Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation

AbstractOBJECTIVESThis study assessed the predictive value of preprocedural C-reactive protein (CRP) levels on six-month clinical and angiographic outcome in patients undergoing coronary stent implantation.BACKGROUNDRecent data indicate that low-grade inflammation as detected by elevated CRP serum levels predicts the risk of recurrent coronary events.METHODSWe prospectively investigated the predictive value of preprocedural CRP-levels on restenosis and six-month clinical outcome in 276 patients after coronary stent implantation. The primary combined end point was death due to cardiac causes, myocardial infarction related to the target vessel and repeat intervention of the stented vessel.RESULTSGrouping patients into tertiles according to preprocedural CRP-levels revealed that, despite identical angiographic and clinical characteristics at baseline and after stent implantation, a primary end point event occurred in 24 (26%) patients of the lowest tertile, in 42 (45.6%) of the middle tertile and in 38 (41.3%) of the highest CRP tertile, p = 0.01. On multivariate analysis, tertiles of CRP levels were independently associated with a higher risk of adverse coronary events (relative risk = 2.0 [1.1 to 3.5], tertile I vs. II and III, p = 0.01) in addition to the minimal lumen diameter after stent (p = 0.04). In addition, restenosis rates were significantly higher in the two upper tertiles compared with CRP levels in the lowest tertile (45.5% vs. 38.3% vs. 18.5%, respectively, p = 0.002).CONCLUSIONSLow-grade inflammation as evidenced by elevated preprocedural serum CRP-levels is an independent predictor of adverse outcome after coronary stent implantation, suggesting that a systemically detectable inflammatory activity is associated with proliferative responses within successfully implanted stents

Standardisierungswettbewerb zwischen parametrisierbarer Standardsoftware und komponentenbasierten Anwendungssystemen

Standardisierungswettbewerb zwischen parametrisierbarer Standardsoftware und komponentenbasierten Anwendungssystemen / Stefan Volkert ; Bernd Reitwiesner. - In: Information age economy / Hans Ulrich Buhl ... (Hrsg.). - Heidelberg : Physica-Verl., 2001. - S. 667-68

Methods for comparative metagenomics

<p>Abstract</p> <p>Background</p> <p>Metagenomics is a rapidly growing field of research that aims at studying uncultured organisms to understand the true diversity of microbes, their functions, cooperation and evolution, in environments such as soil, water, ancient remains of animals, or the digestive system of animals and humans. The recent development of ultra-high throughput sequencing technologies, which do not require cloning or PCR amplification, and can produce huge numbers of DNA reads at an affordable cost, has boosted the number and scope of metagenomic sequencing projects. Increasingly, there is a need for new ways of comparing multiple metagenomics datasets, and for fast and user-friendly implementations of such approaches.</p> <p>Results</p> <p>This paper introduces a number of new methods for interactively exploring, analyzing and comparing multiple metagenomic datasets, which will be made freely available in a new, comparative version 2.0 of the stand-alone metagenome analysis tool MEGAN.</p> <p>Conclusion</p> <p>There is a great need for powerful and user-friendly tools for comparative analysis of metagenomic data and MEGAN 2.0 will help to fill this gap.</p

AxPcoords & parallel AxParafit: statistical co-phylogenetic analyses on thousands of taxa

