Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Tomato 14-3-3 Protein 7 Positively Regulates Immunity-Associated Programmed Cell Death by Enhancing Protein Abundance and Signaling Ability of MAPKKK α[C][W]

14-3-3 proteins bind and regulate phosphorylated client proteins involved in diverse biological processes in eukaryotic organisms. This work reports that a tomato 14-3-3 protein regulates plant immunity by altering the abundance of a positive regulator of cell death

Identification of a Second Asian Soybean Rust Resistance Gene in Hyuuga Soybean

Asian soybean rust (ASR) is an economically significant disease caused by the fungus Phakopsora pachyrhizi. The soybean genes Rpp3 and Rpp?(Hyuuga) confer resistance to specific isolates of the pathogen. Both genes map to chromosome 6 (Gm06) (linkage group [LG] C2). We recently identified 12 additional soybean accessions that harbor ASR resistance mapping to Gm06, within 5 centimorgans of Rpp3 and Rpp?(Hyuuga). To further characterize genotypes with resistance on Gm06, we used a set of eight P. pachyrhizi isolates collected from geographically diverse areas to inoculate plants and evaluate them for differential phenotypic responses. Three isolates elicited different responses from soybean accessions PI 462312 (Ankur) (Rpp3) and PI 506764 (Hyuuga) (Rpp?[Hyuuga]). In all, 11 of the new accessions yielded responses identical to either PI 462312 or Hyuuga and 1 of the new accessions, PI 417089B (Kuro daizu), differed from all others. Additional screening of Hyuuga-derived recombinant inbred lines indicated that Hyuuga carries two resistance genes, one at the Rpp3 locus on Gm06 and a second, unlinked ASR resistance gene mapping to Gm03 (LG-N) near Rpp5. These findings reveal a natural case of gene pyramiding for ASR resistance in Hyuuga and underscore the importance of utilizing multiple isolates of P. pachyrhizi when screening for ASR resistance

MAPKKKα is a positive regulator of cell death associated with both plant immunity and disease

Many plant pathogens cause disease symptoms that manifest over days as regions of localized cell death. Localized cell death (the hypersensitive response; HR) also occurs in disease-resistant plants, but this response appears within hours of attempted infection and may restrict further pathogen growth. We identified a MAP kinase kinase kinase gene (MAPKKKα) that is required for the HR and resistance against Pseudomonas syringae. Significantly, we found that MAPKKKα also regulates cell death in susceptible leaves undergoing P. syringae infection. Overexpression of MAPKKKα in leaves activated MAPKs and caused pathogen-independent cell death. By overexpressing MAPKKKα in leaves and suppressing expression of various MAPKK and MAPK genes by virus-induced gene silencing, we identified two distinct MAPK cascades that act downstream of MAPKKKα. These results demonstrate that signal transduction pathways associated with both plant immunity and disease susceptibility share a common molecular switch

Genetic relationships in an international collection of Puccinia horiana isolates based on newly identitfied molecular markers and demonstration of recombination

The obligate biotrophic pathogen Puccinia horiana is the causal agent of chrysanthemum white rust. Although P. horiana is a quarantine organism, it was able to spread to most chrysanthemum producing regions in the world since the 1960’s, however, the transfer routes are largely obscure. An extremely low level of allelic diversity was observed in a geographically diverse set of eight isolates using Complexity Reduction of Polymorphic Sequences (CRoPS) technology. Only 184 of the 16,196 contigs (1.1 %) showed one or more single nucleotide polymorphisms (SNPs). Thirty two SNPs and one simple sequence repeat (SSR) were translated into molecular markers and used to genotype 45 isolates originating from North and South America, Asia and Europe. Phylogenetic clustering was in most cases related to geographic origin, indicating local establishment. The European isolates mostly grouped in two major populations that may relate to the two historic introductions previously reported. However, evidence of recent geographical transfer was also observed, including transfer events between Europe and South America and between South-East Asia and Europe. In contrast with the presumed clonal propagation of this microcyclic rust, strong indications of marker recombination were observed, presumably as a result of anastomosis, karyogamy and somatic meiosis. Recombination and transfer also explain the geographical dispersal of specific markers. A near-to-significant correlation between the genotypic data and previously obtained pathotype data was observed and one marker was associated withthe most virulent pathotype group. In combination with a fast SNP detection method, the markers presented here will be helpful tools to further elucidate the transfer pathways and local survival of this pathogen

Detection and characterization of fungus (Magnaporthe oryzae pathotype Triticum) causing wheat blast disease on rain-fed grown wheat (Triticum aestivum L.) in Zambia.

