RESUMEN
The outbreak of Fusarium head blight (FHB) poses a serious threat to wheat production as it leads to both significant yield losses and accumulation of several mycotoxins including deoxynivalenol (DON) in the grains, which are harmful to human and livestock. To date, hundreds of FHB-resistance-related quantitative trait loci (QTLs) have been reported, but only a few of them have been cloned and used for breeding. Small interfering RNAs (siRNA) have been reported in plants to mediate host defense against pathogens, but they have rarely been reported in wheat-FHB interaction. In order to identify the key siRNAs that can potentially be used in the improvement of resistance to FHB, siRNAs from the spikes of an FHB-resistant variety Sumai 3 and an FHB-susceptible variety of Chinese Spring (CS) were sequenced after F. graminearum infection and mock inoculation, respectively. The expression patterns of the siRNAs of interest were analyzed. A total of 4019 siRNAs of high-confidence were identified, with 131 being CS-specific, 309 Sumai 3-specific and 3071 being common in both varieties. More than 87% of these siRNAs were 24 nt in length. An overall down-regulation trend was found for siRNAs in the spikes of both varieties after being infected with F. graminearum. The expression patterns for Triticum aestivum Dicer-like 3 (TaDCL3) that synthesizes 24 nt siRNAs were validated by qRT-PCR, which were positively correlated with those of the siRNAs. A total of 85% of the differentially expressed genes putatively targeted by the siRNAs were significantly up-regulated after infection, showing a negative correlation with the overall down-regulated expression of siRNAs. Interestingly, the majority of the up-regulated genes are annotated as disease resistance. These results suggested that the inhibition of siRNA by F. graminearum up-regulated the disease resistance genes, which were putatively suppressed by siRNAs through RNA-directed DNA methylation (RdDM). Consequently, the resistant capability to F. graminearum infection was enhanced. This study provides novel clues for investigating the function of siRNA in wheat-F. graminearum interaction.
Asunto(s)
Fusariosis , Fusarium , Humanos , Triticum/genética , Triticum/metabolismo , Resistencia a la Enfermedad/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Fitomejoramiento , Fusarium/genética , Enfermedades de las Plantas/genéticaRESUMEN
Immune-checkpoint blockade has revolutionized cancer treatment, but some cancers, such as acute myeloid leukemia (AML), do not respond or develop resistance. A potential mode of resistance is immune evasion of T cell immunity involving aberrant major histocompatibility complex class I (MHC-I) antigen presentation (AP). To map such mechanisms of resistance, we identified key MHC-I regulators using specific peptide-MHC-I-guided CRISPR-Cas9 screens in AML. The top-ranked negative regulators were surface protein sushi domain containing 6 (SUSD6), transmembrane protein 127 (TMEM127), and the E3 ubiquitin ligase WWP2. SUSD6 is abundantly expressed in AML and multiple solid cancers, and its ablation enhanced MHC-I AP and reduced tumor growth in a CD8+ T cell-dependent manner. Mechanistically, SUSD6 forms a trimolecular complex with TMEM127 and MHC-I, which recruits WWP2 for MHC-I ubiquitination and lysosomal degradation. Together with the SUSD6/TMEM127/WWP2 gene signature, which negatively correlates with cancer survival, our findings define a membrane-associated MHC-I inhibitory axis as a potential therapeutic target for both leukemia and solid cancers.
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Antígenos de Histocompatibilidad Clase I , Neoplasias , Escape del Tumor , Humanos , Presentación de Antígeno , Linfocitos T CD8-positivos , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos HLA , Neoplasias/inmunología , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer. Here, we describe KaryoCreate (karyotype CRISPR-engineered aneuploidy technology), a system that enables the generation of chromosome-specific aneuploidies by co-expression of an sgRNA targeting chromosome-specific CENPA-binding É-satellite repeats together with dCas9 fused to mutant KNL1. We design unique and highly specific sgRNAs for 19 of the 24 chromosomes. Expression of these constructs leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny, with an average efficiency of 8% for gains and 12% for losses (up to 20%) validated across 10 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, frequent in gastrointestinal cancers, promotes resistance to TGF-ß, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe an innovative technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond.
