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Showing papers by "Ghent University published in 2018"


Journal ArticleDOI
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4  +414 moreInstitutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

5,988 citations


Journal ArticleDOI
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Ilio Vitale3, Stuart A. Aaronson4  +183 moreInstitutions (111)
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Abstract: Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

3,301 citations


Journal ArticleDOI
TL;DR: In this global study of CAR T‐cell therapy, a single infusion of tisagenlecleucel provided durable remission with long‐term persistence in pediatric and young adult patients with relapsed or refractory B‐cell ALL, with transient high‐grade toxic effects.
Abstract: Background In a single-center phase 1–2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) Methods We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months Results For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry The rates of event-f

3,237 citations


Journal ArticleDOI
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1  +1050 moreInstitutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.

2,910 citations


Journal ArticleDOI
22 Jun 2018-Science
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

1,357 citations


Journal ArticleDOI
TL;DR: The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome and this update comes with a new web framework with an interactive and responsive user-interface, along with new features.
Abstract: JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) and TF flexible models (TFFMs) for TFs across multiple species in six taxonomic groups. In the 2018 release of JASPAR, the CORE collection has been expanded with 322 new PFMs (60 for vertebrates and 262 for plants) and 33 PFMs were updated (24 for vertebrates, 8 for plants and 1 for insects). These new profiles represent a 30% expansion compared to the 2016 release. In addition, we have introduced 316 TFFMs (95 for vertebrates, 218 for plants and 3 for insects). This release incorporates clusters of similar PFMs in each taxon and each TF class per taxon. The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome. The predictions are made available to the scientific community through a UCSC Genome Browser track data hub. Finally, this update comes with a new web framework with an interactive and responsive user-interface, along with new features. All the underlying data can be retrieved programmatically using a RESTful API and through the JASPAR 2018 R/Bioconductor package.

1,282 citations


Journal ArticleDOI
TL;DR: This Review focuses on recent findings that suggest that operational taxonomic unit-based analyses should be replaced with new methods that are based on exact sequence variants, methods for integrating metagenomic and metabolomic data, and issues surrounding compositional data analysis.
Abstract: Complex microbial communities shape the dynamics of various environments, ranging from the mammalian gastrointestinal tract to the soil. Advances in DNA sequencing technologies and data analysis have provided drastic improvements in microbiome analyses, for example, in taxonomic resolution, false discovery rate control and other properties, over earlier methods. In this Review, we discuss the best practices for performing a microbiome study, including experimental design, choice of molecular analysis technology, methods for data analysis and the integration of multiple omics data sets. We focus on recent findings that suggest that operational taxonomic unit-based analyses should be replaced with new methods that are based on exact sequence variants, methods for integrating metagenomic and metabolomic data, and issues surrounding compositional data analysis, where advances have been particularly rapid. We note that although some of these approaches are new, it is important to keep sight of the classic issues that arise during experimental design and relate to research reproducibility. We describe how keeping these issues in mind allows researchers to obtain more insight from their microbiome data sets.

992 citations


Journal ArticleDOI
TL;DR: Treatment duration for aspergillosis is strongly recommended based on clinical improvement, degree of immunosuppression and response on imaging, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended.

848 citations


Journal ArticleDOI
15 Aug 2018
TL;DR: The potential of social robots in education is reviewed, the technical challenges are discussed, and how the robot’s appearance and behavior affect learning outcomes are considered.
Abstract: Social robots can be used in education as tutors or peer learners. They have been shown to be effective at increasing cognitive and affective outcomes and have achieved outcomes similar to those of human tutoring on restricted tasks. This is largely because of their physical presence, which traditional learning technologies lack. We review the potential of social robots in education, discuss the technical challenges, and consider how the robot's appearance and behavior affect learning outcomes.

747 citations


Journal ArticleDOI
TL;DR: The frequency of, trends in, determinants of, and inequalities in caesarean section (CS) use, globally, regionally, and in selected countries are described, with considerable variation between regions.

