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Governing UK Biobank: the importance of ensuring public trust.

In the autumn of 2003, UK Biobank published the first draft of its Ethics and Governance Framework. Subsequently, this document has been available for interested parties to comment on and the UK Biobank Board of Directors is expected to adopt the final version in 2004. Here, we aim to contribute to this process and highlight to a wider audience some of the inconsistencies in the issues of consent, governance and right of withdrawal that emerge from the draft of the Framework. These issues will have implications for securing the public trust and long-term support that the success of the project depends on. Therefore, they must be considered carefully because the UK Biobank will be the first ever genetic database of a general population of this size to become operational, and will be used as a model for other projects of this kind.

Biological Specimen Banks↗

UK Biobank: a project in search of a protocol?

Before it has even begun recruiting participants, the UK Biobank project has raised extraordinary passions among scientists. Some scientists are broadly supportive of the project, and feel that it is a scientifically valid, potentially valuable resource, although they still have reservations over the details of the current protocol. Others see it as an ill-conceived, politically motivated project, in which consultations have only been done to give an appearance of legitimacy and in which the scientific case has not been made for its design. There has been resentment over how the protocol has evolved, and the secrecy and legal constraints that surrounded the process for groups bidding to be involved has had the appearance of attempting to stifle debate. For this article even supporters of the project have been unwilling to be quoted on the record. The only point that everyone seems to agree on is that sufficient debate about the project has not taken place.

Aged↗

KID, a Kinase Inhibitor Database project.

The Kinase Inhibitor Database is a small specialized database dedicated to the gathering of information on protein kinase inhibitors. The database is accessible through the World Wide Web system and gives access to structural and bibliographic information on protein kinase inhibitors. The data in the database will be collected and submitted by researchers working in the kinase inhibitor field. The submitted data will be checked by the curator of the database before entry.

Databases as Topic↗

Common phylogeny of catalase-peroxidases and ascorbate peroxidases.

Catalase-peroxidases belong to Class I of the plant, fungal, bacterial peroxidase superfamily, together with yeast cytochrome c peroxidase and ascorbate peroxidases. Obviously these bifunctional enzymes arose via gene duplication of an ancestral hydroperoxidase. A 230-residues long homologous region exists in all eukaryotic members of Class I, which is present twice in both prokaryotic and archaeal catalase-peroxidases. The overall structure of eukaryotic Class I peroxidases may be retained in both halves of catalase-peroxidases, with major insertions in several loops, some of which may participate in inter-domain or inter-subunit interactions. Interspecies distances in unrooted phylogenetic trees, analysis of sequence similarities in distinct structural regions, as well as hydrophobic cluster analysis (HCA) suggest that one single tandem duplication had already occurred in the common ancestor prior to the segregation of the archaeal and eubacterial lines. The C-terminal halves of extant catalase-peroxidases clearly did not accumulate random changes, so prolonged periods of independent evolution of the duplicates can be ruled out. Fusion of both copies must have occurred still very early or even in the course of the duplication. We suggest that the sparse representatives of eukaryotic catalase-peroxidases go back to lateral gene transfer, and that, except for several fungi, only single copy hydroperoxidases occur in the eukaryotic lineage. The N-terminal halves of catalase-peroxidases, which reveal higher homology with the single-copy members of the superfamily, obviously are catalytically active, whereas the C-terminal halves of the bifunctional enzymes presumably control the access to the haem pocket and facilitate stable folding. The bifunctional nature of catalase-peroxidases can be ascribed to several unique sequence peculiarities conserved among all N-terminal halves, which most likely will affect the properties of both haem ligands.

Amino Acid Motifs↗

[Evaluation of clinical practices: methods of data collection and information sources?].

