Review of the detection tools for seed-borne pathogens and the seed treatments that are applicable in organic seed production

With changing climatic conditions and a rapidly growing world population estimated to reach 9 billion by 2050, humankind faces the serious challenge of increasing food production by at least 70 %. The vision of BRESOV is to tackle this challenge by exploring the genetic diversity of three of the economically most significant vegetable crops (broccoli, snap bean, and tomato) and to improve the competitiveness of these three crops in an organic and sustainable environment. The consortium’s overall aim is to increase the plants’ tolerance to biotic and abiotic stresses and adapt the varieties to the specific requirements of organic and low-input production processes. In this frame we have pointed our attention to microbes actively involved in vegetable production generally called plant growth promoting bacteria (PGPBs) and plant growth promoting rhizobacteria (PGPRs) which improve the performance and health of the crops playing a positive role on supplying nutrients to crops, producing phytohormones, biocontrol of pathogens, improving soil structure, bioaccumulation of inorganic compounds and bioremediation of metal contaminated soils. In addition, the natural compounds, as such as glucosinolates (GLSs) or propolis, are widely utilized for pathogens control in organic agrosystems and the list of natural compounds (NCs) useful for this task is long. Sustainable agriculture needs to implement the interactions among beneficial soil microbiome and organic matter, NCs and the plant, improving plant health and soil fertility and reducing the conventional agricultural inputs through combining beneficial microorganisms. It is known that the two main factors affecting the development of organic farming in Europe are the limited quantity and the poor quality of organic seed available on markets (bad germination, pest contamination, and contamination with weed seed). Therefore, WP4 (High quality organic seed production) aims to develop the protocols and tools which suit to the specific conditions of organic farming to maximize yield (T4.1) and ensure high quality (T4.2 and T4.3) of organic seeds in broccoli, snap bean and tomato. Specific objectives of WP4: - O4.1: Develop protocols adapted to the specific conditions of organic farming to improve organic seed yield. - O4.2: Determine products and tools to control the sanitary and genetic quality of organic seed lots. Task 4.2 foresees the evaluation of alternative seed treatments to the use of chemical treatments to control sanitary quality of seed lots. In fact the organic farming prohibits the use of conventional chemicals to control pests and diseases, so alternative Biocontrol agents (BCAs) and NCs, as well as mechanical treatments, will be evaluated on seed for its protection against seed-borne pathogens and for seed vigor enhancement

Plant-Microbe Interaction in Sustainable Agriculture: The Factors That May Influence the Efficacy of PGPM Application

The indiscriminate use of chemical fertilizers and pesticides has caused considerable environmental damage over the years. However, the growing demand for food in the coming years and decades requires the use of increasingly productive and efficient agriculture. Several studies carried out in recent years have shown how the application of plant growth-promoting microbes (PGPMs) can be a valid substitute for chemical industry products and represent a valid eco-friendly alternative. However, because of the complexity of interactions created with the numerous biotic and abiotic factors (i.e., environment, soil, interactions between microorganisms, etc.), the different formulates often show variable effects. In this review, we analyze the main factors that influence the effectiveness of PGPM applications and some of the applications that make them a useful tool for agroecological transition

The Structure of Episodic Memory: Ganeri's ‘Mental Time Travel and Attention’

We offer a framework for assessing what the structure of episodic memory might be, if one accepts the Buddhist denial of persisting selves. This paper is a response to Jonardon Ganeri's paper "Mental time travel and attention", which explores Buddhaghosa's ideas about memory. (It will eventually be published with a reply by Ganeri)

Gammapy: A Python package for gamma-ray astronomy

In this article, we present Gammapy, an open-source Python package for the analysis of astronomical $\gamma$-ray data, and illustrate the functionalities of its first long-term-support release, version 1.0. Built on the modern Python scientific ecosystem, Gammapy provides a uniform platform for reducing and modeling data from different $\gamma$-ray instruments for many analysis scenarios. Gammapy complies with several well-established data conventions in high-energy astrophysics, providing serialized data products that are interoperable with other software packages. Starting from event lists and instrument response functions, Gammapy provides functionalities to reduce these data by binning them in energy and sky coordinates. Several techniques for background estimation are implemented in the package to handle the residual hadronic background affecting $\gamma$-ray instruments. After the data are binned, the flux and morphology of one or more $\gamma$-ray sources can be estimated using Poisson maximum likelihood fitting and assuming a variety of spectral, temporal, and spatial models. Estimation of flux points, likelihood profiles, and light curves is also supported. After describing the structure of the package, we show, using publicly available $\gamma$-ray data, the capabilities of Gammapy in multiple traditional and novel $\gamma$-ray analysis scenarios, such as spectral and spectro-morphological modeling and estimations of a spectral energy distribution and a light curve. Its flexibility and power are displayed in a final multi-instrument example, where datasets from different instruments, at different stages of data reduction, are simultaneously fitted with an astrophysical flux model.Comment: 26 pages, 16 figure

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.

Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809Funder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530Funder: Instituto Nacional de Bioinformática ELIXIR Implementation Studies Centro de Excelencia Severo OchoaFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics

Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient's data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe

Solving unsolved rare neurological diseases-a Solve-RD viewpoint.

Funder: Durch Princess Beatrix Muscle Fund Durch Speeren voor Spieren Muscle FundFunder: University of Tübingen Medical Faculty PATE programFunder: European Reference Network for Rare Neurological Diseases | 739510Funder: European Joint Program on Rare Diseases (EJP-RD COFUND-EJP) | 44140962

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock