Identification of traits for nitrogen use efficiency in oilseed rape (Brassica Napus L.)

Oilseed rape (Brassica napus L.) receives high inputs of Nitrogen (N) fertiliser while N uptake and N harvest index are low. This results in high residual soil N which leaches to water bodies and contributes to greenhouse emissions. Such negative environmental impact could be reduced by better understanding the genetic basis of N metabolism in oilseed rape and designating relevant traits for varietal selection towards high nitrogen use efficiency (NUE) at low N fertiliser inputs. In this study the doubled haploid population (TNDH) from a cross between the Chinese semi-winter variety Ningyou7 and the UK winter variety Tapidor was analysed for N physiology and Quantitative Trait Locus (QTL) mapped for relevant traits. Quantitative Trait Loci were mapped in two N treatments over two consecutive field trials for architectural traits such as plant height, foot length, pod number and chlorophyll content in bracts and leaves; yield and yield component traits such as plant biomass, seed yield, harvest index and N metabolism (seed, plant and total N concentration, N uptake, utilisation and use efficiencies and N harvest index). A larger number of QTL were detected at High N than at Low N. In total 49 QTL were detected at High N versus 44 in Low N during 2005/06, while in 2007/07, 72 versus 62 QTL were detected at High and Low N respectively. Most QTL for different traits were treatment specific. Novel QTL for agronomic traits specific at Low N were identified. The correlations between traits were also studied through QTL co-localisations, particularly for relationships between seed yield, N uptake and N use efficiency. Seven chromosomal regions are discussed for potential candidate genes. Additionally, QTL reproducibility, interval mapping and composite interval mapping, QTL x environment interactions and phenotypic plasticity in oilseed rape are also discussed.EThOS - Electronic Theses Online ServiceSwales Studentship of the School of Agriculture, Food and Rural Development, Newcastle UniversityGBUnited Kingdo

Use of Eculizumab in Pediatric Patients With Transplant Associated Thrombotic Microangiopathy

Complement inhibitor; Eculizumab; Hematopoietic stem cell transplant (HSCT)Inhibidor del complemento; Eculizumab; Trasplante de células madre hematopoyéticas (TCMH)Inhibidor del complement; Eculizumab; Trasplantament de cèl·lules mare hematopoètiques (HSCT)Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a serious complication of hematopoietic stem cell transplantation (HSCT) associated with high morbidity and mortality. High-risk TA-TMA (hrTA-TMA) is characterized by multifactorial endothelial damage caused by environmental stressors, dysregulation of the complement system, and genetic predisposition. Complement inhibitors have significantly decreased mortality and are the current treatment of choice. In this article, we describe our experience with the use of eculizumab in pediatric patients diagnosed with hrT-TMA after HSCT. Method: Retrospective study of pediatric patients with hrTA-TMA treated with eculizumab between January 2016 and December 2020. Results: Four pediatric patients aged 1, 12, 14, and 17 years at the time of HSCT were diagnosed with hrTA-TMA and treated with eculizumab during the study. At diagnosis, they all had renal impairment with proteinuria, and hypertension under treatment with at least two antihypertensive drugs. The patient who presented multisystemic involvement died instead of treatment. The three patients with exclusive renal involvement achieved TA-TMA resolution after treatment with eculizumab for 65, 52, and 40.6 weeks and were able to stop treatment. The two patients with follow-up data one year after eculizumab withdrawal sustained a favorable response. Eculizumab was well tolerated, and with adequate vaccination and antibiotic prophylaxis, did not increase the risk of infection. Conclusions: Eculizumab appears to be both safe and effective for the treatment of hrTA-TMA in patients with renal impairment. Early diagnosis and initiation of treatment may improve response. Eculizumab withdrawal can be contemplated in patients who achieve laboratory and clinical resolution of TA-TMA

Voriconazole Use in Children: Therapeutic Drug Monitoring and Control of Inflammation as Key Points for Optimal Treatment

Infeccions fúngiques pediàtriques; Monitorització terapèutica de fàrmacs; VoriconazolInfecciones fúngicas pediátricas; Monitorización terapéutica de fármacos; VoriconazolPaediatric fungal infections; Therapeutic drug monitoring; VoriconazoleVoriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2–12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged.This research was funded by an Investigator Sponsored Research Grant from Pfizer (Grant Number WI182544

Plasma metabolomic profiles of plant-based dietary indices reveal potential pathways for metabolic syndrome associations

