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Adult Plant Resistance in Maize to Northern Leaf Spot Is a Feature of Partial Loss-of-function Alleles of Hm1

Adult plant resistance (APR) is an enigmatic phenomenon in which resistance genes are ineffective in protecting seedlings from disease but confer robust resistance at maturity. Maize has multiple cases in which genes confer APR to northern leaf spot, a lethal disease caused by Cochliobolus carbonum race 1 (CCR1). The first identified case of APR in maize is encoded by a hypomorphic allele, Hm1A, at the hm1 locus. In contrast, wild type alleles of hm1 provide complete protection at all developmental stages and in every part of the maize plant. Hm1 encodes an NADPH-dependent reductase, which inactivates HC-toxin, a key virulence effector of CCR1. Cloning and characterization of Hm1A ruled out differential transcription or translation for its APR phenotype and identified an amino acid substitution that reduced HC-toxin reductase (HCTR) activity. The possibility of a causal relationship between the weak nature of Hm1A and its APR phenotype was confirmed by the generation of two new APR alleles of Hm1 by mutagenesis. The HCTRs encoded by these new APR alleles had undergone relatively conservative missense changes that partially reduced their enzymatic activity similar to HM1A. No difference in accumulation of HCTR was observed between adult and juvenile plants, suggesting that the susceptibility of seedlings derives from a greater need for HCTR activity, not reduced accumulation of the gene product. Conditions and treatments that altered the photosynthetic output of the host had a dramatic effect on resistance imparted by the APR alleles, demonstrating a link between the energetic or metabolic status of the host and disease resistance affected by HC-toxin catabolism by the APR alleles of HCTR.\n\nAUTHOR SUMMARYAdult plant resistance (APR) is a phenomenon in which disease resistance genes are able to confer resistance at the adult stages of the plant but somehow fail to do so at the seedling stages. Despite the widespread occurrence of APR in various plant diseases, the mechanism underlying this trait remains obscure. It is not due to the differential transcription of these genes, and here we show that it is also not due to the differential translation or activity of the APR alleles of the maize hm1 gene at different stages of development. Using a combination of molecular genetics, biochemistry and physiology, we present multiple lines of evidence that demonstrate that APR is a feature or symptom of weak forms of resistance. While the mature parts of the plant are metabolically robust enough to manifest resistance, seedling tissues are not, leaving them vulnerable to disease. Growth conditions that compromise the photosynthetic output of the plant further deteriorate the ability of the seedlings to protect themselves from pathogens.\n\nOne sentence summaryCharacterization of adult plant resistance in the maize-CCR1 pathosystem reveals a causal link between weak resistance and APR.

pathology

A laboratory demand optimisation project in primary care

BackgroundThere is evidence of increasing use of laboratory tests with substantial variation between clinical teams which is difficult to justify on clinical grounds. The aim of this project was to assess the effect of a demand optimisation intervention on laboratory test requesting in primary care.\n\nMethodsThe intervention comprised educational initiatives, feedback to 55 individual practices on test request rates with ranking relative to other practices, and a small financial incentive for practices to engage and reflect on their test requesting activity. Data on test request numbers were collected from the laboratory databases for consecutive 12 month periods; pre-intervention 2011-12, intervention 2012-13, 2013-14, 2014-15, and post-intervention 2015-16.\n\nResultsThe intervention was associated with a 3.6% reduction in the mean number of profile test requests between baseline and 2015-16, although this was seen only in rural practices. In both rural and urban practices, there was a significant reduction in-between practice variability in request rates. The mean number of HbA1c requests increased from 1.9 to 3.0 per practice patient with diabetes. Variability in HbA1c request rates increased from 23.8% to 36.6%. At all considered time points, test request rates and variability were higher in rural than in urban areas.\n\nConclusionsThe intervention was associated with a reduction in both the volume and between practice variability of profile test requests, with differences noted between rural and urban practices. The increase in HbA1c requests may reflect a more appropriate rate of diabetes monitoring and also the adoption of HbA1c as a diagnostic test.\n\nStrengths & limitations of the studyO_LIWe assessed the effect of a laboratory demand optimisation intervention both on the value and between GP practice variability in laboratory test requesting.\nC_LIO_LIThe changes in laboratory test requesting were separately evaluated for rural and urban GP practices.\nC_LIO_LIOther factors (GP practice organisation, characteristics of general practitioners) potentially affecting between practice differences in laboratory test ordering were not taken into account due to data unavailability.\nC_LIO_LIThe demand management initiative was not accompanied by the cost-effectiveness analysis.\nC_LIO_LIThe demand optimisation intervention was conducted in a Northern Ireland (NI) Western Health and Social Care Trust and the findings have not been independently replicated in any other NI trusts.\nC_LI

pathology

Severely impaired bone material quality in Chihuahua zebrafish resembles classical dominant human osteogenesis imperfecta

AbstractExcessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Since the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how osteogenesis imperfecta manifests at the micro- and nanoscale of bone. In this context, the Chihuahua (Chi/+) zebrafish, carrying a heterozygous glycine substitution in the 1 chain of collagen type I, has recently been proposed as suitable animal model of dominant OI. Similar to human severe OI type III, Chi/+ show skeletal deformities, altered mineralization patterns and a smaller body size. Using a multimodal approach targeting bone quality parameters, this study aims at quantifying the changes in bone morphology, structure and tissue composition of Chi/+ at multiple length scales. Morphological changes were assessed with high-resolution micro-CT imaging and showed that the vertebrae in Chi/+ had a significantly smaller size, thinner cortical shell and distorted shape. Tissue composition in vertebrae was investigated with quantitative backscattered electron microscopy and Fourier-transform infrared spectroscopy, showing higher mean calcium content, greater matrix porosity, as well as lower mineral crystallinity and collagen maturity in comparison to controls. This study provides comprehensive quantitative data on bone quality indices in Chi/+ and thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant osteogenesis imperfecta, both at the whole bone level and the tissue level.

pathology

Profile of Molecular Subtypes of Breast Cancer Among Bangladeshi Women - Audit of Initial Experience

BackgroundReceptor status and molecular subtyping of breast cancer are crucial for patient management. We present here our initial experience on the status of different molecular subtypes and clinicopathological characteristics of invasive breast carcinomas in Bangladeshi population especially in Chittagong zone.\n\nMaterials and methodsA total of 59 histopathologically confirmed cases of invasive ductal carcinoma were selected for this study. Fifteen out of 59 cases were reported as HER2 equivalent and could not be categorized into any subtype because of the lack of availability of fluorescence in situ hybridization. The remaining 44 cases were distributed into different molecular subtypes and then the clinicopathological characteristics were compared for each molecular subtype.\n\nResultsAge ranges from 24-70 years with a mean age of 43.95 years. Most of the patients were in 41-50 years age group. Among the 44 cases, most common subtype was HER2/neu amplification (13 cases, 29.55%). Luminal A, luminal B and basal like subtypes were 11 (25%), 10 (22.73%) and 10 (22.73%) respectively. The mean tumor size was 3.46 cm and the highest mean tumor size was in basal-like subtype (4.01cm). Twenty five out of 59 cases (42.37%) showed axillary lymph node metastasis. Lowest axillary lymph node metastasis was found in luminal A subtype (3/11=27.27%).\n\nConclusionHER2/neu amplification subtype was found to be more common in this region. Luminal A subtype was found to be more favorable in comparison to the other subtypes in terms of axillary lymph node metastasis.

pathology

Deep Convolutional Neural Networks for Breast Cancer Histology Image Analysis

Breast cancer is one of the main causes of cancer death worldwide. Early diagnostics significantly increases the chances of correct treatment and survival, but this process is tedious and often leads to a disagreement between pathologists. Computer-aided diagnosis systems showed potential for improving the diagnostic accuracy. In this work, we develop the computational approach based on deep convolution neural networks for breast cancer histology image classification. Hematoxylin and eosin stained breast histology microscopy image dataset is provided as a part of the ICIAR 2018 Grand Challenge on Breast Cancer Histology Images. Our approach utilizes several deep neural network architectures and gradient boosted trees classifier. For 4-class classification task, we report 87.2% accuracy. For 2-class classification task to detect carcinomas we report 93.8% accuracy, AUC 97.3%, and sensitivity/specificity 96.5/88.0% at the high-sensitivity operating point. To our knowledge, this approach outperforms other common methods in automated histopathological image classification. The source code for our approach is made publicly available at https://github.com/alexander-rakhlin/ICIAR2018

pathology

Non-invasive Assessment of Liver Disease in Rats Using Multiparametric Magnetic Resonance Imaging: A Feasibility Study

