Technical University of Denmark

About: Technical University of Denmark is a education organization based out in Kongens Lyngby, Hovedstaden, Denmark. It is known for research contribution in the topics: Population & Catalysis. The organization has 24126 authors who have published 66394 publications receiving 2443649 citations. The organization is also known as: Danmarks Tekniske Universitet & DTU.

Transcriptome responses to combinations of stresses in Arabidopsis.

Abstract: Biotic and abiotic stresses limit agricultural yields, and plants are often simultaneously exposed to multiple stresses. Combinations of stresses such as heat and drought or cold and high light intensity have profound effects on crop performance and yields. Thus, delineation of the regulatory networks and metabolic pathways responding to single and multiple concurrent stresses is required for breeding and engineering crop stress tolerance. Many studies have described transcriptome changes in response to single stresses. However, exposure of plants to a combination of stress factors may require agonistic or antagonistic responses or responses potentially unrelated to responses to the corresponding single stresses. To analyze such responses, we initially compared transcriptome changes in 10 Arabidopsis (Arabidopsis thaliana) ecotypes using cold, heat, high-light, salt, and flagellin treatments as single stress factors as well as their double combinations. This revealed that some 61% of the transcriptome changes in response to double stresses were not predic from the responses to single stress treatments. It also showed that plants prioritized between potentially antagonistic responses for only 5% to 10% of the responding transcripts. This indicates that plants have evolved to cope with combinations of stresses and, therefore, may be bred to endure them. In addition, using a subset of this data from the Columbia and Landsberg erecta ecotypes, we have delineated coexpression network modules responding to single and combined stresses.

Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System

Abstract: We present a new approach to the study of the immune system that combines techniques of systems biology with information provided by data-driven prediction methods To this end, we have extended an agent-based simulator of the immune response, C-ImmSim, such that it represents pathogens, as well as lymphocytes receptors, by means of their amino acid sequences and makes use of bioinformatics methods for T and B cell epitope prediction This is a key step for the simulation of the immune response, because it determines immunogenicity The binding of the epitope, which is the immunogenic part of an invading pathogen, together with activation and cooperation from T helper cells, is required to trigger an immune response in the affected host To determine a pathogen's epitopes, we use existing prediction methods In addition, we propose a novel method, which uses Miyazawa and Jernigan protein–protein potential measurements, for assessing molecular binding in the context of immune complexes We benchmark the resulting model by simulating a classical immunization experiment that reproduces the development of immune memory We also investigate the role of major histocompatibility complex (MHC) haplotype heterozygosity and homozygosity with respect to the influenza virus and show that there is an advantage to heterozygosity Finally, we investigate the emergence of one or more dominating clones of lymphocytes in the situation of chronic exposure to the same immunogenic molecule and show that high affinity clones proliferate more than any other These results show that the simulator produces dynamics that are stable and consistent with basic immunological knowledge We believe that the combination of genomic information and simulation of the dynamics of the immune system, in one single tool, can offer new perspectives for a better understanding of the immune system

Applying insights from biofilm biology to drug development — can a new approach be developed?

Abstract: Most of the research on bacterial pathogenesis has focused on acute infections, but much less is known about the pathogenesis of infections caused by bacteria that grow as aggregates in biofilms. These infections tend to be chronic as they resist innate and adaptive immune defence mechanisms as well as antibiotics, and the treatment of biofilm infections presents a considerable unmet clinical need. To date, there are no drugs that specifically target bacteria in biofilms; however, several approaches are in early-stage development. Here, we review current insights into biofilm physiology and pathology, and discuss how a deep insight into the physical and biological characteristics of biofilms can inform therapeutic strategies and molecular targets for the development of anti-biofilm drugs.

Identity and effects of quorum-sensing inhibitors produced by Penicillium species.

Abstract: Quorum sensing (QS) communication systems are thought to afford bacteria with a mechanism to strategically cause disease. One example is Pseudomonas aeruginosa, which infects immunocompromised individuals such as cystic fibrosis patients. The authors have previously documented that blockage of the QS systems not only attenuates Ps. aeruginosa but also renders biofilms highly susceptible to treatment with conventional antibiotics. Filamentous fungi produce a battery of secondary metabolites, some of which are already in clinical use as antimicrobial drugs. Fungi coexist with bacteria but lack active immune systems, so instead rely on chemical defence mechanisms. It was speculated that some of these secondary metabolites could interfere with bacterial QS communication. During a screening of 100 extracts from 50 Penicillium species, 33 were found to produce QS inhibitory (QSI) compounds. In two cases, patulin and penicillic acid were identified as being biologically active QSI compounds. Their effect on QS-controlled gene expression in Ps. aeruginosa was verified by DNA microarray transcriptomics. Similar to previously investigated QSI compounds, patulin was found to enhance biofilm susceptibility to tobramycin treatment. Ps. aeruginosa has developed QS-dependent mechanisms that block development of the oxidative burst in PMN neutrophils. Accordingly, when the bacteria were treated with either patulin or penicillic acid, the neutrophils became activated. In a mouse pulmonary infection model, Ps. aeruginosa was more rapidly cleared from the mice that were treated with patulin compared with the placebo group.

Role of autolysin-mediated DNA release in biofilm formation of Staphylococcus epidermidis

Abstract: Staphylococcus epidermidis has become a serious nosocomial pathogen frequently causing infections associated with implanted foreign materials. Biofilm formation is considered a major factor determining S. epidermidis pathogenicity in such device-associated infections. Here, evidence is presented that extracellular DNA is important for the initial phase of biofilm development by S. epidermidis on polystyrene or glass surfaces under static or hydrodynamic conditions. Comparative PCR amplification from S. epidermidis chromosomal and extracellular DNA indicated that the extracellular DNA is similar to chromosomal DNA. Experiments involving the S. epidermidis wild-type and an isogenic atlE mutant indicated that most of the extracellular DNA in S. epidermidis cultures and biofilms is generated through activity of the autolysin AtlE. The presented results suggest that extracellular DNA is generated in S. epidermidis populations through AtlE-mediated lysis of a subpopulation of the bacteria, and that the extracellular DNA promotes biofilm formation of the remaining population.