737 citations


Journal ArticleDOI
TL;DR: In patients with glucocorticoid‐dependent severe asthma, dupilumab treatment reduced oral glucoc Corticoid use while decreasing the rate of severe exacerbations and increasing the FEV1.
Abstract: Background Dupilumab is a fully human anti–interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown. Methods We randomly assigned 210 patients with oral glucocorticoid–treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expira...

Journal ArticleDOI
18 Apr 2018-Nature
TL;DR: A way of integrating photonics with silicon nanoelectronics is described, using polycrystalline silicon on glass islands alongside transistors on bulk silicon complementary metal–oxide–semiconductor chips to address the demand for high-bandwidth optical interconnects in data centres and high-performance computing.
Abstract: Electronic and photonic technologies have transformed our lives-from computing and mobile devices, to information technology and the internet. Our future demands in these fields require innovation in each technology separately, but also depend on our ability to harness their complementary physics through integrated solutions1,2. This goal is hindered by the fact that most silicon nanotechnologies-which enable our processors, computer memory, communications chips and image sensors-rely on bulk silicon substrates, a cost-effective solution with an abundant supply chain, but with substantial limitations for the integration of photonic functions. Here we introduce photonics into bulk silicon complementary metal-oxide-semiconductor (CMOS) chips using a layer of polycrystalline silicon deposited on silicon oxide (glass) islands fabricated alongside transistors. We use this single deposited layer to realize optical waveguides and resonators, high-speed optical modulators and sensitive avalanche photodetectors. We integrated this photonic platform with a 65-nanometre-transistor bulk CMOS process technology inside a 300-millimetre-diameter-wafer microelectronics foundry. We then implemented integrated high-speed optical transceivers in this platform that operate at ten gigabits per second, composed of millions of transistors, and arrayed on a single optical bus for wavelength division multiplexing, to address the demand for high-bandwidth optical interconnects in data centres and high-performance computing3,4. By decoupling the formation of photonic devices from that of transistors, this integration approach can achieve many of the goals of multi-chip solutions 5 , but with the performance, complexity and scalability of 'systems on a chip'1,6-8. As transistors smaller than ten nanometres across become commercially available 9 , and as new nanotechnologies emerge10,11, this approach could provide a way to integrate photonics with state-of-the-art nanoelectronics.

Journal ArticleDOI
12 Jan 2018
TL;DR: It is recommended that a properly powered reaction time experiment with repeated measures has at least 1,600 word observations per condition, considerably more than current practice, and it is shown that researchers must include the number of observations in meta-analyses.
Abstract: In psychology, attempts to replicate published findings are less successful than expected. For properly powered studies replication rate should be around 80%, whereas in practice less than 40% of the studies selected from different areas of psychology can be replicated. Researchers in cognitive psychology are hindered in estimating the power of their studies, because the designs they use present a sample of stimulus materials to a sample of participants, a situation not covered by most power formulas. To remedy the situation, we review the literature related to the topic and introduce recent software packages, which we apply to the data of two masked priming studies with high power. We checked how we could estimate the power of each study and how much they could be reduced to remain powerful enough. On the basis of this analysis, we recommend that a properly powered reaction time experiment with repeated measures has at least 1,600 word observations per condition (e.g., 40 participants, 40 stimuli). This is considerably more than current practice. We also show that researchers must include the number of observations in meta-analyses because the effect sizes currently reported depend on the number of stimuli presented to the participants. Our analyses can easily be applied to new datasets gathered.

Journal ArticleDOI
TL;DR: A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology of PrCa1.
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1. A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

Journal ArticleDOI
TL;DR: Understanding potential mechanisms that link CS with childhood outcomes, such as the role of the developing neonatal microbiome, has potential to inform novel strategies and research for optimising CS use and promote optimal physiological processes and development.


Journal ArticleDOI
TL;DR: The presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available.