Background and aims: Plant-based dietary patterns have been associated with improved health outcomes. This study aims to describe the metabolomic fingerprints of plant-based diet indices (PDI) and examine their association with metabolic syndrome (MetS) and its components in a Danish population. Methods: The MAX study comprised 676 participants (55% women, aged 18-67 y) from Copenhagen. Sociodemographic and dietary data were collected using questionnaires and three 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). Mean dietary intakes were computed, as well as overall PDI, healthful (hPDI) and unhealthful (uPDI) scores, according to food groups for each plant-based index. Clinical variables were also collected at the same time points in a health examination that included complete blood tests. MetS was defined according to the International Diabetes Federation criteria. Plasma metabolites were measured using a targeted metabolomics approach. Metabolites associated with PDI were selected using random forest models and their relationships with PDIs and MetS were analyzed using generalized linear mixed models. Results: The mean prevalence of MetS was 10.8%. High, compared to low, hPDI and uPDI scores were associated with a lower and higher odd of MetS, respectively [odds ratio (95%CI); hPDI: 0.56 (0.43–0.74); uPDI: 1.61 (1.26–2.05)]. Out of 411 quantified plasma metabolites, machine-learning metabolomics fingerprinting revealed 13 metabolites, including food and food-related microbial metabolites, like hypaphorine, indolepropionic acid and lignan-derived enterolactones. These metabolites were associated with all PDIs and were inversely correlated with MetS components (p &lt; 0.05). Furthermore, they had an explainable contribution of 12% and 14% for the association between hPDI or uPDI, respectively, and MetS only among participants with overweight/obesity. Conclusions: Metabolites associated with PDIs were inversely associated with MetS and its components, and may partially explain the effects of plant-based diets on cardiometabolic risk factors

Sustainable intensification for a larger global rice bowl

Future rice systems must produce more grain while minimizing the negative environmental impacts. A key question is how to orient agricultural research & development (R&D) programs at national to global scales to maximize the return on investment. Here we assess yield gap and resource-use efficiency (including water, pesticides, nitrogen, labor, energy, and associated global warming potential) across 32 rice cropping systems covering half of global rice harvested area. We show that achieving high yields and high resource-use efficiencies are not conflicting goals. Most cropping systems have room for increasing yield, resource-use efficiency, or both. In aggregate, current total rice production could be increased by 32%, and excess nitrogen almost eliminated, by focusing on a relatively small number of cropping systems with either large yield gaps or poor resource-use efficiencies. This study provides essential strategic insight on yield gap and resource-use efficiency for prioritizing national and global agricultural R&D investments to ensure adequate rice supply while minimizing negative environmental impact in coming decades

The ontologies community of practice: a CGIAR initiative for Big Data in agrifood systems

Heterogeneous and multidisciplinary data generated by research on sustainable global agriculture and agrifood systems requires quality data labeling or annotation in order to be interoperable. As recommended by the FAIR principles, data, labels, and metadata must use controlled vocabularies and ontologies that are popular in the knowledge domain and commonly used by the community. Despite the existence of robust ontologies in the Life Sciences, there is currently no comprehensive full set of ontologies recommended for data annotation across agricultural research disciplines. In this paper, we discuss the added value of the Ontologies Community of Practice (CoP) of the CGIAR Platform for Big Data in Agriculture for harnessing relevant expertise in ontology development and identifying innovative solutions that support quality data annotation. The Ontologies CoP stimulates knowledge sharing among stakeholders, such as researchers, data managers, domain experts, experts in ontology design, and platform development teams

Results of the COVID-19 mental health international for the general population (COMET-G) study.

INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them

Scatterplot analysis of expression and DNA methylation integration data

Gene expression regulated by DNA methylation patterns has been long studied in relation to cancer. There exists a negative correlation between the expression of a gene and its methylation level. An integrative analysis of expression and methylation arrays was performed using three datasets for colorectal cancer: TCGA, GEO and own data. The datasets had over 11000 genes, 9000 of which were common. Based on the preconception that methylation represses expression, we selected genes that showed an L-shaped expression and methylation scatterplot with 4 different methods. The first method used, naive, was based on a signifi cant negative correlation. Another method was based on Conditional Mutual Information (CMI). A heuristic method was carried out by superimposing a grid on each scatterplot and weighing the cells according to an L-shape. Finally, a scagnostics selection analysis was based on 9 parameters de ning the shape of scatterplots. The scagnostics needed to be used in conjunction with other methods for optimal results. The accuracy, sensitivity and speci city were measured for the various methods and the one with the best diagnostic measures was the Heuristic, followed by the CMI and the naive. The one that fared lowest was the scagnostics. The final gene list was obtained from a pool of all methodologies.It resulted in 179 target genes, mostly coding for ATP-binding, transcription and zinc finger proteins.La expresión génica regulada por patrones de metilación del ADN ha sido estudiada durante mucho tiempo en relación con el cáncer. Existe una correlación negativa entre la expresión. de un gen y su nivel de metilación. El análisis integrador de la expresión y los arreglos de metilación se han realizado utilizando tres conjuntos de datos para el cáncer colorrectal: TCGA, GEO y datos propios. Los conjuntos de datos tienen más de 11000 genes, 9000 de los cuales son comunes. Sobre la base de la idea preconcebida de que la metilación reprime la expresión, seleccionamos genes que mostraron una expresión en forma de L y un gráfico de dispersión de metilación con 4 diferentes metodos. El primer método utilizado, se basó en una significativa correlación negativa. Otro método fue basado en información mutua condicional(CMI). Se realizó un método heurístico mediante la superposición de una cuadrícula en cada dispersión y pesaje de las celdas según una forma de L. Finalmente, el análisis de la selección de los datos estadísticos se basó en 9 parámetros que definen la forma de gráficos de dispersión. Los escagnósticos debían usarse junto con otros métodos para obtener resultados óptimos. La precisión, sensibilidad y especificidad fueron medidas para los diferentes métodos y la que tenía las mejores medidas diagnósticas fue la heurística, seguida de la CMI.L'expressió gènica regulada per patrons de metilació de l'ADN ha estat estudiada durant molt temps en relació amb el càncer. Existeix una correlació negativa entre l'expressiód'un gen i el seu nivell de metilación. L'anàlisi integrador de l'expressió i els arranjaments de metilació s'han realitzat utilitzant tres conjunts de dades per al càncer colorrectal: TCGA, GEO i dades pròpies. Els conjunts de dades tenen més de 11000 gens, 9000 dels quals són comuns. Sobre la base de la idea preconcebuda que la metilació reprimeix l'expressió, seleccionem gens que van mostrar una expressió en forma de L i un gràfic de dispersió de metilación amb 4 diferents métodes. El primer mètode utilitzat, es va basar en una significativa correlació negativa. Un altre mètode va ser basat en informació mútua condicional(CMI). Es va realitzar un mètode heurístic mitjançant la superposició d'una quadrícula en cada dispersió i pesaje de les cel·les segons una forma de L. Finalment, l'anàlisi de la selecció de les dades estadístiques es va basar en 9 paràmetres que defineixen la forma de gràfics de dispersió. Els escagnóstics havien d'usar-se juntament amb altres mètodes per obtenir resultats òptims. La precisió, sensibilitat i especificitat van ser mesurades per als diferents mètodes i la que tenia les millors mesures diagnòstiques va ser l'heurística, seguida de la CMI

Rice Seed Germination Underwater: Morpho-Physiological Responses and the Bases of Differential Expression of Alcoholic Fermentation Enzymes

The water-, energy-, and labor-intensive system of transplanted puddled rice (Oryza sativa) is steadily being replaced by direct seeding due to the progressive scarcity of these resources. However, the alternate dry direct seeding leads to competition with weeds and poor establishment when soils are flooded. Direct seeded rice capable of anaerobic germination (germination in flooded soil, AG) is ideal, which under rainfed ecosystems would also overcome waterlogging during germination. AG tolerance is associated with faster germination and faster elongation of coleoptiles, with the activities of alcoholic fermentation enzymes replacing aerobic respiration as a source of energy. To better understand the variability in the morpho-physiological responses and in the nature of the alcoholic fermentation enzymes during AG, 21 rice genotypes were studied. The genotypes Khao Hlan On (KHO) and IR42 were used as the tolerant and susceptible checks, respectively. KHO exhibited faster germination, with 82.5% of the coleoptiles emerging out of 10 cm of water within 8 days, whereas IR42 exhibited 20% germination and limited coleoptile growth. Among the test genotypes, four performed well, including two that are drought tolerant. Increased content and activity of the alcoholic fermentation enzymes, alcohol dehydrogenase (ADH1) and acetaldehyde dehydrogenase (ALDH2a and ALDH2b), was noted in KHO under anaerobic than under aerobic conditions and also in comparison with IR42 under AG. Gene transcripts for these enzymes were also more in KHO undergoing AG. However, no major differences were observed between KHO and IR42 in the critical cis-acting regulatory elements, such as the auxin, light, and sugar response elements, in the promoters of ADH1, ALDH2a, and ALDH2b genes. Post-transcriptional and post-translational regulatory mechanisms were implicated for the increased transcript and protein content/activity of the enzymes in KHO by observing four different transcripts of ALDH2a and a unique non-glycosylated form of ADH1 under AG. IR42 lacked the non-glycosylated ADH1 and contained only a truncated form of ALDH2a, which lacked the active site. Additionally, KHO exhibited increased activity and more isoforms for reactive oxygen species detoxifying enzymes under AG compared to IR42. These results highlight the need for a deeper functional understanding of the critical enzymes involved in AG