Degradation of Bradykinin by Neutral Endopeptidase (EC 3.4.24.11) in Cultured Human Endothelial Cells

Peer Reviewe

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

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

Genome BLAST distance phylogenies inferred from whole plastid and whole mitochondrion genome sequences

BACKGROUND: Phylogenetic methods which do not rely on multiple sequence alignments are important tools in inferring trees directly from completely sequenced genomes. Here, we extend the recently described Genome BLAST Distance Phylogeny (GBDP) strategy to compute phylogenetic trees from all completely sequenced plastid genomes currently available and from a selection of mitochondrial genomes representing the major eukaryotic lineages. BLASTN, TBLASTX, or combinations of both are used to locate high-scoring segment pairs (HSPs) between two sequences from which pairwise similarities and distances are computed in different ways resulting in a total of 96 GBDP variants. The suitability of these distance formulae for phylogeny reconstruction is directly estimated by computing a recently described measure of "treelikeness", the so-called δ value, from the respective distance matrices. Additionally, we compare the trees inferred from these matrices using UPGMA, NJ, BIONJ, FastME, or STC, respectively, with the NCBI taxonomy tree of the taxa under study. RESULTS: Our results indicate that, at this taxonomic level, plastid genomes are much more valuable for inferring phylogenies than are mitochondrial genomes, and that distances based on breakpoints are of little use. Distances based on the proportion of "matched" HSP length to average genome length were best for tree estimation. Additionally we found that using TBLASTX instead of BLASTN and, particularly, combining TBLASTX and BLASTN leads to a small but significant increase in accuracy. Other factors do not significantly affect the phylogenetic outcome. The BIONJ algorithm results in phylogenies most in accordance with the current NCBI taxonomy, with NJ and FastME performing insignificantly worse, and STC performing as well if applied to high quality distance matrices. δ values are found to be a reliable predictor of phylogenetic accuracy. CONCLUSION: Using the most treelike distance matrices, as judged by their δ values, distance methods are able to recover all major plant lineages, and are more in accordance with Apicomplexa organelles being derived from "green" plastids than from plastids of the "red" type. GBDP-like methods can be used to reliably infer phylogenies from different kinds of genomic data. A framework is established to further develop and improve such methods. δ values are a topology-independent tool of general use for the development and assessment of distance methods for phylogenetic inference

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

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

Corporate boards and the performance of Asian firms: A meta-analysis

The prevalence of ownership concentration in Asian firms presents a challenge to the influential agency theory-based understanding of the role of corporate boards. In this paper we develop and test hypotheses about board attributes and firm performance that reflect Asian institutional conditions. We present the first meta-analysis of the relationship between board attributes and performance of Asian firms using a varied set of meta-analytical techniques on a database of 86 studies covering nine Asian countries. First, we find that board structure and composition preferences are influenced by the identity of the concentrated owner. Second, consistent with US data, we find very limited evidence of a direct relationship between board attributes and firm financial performance in the Asian context. Third, we find that the relationship between board structure and composition and firm performance is mediated by the revealed strategic preferences of Asian firms specifically by the level of R&D investment