A role for peroxisome proliferator-activated receptors in the immunopathology of schistosomiasis?

Peroxisome proliferator-activated receptors (PPARs) have been demonstrated to have a role in immune regulation. In general, they are anti-inflammatory and promote Th2 type responses, and they are associated with the alternative activation of macrophages. Interestingly, helminth infections, such as the schistosome blood flukes that cause schistosomiasis, are characterised by a Th2 response and the accumulation of alternative activated macrophages. This would suggest that at some level, PPARs could have a role in the modulation of the immune response in schistosomiasis. This paper discusses possible areas where PPARs could have a role in this disease

Hepatic stellate cells and parasite-induced liver fibrosis

ABSTRACT: Fibrogenesis is a common feature of many diseases where there is severe insult to the liver. The hepatic stellate cell trans-differentiation into a myofibroblast has been identified as an important event in liver fibrogenesis and has been well investigated over the last few years in a number of liver diseases. The trans-differentiation process can be monitored in vitro by evaluation of biomarkers that are characteristic of normal quiescent hepatic stellate cells or activated myofibroblasts. Two major parasitic diseases associated with liver injury and fibrosis are schistosomiasis and echinococcosis. Recent studies have highlighted a role for activated hepatic stellate cells in both murine and human schistosomiasis as well as demonstrating that schistosome antigens are able to regulate this trans-differentiation process. Study of the hepatic stellate cell and its interaction with parasite-derived antigens may be pivotal in our understanding of the pathology associated with schistosomiasis and other parasitic diseases, including echinococcosis, as well as revealing new information on the trans-differentiation process in this cell type

Role of (p)ppGpp in Viability and Biofilm Formation of Actinobacillus pleuropneumoniae S8.

Actinobacillus pleuropneumoniae is a Gram-negative bacterium and the cause of porcine pleuropneumonia. When the bacterium encounters nutritional starvation, the relA-dependent (p)ppGpp-mediated stringent response is activated. The modified nucleotides guanosine 5'-diphosphate 3'-diphosphate (ppGpp) and guanosine 5'-triphosphate 3'-diphosphate (pppGpp) are known to be signaling molecules in other prokaryotes. Here, to investigate the role of (p)ppGpp in A. pleuropneumoniae, we created a mutant A. pleuropneumoniae strain, S8ΔrelA, which lacks the (p)ppGpp-synthesizing enzyme RelA, and investigated its phenotype in vitro. S8ΔrelA did not survive after stationary phase (starvation condition) and grew exclusively as non-extended cells. Compared to the wild-type (WT) strain, the S8ΔrelA mutant had an increased ability to form a biofilm. Transcriptional profiles of early stationary phase cultures revealed that a total of 405 bacterial genes were differentially expressed (including 380 up-regulated and 25 down-regulated genes) in S8ΔrelA as compared with the WT strain. Most of the up-regulated genes are involved in ribosomal structure and biogenesis, amino acid transport and metabolism, translation cell wall/membrane/envelope biogenesis. The data indicate that (p)ppGpp coordinates the growth, viability, morphology, biofilm formation and metabolic ability of A. pleuropneumoniae in starvation conditions. Furthermore, S8ΔrelA could not use certain sugars nor produce urease which has been associated with the virulence of A. pleuropneumoniae, suggesting that (p)ppGpp may directly or indirectly affect the pathogenesis of A. pleuropneumoniae during the infection process. In summary, (p)ppGpp signaling represents an essential component of the regulatory network governing stress adaptation and virulence in A. pleuropneumoniae

A class of unitarily invariant norms on B(H)

Let H be a complex Hubert space and let B(H) be the algebra of all bounded linear operators on H. For c = (c1, ..., ck), where c1 ≥ ⋯ ≥ Ck > 0 and p ≥ 1, define the (c,p)-norm of A ∈ B(H) by ∥A∥c,p = (∑i=1 kcisi(A)p) 1/p where si(A) denotes the ith s-numbers of A. In this paper we study some basic properties of this norm and give a characterization of the extreme points of its closed unit ball. Using these results, we obtain a description of the corresponding isometric isomorphisms on B(H). ©2000 American Mathematical Society.published_or_final_versio

