Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression

Background. End-stage renal disease (ESRD) results in increased susceptibility to infections, impaired response to vaccination and diffuse B-cell lymphopenia. However, the precise nature and mechanism of ESRD-induced B-cell lymphopenia remains unclear. Therefore, we studied the distribution of major B-cell subsets, B-cell growth, differentiation and survival factors, IL-7 and BAFF, and their receptors in 21 haemodialysis patients and 21 controls

On the Complexity of Query Result Diversification

Query result diversification is a bi-criteria optimization problem for ranking query results. Given a database D, a query Q and a positive integer k, it is to find a set of k tuples from Q(D) such that the tuples are as relevant as possible to the query, and at the same time, as diverse as possible to each other. Subsets of Q(D) are ranked by an objective function defined in terms of relevance and diversity. Query result diversification has found a variety of applications in databases, information retrieval and operations research. This paper studies the complexity of result diversification for relational queries. We identify three problems in connection with query result diversification, to determine whether there exists a set of k tuples that is ranked above a bound with respect to relevance and diversity, to assess the rank of a given k-element set, and to count how many k-element sets are ranked above a given bound. We study these problems for a variety of query languages and for three objective functions. We establish the upper and lower bounds of these problems, all matching, for both combined complexity and data complexity. We also investigate several special settings of these problems, identifying tractable cases. 1

A software pipeline for processing and identification of fungal ITS sequences

<p>Abstract</p> <p>Background</p> <p>Fungi from environmental samples are typically identified to species level through DNA sequencing of the nuclear ribosomal internal transcribed spacer (<it>ITS</it>) region for use in BLAST-based similarity searches in the International Nucleotide Sequence Databases. These searches are time-consuming and regularly require a significant amount of manual intervention and complementary analyses. We here present software – in the form of an identification pipeline for large sets of fungal <it>ITS </it>sequences – developed to automate the BLAST process and several additional analysis steps. The performance of the pipeline was evaluated on a dataset of 350 <it>ITS </it>sequences from fungi growing as epiphytes on building material.</p> <p>Results</p> <p>The pipeline was written in Perl and uses a local installation of NCBI-BLAST for the similarity searches of the query sequences. The variable subregion <it>ITS2 </it>of the <it>ITS </it>region is extracted from the sequences and used for additional searches of higher sensitivity. Multiple alignments of each query sequence and its closest matches are computed, and query sequences sharing at least 50% of their best matches are clustered to facilitate the evaluation of hypothetically conspecific groups. The pipeline proved to speed up the processing, as well as enhance the resolution, of the evaluation dataset considerably, and the fungi were found to belong chiefly to the <it>Ascomycota</it>, with <it>Penicillium </it>and <it>Aspergillus </it>as the two most common genera. The <it>ITS2 </it>was found to indicate a different taxonomic affiliation than did the complete <it>ITS </it>region for 10% of the query sequences, though this figure is likely to vary with the taxonomic scope of the query sequences.</p> <p>Conclusion</p> <p>The present software readily assigns large sets of fungal query sequences to their respective best matches in the international sequence databases and places them in a larger biological context. The output is highly structured to be easy to process, although it still needs to be inspected and possibly corrected for the impact of the incomplete and sometimes erroneously annotated fungal entries in these databases. The open source pipeline is available for UNIX-type platforms, and updated releases of the target database are made available biweekly. The pipeline is easily modified to operate on other molecular regions and organism groups.</p

RAPID: Resource of Asian Primary Immunodeficiency Diseases

Availability of a freely accessible, dynamic and integrated database for primary immunodeficiency diseases (PID) is important both for researchers as well as clinicians. To build a PID informational platform and also as a part of action to initiate a network of PID research in Asia, we have constructed a web-based compendium of molecular alterations in PID, named Resource of Asian Primary Immunodeficiency Diseases (RAPID), which is available as a worldwide web resource at http://rapid.rcai.riken.jp/. It hosts information on sequence variations and expression at the mRNA and protein levels of all genes reported to be involved in PID patients. The main objective of this database is to provide detailed information pertaining to genes and proteins involved in primary immunodeficiency diseases along with other relevant information about protein–protein interactions, mouse studies and microarray gene-expression profiles in various organs and cells of the immune system. RAPID also hosts a tool, mutation viewer, to predict deleterious and novel mutations and also to obtain mutation-based 3D structures for PID genes. Thus, information contained in this database should help physicians and other biomedical investigators to further investigate the role of these molecules in PID

