69 research outputs found
Effector-triggered defence against apoplastic fungal pathogens
Copyright 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license CC BY 3.0 (http://creativecommons.org/licenses/by/3.0/). hR gene-mediated host resistance against apoplastic fungal pathogens is not adequately explained by the terms pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) or effector-triggered immunity (ETI). Therefore, it is proposed that this type of resistance is termed ‘effector-triggered defence’ (ETD). Unlike PTI and ETI, ETD is mediated by R genes encoding cell surface-localised receptor-like proteins (RLPs) that engage the receptor-like kinase SOBIR1. In contrast to this extracellular recognition, ETI is initiated by intracellular detection of pathogen effectors. ETI is usually associated with fast, hypersensitive host cell death, whereas ETD often triggers host cell death only after an elapsed period of endophytic pathogen growth. In this opinion, we focus on ETD responses against foliar fungal pathogens of cropsPeer reviewe
The Lectin Receptor Kinase LecRK-I.9 Is a Novel Phytophthora Resistance Component and a Potential Host Target for a RXLR Effector
In plants, an active defense against biotrophic pathogens is dependent on a functional continuum between the cell wall (CW) and the plasma membrane (PM). It is thus anticipated that proteins maintaining this continuum also function in defense. The legume-like lectin receptor kinase LecRK-I.9 is a putative mediator of CW-PM adhesions in Arabidopsis and is known to bind in vitro to the Phytophthora infestans RXLR-dEER effector IPI-O via a RGD cell attachment motif present in IPI-O. Here we show that LecRK-I.9 is associated with the plasma membrane, and that two T-DNA insertions lines deficient in LecRK-I.9 (lecrk-I.9) have a ‘gain-of-susceptibility’ phenotype specifically towards the oomycete Phytophthora brassicae. Accordingly, overexpression of LecRK-I.9 leads to enhanced resistance to P. brassicae. A similar ‘gain-of-susceptibility’ phenotype was observed in transgenic Arabidopsis lines expressing ipiO (35S-ipiO1). This phenocopy behavior was also observed with respect to other defense-related functions; lecrk-I.9 and 35S-ipiO1 were both disturbed in pathogen- and MAMP-triggered callose deposition. By site-directed mutagenesis, we demonstrated that the RGD cell attachment motif in IPI-O is not only essential for disrupting the CW-PM adhesions, but also for disease suppression. These results suggest that destabilizing the CW-PM continuum is one of the tactics used by Phytophthora to promote infection. As countermeasure the host may want to strengthen CW-PM adhesions and the novel Phytophthora resistance component LecRK-I.9 seems to function in this process
The Transcriptome of Compatible and Incompatible Interactions of Potato (Solanum tuberosum) with Phytophthora infestans Revealed by DeepSAGE Analysis
Late blight, caused by the oomycete Phytophthora infestans, is the most important disease of potato (Solanum tuberosum). Understanding the molecular basis of resistance and susceptibility to late blight is therefore highly relevant for developing resistant cultivars, either by marker-assissted selection or by transgenic approaches. Specific P. infestans races having the Avr1 effector gene trigger a hypersensitive resistance response in potato plants carrying the R1 resistance gene (incompatible interaction) and cause disease in plants lacking R1 (compatible interaction). The transcriptomes of the compatible and incompatible interaction were captured by DeepSAGE analysis of 44 biological samples comprising five genotypes, differing only by the presence or absence of the R1 transgene, three infection time points and three biological replicates. 30.859 unique 21 base pair sequence tags were obtained, one third of which did not match any known potato transcript sequence. Two third of the tags were expressed at low frequency (<10 tag counts/million). 20.470 unitags matched to approximately twelve thousand potato transcribed genes. Tag frequencies were compared between compatible and incompatible interactions over the infection time course and between compatible and incompatible genotypes. Transcriptional changes were more numerous in compatible than in incompatible interactions. In contrast to incompatible interactions, transcriptional changes in the compatible interaction were observed predominantly for multigene families encoding defense response genes and genes functional in photosynthesis and CO2 fixation. Numerous transcriptional differences were also observed between near isogenic genotypes prior to infection with P. infestans. Our DeepSAGE transcriptome analysis uncovered novel candidate genes for plant host pathogen interactions, examples of which are discussed with respect to possible function
OsTIR1 and OsAFB2 Downregulation via OsmiR393 Overexpression Leads to More Tillers, Early Flowering and Less Tolerance to Salt and Drought in Rice
The microRNA miR393 has been shown to play a role in plant development and in the stress response by targeting mRNAs that code for the auxin receptors in Arabidopsis. In this study, we verified that two rice auxin receptor gene homologs (OsTIR1 and OsAFB2) could be targeted by OsmiR393 (Os for Oryza sativa). Two new phenotypes (increased tillers and early flowering) and two previously observed phenotypes (reduced tolerance to salt and drought and hyposensitivity to auxin) were observed in the OsmiR393-overexpressing rice plants. The OsmiR393-overexpressing rice demonstrated hyposensitivity to synthetic auxin-analog treatments. These data indicated that the phenotypes of OsmiR393-overexpressing rice may be caused through hyposensitivity to the auxin signal by reduced expression of two auxin receptor genes (OsTIR1 and OsAFB2). The expression of an auxin transporter (OsAUX1) and a tillering inhibitor (OsTB1) were downregulated by overexpression of OsmiR393, which suggested that a gene chain from OsmiR393 to rice tillering may be from OsTIR1 and OsAFB2 to OsAUX1, which affected the transportation of auxin, then to OsTB1, which finally controlled tillering. The positive phenotypes (increased tillers and early flowering) and negative phenotypes (reduced tolerance to salt and hyposensitivity to auxin) of OsmiR393-overexpressing rice present a dilemma for molecular breeding