A photocatalytic rotating disc reactor with TiO<font size=-1>₂</font> nanowire arrays deposited for industrial watewater treatment

published_or_final_versio

The Generation of Successive Unmarked Mutations and Chromosomal Insertion of Heterologous Genes in Actinobacillus pleuropneumoniae Using Natural Transformation

We have developed a simple method of generating scarless, unmarked mutations in Actinobacillus pleuropneumoniae by exploiting the ability of this bacterium to undergo natural transformation, and with no need to introduce plasmids encoding recombinases or resolvases. This method involves two successive rounds of natural transformation using linear DNA: the first introduces a cassette carrying cat (which allows selection by chloramphenicol) and sacB (which allows counter-selection using sucrose) flanked by sequences to either side of the target gene; the second transformation utilises the flanking sequences ligated directly to each other in order to remove the cat-sacB cassette. In order to ensure efficient uptake of the target DNA during transformation, A. pleuropneumoniae uptake sequences are added into the constructs used in both rounds of transformation. This method can be used to generate multiple successive deletions and can also be used to introduce targeted point mutations or insertions of heterologous genes into the A. pleuropneumoniae chromosome for development of live attenuated vaccine strains. So far, we have applied this method to highly transformable isolates of serovars 8 (MIDG2331), which is the most prevalent in the UK, and 15 (HS143). By screening clinical isolates of other serovars, it should be possible to identify other amenable strains

Visualization of facet-dependent pseudo-photocatalytic behavior of TiO2 nanorods for water splitting using In situ liquid cell TEM

We report an investigation of the pseudo-photocatalytic behavior of rutile TiO2 nanorods for water splitting observed with liquid cell transmission electron microscopy (TEM). The electron beam serves as a “light” source to initiate the catalytic reaction and a “water-in-salt” aqueous solution is employed as the electrolyte. The observation reveals that bubbles are generated preferentially residing near the {110} facet of a rutile TiO2 nanorod under a low electron dose rate (9.3–18.6 e-/Å2·s). These bubbles are ascribed to hydrogen gas generated from the pseudo-photocatalytic water splitting. As the electron beam current density increases to 93 e-/Å2 ·s, bubbles are also found at the {001} and {111} facets as well as in the bulk liquid solution, demonstrating the dominant effects of water electrolysis by electron beam under higher dose rates. The facet-dependent pseudo-photocatalytic behavior of rutile TiO2 nanorods is further validated using density functional theory (DFT)calculation. Our work establishes a facile liquid cell TEM setup for the study of pseudo-photocatalytic water splitting and it may also be applied to investigation of other photo-activated phenomena occurring at the solid-liquid interfaces

Targeted Assembly of Short Sequence Reads

As next-generation sequence (NGS) production continues to increase, analysis is becoming a significant bottleneck. However, in situations where information is required only for specific sequence variants, it is not necessary to assemble or align whole genome data sets in their entirety. Rather, NGS data sets can be mined for the presence of sequence variants of interest by localized assembly, which is a faster, easier, and more accurate approach. We present TASR, a streamlined assembler that interrogates very large NGS data sets for the presence of specific variants, by only considering reads within the sequence space of input target sequences provided by the user. The NGS data set is searched for reads with an exact match to all possible short words within the target sequence, and these reads are then assembled strin-gently to generate a consensus of the target and flanking sequence. Typically, variants of a particular locus are provided as different target sequences, and the presence of the variant in the data set being interrogated is revealed by a successful assembly outcome. However, TASR can also be used to find unknown sequences that flank a given target. We demonstrate that TASR has utility in finding or confirming ge-nomic mutations, polymorphism, fusion and integration events. Targeted assembly is a powerful method for interrogating large data sets for the presence of sequence variants of interest. TASR is a fast, flexible and easy to use tool for targeted assembly

