Characterization of the Mechanisms underlying Plant-Microbe Multipartite Interactions

In nature, plants constantly interact with a multitude of microorganisms, collectively called the plant microbiota. Intimate associations and interdependencies between the plant and its microbiota result in a modulation of plant traits that ultimately determine plant health and yield production. Thus, unraveling the interaction networks, molecular mechanisms, and influencing factors that underlie plant-microbiota interactions is a prerequisite for developing future sustainable agricultural strategies. Fungi of the ecologically relevant order Sebacinales feature a wide geographical distribution and host range. Root colonization by Sebacinales like Serendipita vermifera and Serendipita indica leads to beneficial effects for the host, including increased biomass and resistance to biotic and abiotic stresses. Yet little is known about factors and mechanisms that shape these widespread beneficial interactions. The studies comprised in this thesis aim to investigate the nature and relevance of the beneficial effects of Sebacinales on the host in multiple interactions. The first study addressed the effects of the beneficial root endophyte Serendipita vermifera (Sv) and the cereal pathogen Bipolaris sorokiniana (Bs) on barley in a tripartite system. We showed that Sv exerts a biocontrol function by reducing pathogen colonization and host disease symptoms. Comparing the local and systemic transcriptional responses of all organisms in a gnotobiotic soil-based split-root system, we found that despite some degree of systemic protection, the major antagonistic effects were exerted upon direct contact and exhibited signs of mycoparasitism. In the second study, the tripartite setup was extended by including a second plant host and bacterial synthetic communities (SynCom) to investigate the influence of biotic factors on the Sv-mediated beneficial traits. The combined presence of Sv and members of the core bacterial microbiota provides synergistic protection against Bs on both host plants. In addition, host- and microbe-dependent synergistic early growth promotion was observed. RNA-sequencing analysis revealed that these beneficial activities are not associated with extensive host transcriptional reprogramming but rather with the modulation of expression of fungal effectors and carbohydrate-active enzymes (CAZymes). Abstract 1 Therefore, the third study investigated the regulation of Sv effector and CAZyme expression in biotic interactions, including interactions with three plant hosts, a fungus or a bacterial SynCom at four time points. RNA-seq analysis identified commonalities and differences in the Sv transcriptome during fungal accommodation in planta or microbe-microbe confrontation in the absence of the host. Further, a Sv chitinase was identified and characterized as a determinant of fungal antagonism. The fourth study investigated the Bs-induced expression of barley HvKSL4 and HvCPS2, that was observed in the original tripartite setup. This led to the identification of a barley gene-cluster for barley diterpene synthesis and was a first step in decifering the role of a secreted barley diterpene during biotic interactions. Finally, a protocol to monitor plant health and cell death via Ion leakage and Pulse Amplitude Fluorometry (PAM) was developed. This method is suitable for future multipartite setups as well as for chemical treatments and particularly useful for large- scale screenings. The studies comprised in this thesis expand our knowledge in the fields of plant-microbe interactions and biocontrol and lay the foundation for answering future research questions

Day-Ahead Offering Strategy In The Market For Concentrating Solar Power Considering Thermoelectric Decoupling By A Compressed Air Energy Storage

Due to limited fossil fuel resources, a growing increase in energy demand and the need to maintain positive environmental effects, concentrating solar power (CSP) plant as a promising technology has driven the world to find new sustainable and competitive methods for energy production. The scheduling capability of a CSP plant equipped with thermal energy storage (TES) surpasses a photovoltaic (PV) unit and augments the sustainability of energy system performance. However, restricting CSP plant application compared to a PV plant due to its high investment is a challenging issue. This paper presents a model to assemble a combined heat and power (CHP) with a CSP plant for enhancing heat utilization and reduce the overall cost of the plant, thus, the CSP benefits proved by researches can be implemented more economically. Moreover, the compressed air energy storage (CAES) is used with a CSP-TES-CHP plant in order that the thermoelectric decoupling of the CHP be facilitated. Therefore, the virtual power plant (VPP) created is a suitable design for large power grids, which can trade heat and electricity in response to the market without restraint by thermoelectric constraint. Furthermore, the day-ahead offering strategy of the VPP is modeled as a mixed integer linear programming (MILP) problem with the goal of maximizing the profit in the market. The simulation results prove the efficiency of the proposed model. The proposed VPP has a 2% increase in profit and a maximum 6% increase in the market electricity price per day compared to the system without CAES

Systematically Monitoring Social Media: the case of the German federal election 2017

It is a considerable task to collect digital trace data at a large scale and at the same time adhere to established academic standards. In the context of political communication, important challenges are (1) defining the social media accounts and posts relevant to the campaign (content validity), (2) operationalizing the venues where relevant social media activity takes place (construct validity), (3) capturing all of the relevant social media activity (reliability), and (4) sharing as much data as possible for reuse and replication (objectivity). This project by GESIS - Leibniz Institute for the Social Sciences and the E-Democracy Program of the University of Koblenz-Landau conducted such an effort. We concentrated on the two social media networks of most political relevance, Facebook and Twitter.Comment: PID: http://nbn-resolving.de/urn:nbn:de:0168-ssoar-56149-4, GESIS Papers 2018|

Potential health and economic impacts of dexamethasone treatment for patients with COVID-19

Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for example in low- and middle-income countries

Asymmetric and symmetric dimethylarginine in high altitude pulmonary hypertension (HAPH) and high altitude pulmonary edema (HAPE)

