Background
The Stent‐In 2 trial randomized patients with malignant colonic obstruction to emergency surgery or stent placement as a bridge to elective surgery. The aim of this study was to compare ...the oncological outcomes.
Methods
Disease recurrence, and disease‐free, disease‐specific and overall survival were evaluated, including a subgroup analysis of patients with a stent‐ or guidewire‐related perforation.
Results
Of 98 patients included in the original Stent‐In 2 trial, patients with benign (16) or incurable (23) disease were excluded from this study, along with a patient who had withdrawn from the trial. Of the remaining 58 patients, 32 were randomized to emergency surgery (31 resection, 1 stoma only) and 26 to stenting. Unsuccessful stenting required emergency surgery in six patients owing to wire or stent perforation. Locoregional or distant disease recurrence developed in nine of 32 patients in the emergency surgery group and 13 of 26 in the stent group. Disease‐free survival was worse in the subgroup with stent‐ or guidewire‐related perforation. Five of six patients in this subgroup developed a recurrence, compared with nine of 32 in the emergency surgery group and eight of 20 who had unperforated stenting.
Conclusion
Stent placement for malignant colonic obstruction was associated with a risk of recurrence in this trial, but the numbers are small. There is not enough evidence to refute the approach strongly. Registration number: ISRCTN46462267 (
http://www.controlled‐trials.com).
A cautionary note
Plants have an innate immunity system to defend themselves against pathogens. With the primary immune system, plants recognize microbe-associated molecular patterns (MAMPs) of potential pathogens ...through pattern recognition receptors (PRRs) that mediate a basal defense response. Plant pathogens suppress this basal defense response by means of effectors that enable them to cause disease. With the secondary immune system, plants have gained the ability to recognize effector-induced perturbations of host targets through resistance proteins (RPs) that mediate a strong local defense response that stops pathogen growth. Both primary and secondary immune responses in plants depend on germ line-encoded PRRs and RPs. During induction of local immune responses, systemic immune responses also become activated, which predispose plants to become more resistant to subsequent pathogen attacks. This review gives an update on recent findings that have enhanced our understanding of plant innate immunity and the arms race between plants and their pathogens.
Summary
During tomato leaf colonization, the biotrophic fungus Cladosporium fulvum secretes several effector proteins into the apoplast. Eight effectors have previously been characterized and show no ...significant homology to each other or to other fungal genes. To discover novel C. fulvum effectors that might play a role in virulence, we utilized two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) to visualize proteins secreted during C. fulvum–tomato interactions. Three novel C. fulvum proteins were identified: CfPhiA, Ecp6 and Ecp7. CfPhiA shows homology to proteins found on fungal sporogenous cells called phialides. Ecp6 contains lysin motifs (LysM domains) that are recognized as carbohydrate‐binding modules. Ecp7 encodes a small, cysteine‐rich protein with no homology to known proteins. Heterologous expression of Ecp6 significantly increased the virulence of the vascular pathogen Fusarium oxysporum on tomato. Furthermore, by RNA interference (RNAi)‐mediated gene silencing we demonstrate that Ecp6 is instrumental for C. fulvum virulence on tomato. Hardly any allelic variation was observed in the Ecp6 coding region of a worldwide collection of C. fulvum strains. Although none of the C. fulvum effectors identified so far have obvious orthologues in other organisms, conserved Ecp6 orthologues were identified in various fungal species. Homology‐based modelling suggests that the LysM domains of C. fulvum Ecp6 may be involved in chitin binding.
Mycosphaerellaceae – Chaos or clarity? Videira, S.I.R.; Groenewald, J.Z.; Nakashima, C. ...
