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The genome sequence assembly of the diploid and highly homozygousV. viniferagenotype PN40024 serves as the reference for many grapevine studies. Despite several improvements of the PN40024 genome assembly, its current version PN12X.v2 is quite fragmented and only represents the haploid state of the genome with mixed haplotypes. In fact, despite the PN40024 genome is nearly homozygous, it still contains various heterozygous regions. Taking the opportunity of the improvements that long-read sequencing technologies offer to fully discriminate haplotype sequences and considering that severalVitissp. genomes have recently been assembled with these approaches, an improved version of the reference, called PN40024.v4, was generated.Through incorporating long genomic sequencing reads to the assembly, the continuity of the 12X.v2 scaffolds was highly increased. The number of scaffolds decreased from 2,059 to 640 and the number of N bases was reduced by 88%. Additionally, the full alternative haplotype sequence was built for the first time, the chromosome anchoring was improved and the amount of unplaced scaffolds were reduced by half. To obtain a high-quality gene annotation that outperforms previous versions, a liftover approach was complemented with an optimized annotation workflow forVitis. Integration of the gene reference catalogue and its manual curation have also assisted in improving the annotation, while defining the most reliable estimation to date of 35,230 genes. Finally, we demonstrate that PN40024 resulted from selfings of cv. ‘Helfensteiner’ (cross of cv. ‘Pinot noir’ and ‘Schiava grossa’) instead of a single ‘Pinot noir’. These advances will help maintaining the PN40024 genome as a gold-standard reference also contributing in the eventual elaboration of the grapevine pangenome.

Introduction Body fluid status can be determined by plasma volume status and extracellular water to total body water (ECW/TBW) ratio and is a well-known parameter associated with survival in patients with chronic heart failure (1–3). However, its prognostic impact in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Methods 409 patients with PAH and CTEPH who entered the Giessen PH registry were included in this study (4). Plasma volume status was estimated using Duarte formula (ePVS = (1 − hematocrit) / hemoglobin × 100). ECW was calculated via Peters formula ((−2.47 × 0.842 + 8.76 × body surface area) for men and (−1.96 × 0.572 + 8.05 × body surface area) for women) and TBW via Watson formula ((2.447 − [0.09516 × age] + [0.1073 × height] + [0.3362 × body weight]) for men and (−2.097 + [0.1069 × height] + [0.2466 × body weight]) for women). Statistical analyzes were performed with R (The R Foundation). Results Median age of the included patients was 65 [53, 74] years. Median ePVS and ECW/TBW ratio were 4.5 [3.9, 5.5] and 0.39 [0.37, 0.40]. Correlation analyses revealed that ePVS correlates with pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), cardiac index, and mixed venous oxygen saturation (SvO2), whereas ECW/TBW ratio did not correlate with pulmonary hemodynamics. Accordingly, univariate Cox regression revealed that ePVS but not ECW/TBW ratio was associated with mortality (HR: 1.18 [1.02, 1.37]). ePVS remained as an independent prognostic parameter in multivariate Cox regression analysis. Patients with high ePVS showed significantly decreased survival rates (log-rank p Conclusion ePVS but not ECW/TBW ratio is associated with prognostic parameters such as PVR, cardiac index and SvO2. Thus, ePVS may be an independent prognostic parameter in patients with PAH and CTEPH. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)

The EMBL-EBI Expression Atlas is an added value knowledge base that enables researchers to answer the question of where (tissue, organism part, developmental stage, cell type) and under which conditions (disease, treatment, gender, etc) a gene or protein of interest is expressed. Expression Atlas brings together data from >4500 expression studies from >65 different species, across different conditions and tissues. It makes these data freely available in an easy to visualise form, after expert curation to accurately represent the intended experimental design, re-analysed via standardised pipelines that rely on open-source community developed tools. Each study's metadata are annotated using ontologies. The data are re-analyzed with the aim of reproducing the original conclusions of the underlying experiments. Expression Atlas is currently divided into Bulk Expression Atlas and Single Cell Expression Atlas. Expression Atlas contains data from differential studies (microarray and bulk RNA-Seq) and baseline studies (bulk RNA-Seq and proteomics), whereas Single Cell Expression Atlas is currently dedicated to Single Cell RNA-Sequencing (scRNA-Seq) studies. The resource has been in continuous development since 2009 and it is available at https://www.ebi.ac.uk/gxa.

The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP (

Plant Reactome (https://plantreactome.gramene.org) is an open-source, comparative plant pathway knowledgebase of the Gramene project. It uses Oryza sativa (rice) as a reference species for manual curation of pathways and extends pathway knowledge to another 82 plant species via gene-orthology projection using the Reactome data model and framework. It currently hosts 298 reference pathways, including metabolic and transport pathways, transcriptional networks, hormone signaling pathways, and plant developmental processes. In addition to browsing plant pathways, users can upload and analyze their omics data, such as the gene-expression data, and overlay curated or experimental gene-gene interaction data to extend pathway knowledge. The curation team actively engages researchers and students on gene and pathway curation by offering workshops and online tutorials. The Plant Reactome supports, implements and collaborates with the wider community to make data and tools related to genes, genomes, and pathways Findable, Accessible, Interoperable and Re-usable (FAIR).

