly improve the use of traits and the knowledge of functional diversity in weed science for the future, especially to design and implement more environmentally sustainable weed management strategies

Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicenter, retrospective analysis

Background: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a substantial percentage of patients do not respond to this treatment. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in patients recruited with current stage IV NSCLC. Methods: In this multicentre study, we recruited adult patients from 15 hospitals in France, Spain, and Italy who had histologically proven stage IV NSCLC and had been exposed to PD-1 blockade during the course of the disease. The study structure comprised a discovery cohort to assess the correlation between epigenetic features and clinical benefit with PD-1 blockade and two validation cohorts to assess the validity of our assumptions. We first established an epigenomic profile based on a microarray DNA methylation signature (EPIMMUNE) in a discovery set of tumour samples from patients treated with nivolumab or pembrolizumab. The EPIMMUNE signature was validated in an independent set of patients. A derived DNA methylation marker was validated by a single-methylation assay in a validation cohort of patients. The main study outcomes were progression-free survival and overall survival. We used the Kaplan-Meier method to estimate progression-free and overall survival, and calculated the differences between the groups with the log-rank test. We constructed a multivariate Cox model to identify the variables independently associated with progression-free and overall survival. Findings: Between June 23, 2014, and May 18, 2017, we obtained samples from 142 patients: 34 in the discovery cohort, 47 in the EPIMMUNE validation cohort, and 61 in the derived methylation marker cohort (the T-cell differentiation factor forkhead box P1 [FOXP1]). The EPIMMUNE signature in patients with stage IV NSCLC treated with anti-PD-1 agents was associated with improved progression-free survival (hazard ratio [HR] 0·010, 95% CI 3·29 × 10 −4–0·0282; p=0·0067) and overall survival (0·080, 0·017–0·373; p=0·0012). The EPIMMUNE-positive signature was not associated with PD-L1 expression, the presence of CD8+ cells, or mutational load. EPIMMUNE-negative tumours were enriched in tumour-associated macrophages and neutrophils, cancer-associated fibroblasts, and senescent endothelial cells. The EPIMMUNE-positive signature was associated with improved progression-free survival in the EPIMMUNE validation cohort (0·330, 0·149–0·727; p=0·0064). The unmethylated status of FOXP1 was associated with improved progression-free survival (0·415, 0·209–0·802; p=0·0063) and overall survival (0·409, 0·220–0·780; p=0·0094) in the FOXP1 validation cohort. The EPIMMUNE signature and unmethylated FOXP1 were not associated with clinical benefit in lung tumours that did not receive immunotherapy. Interpretation: Our study shows that the epigenetic milieu of NSCLC tumours indicates which patients are most likely to benefit from nivolumab or pembrolizumab treatments. The methylation status of FOXP1 could be associated with validated predictive biomarkers such as PD-L1 staining and mutational load to better select patients who will experience clinical benefit with PD-1 blockade, and its predictive value should be evaluated in prospective studies

Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicenter, retrospective analysis

Background: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a substantial percentage of patients do not respond to this treatment. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in patients recruited with current stage IV NSCLC. Methods: In this multicentre study, we recruited adult patients from 15 hospitals in France, Spain, and Italy who had histologically proven stage IV NSCLC and had been exposed to PD-1 blockade during the course of the disease. The study structure comprised a discovery cohort to assess the correlation between epigenetic features and clinical benefit with PD-1 blockade and two validation cohorts to assess the validity of our assumptions. We first established an epigenomic profile based on a microarray DNA methylation signature (EPIMMUNE) in a discovery set of tumour samples from patients treated with nivolumab or pembrolizumab. The EPIMMUNE signature was validated in an independent set of patients. A derived DNA methylation marker was validated by a single-methylation assay in a validation cohort of patients. The main study outcomes were progression-free survival and overall survival. We used the Kaplan-Meier method to estimate progression-free and overall survival, and calculated the differences between the groups with the log-rank test. We constructed a multivariate Cox model to identify the variables independently associated with progression-free and overall survival. Findings: Between June 23, 2014, and May 18, 2017, we obtained samples from 142 patients: 34 in the discovery cohort, 47 in the EPIMMUNE validation cohort, and 61 in the derived methylation marker cohort (the T-cell differentiation factor forkhead box P1 [FOXP1]). The EPIMMUNE signature in patients with stage IV NSCLC treated with anti-PD-1 agents was associated with improved progression-free survival (hazard ratio [HR] 0·010, 95% CI 3·29 × 10 −4–0·0282; p=0·0067) and overall survival (0·080, 0·017–0·373; p=0·0012). The EPIMMUNE-positive signature was not associated with PD-L1 expression, the presence of CD8+ cells, or mutational load. EPIMMUNE-negative tumours were enriched in tumour-associated macrophages and neutrophils, cancer-associated fibroblasts, and senescent endothelial cells. The EPIMMUNE-positive signature was associated with improved progression-free survival in the EPIMMUNE validation cohort (0·330, 0·149–0·727; p=0·0064). The unmethylated status of FOXP1 was associated with improved progression-free survival (0·415, 0·209–0·802; p=0·0063) and overall survival (0·409, 0·220–0·780; p=0·0094) in the FOXP1 validation cohort. The EPIMMUNE signature and unmethylated FOXP1 were not associated with clinical benefit in lung tumours that did not receive immunotherapy. Interpretation: Our study shows that the epigenetic milieu of NSCLC tumours indicates which patients are most likely to benefit from nivolumab or pembrolizumab treatments. The methylation status of FOXP1 could be associated with validated predictive biomarkers such as PD-L1 staining and mutational load to better select patients who will experience clinical benefit with PD-1 blockade, and its predictive value should be evaluated in prospective studies