Large-scale benchmark of Endeavour using MetaCore maps.

Summary: Endeavour is a tool that detects the most promising genes within large lists of candidates with respect to a biological process of interest and by combining several genomic data sources. We have benchmarked Endeavour using 450 pathway maps and 826 disease marker sets from MetaCore of GeneGo, Inc. containing a total of 9911 and 12 432 genes, respectively.

A novel microarray approach reveals new tissue-specific signatures of known and predicted mammalian microRNAs.

Microarrays to examine the global expression levels of microRNAs (miRNAs) in a systematic in-parallel manner have become important tools to help unravel the functions of miRNAs and to understand their roles in RNA-based regulation and their implications in human diseases. We have established a novel miRNA-specific microarray platform that enables the simultaneous expression analysis of both known and predicted miRNAs obtained from human or mouse origin. Chemically modified 2'-O-(2-methoxyethyl)-(MOE) oligoribonucleotide probes were arrayed onto Evanescent Resonance (ER) microchips by robotic spotting.

Signal peptide peptidase dependent cleavage of type II transmembrane substrates releases intracellular and extracellular signals.

The intramembrane-cleaving proteases (I-CLiPs) presenilin-1 and -2 (PS1 and PS2), signal peptide peptidase (SPP) and the Site-2 protease (S2P) catalyze critical steps in cell signaling and are implicated in diseases such as Alzheimer's disease, hepatitis C virus (HCV) infection and cholesterol homeostasis. Here we describe the development of a cellular assay based on cleavage of the transmembrane sequence of the HCV core protein precursor, releasing intra- and extra-cellular signals that represent sequential signal peptidase and SPP cleavage, respectively. We find that the SPP inhibitor (Z-LL)2-ketone (IC50 = 1.

Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins.

The human genome encodes seven intramembrane-cleaving GXGD aspartic proteases. These are the two presenilins that activate signaling molecules and are implicated in Alzheimer's disease, signal peptide peptidase (SPP), required for immune surveillance, and four SPP-like candidate proteases (SPPLs), of unknown function. Here we describe a comparative analysis of the topologies of SPP and its human homologues, SPPL2a, -2b, -2c, and -3.

3Dee: a database of protein structural domains.

Unlabelled: The 3Dee database is a repository of protein structural domains. It stores alternative domain definitions for the same protein, organises domains into sequence and structural hierarchies, contains non-redundant set(s) of sequences and structures, multiple structure alignments for families of domains, and allows previous versions of the database to be regenerated.

Availability: 3Dee is accessible on the World Wide Web at the URL http://barton.