Wheat blast caused by Magnaporthe oryzae pathotype Triticum (MoT) is a threat to wheat production especially in the warmer-humid environments. In Zambia, wheat blast symptoms were observed for the first time on wheat (Triticum aestivum L.) grown in experimental plots and five farmers' fields in Mpika district of Muchinga Province during the 2017-18 rainy season. Infected plants showed the typical wheat blast symptoms with the spike becoming partially or completely bleached with the blackening of the rachis in a short span of time. Incidence of blast symptoms on nearly all wheat heads was high and ranged from 50 to 100%. Examination of diseased plant leaves showed the presence of elliptical, grayish to tan necrotic lesions with dark borders on the leaf often mixed with other foliar diseases. A study was conducted to isolate and identify the causal pathogen(s) using classical and molecular methods and determine the pathogenicity of the detected disease causal agent. Morphobiometrical determination of causal pathogen revealed conidia with characteristic pear shaped 2-septate hyaline spores associated with M. oryzae species. Preliminary polymerase chain reaction screening of six isolates obtained from wheat blast infected samples with diagnostic primers (MoT3F/R) was conducted at ZARI, Zambia, and subsequent analysis of two isolates with MoT3F/R and C17F/R was performed at USDA-ARS, USA. Both experiments confirmed that MoT is the causal agent of wheat blast in Zambia. Further, pathogenicity tests performed with pure culture isolates from samples WS4 and WS5 produced typical blast symptoms on all the six inoculated wheat genotypes. Results of this study indicate that MoT is causing wheat blast in rain-fed wheat grown in Zambia, thus making it the first report of MoT in Zambia and Africa. This inter-continental movement of the pathogen (disease) has serious implication for wheat production and trade that needs to be urgently addressed

Preliminary assessment of resistance among U.S. wheat cultivars to the Triticum pathotype of Magnaporthe oryzae

Citation: Cruz, C., . . . & Peterson, G. (2009). Preliminary Assessment of Resistance Among U.S. Wheat Cultivars to the Triticum Pathotype of Magnaporthe oryzae. Plant Disease, 96, 1501-1505. https://doi.org/10.1094/PDIS-11-11-0944-REMagnaporthe oryzae is the causal agent of blast disease on several graminaceous plants. The M. oryzae population causing wheat blast has not been officially reported outside South America. Wheat production in the United States is at risk to this pathogen if it is introduced and established. Proactive testing of U.S. wheat cultivars for their reaction to blast and identification of resistance resources is crucial due to the national and global importance of the U.S. wheat industry. In this preliminary study, the phenotypic reaction of 85 U.S. wheat cultivars to M. oryzae (Triticum pathotype) was determined. Although there was a significant correlation in the reaction to blast at the seedling and adult plant stages, only 57% of the head reaction was explained by the seedling reaction. Because of the importance of disease development at the head stage in the field, assessment of all 85 cultivars occurred at the head stage. Among cultivars tested, a continuum in severity to head blast was observed; cultivars Everest and Karl 92 were highly susceptible with more than 90% disease severity, while cultivars Postrock, JackPot, Overley, Jagalene, Jagger, and Santa Fe showed less than 3% infection. No evidence of the presence of physiological races among isolates T-7, T-12, T-22, and T-25 was found

<i>Pp</i>EC23 is a modular SSCRP that is present in diverse <i>P</i>. <i>pachyrhizi</i> isolates.

