Discovery of a new M32-like "Compact Elliptical" galaxy in the halo of the Abell 496 cD galaxy

Aims: ``Compact ellipticals'' are so rare that a search for M32 analogs is needed to ensure the very existence of this class. Methods: We report here the discovery of A496cE, a M32 twin in the cluster Abell 496, located in the halo of the central cD. Results: Based on CFHT and HST imaging we show that the light profile of A496cE requires a two component fit: a Sersic bulge and an exponential disc. The spectrum of A496cE obtained with the ESO-VLT FLAMES/Giraffe spectrograph can be fit by a stellar synthesis spectrum dominated by old stars, with high values of [Mg/Fe] and velocity dispersion. Conclusions: The capture of A496cE by the cD galaxy and tidal stripping of most of its disc are briefly discussed.Comment: 4 pages, 4 figures, accepted for publication in A&A Letter

Comparison of chemical clustering methods using graph- and fingerprint-based similarity measures

This paper compares several published methods for clustering chemical structures, using both graph- and fingerprint-based similarity measures. The clusterings from each method were compared to determine the degree of cluster overlap. Each method was also evaluated on how well it grouped structures into clusters possessing a non-trivial substructural commonality. The methods which employ adjustable parameters were tested to determine the stability of each parameter for datasets of varying size and composition. Our experiments suggest that both graph- and fingerprint-based similarity measures can be used effectively for generating chemical clusterings; it is also suggested that the CAST and Yin–Chen methods, suggested recently for the clustering of gene expression patterns, may also prove effective for the clustering of 2D chemical structures

Interoperability between biomedical ontologies through relation expansion, upper-level ontologies and automatic reasoning

Researchers design ontologies as a means to accurately annotate and integrate experimental data across heterogeneous and disparate data- and knowledge bases. Formal ontologies make the semantics of terms and relations explicit such that automated reasoning can be used to verify the consistency of knowledge. However, many biomedical ontologies do not sufficiently formalize the semantics of their relations and are therefore limited with respect to automated reasoning for large scale data integration and knowledge discovery. We describe a method to improve automated reasoning over biomedical ontologies and identify several thousand contradictory class definitions. Our approach aligns terms in biomedical ontologies with foundational classes in a top-level ontology and formalizes composite relations as class expressions. We describe the semi-automated repair of contradictions and demonstrate expressive queries over interoperable ontologies. Our work forms an important cornerstone for data integration, automatic inference and knowledge discovery based on formal representations of knowledge. Our results and analysis software are available at http://bioonto.de/pmwiki.php/Main/ReasonableOntologies

The OBO Foundry: Coordinated Evolution of Ontologies to Support Biomedical Data Integration

The value of any kind of data is greatly enhanced when it exists in a form that allows it to be integrated with other data. One approach to integration is through the annotation of multiple bodies of data using common controlled vocabularies or ‘ontologies’. Unfortunately, the very success of this approach has led to a proliferation of ontologies, which itself creates obstacles to integration. The Open Biomedical Ontologies (OBO) consortium has set in train a strategy to overcome this problem. Existing OBO ontologies, including the Gene Ontology, are undergoing a process of coordinated reform, and new ontologies being created, on the basis of an evolving set of shared principles governing ontology development. The result is an expanding family of ontologies designed to be interoperable, logically well-formed, and to incorporate accurate representations of biological reality. We describe the OBO Foundry initiative, and provide guidelines for those who might wish to become involved in the future

In vitro selection and characterisation of human anti-HIV-1 antibody fragments

Generation of neutralising antibodies with broad specificity would be one of the effective approaches to control HIV-1 spread. It is clear that a method that allows rapid generation of neutralising antibodies is needed. This project aims at developing a novel approach to rapidly access human anti-HIV-1 antibodies in vitro by using ribosome display and selection from DNA libraries of HIV-1 patients. Two single-chain antibody libraries (M325 and K530) were constructed from two HIV-1 long-term non-progressors, whose sera showed cross-neutralising activities against various HIV-1 strains across a range of clades. In each library, total RNA was extracted from blood of each donor and used to synthesise cDNA. Families of 4 κ light chains, 9 λ light chains and 8 heavy chains were generated by using RT-PCR amplification. These fragments were then assembled with all possible combinatorial pairs to form diversified repertories in the form of VL-link-VH-partial CH. Both libraries were subjected to ribosome display for in vitro selection of functional antibodies. Ribosome display is a cell-free technique used to generate proteins that can bind to an immobilised antigen. During this process, the translated proteins are associated with their mRNAs, enabling a simultaneous selection of functional proteins and their gene. The employment of ribosome display facilitated rapid screening of two large libraries against recombinant gp120 (generated from patient K530)

A Peptide Core Motif for Binding to Heterotrimeric G Protein α Subunits

Recently, in vitro selection using mRNA display was used to identify a novel peptide sequence that binds with high affinity to G{alpha}i1. The peptide was minimized to a 9-residue sequence (R6A-1) that retains high affinity and specificity for the GDP-bound state of G{alpha}i1 and acts as a guanine nucleotide dissociation inhibitor (GDI). Here we demonstrate that the R6A-1 peptide interacts with G{alpha} subunits representing all four G protein classes, acting as a core motif for G{alpha} interaction. This contrasts with the consensus G protein regulatory(GPR) sequence, a 28-mer peptide GDI derived from the GoLoco (G{alpha}i/0-Loco interaction)/GPR motif that shares no homology with R6A-1 and binds only to G{alpha}i1-3 in this assay. Binding of R6A-1 is generally specific to the GDP-bound state of the G{alpha} subunits and excludes association with G{beta}{gamma}. R6A-G{alpha}i1 complexes are resistant to trypsin digestion and exhibit distinct stability in the presence of Mg2+, suggesting that the R6A and GPR peptides exert their activities using different mechanisms. Studies using G{alpha}i1/G{alpha}s chimeras identify two regions of G{alpha}i1 (residues 1–35 and 57–88) as determinants for strong R6A-Gi{alpha}1 interaction. Residues flanking the R6A-1 peptide confer unique binding properties, indicating that the core motif could be used as a starting point for the development of peptides exhibiting novel activities and/or specificity for particular G protein subclasses or nucleotide-bound states