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Centrómero , Técnicas Genéticas , Humanos , Aneuploidia , Centrómero/genética , Deleción Cromosómica , Neoplasias/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente EspaciadasRESUMEN
BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 overexpression is sufficient to drive resistance to BH3 mimetics in AML. Insensitivity to BH3 mimetics is accompanied by enhanced mitochondria-endoplasmic reticulum interactions and augmented mitophagy flux, which acts as a prosurvival mechanism to eliminate mitochondrial damage. Genetic or pharmacologic MFN2 targeting synergizes with BH3 mimetics by impairing mitochondrial clearance and enhancing apoptosis in AML. SIGNIFICANCE: AML remains one of the most difficult-to-treat blood cancers. BH3 mimetics represent a promising therapeutic approach to eliminate AML blasts by activating the apoptotic pathway. Enhanced mitochondrial clearance drives resistance to BH3 mimetics and predicts poor prognosis. Reverting excessive mitophagy can halt BH3-mimetic resistance in AML. This article is highlighted in the In This Issue feature, p. 1501.
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Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Mitofagia , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Apoptosis , Muerte Celular , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Symbiotic nitrogen fixation boosts legume growth and production in nitrogen-poor soils. It has long been assumed that fixed nitrogen increases reproductive success, but until now, the regulatory mechanism was unknown. Here, we report a symbiotic flowering pathway that couples symbiotic and nutrient signals to the flowering induction pathway in legumes. We show that the symbiotic microRNA-microRNA172c (miR172c) and fixed nitrogen systemically and synergistically convey symbiotic and nutritional cues from roots to leaves to promote soybean (Glycine max) flowering. The combinations of symbiotic miR172c and local miR172c elicited by fixed nitrogen and development in leaves activate florigen-encoding FLOWERING LOCUS T (FT) homologs (GmFT2a/5a) by repressing TARGET OF EAT1-like 4a (GmTOE4a). Thus, FTs trigger reproductive development, which allows legumes to survive and reproduce under low-nitrogen conditions.
Asunto(s)
Glycine max , Fijación del Nitrógeno , Nitrógeno/metabolismo , Fijación del Nitrógeno/fisiología , Glycine max/genética , Simbiosis/fisiología , MicroARNs , ARN de Planta , Genes de PlantasRESUMEN
Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive census of the bone marrow immune microenvironment in adult and pediatric patients with AML. We characterize unique inflammation signatures in a subset of AML patients, associated with inferior outcomes. We identify atypical B cells, a dysfunctional B-cell subtype enriched in patients with high-inflammation AML, as well as an increase in CD8+GZMK+ and regulatory T cells, accompanied by a reduction in T-cell clonal expansion. We derive an inflammation-associated gene score (iScore) that associates with poor survival outcomes in patients with AML. Addition of the iScore refines current risk stratifications for patients with AML and may enable identification of patients in need of more aggressive treatment. This work provides a framework for classifying patients with AML based on their immune microenvironment and a rationale for consideration of the inflammatory state in clinical settings.