Background Current tools for Co-phylogenetic analyses are not able to cope with the continuous accumulation of phylogenetic data. The sophisticated statistical test for host-parasite co-phylogenetic analyses implemented in Parafit does not allow it to handle large datasets in reasonable times. The Parafit and DistPCoA programs are the by far most compute-intensive components of the Parafit analysis pipeline. We present AxParafit and AxPcoords (Ax stands for Accelerated) which are highly optimized versions of Parafit and DistPCoA respectively. Results Both programs have been entirely re-written in C. Via optimization of the algorithm and the C code as well as integration of highly tuned BLAS and LAPACK methods AxParafit runs 5–61 times faster than Parafit with a lower memory footprint (up to 35% reduction) while the performance benefit increases with growing dataset size. The MPI-based parallel implementation of AxParafit shows good scalability on up to 128 processors, even on medium-sized datasets. The parallel analysis with AxParafit on 128 CPUs for a medium-sized dataset with an 512 by 512 association matrix is more than 1,200/128 times faster per processor than the sequential Parafit run. AxPcoords is 8–26 times faster than DistPCoA and numerically stable on large datasets. We outline the substantial benefits of using parallel AxParafit by example of a large-scale empirical study on smut fungi and their host plants. To the best of our knowledge, this study represents the largest co-phylogenetic analysis to date. Conclusion The highly efficient AxPcoords and AxParafit programs allow for large-scale co-phylogenetic analyses on several thousands of taxa for the first time. In addition, AxParafit and AxPcoords have been integrated into the easy-to-use CopyCat tool

Species Delimitation in Taxonomically Difficult Fungi: The Case of Hymenogaster

False truffles are ecologically important as mycorrhizal partners of trees and evolutionarily highly interesting as the result of a shift from epigeous mushroom-like to underground fruiting bodies. Since its first description by Vittadini in 1831, inappropriate species concepts in the highly diverse false truffle genus Hymenogaster has led to continued confusion, caused by a large variety of prevailing taxonomical opinions.In this study, we reconsidered the species delimitations in Hymenogaster based on a comprehensive collection of Central European taxa comprising more than 140 fruiting bodies from 20 years of field work. The ITS rDNA sequence dataset was subjected to phylogenetic analysis as well as clustering optimization using OPTSIL software.Among distinct species concepts from the literature used to create reference partitions for clustering optimization, the broadest concept resulted in the highest agreement with the ITS data. Our results indicate a highly variable morphology of H. citrinus and H. griseus, most likely linked to environmental influences on the phenology (maturity, habitat, soil type and growing season). In particular, taxa described in the 19(th) century frequently appear as conspecific. Conversely, H. niveus appears as species complex comprising seven cryptic species with almost identical macro- and micromorphology. H. intermedius and H. huthii are described as novel species, each of which with a distinct morphology intermediate between two species complexes. A revised taxonomy for one of the most taxonomically difficult genera of Basidiomycetes is proposed, including an updated identification key. The (semi-)automated selection among species concepts used here is of importance for the revision of taxonomically problematic organism groups in general

Improving phylogeny reconstruction at the strain level using peptidome datasets

Typical bacterial strain differentiation methods are often challenged by high genetic similarity between strains. To address this problem, we introduce a novel in silico peptide fingerprinting method based on conventional wet-lab protocols that enables the identification of potential strain-specific peptides. These can be further investigated using in vitro approaches, laying a foundation for the development of biomarker detection and application-specific methods. This novel method aims at reducing large amounts of comparative peptide data to binary matrices while maintaining a high phylogenetic resolution. The underlying case study concerns the Bacillus cereus group, namely the differentiation of Bacillus thuringiensis, Bacillus anthracis and Bacillus cereus strains. Results show that trees based on cytoplasmic and extracellular peptidomes are only marginally in conflict with those based on whole proteomes, as inferred by the established Genome-BLAST Distance Phylogeny (GBDP) method. Hence, these results indicate that the two approaches can most likely be used complementarily even in other organismal groups. The obtained results confirm previous reports about the misclassification of many strains within the B. cereus group. Moreover, our method was able to separate the B. anthracis strains with high resolution, similarly to the GBDP results as benchmarked via Bayesian inference and both Maximum Likelihood and Maximum Parsimony. In addition to the presented phylogenomic applications, whole-peptide fingerprinting might also become a valuable complementary technique to digital DNA-DNA hybridization, notably for bacterial classification at the species and subspecies level in the future.This research was funded by Grant AGL2013-44039-R from the Spanish “Plan Estatal de I+D+I”, and by Grant EM2014/046 from the “Plan Galego de investigación, innovación e crecemento 2011-2015”. BS was recipient of a Ramón y Cajal postdoctoral contractfrom the Spanish Ministry of Economyand Competitiveness. This work was also partially funded by the [14VI05] Contract-Programme from the University of Vigo and the Agrupamento INBIOMED from DXPCTSUG-FEDER unha maneira de facer Europa (2012/273).The research leading to these results has also received funding from the European Union’s Seventh Framework Programme FP7/REGPOT-2012-2013.1 under grant agreement n˚ 316265, BIOCAPS. This document reflects only the authors’ views and the European Union is not liable for any use that may be made of the information contained herein. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Codivergence of Mycoviruses with Their Hosts