Studies in mycology,
06/2017, Letnik:
87, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The Mycosphaerellaceae represent thousands of fungal species that are associated with diseases on a wide range of plant hosts. Understanding and stabilising the taxonomy of genera and species of ...Mycosphaerellaceae is therefore of the utmost importance given their impact on agriculture, horticulture and forestry. Based on previous molecular studies, several phylogenetic and morphologically distinct genera within the Mycosphaerellaceae have been delimited. In this study a multigene phylogenetic analysis (LSU, ITS and rpb2) was performed based on 415 isolates representing 297 taxa and incorporating ex-type strains where available. The main aim of this study was to resolve the phylogenetic relationships among the genera currently recognised within the family, and to clarify the position of the cercosporoid fungi among them. Based on these results many well-known genera are shown to be paraphyletic, with several synapomorphic characters that have evolved more than once within the family. As a consequence, several old generic names including Cercosporidium, Fulvia, Mycovellosiella, Phaeoramularia and Raghnildiana are resurrected, and 32 additional genera are described as new. Based on phylogenetic data 120 genera are now accepted within the family, but many currently accepted cercosporoid genera still remain unresolved pending fresh collections and DNA data. The present study provides a phylogenetic framework for future taxonomic work within the Mycosphaerellaceae.
We sequenced and compared the genomes of the Dothideomycete fungal plant pathogens Cladosporium fulvum (Cfu) (syn. Passalora fulva) and Dothistroma septosporum (Dse) that are closely related ...phylogenetically, but have different lifestyles and hosts. Although both fungi grow extracellularly in close contact with host mesophyll cells, Cfu is a biotroph infecting tomato, while Dse is a hemibiotroph infecting pine. The genomes of these fungi have a similar set of genes (70% of gene content in both genomes are homologs), but differ significantly in size (Cfu >61.1-Mb; Dse 31.2-Mb), which is mainly due to the difference in repeat content (47.2% in Cfu versus 3.2% in Dse). Recent adaptation to different lifestyles and hosts is suggested by diverged sets of genes. Cfu contains an α-tomatinase gene that we predict might be required for detoxification of tomatine, while this gene is absent in Dse. Many genes encoding secreted proteins are unique to each species and the repeat-rich areas in Cfu are enriched for these species-specific genes. In contrast, conserved genes suggest common host ancestry. Homologs of Cfu effector genes, including Ecp2 and Avr4, are present in Dse and induce a Cf-Ecp2- and Cf-4-mediated hypersensitive response, respectively. Strikingly, genes involved in production of the toxin dothistromin, a likely virulence factor for Dse, are conserved in Cfu, but their expression differs markedly with essentially no expression by Cfu in planta. Likewise, Cfu has a carbohydrate-degrading enzyme catalog that is more similar to that of necrotrophs or hemibiotrophs and a larger pectinolytic gene arsenal than Dse, but many of these genes are not expressed in planta or are pseudogenized. Overall, comparison of their genomes suggests that these closely related plant pathogens had a common ancestral host but since adapted to different hosts and lifestyles by a combination of differentiated gene content, pseudogenization, and gene regulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plant pathogens use a complex arsenal of weapons, such as toxic secondary metabolites, to invade and destroy their hosts. Knowledge of how secondary metabolite pathways evolved is central to ...understanding the evolution of host specificity. The secondary metabolite dothistromin is structurally similar to aflatoxins and is produced by the fungal pine pathogen Dothistroma septosporum. Our study focused on dothistromin genes, which are widely dispersed across one chromosome, to determine whether this unusual distributed arrangement evolved from an ancestral cluster.
We combined comparative genomics and population genetics approaches to elucidate the origins of the dispersed arrangement of dothistromin genes over a broad evolutionary time-scale at the phylum, class and species levels.
Orthologs of dothistromin genes were found in two major classes of fungi. Their organization is consistent with clustering of core pathway genes in a common ancestor, but with intermediate cluster fragmentation states in the Dothideomycetes fungi. Recombination hotspots in a D. septosporum population matched sites of gene acquisition and cluster fragmentation at higher evolutionary levels.
The results suggest that fragmentation of a larger ancestral cluster gave rise to the arrangement seen in D. septosporum. We propose that cluster fragmentation may facilitate metabolic retooling and subsequent host adaptation of plant pathogens.