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Leucemia Mieloide Aguda , Adulto , Humanos , Niño , Leucemia Mieloide Aguda/genética , Médula Ósea/patología , Linfocitos T Reguladores/patología , Inflamación/patología , Medición de Riesgo , Microambiente TumoralRESUMEN
KEY MESSAGE: Identification and mapping of an inhibitor of Ndhrl1 mediating nitrogen-dependent hypersensitive reaction-like phenotype in wheat. Hypersensitive reaction-like (HRL) traits are characteristic of spontaneous lesions including yellowish spots, brown spots or white-stripe that appeared randomly and dispersedly on all the leaves in the absence of plant pathogens. Our previous studies have shown that the wheat line P7001 showed an HRL trait at low nitrogen supply, and this trait was controlled by the gene Ndhrl1 (Nitrogen-dependent hypersensitive reaction-like 1). In order to investigate the robustness of the trait expression mediated by Ndhrl1 under different genetic backgrounds, seven genetic populations, with P7001 being the common female parent, were constructed and analyzed. F1 plants from six of the seven combinations showed HRL trait and Ndhrl1 segregated in a dominant way of HRL: non-HRL = 3:1 in the six populations (F2). Exceptionally, the F1 plants of P7001/Fielder combination showed non-HRL trait and HRL trait in the F2 population showed a contrasting recessive segregation ratio of HRL: non-HRL = 1:3, suggesting Fielder may have another HRL-related gene. Using 55 K SNP array and PCR-based markers, the HRL-related gene in Fielder was mapped to an interval of 5.63-12.91 Mb on the short arm of chromosome 2B with the flanking markers Yzu660R075552 and Yzu660F075941. A recombinant with genomic region of Fielder at Ndhrl1 locus showing HRL trait demonstrated that Fielder also harbored Ndhrl1 same as P7001. Thus, Fielder carries a single dominant suppressor of Ndhrl1, designated as Ihrl1 (Inhibitor of hypersensitive reaction-like). Interestingly, Ihrl1 is tightly linked to Ndhrl1 and may be also involved in nitrogen metabolic and (or) signaling pathways.
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Nitrógeno , Triticum , Mapeo Cromosómico , Genes Dominantes , Genes de Plantas , Ligamiento Genético , Fenotipo , Enfermedades de las Plantas/genética , Triticum/genéticaRESUMEN
The disease severity and mycotoxin DON content in grains caused by fusarium head blight (FHB) have been two prioritized economical traits in wheat. Reliable phenotyping is a prerequisite for genetically improving wheat resistances to these two traits. In this study, three inoculation methods: upper bilateral floret injection (UBFI), basal bilateral floret injection (BBFI), and basal rachis internode injection (BRII), were applied in a panel of 22 near-isogenic lines (NILs) contrasting in Fhb1 alleles. The results showed that inoculation methods had significant influence on both disease severity and mycotoxin accumulation in grains, and the relationship between them. UBFI method caused chronic FHB symptom characterized as slow progress of the pathogen downward from the inoculation site, which minimized the difference in disease severity of the NILs, but, unexpectedly, maximized the difference in DON content between them. The BBFI method usually caused an acute FHB symptom in susceptible lines characterized as premature spike death (PSD), which maximized the difference in disease severity, but minimized the difference in DON content in grains between resistant and susceptible lines. The BRII method occasionally caused acute FHB symptoms for susceptible lines and had relatively balanced characteristics of disease severity and DON content in grains. Therefore, two or more inoculation methods are recommended for precise and reliable evaluation of the overall resistance to FHB, including resistances to both disease spread within a spike and DON accumulation in grains.
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Fusarium , Micotoxinas , Tricotecenos , Enfermedades de las Plantas , Triticum/genéticaRESUMEN
Fusarium graminearum (F. graminearum) can cause huge yield reductions and contamination of grain with deoxynivalenol (DON), and thus is one of the most problematic pathogen of wheat worldwide. Although great efforts have been paid and great achievements have been made to control the pathogens, there is still a wide gap for understanding the mechanism underlying F. graminearum resistance. Plant LACCASEs (LACs) catalyze the oxidative polymerization of monolignols by reinforcing cell-wall of various cell types to provide mechanical support, xylem sap transportation, and defense against pest and pathogens. To date, little has been known about LAC genes in bread wheat and their potential roles in wheat-F. graminearum interaction. Through systematic analysis of the genome-wide homologs and transcriptomes of wheat, a total of 95 Triticum aestivum laccases (TaLACs) were identified, and 14 of them were responsive to F. graminearum challenge. 3D structure modelings of the 14 TaLAC proteins showed that only TaLAC78 contains the entire activity center for oxidation and the others lack the type 1 copper ion ligand (T1Cu). Both amino acid sequence alignment and three-dimensional reconstruction after amino acid mutation showed that the loss of T1Cu is not only related to variation of the key amino acid coordinating T1Cu, but also closely related to the flanking amino acids. Significantly differential temporal expression patterns of TaLACs suggested that their subfunctionalization might occur. Promoter array analysis indicated that the induction of TaLACs may be closely associated with salicylic acid signaling, dehydration, and low-oxygen stress under F. graminearum infection. Molecular docking simulation demonstrated that TaLACs can not only catalyze lignin as a substrate, but also interact with DON, which may be docked into the binding position of the monolignols, where the LACs recognize substrates. The current study provides clues for exploring the novel functions of TaLACs in wheat resistance to F. graminearum, and TaLACs maybe candidates for conferring a high level of resistance against F. graminearum in wheat.
