Improving host resistance to Fusarium head blight in wheat (Triticum aestivum L.) and Gibberella ear rot in maize (Zea mays L.)

Fusarium head blight (FHB) in wheat and Fusarium (FER) and Gibberella ear rot (GER) in maize are major cereal diseases which reduce yield and contaminate kernels with several mycotoxins. In Europe, these diseases contribute to significant yield gaps and high mycotoxin risks across countries. However, existing management strategies related to agronomic practices are not fully effective, with some of them being cost-prohibitive. Enhancing host plant resistance is additionally required for managing the diseases more effectively and sustainably. Unfortunately, breeding for FHB resistance is challenged by complex interactions with morphological traits and the quantitative nature of the trait. In maize, available genetic resources have not been fully exploited to improve GER resistance in elite materials. In this work, we elucidated the complex interactions between FHB resistance and morphological traits, like plant height (PH) and anther retention (AR) in wheat. The effect of reduced height (Rht) gene Rht24 on AR and the contribution of genomic background (GB) to FHB resistance in semi-dwarf genotypes were also assessed. GB refers to all genomic loci, except major Rht genes, that affect the traits. To achieve this, 401 winter wheat cultivars were evaluated across five environments (location × year combination). All cultivars were genotyped using Illumina 25 K Infinium single-nucleotide polymorphism array. We performed correlation and path coefficient analysis, and combined single and multi-trait genome-wide association studies (GWAS). Our findings revealed significant genotypic correlations and path effects between FHB severity with PH and AR, which were controlled by several pleiotropic loci. FHB severity and PH shared both negatively and positively acting pleiotropic loci, while only positively acting pleiotropic loci were detected between FHB severity and AR. Rht-D1 is a major pleiotropic gene which exerted a negative effect on FHB resistance. These pleiotropic loci contribute to our understanding of the complex genetic basis of FHB resistance, and their exploitation can help to simultaneously select for FHB resistance with PH and AR. Contrary to Rht-D1b, Rht24b had no negative effect on FHB resistance and AR. This exhibits Rht24 as an important FHB-neutral Rht gene which can be integrated into breeding programs. Genomic estimated breeding values (GEBV) were calculated for each cultivar to assess GB. We observed highly negative GEBV for FHB severity within resistant wheat cultivars. Susceptible cultivars exhibited positive GEBV. Genomic prediction has a great potential and can be exploited by selecting for semi-dwarf winter wheat genotypes with higher FHB resistance due to their genomic background resistance. To tackle maize ear rot diseases, refined and stable quantitative trait loci (QTL) harboring candidate genes conferring resistances to FER and GER were identified. The effectiveness of introgression of two European flint landraces, namely Kemater Gelb Landmais (KE) and Petkuser Ferdinand Rot (PE) was evaluated. The prediction accuracy of using line performance as a predictor of hybrid performance for GER resistance was also evaluated within the two landraces. We applied a meta-QTL (MQTL) analysis based on 15 diverse SNP-based QTL mapping studies and performed gene expression analysis using published RNA-seq data on GER resistance. In total, 40 MQTL were identified, of which 14 most refined MQTL harbored promising candidate genes for use in breeding programs for improving FER and GER resistances. 28 MQTL were common to both FER and GER, with most of them being shared between silk (channel) and kernel resistances. This highlights the co-inheritance of FER and GER resistances as well as types of active resistance. Resistance genes can be transferred into elite cultivars by integrating refined MQTL into genomics-assisted breeding strategies. Afterwards, four GER resistant doubled haploid (DH) lines from both KE and PE landraces were crossed with two susceptible elite lines to generate six bi-parental populations with a total of 534 DH lines which were evaluated for GER resistance. GER severity within the six landrace-derived populations were reduced by 39−61% compared to the susceptible elite lines. Moderate to high genetic advance was observed within each population, and the use of KE landrace as a donor was generally more effective than PE landrace. This shows promise in enhancing resistance to GER in elite materials using the European flint landraces as donors. Furthermore, per se performance of 76 DH lines from both landraces was used to predict GER resistance of their corresponding testcrosses (TC). Moderate phenotypic and genomic prediction accuracy between TC and line per se performance was found for GER resistance. This implies that pre-selecting lines for GER resistance is feasible; however, TC should be additionally tested on a later selection stage to aim for GER-resistant hybrid cultivars.