Introduction: High altitude exposure may lead to high altitude pulmonary hypertension (HAPH) and high altitude pulmonary edema (HAPE). The pathophysiologic processes of both entities have been linked to decreased nitric oxide (NO) availability.Methods: We studied the effect of acute high altitude exposure on the plasma concentrations of asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-arginine, L-ornithine, and L-citrulline in two independent studies. We further investigated whether these biomarkers involved in NO metabolism were related to HAPH and HAPE, respectively. Fifty (study A) and thirteen (study B) non-acclimatized lowlanders were exposed to 4,559 m for 44 and 67 h, respectively. In contrast to study A, the participants in study B were characterized by a history of at least one episode of HAPE. Arterial blood gases and biomarker concentrations in venous plasma were assessed at low altitude (baseline) and repeatedly at high altitude. HAPE was diagnosed by chest radiography, and HAPH by measuring right ventricular to atrial pressure gradient (RVPG) with transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and the AMS-C score.Results: In both studies SDMA concentration significantly increased at high altitude. ADMA baseline concentrations were higher in individuals with HAPE susceptibility (study B) compared to those without (study A). However, upon high altitude exposure ADMA only increased in individuals without HAPE susceptibility, while there was no further increase in those with HAPE susceptibility. We observed an acute and transient decrease of L-ornithine and a more delayed but prolonged reduction of L-citrulline during high altitude exposure. In both studies SDMA positively correlated and L-ornithine negatively correlated with RVPG. ADMA was significantly associated with the occurrence of HAPE (study B). ADMA and SDMA were inversely correlated with alveolar PO2, while L-ornithine was inversely correlated with blood oxygenation and haemoglobin levels, respectively.Discussion: In non-acclimatized individuals ADMA and SDMA, two biomarkers decreasing endothelial NO production, increased after acute exposure to 4,559 m. The observed biomarker changes suggest that both NO synthesis and arginase pathways are involved in the pathophysiology of HAPH and HAPE

Inflammaging is driven by upregulation of innate immune receptors and systemic interferon signaling and is ameliorated by dietary restriction

Aging is characterized by a chronic low-grade inflammation known as inflammaging in multiple tissues, representing a risk factor for age-related diseases. Dietary restriction (DR) is the best-known non-invasive method to ameliorate aging in many organisms. However, the molecular mechanism and the signaling pathways that drive inflammaging across different tissues and how they are modulated by DR are not yet understood. Here we identify a multi-tissue gene network regulating inflammaging. This network is characterized by chromatin opening and upregulation in the transcription of innate immune system receptors and by activation of interferon signaling through interferon regulatory factors, inflammatory cytokines, and Stat1-mediated transcription. DR ameliorates aging-induced alterations of chromatin accessibility and RNA transcription of the inflammaging gene network while failing to rescue those alterations on the rest of the genome. Our results present a comprehensive understanding of the molecular network regulating inflammation in aging and DR and provide anti-inflammaging therapeutic targets

Lipopolysaccharide O-antigen molecular and supramolecular modifications of plant root microbiota are pivotal for host recognition

11 pags., 5 figs.Lipopolysaccharides, the major outer membrane components of Gram-negative bacteria, are crucial actors of the host-microbial dialogue. They can contribute to the establishment of either symbiosis or bacterial virulence, depending on the bacterial lifestyle. Plant microbiota shows great complexity, promotes plant health and growth and assures protection from pathogens. How plants perceive LPS from plant-associated bacteria and discriminate between beneficial and pathogenic microbes is an open and urgent question. Here, we report on the structure, conformation, membrane properties and immune recognition of LPS isolated from the Arabidopsis thaliana root microbiota member Herbaspirillum sp. Root189. The LPS consists of an O-methylated and variously acetylated D-rhamnose containing polysaccharide with a rather hydrophobic surface. Plant immunology studies in A. thaliana demonstrate that the native acetylated O-antigen shields the LPS from immune recognition whereas the O-deacylated one does not. These findings highlight the role of Herbaspirillum LPS within plant-microbial crosstalk, and how O-antigen modifications influence membrane properties and modulate LPS host recognition.This study was supported by PRIN 2017 "Glytunes" (2017XZ2ZBK, 2019-2022) to AS; by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 851356 to RM. Neutron Reflectivity (NR) measurements were performed at the INTER instrument at ISIS Pulsed Neutron and Muon Source, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Didcot, UK. The authors thank the ISIS facility for provision of beam time. MACR and DS gratefully acknowl- edge financial support from the Spanish Ministry of Science, Innovation, and Universities (RTI2018-099985-B-I00), and the CIBER of Respiratory Diseases (CIBERES), an initiative from the Spanish Institute of Health Carlos III (ISCIII). AZ and LM acknowledge support from the Cluster of Excellence on Plant Sciences (CEPLAS) funded by the Deutsche For- schungsgemeinschaft (DFG, German Research Foundation) under Ger- many’s Excellence Strategy-EXC 2048/1-Project ID: 390686111 and project ZU 263/11-1 (SPP DECRyPT)Peer reviewe

Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals

IMPORTANCE: Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE: To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer's Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES: The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS: The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer's Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE: To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals

Potential health and economic impacts of dexamethasone treatment for patients with COVID-19

Acknowledgements We thank all members of the COVID-19 International Modelling Consortium and their collaborative partners. This work was supported by the COVID-19 Research Response Fund, managed by the Medical Sciences Division, University of Oxford. L.J.W. is supported by the Li Ka Shing Foundation. R.A. acknowledges funding from the Bill and Melinda Gates Foundation (OPP1193472).Peer reviewedPublisher PD

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise. The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included.Peer reviewe