OBJECTIVE: The aim of our study is to present the methods used to observe clinical practices, to evaluate their advantages and limits, and to specify the context in which they are preformed. METHODS: We conducted a bibliographical search on MEDLINE using key words, completed by an offline search. We selected articles published in French or English between 1985 and 2003. RESULTS: Thirty articles, of which 3 were reviews, as well as an additional 5 reports and 9 books, were selected. We distinguished direct or objective approaches to clinical practices as well as indirect or declarative approaches. We also noted whether the approach was individual with data collected from individual practitioners, or collective, with data coming from databases. Most methods of collecting data used medical records, often in the context of internal or external clinical audits or peer reviews. The other sources of data were self-administered questionnaires, written case simulations and simulated patients. Data was also extracted from previously existing databases: claims databases, registries and ad hoc databases. CONCLUSION: An objective individual approach insures the highest quality of information, but possible high costs can limit the use of this approach. It is necessary to continue researching the best means of collecting data on clinical practices, because of the obligation of each practitioner to evaluate individual clinical practices.

Data Collection↗

Generalized anxiety disorder publications: so where do we stand?

Although generalized anxiety disorder (GAD) has traditionally been understudied, several authors have stated that interest in GAD has recently increased. However, no data exist to confirm or refute this assertion. The present study investigates publication rates for the anxiety disorders from 1980 to 1997 in two extensive databases: PsycLIT and MEDLINE. GAD publications were examined in two ways. First, the annual percentage of anxiety disorder publications devoted to GAD was calculated. Second, GAD publications were classified into one of four categories: descriptive, process, treatment, and review. The results show that GAD is considerably less studied than panic disorder/agoraphobia, posttraumatic stress disorder and obsessive-compulsive disorder. Though the percentage of anxiety disorder publications devoted to GAD increased considerably during the 1980s, it has generally remained stable in the 1990s. The results also show that descriptive and treatment issues account for the vast majority of GAD publications. The author concludes that the paucity of research into process issues is unfortunate because intensified investigation of the specific processes involved in GAD may lead to new breakthroughs in our understanding and treatment of this anxiety disorder.

Agoraphobia↗

Preliminary study on puffer fish proteome-species identification of puffer fish by two-dimensional electrophoresis.

The aims of this work were to determine the differential characterization of the urea soluble protein components of puffer fish species and to establish a preliminary proteomic database using an immobilized pH gradient two-dimensional electrophoresis (2DE) technique. The puffer fish muscle proteins resolved into 171-260 spots in the 2DE gels, with a pI range of 3-10 and molecular mass range of 7.4-205.0 kDa, following Comassie blue staining. Puffer fish muscle proteins fell in the region with pI values of 3.5-7.0, and molecular masses of 7.4-45.0 kDa were well-resolved and were good for species comparison. The more acidic proteins of lower molecular masses showed species specific characteristics. Therefore, the species of puffer fish can be differentiated from the comparison of the characteristic 2DE protein patterns.

Animals↗

Data-dependent electron capture dissociation FT-ICR mass spectrometry for proteomic analyses.

Electron capture dissociation (ECD) offers many benefits for the analysis of peptides and proteins, and consequently shows great potential for the field of proteomics. Recent developments have reduced the time scale required for ECD to milliseconds resulting in the technique's compatibility with on-line separation techniques, e.g., HPLC. Here, we demonstrate incorporation of ECD into a high-throughput data-dependent LC-MS/MS approach for the analysis of proteomic samples. The approach is applied to analysis of the protein Fc-ROR2 isolated from chondrocytes and is the first example of LC-ECD-MS/MS of such a sample. Protein sequence coverage was 29%. Within that coverage, fifteen peptides were isolated and subjected to ECD. In most cases, the sequence tag generated by ECD was over 70% (in terms of the number of peptide backbone cleavages). The ECD data were searched against the nonredundant human NCBI database using the SEQUEST algorithm. Protein ROR2 was assigned, as was IgG (Fc domain). The results demonstrate the suitability of ECD as an integral technique in high-throughput proteomic strategies.

Algorithms↗