Ährenfusariosen (FHB) bei Weizen und Fusarium- (FER) und Gibberella-Kolbenfäule (GER) bei Mais sind wichtige Getreidekrankheiten. In Europa tragen diese Krankheiten zu erheblichen Ertragseinbußen und hohen Mykotoxinrisiken in den einzelnen Ländern bei. Die bestehenden Kontrollstrategien im Zusammenhang mit pflanzenbaulichen Praktiken sind jedoch nicht voll wirksam, und einige von ihnen sind zu kostspielig. Um die Krankheiten wirksamer und nachhaltiger zu bekämpfen, muss deshalb die Resistenz der Wirtspflanzen gestärkt werden. Leider wird die Züchtung auf FHB-Resistenz durch komplexe Wechselwirkungen mit morphologischen Merkmalen und der quantitativen Natur des Merkmals erschwert. Bei Mais wurden die verfügbaren genetischen Ressourcen bisher nicht vollständig genutzt, um die GER-Resistenz von Elitematerial zu verbessern. In dieser Arbeit haben wir die komplexen Wechselwirkungen zwischen FHB-Resistenz und morphologischen Merkmalen wie Wuchshöhe (PH) und Antherenretention (AR) bei Weizen aufgeklärt. Außerdem wurden die Auswirkungen des Gens Rht24 für reduzierte Wuchshöhe (reduced height, Rht) auf AR und der Beitrag des genomischen Hintergrunds (GB) zur FHB-Resistenz bei kurzstrohigen Genotypen untersucht. GB bezieht sich auf alle Genloci, mit Ausnahme der bekannten Rht-Gene, die die jeweiligen Merkmale beeinflussen. Zu diesem Zweck wurden 401 Winterweizensorten in fünf Umwelten (Ort × Jahr-Kombinationen) bewertet. Alle Sorten wurden mit dem Illumina 25k Infinium Single-Nukleotid-Polymorphismus-Array genotypisiert. Wir führten Korrelations- und Pfadkoeffizientenanalysen durch und kombinierten genomweite Assoziationsstudien (GWAS) mit einzelnen bzw. mehreren Merkmalen. Unsere Ergebnisse zeigten signifikante genotypische Korrelationen und Pfadeffekte zwischen FHB-Befallsstärke und PH und AR, die von mehreren pleiotropen Loci kontrolliert wurden. FHB-Befallsstärke und PH hatten sowohl negativ als auch positiv wirkende pleiotrope Loci gemeinsam, während zwischen FHB-Befallsstärke und AR nur positiv wirkende pleiotrope Loci gefunden wurden. Rht-D1 ist ein wichtiges pleiotropes Gen, dessen kurzstrohiges Allel einen negativen Einfluss auf die FHB-Resistenz ausübt. Diese pleiotropen Loci tragen zu unserem Verständnis der komplexen genetischen Grundlage der FHB-Resistenz bei, und ihre Nutzung kann dazu beitragen, gleichzeitig mit verringerter PH und AR auf FHB-Resistenz zu selektieren. Im Gegensatz zu Rht-D1b hatte Rht24b keine Auswirkungen auf FHB-Resistenz und AR. Dies zeigt, dass Rht24 ein wichtiges FHB-neutrales Rht-Gen ist, das in Zuchtprogramme integriert werden kann. Zur Bewertung des GB wurden für jede Sorte genomisch geschätzte Zuchtwerte (GEBV) berechnet. Bei resistenten Weizensorten beobachteten wir einen stark negativen GEBV für FHB-Befallsstärke. Anfällige Sorten wiesen einen positiven GEBV auf. Die genomische Vorhersage hat ein großes Potenzial und kann durch die Selektion von kurzstrohigen Winterweizengenotypen mit höherer FHB-Resistenz aufgrund ihrer genomischen Hintergrundresistenz genutzt werden. Zur Bekämpfung von Mais-Kolbenfäule wurden stabile quantitative Merkmalsloci (QTL) identifiziert, die Kandidatengene für Resistenzen gegen FER und GER beherbergen. Die Wirksamkeit der Introgression von Resistenzen aus zwei europäischen Flint-Landrassen, nämlich "Kemater Gelber Landmais" (KE) und "Petkuser Ferdinand Rot" (PE), wurde bewertet. Die Vorhersagegenauigkeit der Verwendung der Linienleistung als Vorhersage für die Hybridleistung bei der GER-Resistenz wurde ebenfalls innerhalb der beiden Landrassen bewertet. Wir haben eine Meta-QTL-Analyse (MQTL) auf der Grundlage von 15 SNP-basierten QTL-Kartierungsstudien durchgeführt und eine Genexpressionsanalyse anhand veröffentlichter RNAseq-Daten zur GER-Resistenz vorgenommen. Insgesamt wurden 40 MQTL identifiziert, von denen die 14 stabilsten MQTL vielversprechende Kandidatengene für den Einsatz in Zuchtprogrammen zur Verbesserung von FER- und GER-Resistenzen enthielten. 28 MQTL waren sowohl für FER- als auch GER-Resistenz verantwortlich, wobei die meisten sowohl für Narbenfaden- als auch Körnerresistenz verantwortlich waren. Die Resistenz kann in Elitesorten übertragen werden, indem präzisierte MQTL in genomgestützte Züchtungsstrategien integriert werden. Anschließend wurden vier GER-resistente doppelhaploide (DH) Linien aus KE- und PE-Landrassen mit zwei anfälligen Elitelinien gekreuzt, um sechs bi-parentale Populationen mit insgesamt 534 DH-Linien zu erzeugen, die mehrortig auf GER-Resistenz untersucht wurden. Der GER-Befallsstärke war bei den sechs von Landrassen abgeleiteten Populationen im Vergleich zu den anfälligen Elitelinien im Mittel um 39-61% reduziert. Durch Einkreuzung der jeweiligen Population kann ein mäßiger bis hoher genetischer Fortschritt erzielt werden, die Verwendung der KE-Landrasse als Spender war effektiver als die der PE-Landrasse. Dies ist ein vielversprechender Ansatz, um die Resistenz von Elitematerialien gegen GER zu verbessern. Darüber hinaus wurde die Leistung von 76 DH-Linien aus beiden Landrassen zur Vorhersage der GER-Resistenz der entsprechenden Testkreuzungen (TC) verwendet. Für die GER-Resistenz wurde eine mäßige phänotypische und genomische Vorhersagegenauigkeit zwischen TC und der Leistung der Linie festgestellt. Eine Vorselektion von Linien auf GER-Resistenz ist deshalb möglich; die Leistung der TC sollte jedoch in einer späteren Selektionsphase zusätzlich getestet werden, um GER-resistente Hybridsorten zu erhalten