To build a large-scale genomic resource for functional validation of sorghum genes through EMS-mutagenized BTx623 seeds, we deep sequenced (30-60X) an additional 445 phenotyped EMS mutant lines. 4.2 million EMS mutations are called with nearly 36,800 mutations that could have a disruptive effect on functions of over 15,500 genes. Combining variants carried by both the natural population and previous EMS efforts, over 69% of sorghum coding genes (23644) are now presented with one or more mutations that are, or are predicted to be, disruptive to their functions. Our results show that the EMS population carries more significant mutations but less in each sample than the natural population, which makes it more powerful in elucidating sorghum gene functions on a large scale and requiring less work in validation of candidate causal genes. We have made the data available through two ways, one is the integration with the BSAseq workflow that supports retrieving independent EMS samples carrying the same genes with significant mutation for complementary testing, and the other is a web application for directly querying genes with significant mutations on SciApps.org.

We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The data indicate that the number of pan-genes exceeds 103,000 and that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres further reveal the locations and internal structures of major cytological landmarks. We show that combining structural variation with SNPs can improve the power of quantitative mapping studies. Finally, we document variation at the level of DNA methylation, and demonstrate that unmethylated regions are enriched for cis-regulatory elements that overlap QTL and contribute to changes in gene expression.One sentence summaryA multi-genome analysis of maize reveals previously unknown variation in gene content, genome structure, and methylation.

An a-maize-ing set of genomes Maize is an important crop cultivated worldwide. As maize spread across the world, selection for local environments resulted in variation, but the impact on differences between the genome has not been quantified. By producing high-quality genomic sequences of the 26 lines used in the maize nested association mapping panel, Hufford et al . map important traits and demonstrate the diversity of maize. Examining RNA and methylation of genes across accessions, the authors identified a core set of maize genes. Beyond this core set, comparative analysis across lines identified high levels of variation in the total set of genes, the maize pan-genome. The value of this resource was further exemplified by mapping quantitative traits of interest, including those related to pathogen resistance. —LMZ

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them., National Science Foundation 1916797 David W Ehrhardt, Kenneth D Birnbaum, Seung Yon Rhee; National Science Foundation 2052590 Seung Yon Rhee

Die nosokomiale Pneumonie ist eine haufige Komplikation von Krankenhausaufenthalten mit einer nicht zu vernachlassigenden Letalitat. Im Zuge der Zunahme der multiresistenten Erreger ist eine empirische adaquate Initialtherapie schwierig und bedarf einer genauen Einschatzung des Risikos fur multiresistente Erreger. Dabei ist eine zielgerichtete, zeitlich begrenzte antibiotische Therapie essenziell. Diese sollte nach rationaler und fokussierter Diagnostik erfolgen. Eine Reevaluation der begonnenen Therapie ist unabdingbar, um eventuelle Differenzialdiagnosen nicht zu ubersehen und um die Therapie den mikrobiologischen Befunde sowie dem klinischen und laborchemischen Verlauf anzupassen. In der vorliegenden Ubersichtsarbeit werden die aktuellen nationalen Leitlinien zur Diagnostik und Therapie der nosokomial erworbenen Pneumonie vorgestellt. Besonderer Fokus wird auf die zielgerichtete, risikoadaptierte Therapie gelegt.

Community-acquired pneumonia (CAP) is a frequent and potentially fatal disorder. Due to the notably high mortality within the first days, the immediate initiation of rational diagnostic pathways and treatment is of tremendous prognostic impact. In this review article, the current German guideline on the diagnosis and therapy of CAP is presented. Special focus is put on structured patient management based on the individual risk for early identification of critically ill patients. In particular, risk assessment directly influences rational diagnostics and adequate therapy. New recommendations concerning preventive strategies are also discussed in this article.

The term pulmonary arterial hypertension comprises a group of pulmonary vascular diseases of different etiologies that are characterized by similar precapillary vascular remodeling processes and result in exertional dyspnea and right heart insufficiency. The specific pharmacological treatment approach considers the risk of mortality and phenotypical properties and includes treatment with phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostanoids, as well as with more novel substances, such as a soluble guanylyl cyclase stimulator and an oral prostacyclin receptor agonist. The prognosis of the disease is mainly determined by the right heart insufficiency for which there is currently no specific pharmacological treatment. Lung transplantation may be offered as a last option. This review provides an overview of the current European guidelines from 2015 and the recommendations of the Cologne Consensus Conference for pulmonary hypertension from 2016.