Mobilizing patient and public involvement in the development of real-world digital technology solutions: tutorial
Although the value of patient and public involvement and engagement (PPIE) activities in the development of new interventions and tools is well known, little guidance exists on how to perform these activities in a meaningful way. This is particularly true within large research consortia that target multiple objectives, include multiple patient groups, and work across many countries. Without clear guidance, there is a risk that PPIE may not capture patient opinions and needs correctly, thereby reducing the usefulness and effectiveness of new tools. Mobilise-D is an example of a large research consortium that aims to develop new digital outcome measures for real-world walking in 4 patient cohorts. Mobility is an important indicator of physical health. As such, there is potential clinical value in being able to accurately measure a person’s mobility in their daily life environment to help researchers and clinicians better track changes and patterns in a person’s daily life and activities. To achieve this, there is a need to create new ways of measuring walking. Recent advancements in digital technology help researchers meet this need. However, before any new measure can be used, researchers, health care professionals, and regulators need to know that the digital method is accurate and both accepted by and produces meaningful outcomes for patients and clinicians. Therefore, this paper outlines how PPIE structures were developed in the Mobilise-D consortium, providing details about the steps taken to implement PPIE, the experiences PPIE contributors had within this process, the lessons learned from the experiences, and recommendations for others who may want to do similar work in the future. The work outlined in this paper provided the Mobilise-D consortium with a foundation from which future PPIE tasks can be created and managed with clearly defined collaboration between researchers and patient representatives across Europe. This paper provides guidance on the work required to set up PPIE structures within a large consortium to promote and support the creation of meaningful and efficient PPIE related to the development of digital mobility outcomes.
J Med Internet Res 2023;25:e44206
doi:10.2196/4420
Laboratory and free-living gait performance in adults with COPD and healthy controls
Background Gait characteristics are important risk factors for falls, hospitalisations and mortality in older adults, but the impact of COPD on gait performance remains unclear. We aimed to identify differences in gait characteristics between adults with COPD and healthy age-matched controls during 1) laboratory tests that included complex movements and obstacles, 2) simulated daily-life activities (supervised) and 3) free-living daily-life activities (unsupervised).
Methods This case–control study used a multi-sensor wearable system (INDIP) to obtain seven gait characteristics for each walking bout performed by adults with mild-to-severe COPD (n=17; forced expiratory volume in 1 s 57±19% predicted) and controls (n=20) during laboratory tests, and during simulated and free-living daily-life activities. Gait characteristics were compared between adults with COPD and healthy controls for all walking bouts combined, and for shorter (≤30 s) and longer (>30 s) walking bouts separately.
Results Slower walking speed (−11 cm·s−1, 95% CI: −20 to −3) and lower cadence (−6.6 steps·min−1, 95% CI: −12.3 to −0.9) were recorded in adults with COPD compared to healthy controls during longer (>30 s) free-living walking bouts, but not during shorter (≤30 s) walking bouts in either laboratory or free-living settings. Double support duration and gait variability measures were generally comparable between the two groups.
Conclusion Gait impairment of adults with mild-to-severe COPD mainly manifests during relatively long walking bouts (>30 s) in free-living conditions. Future research should determine the underlying mechanism(s) of this impairment to facilitate the development of interventions that can improve free-living gait performance in adults with COPD
Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement–the Mobilise-D study protocol
Background
The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions.
Methods/design
The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability.
Discussion
The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility
The miRNAome of durum wheat: isolation and characterisation of conserved and novel microRNAs and their target genes
Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device
This study aimed to validate a wearable device’s walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson’s Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and − 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application.
Trial registration: ISRCTN – 12246987
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