Auftreten und Kinetik falschpositiver Candida- und Aspergillus- Antigentests nach Applikation parenteraler Ernährung und Piperacillin-Tazobactam bei Patienten auf einer hämatologisch-onkologischen Station

Diese Arbeit untersucht das Auftreten falschpositiver Mannan- und Galactomannanergebnisse bei hämatologischen Patienten nach allogener Stammzelltransplantation, die parenteral ernährt werden müssen oder eine antibiotische Therapie mit Piperacillin-Tazobactam erhalten. Die Kenntnis von Quellen, die die Spezifität des Platelia™ Candida Ag plus und den Platelia™ Aspergillus EIA beeinflussen, ist ein wichtiger Beitrag zur Diagnostik systemischer Pilzinfektionen.This study investigates the occurrence of false-positive mannan and galactomannan results in hematological patients undergoing allogeneic hematopoietic cell transplantation with current parenteral nutrition or antibiotic treatment with piperacillin-tazobactam. The knowledge of sources influencing specificity of Platelia™ Candida Ag plus and Platelia™ Aspergillus EIA contributes to the diagnosis of invasive fungal infections

Deciphering the transcriptional network of the distinct heart cell types after myocardial infarction

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 29-03-2017Esta tesis tiene embargado el acceso al texto completo hasta el 29-09-201

Targeting Polo-Like Kinase 4 (PLK4) Triggers Polyploidy and Apoptosis in TP53-mutant Acute Myeloid Leukemia and Results in Improved Survival

https://openworks.mdanderson.org/sumexp22/1020/thumbnail.jp

Massive parallel sequencing unveils homologous recombination deficiency in follicular dendritic cell sarcoma

Standardized treatment options are lacking for patients with unresectable or multifocal follicular dendritic cell sarcoma (FDCS) and disease-related mortality is as high as 20%. Applying whole-genome sequencing (WGS) in one case and whole-exome sequencing (WES) in additional twelve cases, this study adds information on the molecular landscape of FDCS, expanding knowledge on pathobiological mechanisms and identifying novel markers of potential theragnostic significance. Massive parallel sequencing showed high frequency of mutations on oncosuppressor genes, particularly in RB1, CARS and BRCA2 and unveiled alterations on homologous recombination DNA damage repair-related genes in 70% (9/13) of cases. This indicates that patients with high-stage FDCS may be eligible for poly ADP ribose polymerase inhibition protocols. Low tumor mutational burden was confirmed in this study despite common PDL1 expression in FDCS arguing on the efficacy of immune checkpoint inhibitors. CDKN2A deletion, detected by WGS and confirmed by fluorescence in situ hybridization in 41% of cases (9/22) indicates that impairment of cell cycle regulation may sustain oncogenesis in FDCS. Absence of mutations in the RAS/RAF/MAPK pathway and lack of clonal hematopoiesis-related mutations in FDCS sanction its differences from dendritic cell-derived neoplasms of hematopoietic derivation. WGS and WES in FDCS provides additional information on the molecular landscape of this rare tumor, proposing novel candidate genes for innovative therapeutical approaches to improve survival of patients with multifocal disease

Phagocytosis imprints heterogeneity in tissue-resident macrophages

Tissue-resident macrophages display varying phenotypic and functional properties that are largely specified by their local environment. One of these functions, phagocytosis, mediates the natural disposal of billions of cells, but its mechanisms and consequences within living tissues are poorly defined. Using a parabiosis-based strategy, we identified and isolated macrophages from multiple tissues as they phagocytosed blood-borne cellular material. Phagocytosis was circadianally regulated and mediated by distinct repertoires of receptors, opsonins, and transcription factors in macrophages from each tissue. Although the tissue of residence defined the core signature of macrophages, phagocytosis imprinted a distinct antiinflammatory profile. Phagocytic macrophages expressed CD206, displayed blunted expression of Il1b, and supported tissue homeostasis. Thus, phagocytosis is a source of macrophage heterogeneity that acts together with tissue-derived factors to preserve homeostasis

GOplot: an R package for visually combining expression data with functional analysis

UNLABELLED: Despite the plethora of methods available for the functional analysis of omics data, obtaining comprehensive-yet detailed understanding of the results remains challenging. This is mainly due to the lack of publicly available tools for the visualization of this type of information. Here we present an R package called GOplot, based on ggplot2, for enhanced graphical representation. Our package takes the output of any general enrichment analysis and generates plots at different levels of detail: from a general overview to identify the most enriched categories (bar plot, bubble plot) to a more detailed view displaying different types of information for molecules in a given set of categories (circle plot, chord plot, cluster plot). The package provides a deeper insight into omics data and allows scientists to generate insightful plots with only a few lines of code to easily communicate the findings. AVAILABILITY AND IMPLEMENTATION: The R package GOplot is available via CRAN-The Comprehensive R Archive Network: http://cran.r-project.org/web/packages/GOplot. The shiny web application of the Venn diagram can be found at: https://wwalter.shinyapps.io/Venn/. A detailed manual of the package with sample figures can be found at https://wencke.github.io/ CONTACT: [email protected] or [email protected] Ministry of Economy and Competitiveness [SAF2012-31483]; Fundacion Marato TV3; European Commision FP7 [CardioNext-ITN-608027]; Spanish Ministry of Economy and Competitiveness; Pro-CNIC FoundationS

Improving the accuracy of expression data analysis in time course experiments using resampling

BACKGROUND: As time series experiments in higher eukaryotes usually obtain data from different individuals collected at the different time points, a time series sample itself is not equivalent to a true biological replicate but is, rather, a combination of several biological replicates. The analysis of expression data derived from a time series sample is therefore often performed with a low number of replicates due to budget limitations or limitations in sample availability. In addition, most algorithms developed to identify specific patterns in time series dataset do not consider biological variation in samples collected at the same conditions. RESULTS: Using artificial time course datasets, we show that resampling considerably improves the accuracy of transcripts identified as rhythmic. In particular, the number of false positives can be greatly reduced while at the same time the number of true positives can be maintained in the range of other methods currently used to determine rhythmically expressed genes. CONCLUSIONS: The resampling approach described here therefore increases the accuracy of time series expression data analysis and furthermore emphasizes the importance of biological replicates in identifying oscillating genes. Resampling can be used for any time series expression dataset as long as the samples are acquired from independent individuals at each time point. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-014-0352-8) contains supplementary material, which is available to authorized users