RESUMEN
Fusarium head blight (FHB) caused by Fusarium graminearum is a worldwide disease which has destructive effects on wheat production, resulting in severe yield reduction and quality deterioration, while FHB-infected wheat grains are toxic to people and animals due to accumulation of fungal toxins. Although impressive progress towards understanding host resistance has been achieved, our knowledge of the mechanism underlying host resistance is still quite limited due to the complexity of wheat-pathogen interactions. In recent years, disease epidemics, the resistance germplasms and components, the genetic mechanism of FHB, and disease management and control, etc., have been well reviewed. However, the resistance mechanism of FHB is quite complex with Type I, II to V resistances. In this review, we focus on the potential resistance mechanisms by linking different resistance types to multi-omics and emphasize the pathways or genes that may play significant roles in the different types of resistance. Deciphering the complicated mechanism of FHB resistance types in wheat at the integral levels based on multi-omics may help discover the genes or pathways that are critical for different FHB resistance, which could then be utilized and manipulated to improve FHB resistance in wheat breeding programs by using transgenic approaches, gene editing, or marker assisted selection strategies.
Asunto(s)
Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Triticum/genética , Triticum/microbiología , Animales , Fusarium/patogenicidad , Humanos , Fitomejoramiento/métodos , Enfermedades de las Plantas/microbiología , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Fusarium head blight (FHB) caused by Fusarium graminearum is a devastating fungal disease of wheat. The mechanism underlying F. graminearum-wheat interaction remains largely unknown. tRNA-derived fragments (tRFs) are RNase-dependent small RNAs derived from tRNAs, and they have not been reported in wheat yet, and whether tRFs are involved in wheat-F. graminearum interactions remains unknown. RESULTS: Herein, small RNAs from the spikelets inoculated with F. graminearum and mock from an FHB-susceptible variety Chinese Spring (CS) and an FHB-resistant variety Sumai3 (SM) were sequenced respectively. A total of 1249 putative tRFs were identified, in which 15 tRFs was CS-specific and 12 SM-specific. Compared with mock inoculation, 39 tRFs were significantly up-regulated across both wheat varieties after F. graminearum challenge and only nine tRFs were significantly down-regulated. tRFGlu, tRFLys and tRFThr were dramatically induced by F. graminearum infection, with significantly higher fold changes in CS than those in SM. The expression patterns of the three highly induced tRFs were further validated by stem-loop qRT-PCR. The accumulation of tRFs were closely related to ribonucleases T2 family members, which were induced by F. graminearum challenge. The tRFs' targets in host were predicted and were validated by RNA sequencing. CONCLUSION: Integrative analysis of the differentially expressed tRFs and their candidate targets indicated that tRFGlu, tRFLys and tRFThr might negatively regulate wheat resistance to FHB. Our results unvealed the potential roles of tRFs in wheat-F. graminearum interactions.
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Fusarium/fisiología , Enfermedades de las Plantas/genética , ARN de Planta/genética , ARN de Transferencia/genética , Triticum/genética , Susceptibilidad a Enfermedades/microbiología , Enfermedades de las Plantas/microbiología , ARN de Planta/metabolismo , ARN de Transferencia/metabolismo , Triticum/metabolismo , Triticum/microbiologíaRESUMEN
Symbiotic nodulation is initiated in the roots of legumes in response to low nitrogen and rhizobial signal molecules and is dynamically regulated by a complex regulatory network that coordinates rhizobial infection and nodule organogenesis. It has been shown that the miR156-SPL module mediates nodulation in legumes; however, conclusive evidence of how this module exerts its function during nodulation remains elusive. Here, we report that the miR156b-GmSPL9d module regulates symbiotic nodulation by targeting multiple key regulatory genes in the nodulation signalling pathway of soybean. miR156 family members are differentially expressed during nodulation, and miR156b negatively regulates nodulation by mainly targeting soybean SQUAMOSA promoter-binding protein-like 9d (GmSPL9d), a positive regulator of soybean nodulation. GmSPL9d directly binds to the miR172c promoter and activates its expression, suggesting a conserved role of GmSPL9d. Furthermore, GmSPL9d was coexpressed with the soybean nodulation marker genes nodule inception a (GmNINa) and GmENOD40-1 during nodule formation and development. Intriguingly, GmSPL9d can bind to the promoters of GmNINa and GmENOD40-1 and regulate their expression. Our data demonstrate that the miR156b-GmSPL9d module acts as an upstream master regulator of soybean nodulation, which coordinates multiple marker genes involved in soybean nodulation.
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Fabaceae , MicroARNs/genética , Rhizobium , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nodulación de la Raíz de la Planta/genética , Rhizobium/fisiología , Glycine max/metabolismo , Simbiosis/genéticaRESUMEN
Wheat (Triticum aestivum L.) spike architecture is an important trait associated with spike development and grain yield. Here, we report a naturally occurring wheat mutant with branched spikelets (BSL) from its wild-type YD-16, which has a normal spike trait and confers a moderate level of resistance to wheat Fusarium head blight (FHB). The lateral meristems positioned at the basal parts of the rachis node of the BSL mutant develop into ramified spikelets characterized as multiple spikelets. The BSL mutant shows three to four-day longer growth period but less 1000-grain weight than the wild type, and it becomes highly susceptible to FHB infection, indicating that the locus controlling the BSL trait may have undergone an intensively artificial and/or natural selection in modern breeding process. The self-pollinated descendants of the lines with the BSL trait consistently segregated with an equal ratio of branched and normal spikelets (NSL) wheat, and homozygotes with the BSL trait could not be achieved even after nine cycles of self-pollination. Distinct segregation patterns both from the self-pollinated progenies of the BSL plants and from the reciprocal crosses between the BSL plants with their sister NSL plants suggested that gametophytic male sterility was probably associated with the heterozygosity for the BSL trait. Transcriptome sequencing of the RNA bulks contrasting in the two types of spike trait at the heading stage indicated that the genes on chromosome 2DS may be critical for the BSL trait formation since 329 out of 2540 differentially expressed genes (DEGs) were located on that chromosome, and most of them were down-regulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that carbohydrate metabolism may be involved in the BSL trait expression. This work provides valuable clues into understanding development and domestication of wheat spike as well as the association of the BSL trait with FHB susceptibility.