Patients’, Caregivers’, and Providers’ Perceived Strategies for Diabetes Care

Objectives: To explore strategies to improve type 2 diabetes mellitus (T2DM) self-management among low-income and minority groups. Methods: Focus groups centered on T2DM self-care behaviors were conducted using convenient sample of patients with T2DM (N = 17), caregivers (N = 5) and healthcare providers (N = 15). Results: Patients and caregivers perceived strategies included improving patient-provider communication, providers’ accessibility and compassion, and flexible clinic hours. Strategies identified by providers were realistic patient’s expectations, family support, and community resources. Conclusions: To our knowledge, this study is the first to elicit strategies to improve T2DM self-management through a joint meeting of patients, caregivers, and healthcare providers. Study findings could help inform future efforts to assist patients better manage their T2DM

Increased levels of the inflammatory biomarker C-reactive protein at baseline are associated with childhood sickle cell vasocclusive crises

Several lines of evidence suggest that sickle cell disease (SCD) is associated with a chronic inflammatory state. In this study of 70 children with SCD at steady state evaluated by a broad panel of biomarkers representing previously examined mechanisms of pathogenicity in SCD, high sensitivity C-reactive protein (hs-CRP), a marker of low-grade, systemic inflammation, emerged as the most significant laboratory correlate of hospitalizations for pain or vaso-occlusive (VOC) events. While markers of increased haemolytic status, endothelial activation and coagulation activation all correlated positively with VOC events by univariate analysis, baseline hs-CRP levels provided the most significant contribution to the association in multiple regression models (22%), and, hs-CRP, along with age, provided the best fit in negative binomial models. These data highlight the clinical relevance of the role of inflammation in paediatric VOC, providing both a rationale for future therapeutic strategies targeting inflammation in microvessel occlusive complications of SCD, and the potential clinical use of hs-CRP as a biomarker in childhood SCD

N-acetylcysteine reduces oxidative stress in sickle cell patients

Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ0-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress

Sickle Cells Abolish Melanoma Tumorigenesis in Hemoglobin SS Knockin Mice and Augment the Tumoricidal Effect of Oncolytic Virus In Vivo

Insights from the study of cancer resistance in animals have led to the discovery of novel anticancer pathways and opened new venues for cancer prevention and treatment. Sickle cells (SSRBCs) from subjects with homozygous sickle cell anemia (SCA) have been shown to target hypoxic tumor niches, induce diffuse vaso-occlusion, and potentiate a tumoricidal response in a heme- and oxidant-dependent manner. These findings spawned the hypothesis that SSRBCs and the vasculopathic microenvironment of subjects with SCA might be inimical to tumor outgrowth and thereby constitute a natural antitumor defense. We therefore implanted the B16F10 melanoma into humanized hemoglobin SS knockin mice which exhibit the hematologic and vasculopathic sequelae of human SCA. Over the 31-day observation period, hemoglobin SS mice showed no significant melanoma outgrowth. By contrast, 68–100% of melanomas implanted in background and hemoglobin AA knockin control mice reached the tumor growth end point (p < 0.0001). SS knockin mice also exhibited established markers of underlying vasculopathy, e.g., chronic hemolysis (anemia, reticulocytosis) and vascular inflammation (leukocytosis) that differed significantly from all control groups. Genetic differences or normal AA gene knockin do not explain the impaired tumor outgrowth in SS knockin mice. These data point instead to the chronic pro-oxidative vasculopathic network in these mice as the predominant cause. In related studies, we demonstrate the ability of the sickle cell component of this system to function as a therapeutic vehicle in potentiating the oncolytic/vasculopathic effect of RNA reovirus. Sickle cells were shown to efficiently adsorb and transfer the virus to melanoma cells where it induced apoptosis even in the presence of anti-reovirus neutralizing antibodies. In vivo, SSRBCs along with their viral cargo rapidly targeted the tumor and initiated a tumoricidal response exceeding that of free virus and similarly loaded normal RBCs without toxicity. Collectively, these data unveil two hitherto unrecognized findings: hemoglobin SS knockin mice appear to present a natural barrier to melanoma tumorigenesis while SSRBCs demonstrate therapeutic function as a vehicle for enhancing the oncolytic effect of free reovirus against established melanoma