Proceedings ArticleDOI
26 Jun 2018
TL;DR: This system can learn quadruped locomotion from scratch using simple reward signals and users can provide an open loop reference to guide the learning process when more control over the learned gait is needed.
Abstract: Designing agile locomotion for quadruped robots often requires extensive expertise and tedious manual tuning. In this paper, we present a system to automate this process by leveraging deep reinforcement learning techniques. Our system can learn quadruped locomotion from scratch using simple reward signals. In addition, users can provide an open loop reference to guide the learning process when more control over the learned gait is needed. The control policies are learned in a physics simulator and then deployed on real robots. In robotics, policies trained in simulation often do not transfer to the real world. We narrow this reality gap by improving the physics simulator and learning robust policies. We improve the simulation using system identification, developing an accurate actuator model and simulating latency. We learn robust controllers by randomizing the physical environments, adding perturbations and designing a compact observation space. We evaluate our system on two agile locomotion gaits: trotting and galloping. After learning in simulation, a quadruped robot can successfully perform both gaits in the real world.

Posted Content
TL;DR: A single-layer recurrent neural network with a dual softmax layer that matches the quality of the state-of-the-art WaveNet model, the WaveRNN, and a new generation scheme based on subscaling that folds a long sequence into a batch of shorter sequences and allows one to generate multiple samples at once.
Abstract: Sequential models achieve state-of-the-art results in audio, visual and textual domains with respect to both estimating the data distribution and generating high-quality samples. Efficient sampling for this class of models has however remained an elusive problem. With a focus on text-to-speech synthesis, we describe a set of general techniques for reducing sampling time while maintaining high output quality. We first describe a single-layer recurrent neural network, the WaveRNN, with a dual softmax layer that matches the quality of the state-of-the-art WaveNet model. The compact form of the network makes it possible to generate 24kHz 16-bit audio 4x faster than real time on a GPU. Second, we apply a weight pruning technique to reduce the number of weights in the WaveRNN. We find that, for a constant number of parameters, large sparse networks perform better than small dense networks and this relationship holds for sparsity levels beyond 96%. The small number of weights in a Sparse WaveRNN makes it possible to sample high-fidelity audio on a mobile CPU in real time. Finally, we propose a new generation scheme based on subscaling that folds a long sequence into a batch of shorter sequences and allows one to generate multiple samples at once. The Subscale WaveRNN produces 16 samples per step without loss of quality and offers an orthogonal method for increasing sampling efficiency.

Journal ArticleDOI
16 Oct 2018-Immunity
TL;DR: Emerging concepts in monocyte heterogeneity, emergency monopoiesis, and trained immunity are outlined and discussed and how these bring new perspectives to monocyte research are discussed.

Journal ArticleDOI
TL;DR: The suitability of hybrid beamforming methods, both, existing and proposed till first quarter of 2017, are explored, and the exciting future challenges in this domain are identified.
Abstract: The increasing wireless data traffic demands have driven the need to explore suitable spectrum regions for meeting the projected requirements. In the light of this, millimeter wave (mmWave) communication has received considerable attention from the research community. Typically, in fifth generation (5G) wireless networks, mmWave massive multiple-input multiple-output (MIMO) communications is realized by the hybrid transceivers which combine high dimensional analog phase shifters and power amplifiers with lower-dimensional digital signal processing units. This hybrid beamforming design reduces the cost and power consumption which is aligned with an energy-efficient design vision of 5G. In this paper, we track the progress in hybrid beamforming for massive MIMO communications in the context of system models of the hybrid transceivers’ structures, the digital and analog beamforming matrices with the possible antenna configuration scenarios and the hybrid beamforming in heterogeneous wireless networks. We extend the scope of the discussion by including resource management issues in hybrid beamforming. We explore the suitability of hybrid beamforming methods, both, existing and proposed till first quarter of 2017, and identify the exciting future challenges in this domain.