BACKGROUND: The associations between pathogens and their hosts are complex and can result from any combination of evolutionary events such as codivergence, switching, and duplication of the pathogen. Mycoviruses are RNA viruses which infect fungi and for which natural vectors are so far unknown. Thus, lateral transfer might be improbable and codivergence their dominant mode of evolution. Accordingly, mycoviruses are a suitable target for statistical tests of virus-host codivergence, but inference of mycovirus phylogenies might be difficult because of low sequence similarity even within families. METHODOLOGY: We analyzed here the evolutionary dynamics of all mycovirus families by comparing virus and host phylogenies. Additionally, we assessed the sensitivity of the co-phylogenetic tests to the settings for inferring virus trees from their genome sequences and approximate, taxonomy-based host trees. CONCLUSIONS: While sequence alignment filtering modes affected branch support, the overall results of the co-phylogenetic tests were significantly influenced only by the number of viruses sampled per family. The trees of the two largest families, Partitiviridae and Totiviridae, were significantly more similar to those of their hosts than expected by chance, and most individual host-virus links had a significant positive impact on the global fit, indicating that codivergence is the dominant mode of virus diversification. However, in this regard mycoviruses did not differ from closely related viruses sampled from non-fungus hosts. The remaining virus families were either dominated by other evolutionary modes or lacked an apparent overall pattern. As this negative result might be caused by insufficient taxon sampling, the most parsimonious hypothesis still is that host-parasite evolution is basically the same in all mycovirus families. This is the first study of mycovirus-host codivergence, and the results shed light not only on how mycovirus biology affects their co-phylogenetic relationships, but also on their presumable host range itself

The Nitric Oxide Pathway Provides Innate Antiviral Protection in Conjunction with the Type I Interferon Pathway in Fibroblasts

The innate host response to virus infection is largely dominated by the production of type I interferon and interferon stimulated genes. In particular, fibroblasts respond robustly to viral infection and to recognition of viral signatures such as dsRNA with the rapid production of type I interferon; subsequently, fibroblasts are a key cell type in antiviral protection. We recently found, however, that primary fibroblasts deficient for the production of interferon, interferon stimulated genes, and other cytokines and chemokines mount a robust antiviral response against both DNA and RNA viruses following stimulation with dsRNA. Nitric oxide is a chemical compound with pleiotropic functions; its production by phagocytes in response to interferon-γ is associated with antimicrobial activity. Here we show that in response to dsRNA, nitric oxide is rapidly produced in primary fibroblasts. In the presence of an intact interferon system, nitric oxide plays a minor but significant role in antiviral protection. However, in the absence of an interferon system, nitric oxide is critical for the protection against DNA viruses. In primary fibroblasts, NF-κB and interferon regulatory factor 1 participate in the induction of inducible nitric oxide synthase expression, which subsequently produces nitric oxide. As large DNA viruses encode multiple and diverse immune modulators to disable the interferon system, it appears that the nitric oxide pathway serves as a secondary strategy to protect the host against viral infection in key cell types, such as fibroblasts, that largely rely on the type I interferon system for antiviral protection