Background & AimsNon-invasive quantitation of chronic liver disease using multiparametric MRI has the potential to refine clinical care pathways, trial design and preclinical drug development. The aim of the study was to evaluate the use of multiparametric liver MRI in experimental rat models of chronic liver disease. Methods: Liver injury was induced in male wild-type Sprague-Dawley rats using 4 or 12 weeks carbon tetrachloride (CCl4) intoxication and 4 or 8 weeks methionine and choline deficient (MCD) diet. Liver MRI was performed using a 7.0 Tesla small animal scanner at baseline and specified timepoints after liver injury. Multiparametric liver MRI parameters (T1 mapping, T2* mapping and proton density fat fraction (PDFF)) were correlated with gold standard histopathological measures, assessed by a blinded expert adjudicator. One-way analysis of variance with Tukeys post-hoc test was used to assess differences between groups and Spearmans rank-order correlation to examine associations.\n\nResultsMean hepatic T1 increased significantly in rats treated with CCl4 for 12 weeks compared to controls (1122{+/-}78 ms vs. 959{+/-}114 ms; d=162.7, 95% CI (11.92, 313.4), P=0.038) and correlated strongly with histological collagen content (rs=0.717, P=0.037). In MCD diet-treated rats, hepatic PDFF correlated strongly with histological fat content (rs=0.819, P<0.0001), steatosis grade (rs=0.850, P<0.0001) and steatohepatitis score (rs=0.818, P<0.0001). Although there was minimal histological iron, progressive fat accumulation in MCD diet-treated liver significantly shortened T2*.\n\nConclusionsIn preclinical models, quantitative MRI markers correlated with histopathological assessments, especially for fatty liver disease. Validation in longitudinal studies is required.\n\nKey pointsO_LINon-invasive quantitative measures of chronic liver injury are needed for stratification and monitoring of disease in clinical practice and in drug development\nC_LIO_LIWe adapted and applied a clinically-relevant non-contrast multiparametric MRI protocol in well-established preclinical liver disease models, for simultaneous quantitation of hepatic fat, fibro-inflammatory injury and iron\nC_LIO_LIMultiparametric liver MRI was feasible at 7.0 Tesla in experimental rat models and imaging parameters correlated with gold standard histopathological assessments, especially characteristics of fatty liver disease\nC_LIO_LIFurther development of multiparametric liver MRI could refine drug development strategies and impact upon trial design and clinical care pathways\nC_LI

pathology

Lower performance of Toxoplasma-infected, Rh-negative subjects in the weight holding and hand-grip tests

Toxoplasma, a protozoan parasite of cats, infects many species of intermediate and paratenic hosts, including about one-third of humans worldwide. After a short phase of acute infection, the tissue cysts containing slowly dividing bradyzoites are formed in various organs and toxoplasmosis proceeds spontaneously in its latent form. In immunocompetent subjects, latent toxoplasmosis was considered asymptomatic. However, dozens of studies performed on animals and humans in the past twenty years have shown that it is accompanied by a broad spectrum of specific behavioural, physiological and even morphological changes. In human hosts, the changes often go in the opposite direction in men and women, and are mostly weaker or non-existent in Rh-positive subjects. Here, we searched for the indices of lower endurance of the infected subjects by examining the performance of nearly five hundred university students tested for toxoplasmosis and Rh phenotype in two tests, a weight holding test and a grip test. The results confirmed the existence of a negative association of latent toxoplasmosis with the performance of students, especially Rh-negative men, in these tests. Surprisingly, but in an accordance with some already published data, Toxoplasma-infected, Rh-positive subjects expressed a higher, rather than lower, performance in our endurance tests. Therefore, the results only partly support the hypothesis for the lower endurance of Toxoplasma infected subjects as the performance of Rh-positive subjects (representing majority of population) correlated positively with the Toxoplasma infection.

pathology

A functional landscape of chronic kidney disease entities from public transcriptomic data