RESUMEN
Fusarium head blight (FHB) causes wheat yield loss and mycotoxin (deoxynivalenol, DON) accumulation in wheat kernel. Developing wheat cultivars with overall resistance to both FHB spread within a spike and DON accumulation in kernels is crucial for ensuring food security and food safety. Here, two relatively novel inoculation methods, bilateral floret inoculation (BFI) and basal rachis internode injection (BRII), were simultaneously employed to evaluate disease severity and DON content in kernels in a segregating population of recombinant inbred lines (RILs) developed from Ning 7840 (carrying Fhb1) and Clark (without Fhb1). Under both inoculation methods, four contrasting combinations of disease severity and DON content were identified: high severity/high DON (HSHD), high severity/low DON (HSLD), low severity/high DON (LSHD) and low severity/low DON (LSLD). Unexpectedly, the BRII method clearly indicated that disease severity was not necessarily relevant to DON concentration. The effects of Fhb1 on disease severity, and on DON concentrations, agreed very well across the two methods. Several lines carrying Fhb1 showed extremely higher severity and (or) DON content under both inoculation methods. The "Mahalanobis distance" (MD) method was used to rate overall resistance of a line by inclusion of both disease severity and DON content over both methods to select LSLD lines.
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Fusarium/patogenicidad , Enfermedades de las Plantas/microbiología , Tricotecenos/metabolismo , Triticum/microbiología , Micotoxinas/metabolismoRESUMEN
Fusarium head blight (FHB) is one of the most destructive fungal diseases of wheat. However, difficulties in reliably phenotyping of this disease have greatly hindered the understanding of the mechanism of wheat-pathogen interaction and genetic improvement of FHB resistance. Here we report a novel inoculation method called basal rachis internode injection (BRII), in which inoculum is injected into the basal internode of a rachis instead of a floret, as is done in single floret inoculation (SFI). One of the prominent advantages of BRII over SFI and other traditional methods lies in its independence from the moisture-maintaining system that is necessary for all existing methods, making it insensitive to environmental humidity and hence cost-effective. Another unique feature of BRII is that this method produces nearly clear-cut reaction types, by which FHB resistance can be treated as a qualitative trait because generally no FHB symptoms appear on the spikelets of resistant genotypes. In addition, BRII outperformed SFI with a higher infection rate and better goodness of fit with known FHB resistance and quantitative trait locus components in a panel of 15 genotypes, as well as two populations of recombinant inbred lines segregating in Fhb1. Note that BRII and SFI methods are not mutually exclusive but rather complementary because each method has its own advantages in differentiating FHB resistance between genotypes. Combining these two methods would significantly improve the reliability and consistency of FHB phenotyping in wheat.
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Fusarium , Enfermedades de las Plantas , Reproducibilidad de los Resultados , Triticum/genéticaRESUMEN
Fusarium head blight (FHB) caused by Fusarium graminearum not only results in severe yield losses, but also contaminates wheat grains with deoxynivalenol (DON) toxins. Prevention and control of FHB and DON contamination rely mainly on resistant varieties and fungicides. Selenium (Se) is an essential element for humans and animals, and also a beneficial element for plants. In this work, four Se compounds, i.e., sodium selenite (Na2SeO3), sodium selenate (Na2SeO4), selenomethionine (SeMet) and selenocysteine (SeCys2), were supplemented in a trichothecene biosynthesis induction (TBI) solid medium at different dosages in in vitro experiments. The four Se compounds at the dosage of 20 mgâL-1 were sprayed onto wheat spikes immediately after inoculation at anthesis. All four of the Se compounds significantly inhibited the mycelial growth and DON production in the in vitro experiment; however, in planta, their effects on FHB severity and toxin accumulation in grains were compound-dependent. SeMet consistently negatively regulated fungal growth and DON accumulation both in vitro and in planta, which could be a novel and proconsumer strategy for reducing the detriment of wheat FHB disease and DON accumulation.