Question addressedEchocardiography is not currently considered as providing sufficient prognostic information to serve as an integral part of treatment goals in pulmonary arterial hypertension (PAH). We tested the hypothesis that incorporation of multiple parameters reflecting right heart function would improve the prognostic value of this imaging modality.Methods and main resultsWe pooled individual patient data from a total of 517 patients (mean age 52±15 years, 64.8% females) included in seven observational studies conducted at five European and United States academic centres. Patients were subdivided into three groups representing progressive degrees of right ventricular dysfunction based on a combination of echocardiographic measurements, as follows. Group 1 (low risk): normal tricuspid annular plane systolic excursion (TAPSE) and nonsignificant tricuspid regurgitation (TR) (n=129); group 2 (intermediate risk): normal TAPSE and significant TR or impaired TAPSE and nondilated inferior vena cava (IVC) (n=256); group 3 (high risk): impaired TAPSE and dilated IVC (n=132). The 5-year cumulative survival rate was 82% in group 1, 63% in group 2 and 43% in group 3. Low-risk patients had better survival rates than intermediate-risk patients (log-rank Chi-squared 12.25; pAnswer to the questionThe proposed echocardiographic approach integrating the evaluation of TAPSE, TR grade and IVC is effective in stratifying the risk for all-cause mortality in PAH patients, outperforming the prognostic parameters suggested by current guidelines.

Gramene (http://www.gramene.org) is an online, open source, curated resource for plant comparative genomics and pathway analysis designed to support researchers working in plant genomics, breeding, evolutionary biology, system biology, and metabolic engineering. It exploits phylogenetic relationships to enrich the annotation of genomic data and provides tools to perform powerful comparative analyses across a wide spectrum of plant species. It consists of an integrated portal for querying, visualizing and analyzing data for 44 plant reference genomes, genetic variation data sets for 12 species, expression data for 16 species, curated rice pathways and orthology-based pathway projections for 66 plant species including various crops. Here we briefly describe the functions and uses of the Gramene database.

Pulmonary hypertension (PH) comprises a group of pulmonary vascular diseases that are characterized by progressive exertional dyspnea and right heart insufficiency ultimately resulting in right heart decompensation. The classification is into five clinical subgroups that form the absolutely essential basis for decisions on the indications for different pharmacological and non-pharmacological forms of treatment. The guidelines were updated in 2015 and in addition to the hitherto existing pharmacological treatment options of phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclins, the soluble guanylate cyclase stimulator riociguat has now been incorporated for treatment of certain forms of PH. This article provides an overview of the new treatment recommendations in the current guidelines, e. g. for PH patients who are in intensive care units due to surgical interventions or progressive right heart insufficiency.

The sophistication of gene prediction algorithms and the abundance of RNA-based evidence for the maize genome may suggest that manual curation of gene models is no longer necessary. However, quality metrics generated by the MAKER-P gene annotation pipeline identified 17,225 of 130,330 (13%) protein-coding transcripts in the B73 Reference Genome V4 gene set with models of low concordance to available biological evidence. Working with eight graduate students, we used the Apollo annotation editor to curate 86 transcript models flagged by quality metrics and a complimentary method using the Gramene gene tree visualizer. All of the triaged models had significant errors – including missing or extra exons, non-canonical splice sites, and incorrect UTRs. A correct transcript model existed for about 60% of genes (or transcripts) flagged by quality metrics; we attribute this to the convention of elevating the transcript with the longest coding sequence (CDS) to the canonical, or first, position. The remaining 40% of flagged genes resulted in novel annotations and represent a manual curation space of about 10% of the maize genome (~4,000 protein-coding genes). MAKER-P metrics have a specificity of 100%, and a sensitivity of 85%; the gene tree visualizer has a specificity of 100%. Together with the Apollo graphical editor, our double triage provides an infrastructure to support the community curation of eukaryotic genomes by scientists, students, and potentially even citizen scientists.

Hospital-acquired pneumonia (HAP) is a frequent complication of hospitalisation. Due to rising multidrug resistant bacteria an appropriate, empiric and targeted therapy is essential and requires an accurate assessment of risk for multidrug resistant bacteria. A targeted, temporal therapy is indispensable and should begin after a focussed diagnosis. Re-evaluation of therapy is important, as clinical course, microbiological and laboratory results might lead to de-escalation of therapy. In this review article the current German guidelines on the diagnosis and therapy of hospital-acquired pneumonia are summarized. Special focus is put on targeted, risk-adapted therapy.

Die pulmonale Hypertonie (PH) ist eine chronisch progrediente Erkrankung der pulmonalen Zirkulation multifaktorieller Ursache. Die aktuelle diagnostische Klassifikation der PH unterscheidet funf Hauptgruppen, die als Gemeinsamkeit einen erhohten mittleren pulmonalarteriellen Druck und pulmonalen Gefaswiderstand aufweisen. Klassifiziert werden die pulmonalarterielle Hypertonie (PAH), die PH durch Linksherzerkrankung, die PH bei Lungenerkrankungen und/oder Hypoxie, die chronische thromboembolische pulmonale Hypertonie (CTEPH) und die PH mit unklaren bzw. multifaktoriellen Mechanismen. Aktuelle Fortschritte in der Grundlagenforschung sowie die Zulassung neuer Medikamente und Etablierung von Therapiestrategien vor allem bei der PAH und CTEPH erfordern eine differenzierte Betrachtung der Erkrankung, eine sorgfaltige Diagnosestellung und Therapieeinleitung sowie regelmasige Verlaufskontrollen. In diesem Beitrag mochten wir einen aktuellen Uberblick uber die komplexe medikamentose Therapie der PAH geben.