To develop efficient therapies and identify novel early biomarkers for chronic kidney disease an understanding of the molecular mechanisms orchestrating it is essential. We here set out to understand how differences in CKD origin are reflected in gene expression. To this end, we integrated publicly available human glomerular microarray gene expression data for nine kidney disease entities that account for a majority of CKD worldwide. We included data from five distinct studies and compared glomerular gene expression profiles to that of non-tumor parts of kidney cancer nephrectomy tissues. A major challenge was the integration of the data from different sources, platforms and conditions, that we mitigated with a bespoke stringent procedure. This allowed us to perform a global transcriptome-based delineation of different kidney disease entities, obtaining a landscape of their similarities and differences based on the genes that acquire a consistent differential expression between each kidney disease entity and nephrectomy tissue. Furthermore, we derived functional insights by inferring activity of signaling pathways and transcription factors from the collected gene expression data, and identified potential drug candidates based on expression signature matching. We validated representative findings by immunostaining in human kidney biopsies indicating e.g. that the transcription factor FOXM1 is significantly and specifically expressed in parietal epithelial cells in RPGN whereas not expressed in control kidney tissue. These results provide a foundation to comprehend the specific molecular mechanisms underlying different kidney disease entities, that can pave the way to identify biomarkers and potential therapeutic targets. To facilitate this, we provide our results as a free interactive web application: https://saezlab.shinyapps.io/ckd_landscape/. Translational StatementChronic kidney disease is a combination of entities with different etiologies. We integrate and analyse transcriptomics analysis of glomerular from different entities to dissect their different pathophysiology, what might help to identify novel entity-specific therapeutic targets.

pathology

The Constriction Ring of Amniotic Band Syndrome Reveals Idiosyncrasies of Wound Repair in Infancy

We hypothesized that the constriction rings in Amniotic Band Syndrome (ABS) are the sequelae of localized mechanical injury. Typical scarring pattern was examined in skin tissue of ABS origin, containing an amniotic band constriction, for collagen and elastin distribution, and the ratio of collagen I to collagen III (CI:CIII). A skin sample from an extra finger was the control. In the ABS specimens, sub-epidermal structures were intact and present throughout, and collagen I exhibited a normal basket-weave pattern. At the site of constriction in both ABS samples, reticular dermis elastin fibers were fragmented and papillary dermis elastin fibers were absent. In the control tissue, the reticular dermis contained relatively thick, branching fibers of elastin, and papillary dermis elastin was present.\n\nThe elastin fragmentation at the constriction ring indicates localized elastin remodeling in response to injury. The absence of elastin in the papillary dermis of the constriction likely indicates a localized disruption in elastin formation. The formation and deposition of collagen and the presence of sub-epidermal structures favor a non-scarring phenotype, while the organization of elastin favors that of localized scarring.\n\nSummary StatementA rare, fetal model of healing after constrictive injury of skin, in which elastin fragmentation at the constriction injury indicates remodeling explained by the differential expression of elastin during gestation.

pathology

Exosomes and exosomal miRNAs from muscle-derived fibroblasts promote skeletal muscle fibrosis

We investigated in vitro and in vivo the pro-fibrotic role of exosomes released by muscle-derived fibroblasts of Duchenne muscular dystrophy (DMD) patients, and of miRNAs carried by exosomes. We found that exosomes from DMD fibroblasts, but not from myoblasts, had significantly higher levels of miR-199a-5p, a miRNA up-regulated in fibrotic conditions, compared to control exosomes. In control fibroblasts, exposure to DMD fibroblast-derived exosomes induced a myofibroblastic phenotype with increase in -smooth actin, collagen and fibronectin transcript and protein expression, soluble collagen production and deposition, cell proliferation, and activation of Akt and ERK signalling, while exposure to control exosomes did not. These findings were related to transfer of high levels of miR-199a-5p and to reduction of its target caveolin-1. Finally, injection of DMD fibroblast-derived exosomes into mouse tibialis anterior muscle after cardiotoxin-induced necrosis, produced greater fibrosis than control exosomes.\n\nOur findings indicate that exosomes produced by local fibroblasts in the DMD muscle are able to induce phenotypic conversion of normal fibroblasts to myofibroblasts thereby increasing the fibrotic response; and suggest miR-199a-5p and caveolin-1as potential therapeutic targets.

pathology

Light Pollution Increases West Nile Virus Competence in a Ubiquitous Passerine Reservoir Species