Journal ArticleDOI
Haramaya University1, Université de Moncton2, Université de Montréal3, University of Ibadan4, National Heart Foundation of Australia5, University of La Frontera6, University of Cuenca7, University of Waterloo8, University of the Republic9, Ghent University10, National Taiwan University11, Karolinska Institutet12, University of Ottawa13, Technische Universität München14, University of the Witwatersrand15, University of Cape Town16, Swansea University17, Lithuanian Sports University18, Emory University19, University of Los Andes20, Central University of Venezuela21, Hong Kong Baptist University22, Qatar Airways23, University of Tartu24, University of Regina25, Mahidol University26, The Chinese University of Hong Kong27, Pennington Biomedical Research Center28, University of Queensland29, Seoul National University30, Queen's University31, Linköping University32, University of Medicine and Health Sciences33, University of Guadalajara34, Shanghai University of Sport35, National University of Science and Technology36, University of Primorska37, University of Porto38, University of Ghana39, University of Strathclyde40, Carlos III Health Institute41, University of Girona42, Universidade Federal de Santa Catarina43, Katholieke Universiteit Leuven44, University of South Australia45, University of Southern Denmark46, University of Auckland47, Bath Spa University48, University of Ljubljana49, Tribhuvan University50, Utrecht University51, J. F. Oberlin University52, University of Botswana53, Stamford University Bangladesh54, National Chung Hsing University55, University of Warsaw56
TL;DR: The present study provides rich new evidence showing that the situation regarding the physical activity of children and youth is a concern worldwide and strategic public investments to implement effective interventions to increase physical activity opportunities are needed.
Abstract: Background: Accumulating sufficient moderate to vigorous physical activity is recognized as a key determinant of physical, physiological, developmental, mental, cognitive, and social health among children and youth (aged 5–17 y). The Global Matrix 3.0ofReportCardgradesonphysicalactivitywasdevelopedtoachieveabetterunderstandingoftheglobalvariationinchildand youth physical activity and associated supports. Methods: Work groups from 49 countries followed harmonized procedures to develop their Report Cards by grading 10 common indicators using the best available data. The participating countries were divided into 3 categories using the United Nations’ human development index (HDI) classification (low or medium, high, and very high HDI). Results: A total of 490 grades, including 369 letter grades and 121 incomplete grades, were assigned by the 49 work groups. Overall, an average grade of “C−,”“D+,” and “C−” was obtained for the low and medium HDI countries, high HDI countries, and very high HDI countries, respectively. Conclusions: The present study provides rich new evidence showing that the situation regarding the physical activity of children and youth is a concern worldwide. Strategic public investments to implement effective interventions to increase physical activity opportunities are needed.

Journal ArticleDOI
24 Dec 2018
TL;DR: This paper conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings, and found that very little heterogeneity was attributable to the order in which the tasks were performed or whether the task were administered in lab versus online.
Abstract: We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance (p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion (p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely high-powered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.

Journal ArticleDOI
TL;DR: A vision is presented on 3D printing with concrete, considering technical, economic and environmental aspects, and it is expected that for structures with the same functionality, DFC will environmentally perform better over the entire service life in comparison with conventionally produced concrete structures.

Journal ArticleDOI
TL;DR: It is shown that root-specific transcription factor MYB72 regulates the excretion of the coumarin scopoletin, an iron-mobilizing phenolic compound with selective antimicrobial activity that shapes the root-associated microbial community.
Abstract: Plant roots nurture a tremendous diversity of microbes via exudation of photosynthetically fixed carbon sources. In turn, probiotic members of the root microbiome promote plant growth and protect the host plant against pathogens and pests. In the Arabidopsis thaliana-Pseudomonas simiae WCS417 model system the root-specific transcription factor MYB72 and the MYB72-controlled β-glucosidase BGLU42 emerged as important regulators of beneficial rhizobacteria-induced systemic resistance (ISR) and iron-uptake responses. MYB72 regulates the biosynthesis of iron-mobilizing fluorescent phenolic compounds, after which BGLU42 activity is required for their excretion into the rhizosphere. Metabolite fingerprinting revealed the antimicrobial coumarin scopoletin as a dominant metabolite that is produced in the roots and excreted into the rhizosphere in a MYB72- and BGLU42-dependent manner. Shotgun-metagenome sequencing of root-associated microbiota of Col-0, myb72, and the scopoletin biosynthesis mutant f6'h1 showed that scopoletin selectively impacts the assembly of the microbial community in the rhizosphere. We show that scopoletin selectively inhibits the soil-borne fungal pathogens Fusarium oxysporum and Verticillium dahliae, while the growth-promoting and ISR-inducing rhizobacteria P. simiae WCS417 and Pseudomonas capeferrum WCS358 are highly tolerant of the antimicrobial effect of scopoletin. Collectively, our results demonstrate a role for coumarins in microbiome assembly and point to a scenario in which plants and probiotic rhizobacteria join forces to trigger MYB72/BGLU42-dependent scopolin production and scopoletin excretion, resulting in improved niche establishment for the microbial partner and growth and immunity benefits for the host plant.