\u3cem\u3eLa carte d’identité\u3c/em\u3e de Jean-Marie Adiaffi ou la quête identitaire à travers la symbolique de l’initiation allégorique

Since the earliest contact between Sub-Saharan Africans and Europeans, European literature tends to erase African history and civilization. Later, after an unsuccessful erasure, colonial literature denigrates it as primitive. Using the “identity card” as a motif in his novel, Jean-Marie Adiaffi exposes the defects of European colonization in its African colonies. Through an approach of allegorical initiation symbolism, Addiaffi revalorizes his culture, tradition, and identity all denied by colonial rule

Effectiveness of introgression of resistance loci for Gibberella ear rot from two European flint landraces into adapted elite maize (Zea mays L.).

European flint landraces are a major class of maize possessing favorable alleles for improving host resistance to Gibberella ear rot (GER) disease which reduces yield and contaminates the grains with mycotoxins. However, the incorporation of these landraces into breeding programs requires a clear understanding of the effectiveness of their introgression into elite materials. We evaluated 15 pre-selected doubled haploid (DH) lines from two European flint landraces, "Kemater Landmais Gelb" (KE) and "Petkuser Ferdinand Rot" (PE), together with two adapted elite flint lines and seven standard lines for GER severity as the main trait, and several adaptation traits (plant height, days to silking, seed-set, plant vigor) across four environments. From this evaluation, three KE DH lines and one PE DH line, with the lowest GER severity, were selected and used as donor parents that were crossed with the two adapted and GER susceptible flint lines (Flint1 and Flint2) to develop six bi-parental DH populations with 34-145 DH lines each. Each DH population was evaluated across two locations. Correlations between GER severity, which was the target trait, and adaptation traits were weak (-0.02 to 0.19). GER severity of lines from PE landrace was on average 2-fold higher than lines from KE landrace, indicating a clear superiority of the KE landrace lines. Mean GER severity of the DH populations was 39.4-61.0% lower than the adapted elite flint lines. All KE-derived DH populations were on average more resistant (27.0-36.7%) than the PE-derived population (51.0%). Highly resistant lines (1.3-5.2%) were found in all of the populations, suggesting that the DH populations can be successfully integrated into elite breeding programs. The findings demonstrate that selected KE landrace lines used as donors were effective in improving GER resistance of the adapted elite inbreds

Variance Components and Correlations between Doubled Haploid Lines from Two European Flint Landraces and Their Corresponding Testcrosses for Gibberella Ear Rot Resistance, Silking Time, and Plant Height in Maize

Predicting the resistance of hybrids from lines is a relevant approach for accelerating the improvement of disease resistance in hybrid breeding. In this study, genetic variation and covariation among 76 DH lines from two flint landraces, Kemater (KE) and Petkuser (PE), and their corresponding testcrosses (TC) were estimated for the first time for this material for Gibberella ear rot (GER), days to silking (DS), and plant height (PHT). Lines and TC were evaluated in four and two environments, respectively, under artificial infection with GER. TC were, on average, 42% less GER infected than their lines. TC matured 3–4 days earlier and were about 110 cm taller than the lines. GER resistance was 10% higher in KE lines and TC than PE lines and TC. Significant (p &lt; 0.001) genotypic and genotype-by-environment interaction variances were found for all traits. Genotypic variances were generally smaller among TC than lines. Broad-sense heritability estimates were moderate to high for GER severity (0.56–0.82) and high for DS (0.78–0.88) and PHT (0.86–0.94) with higher values always observed in lines. Significant, moderate correlations between TC and line per se performance were found for GER resistance in both KE and PE (r = 0.37 and 0.55, respectively). For the two agronomic traits, correlations were higher (r = 0.59–0.76) than for GER resistance. Genomic prediction accuracies were moderate to high for GER resistance (r = 0.49–0.63) and generally higher for DS and PHT. In conclusion, a pre-selection of DH lines for GER resistance should be feasible; however, TC should be additionally tested on a later selection stage to aim for GER-resistant hybrid cultivars