One sentence summaryLight pollution increases host infectiousness.\n\nAbstractLight pollution is a growing problem, but its impacts on infectious disease risk have not been considered. Previous research has revealed that dim light at night (dLAN) dysregulates various immune functions and biorhythms, which hints that dLAN could change the risk of disease epidemics. Here, we demonstrate that dLAN enhances infectiousness of the house sparrow (Passer domesticus), an urban-dwelling avian host of West Nile virus (WNV). Sparrows exposed to dLAN maintained viral titers above the transmission threshold to a biting vector (105 plaque-forming units) for two days longer than controls but did not die at higher rates. A mathematical model revealed that such effects could increase WNV outbreak potential by ~41%. dLAN likely affects other host and vector traits relevant to transmission, so additional research is needed to advise management of zoonotic diseases in light polluted areas.

pathology

A novel model for the induction of postnatal murine hip deformity

Acetabular dysplasia is a recognized cause of hip osteoarthritis (OA). A paucity of animal models exists to investigate structural and functional changes that mediate morphology of the dysplastic hip and drive the subsequent arthritic cascade. Utilizing a novel murine model, this study investigated the role of surgically-induced unilateral instability of the postnatal hip on the initiation and progression of acetabular dysplasia and impingement up to 8-weeks post-injury. Specifically, C57BL6 mice were used to develop titrated levels of hip instability (mild, moderate, severe, and femoral head removal) at 3-weeks of age, a critical time for hip maturation. Joint shape, acetabular coverage, histomorphology, immunohistochemistry, and statistical shape modeling were used to assess overall quality of joint health and three-dimensional hip shape following 8 weeks of titrated destabilization. This titrated approach included mild, moderate, severe, and complete instability via surgical destabilization of the murine hip. Acetabular coverage was reduced following severe, but not moderate, instability. Moderate instability induced lateralization of the femoral head without dislocation, whereas severe instability led to complete dislocation and formation of pseudoacetabula. Mild instability did not result in statistically significant morphological changes to the hip. Complete destabilization via femoral head removal led to reduced joint space volume and reduced bone volume ratio in the remnant proximal femur. Collectively, these results support the notion that hip instability, driven by loss of function, leads to morphometric changes in the maturing mouse hip. This model could be useful for future studies investigating the mechanical and cellular adaptations to hip instability during maturation.

pathology

Patterns of recurrence after curative-intent surgery for pancreas cancer reinforce the importance of locoregional control and adjuvant chemotherapy.

IntroductionThe pattern of recurrence after surgical excision of pancreas cancer may guide alternative pre-operative strategies to either detect occult disease or need for chemotherapy. This study investigated patterns of recurrence after pancreatic surgery.\n\nMethodsRecurrence patterns were described in a series of resected pancreas cancers over a 2-year period and recurrence risk expressed as odds ratio (OR) with 95% confidence interval (C.I.). Survival was displayed by Kaplan-Meier curves.\n\nResultsOf 107 pancreas resections, 69 (65%) had pancreatic cancer. R0 resection was achieved in 21 of 69 (30.4%). Analysis was based on 66 patients who survived 30 days after surgery with median follow up 21 months. Recurrence developed in 41 (62.1%) patients with median time to first recurrence of 13.3 months (interquartile range 6.9, 20.8 months). Recurrence site was most frequently locoregional (n=28, 42%), followed by liver (n=23, 35%), lymph nodes (n=21, 32%), and lungs (n=13, 19%). In patients with recurrence, 9 of 41 had single site recurrence; the remaining 32 patients had more than one site of recurrence. Locoregional recurrence was associated with R+ resection (53% vs 25% for R+ vs R0, respectively; OR 3.5, 95% C.I. 1.1-11.2; P=0.034). Venous invasion was associated with overall recurrence risk (OR 3.3, 95% C.I. 1.1-9.4; P=0.025). In multivariable analysis, R-stage and adjuvant chemotherapy predicted longer survival.\n\nDiscussionThe predominant locoregional recurrence pattern, multiple sites of recurrence and a high R+ resection rate reflect the difficulty in achieving initial local disease control.

pathology

Quantitative Temporal Analysis of Protein Dynamics in Maladaptive Cardiac Remodeling