<p>A. Diagram depicting the different motifs of <i>Pp</i>EC23. SP, signal peptide; CM1, ten-cysteine motif 1; L, linker; CM2, ten-cysteine motif 2; CTLC, C-terminal low complexity motif. B. Sequence alignment of the two CMs in <i>Pp</i>EC23 (top) and the consensus sequence of CM for all members of cluster 112, generated by WebLogo (bottom). C. Genomic structure of the <i>PpEC23</i> gene. Colors of the exons shown as blocks correspond with motif colors in panel A. Arrows show the SNPs, together with the nucleotide position, among ten geographically distinct isolates. Hollow gray, solid gray and black arrows show the intron SNPs, synonymous SNPs, and nonsynonymous SNPs, respectively. D. Transcript levels of <i>Pp</i>EC23 at different developmental stages. Transcript levels were normalized to the expression of the fungal reference genes, <i>RPS14</i> and <i>PDK</i>. Three independent biological and four technical replicates were performed. Error bars = standard deviation. E. The <i>Pp</i>EC23 signal peptide directs protein secretion in yeast. Fusion constructs of <i>Pp</i>EC23 in the secretion signal trap plasmid: 1) pSuc2t7M13ori::<i>Pp</i>EC23, 2) pSuc2t7M13ori::<i>Pp</i>EC23_ns, 3) pSuc2t7M13ori::<i>Pp</i>EC23Sp-CM1-L, 4) pSuc2t7M13ori::<i>Pp</i>EC23L-CM2-CTLC, 5) pSuc2t7M13ori::<i>Pp</i>EC23Sp, 6) pSuc2t7M13ori EV control. YPRAA and CMD/-W indicates the selective and non-selective medium, respectively. Numbers below indicate the fold dilution of the yeast strains. F. Symptoms on leaves of <i>N</i>. <i>tabacum</i> cv. Xanthi (left) and <i>G</i>. <i>max</i> cv. Williams 82 (middle) infiltrated with <i>Pst</i> DC3000 carrying EV, <i>Pp</i>EC23_ns, and various truncated constructs of <i>Pp</i>EC23. The name and structural diagram of each construct is provided in the right panel. Leaves were infiltrated with bacteria at OD _{600 nm} = 0.02. Leaves were photographed at 18 hpi for tobacco (left) and at 30 hpi for Williams 82 soybean (middle). Representative images are shown (n ≥ 8).</p

Gene Flow between Divergent Cereal- and Grass-Specific Lineages of the Rice Blast Fungus Magnaporthe oryzae

Delineating species and epidemic lineages in fungal plant pathogens is critical to our understanding of disease emergence and the structure of fungal biodiversity and also informs international regulatory decisions. Pyricularia oryzae (syn. Magnaporthe oryzae) is a multihost pathogen that infects multiple grasses and cereals, is responsible for the most damaging rice disease (rice blast), and is of growing concern due to the recent introduction of wheat blast to Bangladesh from South America. However, the genetic structure and evolutionary history of M. oryzae, including the possible existence of cryptic phylogenetic species, remain poorly defined. Here, we use whole-genome sequence information for 76 M. oryzae isolates sampled from 12 grass and cereal genera to infer the population structure of M. oryzae and to reassess the species status of wheat-infecting populations of the fungus. Species recognition based on genealogical concordance, using published data or extracting previously used loci from genome assemblies, failed to confirm a prior assignment of wheat blast isolates to a new species (Pyricularia graminis-tritici). Inference of population subdivisions revealed multiple divergent lineages within M. oryzae, each preferentially associated with one host genus, suggesting incipient speciation following host shift or host range expansion. Analyses of gene flow, taking into account the possibility of incomplete lineage sorting, revealed that genetic exchanges have contributed to the makeup of multiple lineages within M. oryzae. These findings provide greater understanding of the ecoevolutionary factors that underlie the diversification of M. oryzae and highlight the practicality of genomic data for epidemiological surveillance in this important multihost pathogen. IMPORTANCE Infection of novel hosts is a major route for disease emergence by pathogenic microorganisms. Understanding the evolutionary history of multihost pathogens is therefore important to better predict the likely spread and emergence of new diseases. Magnaporthe oryzae is a multihost fungus that causes serious cereal diseases, including the devastating rice blast disease and wheat blast, a cause of growing concern due to its recent spread from South America to Asia. Using whole-genome analysis of 76 fungal strains from different hosts, we have documented the divergence of M. oryzae into numerous lineages, each infecting a limited number of host species. Our analyses provide evidence that interlineage gene flow has contributed to the genetic makeup of multiple M. oryzae lineages within the same species. Plant health surveillance is therefore warranted to safeguard against disease emergence in regions where multiple lineages of the fungus are in contact with one another