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Fungicidas Industriales/farmacología , Fusarium/efectos de los fármacos , Enfermedades de las Plantas/prevención & control , Selenometionina/farmacología , Tricotecenos/metabolismo , Triticum/microbiología , Fusarium/crecimiento & desarrollo , Fusarium/metabolismo , Enfermedades de las Plantas/microbiología , Ácido Selénico/farmacología , Selenocisteína/farmacología , Selenito de Sodio/farmacología , Tricotecenos/toxicidadRESUMEN
Immunity to fungal infections is mediated by cells of the innate and adaptive immune system including Th17 cells. Ca2+ influx in immune cells is regulated by stromal interaction molecule 1 (STIM1) and its activation of the Ca2+ channel ORAI1. We here identify patients with a novel mutation in STIM1 (p.L374P) that abolished Ca2+ influx and resulted in increased susceptibility to fungal and other infections. In mice, deletion of STIM1 in all immune cells enhanced susceptibility to mucosal C. albicans infection, whereas T cell-specific deletion of STIM1 impaired immunity to systemic C. albicans infection. STIM1 deletion impaired the production of Th17 cytokines essential for antifungal immunity and compromised the expression of genes in several metabolic pathways including Foxo and HIF1α signaling that regulate glycolysis and oxidative phosphorylation (OXPHOS). Our study further revealed distinct roles of STIM1 in regulating transcription and metabolic programs in non-pathogenic Th17 cells compared to pathogenic, proinflammatory Th17 cells, a finding that may potentially be exploited for the treatment of Th17 cell-mediated inflammatory diseases.
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Calcio , Células Th17 , Animales , Antifúngicos , Calcio/metabolismo , Canales de Calcio/genética , Humanos , Ratones , Proteínas de Neoplasias , Proteína ORAI1 , Molécula de Interacción Estromal 1/genética , Células Th17/metabolismoRESUMEN
Fusarium head blight (FHB) caused by Fusarium species is a globally important wheat disease. Host resistance to FHB is composed of multiple mechanisms, including resistance to initial infection (type I), disease spread (type II), toxin accumulation (type III), kernel infection (type IV), and yield loss (type V), of which the last three have been less studied. Traditionally, the Fusarium-damaged kernel rate (FDK; percentage of Fusarium-infected grains) from point- or spray-inoculated experiments was used as the parameter for type IV resistance, which may be problematic because of the influence of type II resistance. Here we propose a new definition for type IV resistance: that is, the resistance against Fusarium infection expressed in wheat grains that have the same chance in contact with the pathogen, under favorable temperature and humidity for infection. Fhb1 confers strong type II resistance, leading to significantly reduced FHB severity and FDK. To investigate the role of Fhb1 in type IV resistance, a pair of near-isogenic lines, R22W (Fhb1 carrier, resistant in terms of type II resistance) and S22V (non-Fhb1, susceptible), along with eight wheat genotypes differing at Fhb1 were inoculated at different grain development stages with Fusarium macrospores both in vivo and in vitro. The in vivo experiments with all florets inoculated demonstrated a significant reduction in thousand kernel weight (TKW) in inoculated grains, regardless of their Fhb1 status and developmental stages. Surprisingly, R22W showed more TKW reduction than S22V, which was supported by the scanning electron microscopy observation that confirmed the more severe degradation of starch granules in R22W grains. The in vitro experiments demonstrated that grains from both R22W and S22V promoted fungal colonization, but no significant difference was found between the two lines. In summary, our results indicated that the proposed type IV evaluation system is effective in determining different grain resistance levels, providing novel tools for FHB resistance breeding. The finding that Fhb1 is not associated with type IV resistance enriches our understanding of this gene.
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Fusarium , Grano Comestible , Genotipo , Enfermedades de las Plantas , TriticumRESUMEN
Nitrogen (N) plays a very important role in crop growth and development. Many N-metabolism-related genes responsive to N application have been identified in many plants such as Arabidopsis, rice and maize; however, few genes have been reported in wheat, which is one of the most widely grown crops in the world. In this study, a wheat wild type with N dependent lesion mimic (LM) and its mutants without LM were used to identify conserved N-metabolism-related genes. TaPAP, TaUPS and TaNMR were differentially expressed among N levels both in the wild type and two of its mutants, and the expression patterns of these genes were further studied under application of three chemotypes of N (NH4+ , NO3- and NH4NO3). The results showed that these genes are conserved N-metabolism-related genes and TaNMR is a novel player in N-metabolism.