Cytotoxic Withanolide Constituents of Physalis longifolia

Fourteen new withanolides, 1–14, named withalongolides A–N, respectively, were isolated from the aerial parts of Physalis longifolia together with eight known compounds (15–22). The structures of compounds 1–14 were elucidated through spectroscopic techniques and chemical methods. In addition, the structures of withanolides 1, 2, 3, and 6 were confirmed by X-ray crystallographic analysis. Using a MTS viability assay, eight withanolides (1, 2, 3, 7, 8, 15, 16, and 19) and four acetylated derivatives (1a, 1b, 2a, and 2b) showed potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal fibroblast (MRC-5) cells with IC50 values in the range between 0.067 and 9.3 μM

Gender Differences in Aspirin use Among Adults With Coronary Heart Disease in the United States

BACKGROUND: Aspirin reduces mortality for men and women with coronary heart disease (CHD). Previous research suggests women with acute coronary syndromes receive less aggressive care, including less frequent early administration of aspirin. The presence of gender differences in aspirin use for secondary prevention is less clear. OBJECTIVE: To determine if a gender difference exists in the use of aspirin for secondary prevention among individuals with CHD. DESIGN: We analyzed data from the nationally representative 2000–2002 Medical Expenditure Panel Surveys to determine the prevalence of regular aspirin use among men and women with CHD. PARTICIPANTS: Participants, 1,869, 40 years and older who reported CHD or prior myocardial infarction. RESULTS: Women were less likely than men to use aspirin regularly (62.4% vs 75.6%, p < .001) even after adjusting for demographic, socioeconomic and clinical characteristics (adjusted OR = 0.62, 95% CI, 0.48–0.79). This difference narrowed but remained significant when the analysis was limited to those without self-reported contraindications to aspirin (79.8% vs 86.4%, P = .002, adjusted OR = 0.68, 95% CI, 0.48–0.97). Women were more likely than men to report contraindications (20.5% vs 12.5%, P < .001). Differences in aspirin use were greater between women and men with private health insurance (61.8% vs 79.0%, P < .001, adjusted OR = 0.48, 95% CI, 0.35–0.67) than among those with public coverage (62.5% vs 70.7%, P = .04, adjusted OR = 0.74, 95% CI, 0.50–1.11) (P < .001 for gender–insurance interaction). CONCLUSION: We found a gender difference in aspirin use among patients with CHD not fully explained by differences in patient characteristics or reported contraindications. These findings suggest a need for improved secondary prevention of cardiovascular events for women with CHD

A Compendium of Potential Biomarkers of Pancreatic Cancer

Akhilesh Pandey and colleagues describe a compendium of potential biomarkers that can be systematically validated by the pancreatic cancer community

Increased Expression of Toll-Like Receptors by Monocytes and Natural Killer Cells in ANCA-Associated Vasculitis

INTRODUCTION: Toll-like receptors (TLRs) are a family of receptors that sense pathogen associated patterns such as bacterial cell wall proteins. Bacterial infections are associated with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Here, we assessed the expression of TLRs 2, 4, and 9 by peripheral blood leukocytes from patients with AAV, and investigated TLR mediated responses ex vivo. METHODS: Expression of TLRs was determined in 38 AAV patients (32 remission, 6 active disease), and 20 healthy controls (HC). Membrane expression of TLRs 2, 4, and 9, and intracellular expression of TLR9 by B lymphocytes, T lymphocytes, NK cells, monocytes and granulocytes was assessed using 9-color flowcytometry. Whole blood from 13 patients and 7 HC was stimulated ex vivo with TLR 2, 4 and 9 ligands and production of cytokines was analyzed. RESULTS: In patients, we observed increased proportions of TLR expressing NK cells. Furthermore, patient monocytes expressed higher levels of TLR2 compared to HC, and in a subset of patients an increased proportion of TLR4(+) monocytes was observed. Monocytes from nasal carriers of Staphylococcus aureus expressed increased levels of intracellular TLR9. Membrane expression of TLRs by B lymphocytes, T lymphocytes, and granulocytes was comparable between AAV patients and HC. Patients with active disease did not show differential TLR expression compared to patients in remission. Ex vivo responses to TLR ligands did not differ significantly between patients and HC. CONCLUSIONS: In AAV, monocytes and NK cells display increased TLR expression. Increased TLR expression by these leukocytes, probably resulting from increased activation, could play a role in disease (re)activation