Plants lack the seemingly unlimited receptor diversity of a somatic adaptive immune system as found in vertebrates and rely on only a relatively small set of innate immune receptors to resist a ...myriad of pathogens. Here, we show that disease-resistant tomato plants use an efficient mechanism to leverage the limited nonself recognition capacity of their innate immune system. We found that the extracellular plant immune receptor protein Cf-2 of the red currant tomato (Solanum pimpinellifolium) has acquired dual resistance specificity by sensing perturbations in a common virulence target of two independently evolved effectors of a fungus and a nematode. The Cf-2 protein, originally identified as a monospecific immune receptor for the leaf mold fungus Cladosporium fulvum , also mediates disease resistance to the root parasitic nematode Globodera rostochiensis pathotype Ro1-Mierenbos. The Cf-2–mediated dual resistance is triggered by effector-induced perturbations of the apoplastic Rcr3 ᵖⁱᵐ protein of S. pimpinellifolium . Binding of the venom allergen-like effector protein Gr-VAP1 of G. rostochiensis to Rcr3 ᵖⁱᵐ perturbs the active site of this papain-like cysteine protease. In the absence of the Cf-2 receptor, Rcr3 ᵖⁱᵐ increases the susceptibility of tomato plants to G. rostochiensis , thus showing its role as a virulence target of these nematodes. Furthermore, both nematode infection and transient expression of Gr-VAP1 in tomato plants harboring Cf-2 and Rcr3 ᵖⁱᵐ trigger a defense-related programmed cell death in plant cells. Our data demonstrate that monitoring host proteins targeted by multiple pathogens broadens the spectrum of disease resistances mediated by single plant immune receptors.
Objectives
The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of ...cardiovascular disease (CVD) and diabetes.
Methods
We analysed data from the Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre‐ART) to 1 year after initiation (continuous variable) in treatment‐naïve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI weight (kg)/(height (m))2 was categorized as underweight (< 18.5), normal (18.5–25), overweight (25–30) and obese (> 30). Poisson regression models were fitted stratified for each pre‐ART BMI category to allow for category‐specific estimates of incidence rate ratio (IRR). Models were adjusted for pre‐ART BMI and CD4 count, key known risk factors (time‐updated where possible) and calendar year.
Results
A total of 97 CVD events occurred in 43 982 person‐years (n = 9321) and 125 diabetes events in 43 278 person‐years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre‐ART BMI category, was: underweight, 0.90 (0.60–1.37); normal, 1.18 (1.05–1.33); overweight, 0.87 (0.70–1.10), and obese, 0.95 (0.71–1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre‐ART BMI (P for interaction > 0.05).
Conclusions
Short‐term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre‐ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre‐ART BMI.
Receptor-like proteins (RLPs) are cell surface receptors that typically consist of an extracellular leucine-rich repeat domain, a transmembrane domain, and a short cytoplasmatic tail. In several ...plant species, RLPs have been found to play a role in disease resistance, such as the tomato (Solanum lycopersicum) Cf and Ve proteins and the apple (Malus domestica) HcrVf2 protein that mediate resistance against the fungal pathogens Cladosporium fulvum, Verticillium spp., and Venturia inaequalis, respectively. In addition, RLPs play a role in plant development; Arabidopsis (Arabidopsis thaliana) TOO MANY MOUTHS (TMM) regulates stomatal distribution, while Arabidopsis CLAVATA2 (CLV2) and its functional maize (Zea mays) ortholog FASCINATED EAR2 regulate meristem maintenance. In total, 57 RLP genes have been identified in the Arabidopsis genome and a genome-wide collection of T-DNA insertion lines was assembled. This collection was functionally analyzed with respect to plant growth and development and sensitivity to various stress responses, including susceptibility toward pathogens. A number of novel developmental phenotypes were revealed for our CLV2 and TMM insertion mutants. In addition, one AtRLP gene was found to mediate abscisic acid sensitivity and another AtRLP gene was found to influence nonhost resistance toward Pseudomonas syringae pv phaseolicola. This genome-wide collection of Arabidopsis RLP gene T-DNA insertion mutants provides a tool for future investigations into the biological roles of RLPs.
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