Journal ArticleDOI
TL;DR: This study demonstrates that Arabidopsis thaliana specifically promotes three bacterial species in the rhizosphere upon foliar defense activation by the downy mildew pathogen Hyaloperonospora arabidopsidis, and indicates that plants can adjust their root microbiome upon pathogen infection and specifically recruit a group of disease resistance-inducing and growth-promoting beneficial microbes.
Abstract: Disease suppressive soils typically develop after a disease outbreak due to the subsequent assembly of protective microbiota in the rhizosphere. The role of the plant immune system in the assemblage of a protective rhizosphere microbiome is largely unknown. In this study, we demonstrate that Arabidopsis thaliana specifically promotes three bacterial species in the rhizosphere upon foliar defense activation by the downy mildew pathogen Hyaloperonospora arabidopsidis. The promoted bacteria were isolated and found to interact synergistically in biofilm formation in vitro. Although separately these bacteria did not affect the plant significantly, together they induced systemic resistance against downy mildew and promoted growth of the plant. Moreover, we show that the soil-mediated legacy of a primary population of downy mildew infected plants confers enhanced protection against this pathogen in a second population of plants growing in the same soil. Together our results indicate that plants can adjust their root microbiome upon pathogen infection and specifically recruit a group of disease resistance-inducing and growth-promoting beneficial microbes, therewith potentially maximizing the chance of survival of their offspring that will grow in the same soil.

Journal ArticleDOI
TL;DR: This review focuses on how ethylene regulates shoot growth, with an emphasis on leaves, and alters the expression of ethylene response factors (ERFs) provides a new strategy for targeted ethylene-response engineering.

Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Federico Ambrogi1  +2238 moreInstitutions (159)
TL;DR: In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented.
Abstract: Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The b jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV).

Journal ArticleDOI
TL;DR: It is argued that stronger and more innovative connections to data are required to address gaps in understanding, and that constrained predictions at ecologically relevant spatial and temporal scales will require a similar investment of effort and intensified inter-disciplinary communication.
Abstract: Numerous current efforts seek to improve the representation of ecosystem ecology and vegetation demographic processes within Earth System Models (ESMs). These developments are widely viewed as an important step in developing greater realism in predictions of future ecosystem states and fluxes. Increased realism, however, leads to increased model complexity, with new features raising a suite of ecological questions that require empirical constraints. Here, we review the developments that permit the representation of plant demographics in ESMs, and identify issues raised by these developments that highlight important gaps in ecological understanding. These issues inevitably translate into uncertainty in model projections but also allow models to be applied to new processes and questions concerning the dynamics of real-world ecosystems. We argue that stronger and more innovative connections to data, across the range of scales considered, are required to address these gaps in understanding. The development of first-generation land surface models as a unifying framework for ecophysiological understanding stimulated much research into plant physiological traits and gas exchange. Constraining predictions at ecologically relevant spatial and temporal scales will require a similar investment of effort and intensified inter-disciplinary communication.

Journal ArticleDOI
TL;DR: Using 16 key molecular features, five prognostic subtypes were identified and a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories was developed, raising potential implications for immunotherapy.