Maladaptive cardiac remodeling (MCR) is a complex dynamic process common to many heart diseases. MCR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of MCR, but greater insight into the processes and mechanisms has the potential to identify new therapeutic targets. To provide a deeper understanding of this important cardiac process, we applied a new proteomic technique, PALM (Pulse Azidohomoalanine in Mammals), to quantitate the newly-synthesized protein (NSP) changes during the progression of isoproterenol (ISO)-induced MCR in the mouse left ventricle. This analysis revealed a complex combination of adaptive and maladaptive alterations at acute and prolonged time points including the identification of proteins not previously associated with MCR. We also combined the PALM dataset with our published protein turnover rate dataset to identify putative biochemical mechanisms underlying MCR. The novel integration of analyzing NSPs together with their protein turnover rates demonstrated that alterations in specific biological pathways (e.g., inflammation and oxidative stress) are produced by differential regulation of protein synthesis and degradation.

pathology

Kynurenine 3-monooxygenase (KMO) is a critical regulator of renal ischemia-reperfusion injury

Acute kidney injury (AKI) following ischemia-reperfusion injury (IRI) has a high mortality and lacks specific therapies. Here, we report that mice lacking kynurenine 3-monooxygenase (KMO) activity (Kmonull mice) are protected against AKI after renal IRI. This advances our previous work showing that KMO blockade protects against acute lung injury and AKI in experimental multiple organ failure caused by acute pancreatitis. We show that KMO is highly expressed in the kidney and exerts major metabolic control over the biologically-active kynurenine metabolites 3-hydroxykynurenine, kynurenic acid and downstream metabolites. In experimental AKI induced by unilateral kidney IRI, Kmonull mice had preserved renal function, reduced renal tubular cell injury, and fewer infiltrating neutrophils compared to wild-type (Kmowt) control mice. Together, these data confirm that flux through KMO contributes to AKI after IRI, and supports the rationale for KMO inhibition as a therapeutic strategy to protect against AKI during critical illness.

pathology

Epigallocatechin-3-Gallate Improves Facial Dysmorphology Associated with Down Syndrome

In Down syndrome (DS), the overall genetic imbalance caused by trisomy of chromosome 21 leads to a complex pleiotropic phenotype that involves a recognizable set of facial traits. Several studies have shown the potential of epigallocatechin-3-gallate (EGCG), a green tea flavanol, as a therapeutic tool for alleviating different developmental alterations associated with DS, such as cognitive impairment, skull dysmorphologies, and skeletal deficiencies. Here we provide for the first time experimental and clinical evidence of the potential benefits of EGCG treatment to facial morphology. Our results showed that mouse models treated with low dose of EGCG during pre- and postnatal development improved facial dysmorphology. However, the same treatment at high dose produced disparate facial morphology changes with an extremely wide and abnormal range of variation. Our observational study in humans revealed that EGCG treatment since early in development is associated with intermediate facial phenotypes and significant facial improvement scores. Overall, our findings suggest a potential beneficial effect of ECGC on facial development, which requires further research to pinpoint the optimal dosages of EGCG that reliably improve DS phenotypes. Current evidence warns against the non-prescribed intake of this supplement as a health-promoting measure.

pathology

Automated sequential chromogenic IHC double staining with two HRP substrates.

Automated IHC double staining using DAB and HRP Magenta is illustrated utilizing a new acid block with sulfuric acid to prevent cross-reactivity. Residual cross-reactivity in double staining is determined to arise from chromogenic-bound antibodies and amplification system during the first part of the double staining.

pathology

Detection of race-specific resistance against Puccinia coronata f. sp. avenae in Brachypodium species

Oat crown rust caused by Puccinia coronata f. sp. avenae is the most destructive foliar disease of cultivated oat. Characterization of genetic factors controlling resistance responses to Puccinia coronata f. sp. avenae in non-host species could provide new resources for developing disease protection strategies in oat. We examined symptom development and fungal colonization levels of a collection of Brachypodium distachyon and B. hybridum accessions infected with three North American P. coronata f. sp. avenae isolates. Our results demonstrated that colonization phenotypes are dependent on both host and pathogen genotypes, indicating a role for race-specific responses in these interactions. These responses were independent of the accumulation of reactive oxygen species. Expression analysis of several defense-related genes suggested that salicylic acid and ethylene-mediated signaling, but not jasmonic acid are components of resistance reaction to P. coronata f. sp. avenae. Our findings provide the basis to conduct a genetic inheritance study to examine if effector-triggered immunity contributes to non-host resistance to P. coronata f. sp. avenae in Brachypodium species.

pathology