Characterisation of the Actinobacillus pleuropneumoniae SXT-related Integrative and Conjugative Element ICEApl2, and analysis of the encoded FloR protein: hydrophobic residues in transmembrane domains contribute dynamically to florfenicol and chloramphenicol efflux

Objectives To characterize ICEApl2, an SXT-related integrative and conjugative element (ICE) found in a clinical isolate of the porcine pathogen Actinobacillus pleuropneumoniae, and analyse the functional nature of the encoded FloR. Methods ICEApl2 was identified in the genome of A. pleuropneumoniae MIDG3553. Functional analysis was done using conjugal transfer experiments. MIDG3553 was tested for susceptibility to the antimicrobials for which resistance genes are present in ICEApl2. Lack of florfenicol/chloramphenicol resistance conferred by the encoded FloR protein was investigated by cloning and site-directed mutagenesis experiments in Escherichia coli. Results ICEApl2 is 92 660 bp and contains 89 genes. Comparative sequence analysis indicated that ICEApl2 is a member of the SXT/R391 ICE family. Conjugation experiments showed that, although ICEApl2 is capable of excision from the chromosome, it is not self-transmissible. ICEApl2 encodes the antimicrobial resistance genes floR, strAB, sul2 and dfrA1, and MIDG3553 is resistant to streptomycin, sulfisoxazole and trimethoprim, but not florfenicol or chloramphenicol. Cloning and site-directed mutagenesis of the floR gene revealed the importance of the nature of the hydrophobic amino acid residues at positions 160 and 228 in FloR for determining resistance to florfenicol and chloramphenicol. Conclusions Our results indicate that the nature of hydrophobic residues at positions 160 and 228 of FloR contribute dynamically to specific efflux of florfenicol and chloramphenicol, although some differences in resistance levels may depend on the bacterial host species. This is also, to our knowledge, the first description of an SXT/R391 ICE in A. pleuropneumoniae or any member of the Pasteurellaceae

ArrayWiki: an enabling technology for sharing public microarray data repositories and meta-analyses

© 2008 Stokes et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.DOI: 10.1186/1471-2105-9-S6-S18Background. A survey of microarray databases reveals that most of the repository contents and data models are heterogeneous (i.e., data obtained from different chip manufacturers), and that the repositories provide only basic biological keywords linking to PubMed. As a result, it is difficult to find datasets using research context or analysis parameters information beyond a few keywords. For example, to reduce the "curse-of-dimension" problem in microarray analysis, the number of samples is often increased by merging array data from different datasets. Knowing chip data parameters such as pre-processing steps (e.g., normalization, artefact removal, etc), and knowing any previous biological validation of the dataset is essential due to the heterogeneity of the data. However, most of the microarray repositories do not have meta-data information in the first place, and do not have a a mechanism to add or insert this information. Thus, there is a critical need to create "intelligent" microarray repositories that (1) enable update of meta-data with the raw array data, and (2) provide standardized archiving protocols to minimize bias from the raw data sources. Results. To address the problems discussed, we have developed a community maintained system called ArrayWiki that unites disparate meta-data of microarray meta-experiments from multiple primary sources with four key features. First, ArrayWiki provides a user-friendly knowledge management interface in addition to a programmable interface using standards developed by Wikipedia. Second, ArrayWiki includes automated quality control processes (caCORRECT) and novel visualization methods (BioPNG, Gel Plots), which provide extra information about data quality unavailable in other microarray repositories. Third, it provides a user-curation capability through the familiar Wiki interface. Fourth, ArrayWiki provides users with simple text-based searches across all experiment meta-data, and exposes data to search engine crawlers (Semantic Agents) such as Google to further enhance data discovery. Conclusions. Microarray data and meta information in ArrayWiki are distributed and visualized using a novel and compact data storage format, BioPNG. Also, they are open to the research community for curation, modification, and contribution. By making a small investment of time to learn the syntax and structure common to all sites running MediaWiki software, domain scientists and practioners can all contribute to make better use of microarray technologies in research and medical practices. ArrayWiki is available at http://www.bio-miblab.org/arraywiki