PDBe: Protein Data Bank in Europe.

The Protein Data Bank in Europe (PDBe) (http://www.ebi.ac.uk/pdbe/) is actively working with its Worldwide Protein Data Bank partners to enhance the quality and consistency of the international archive of bio-macromolecular structure data, the Protein Data Bank (PDB). PDBe also works closely with its collaborators at the European Bioinformatics Institute and the scientific community around the world to enhance its databases and services by adding curated and actively maintained derived data to the existing structural data in the PDB. We have developed a new database infrastructure based on the remediated PDB archive data and a specially designed database for storing information on interactions between proteins and bound molecules. The group has developed new services that allow users to carry out simple textual queries or more complex 3D structure-based queries. The newly designed 'PDBeView Atlas pages' provide an overview of an individual PDB entry in a user-friendly layout and serve as a starting point to further explore the information available in the PDBe database. PDBe's active involvement with the X-ray crystallography, Nuclear Magnetic Resonance spectroscopy and cryo-Electron Microscopy communities have resulted in improved tools for structure deposition and analysis.

SPINE bioinformatics and data-management aspects of high-throughput structural biology.

SPINE (Structural Proteomics In Europe) was established in 2002 as an integrated research project to develop new methods and technologies for high-throughput structural biology. Development areas were broken down into workpackages and this article gives an overview of ongoing activity in the bioinformatics workpackage. Developments cover target selection, target registration, wet and dry laboratory data management and structure annotation as they pertain to high-throughput studies. Some individual projects and developments are discussed in detail, while those that are covered elsewhere in this issue are treated more briefly. In particular, this overview focuses on the infrastructure of the software that allows the experimentalist to move projects through different areas that are crucial to high-throughput studies, leading to the collation of large data sets which are managed and eventually archived and/or deposited.

E-MSD: an integrated data resource for bioinformatics.

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD 'atlas pages' show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www. ebi.ac.uk/msd-srv/docs/roadshow_tutorial/).

The active site of drosomycin, a small insect antifungal protein, delineated by comparison with the modeled structure of Rs-AFP2, a plant antifungal protein.

Drosomycin is the first strictly antifungal protein isolated from an insect (Drosophila melanogaster). The solution structure of this 44-residue protein has been reported previously. It involves a three-stranded beta-sheet and an alpha-helix, the protein global fold being maintained by four disulfide bridges. Rs-AFP2 is a plant antifungal protein exhibiting 41% sequence similarity with drosomycin. Mutational analysis of Rs-AFP2 showed the importance of some residues in the antifungal activity of the protein against the fungus target. In order to determine the structural features responsible for antifungal activity in both drosomycin and Rs-AFP2, we modeled the three-dimensional structure of Rs-AFP2, and of other antifungal proteins, using the solution structure of drosomycin as a template. Structure analysis of drosomycin and Rs-AFP2, and comparisons with the other modeled antifungal structures, revealed that the two proteins shared a hydrophobic cluster located at the protein surface in which a lysine residue is embedded. Based on these close structural similarities and the experimental data available for Rs-AFP2 mutants, an antifungal active site of the insect protein is proposed.

[Lung volume reduction in patients with emphysema after prolonged ventilatory assistance]. / Réduction de volume pulmonaire chez un patient avec emphysème après ventilation assistée prolongée.

A 42-year-old patient with emphysema was hospitalized in the intensive care unit for an episode of acute respiratory failure. The patient became dependent on invasive mechanical ventilation and surgical lung volume reduction was performed. The indication of lung volume reduction in this pathological situation but was followed by rapid weaning 48 hours postoperatively. The patient was discharged without ventilatory assistance and has not required further ventilatory assistance after more than 2 years follow-up.

Central sleep apnoea syndrome with upper airway collapse.

We report on an 83 yr old man with hypersomnia and central sleep apnoea (CSA). He had several possible causes for CSA, including a central nervous system lesion, hypocapnia and anatomical narrowing of the airway at the hypopharyngeal level. We postulate that reduced central respiratory drive occurring in conjunction with upper airway narrowing may have led to central apnoeas. These in turn could have facilitated a complete passive hypopharyngeal collapse at the end of each apnoea, as visualized by somnofluoroscopy. The CSA could also have been favoured by respiratory instability due to chronic hypocapnia.

Muscle protein degradation in severely malnourished patients with chronic obstructive pulmonary disease subject to short-term total parenteral nutrition.

Patients with chronic obstructive pulmonary disease (COPD) often lose weight and muscle mass with progression of the disease. Muscle protein degradation in patients with COPD has never been examined before and during hypercaloric feeding. Eight severely malnourished patients with COPD were examined at home consuming their usual intake, in the hospital after 3 days of a meat-free regular oral diet (period B), and during a hypercaloric (55 kcal/kg) high-lipid (55%) parenteral formula (total parenteral nutrition [TPN]). During period B, 8 well-nourished patients and 10 malnourished cancer patients were used as control groups. Measurements included plasma assays, leg blood flow, leg exchange (of 3-methylhistidine [3MeH], glucose, lactate, and oxygen) and urinary measures of 3MeH, creatinine, and nitrogen. During period B, net release of 3MeH across the leg in patients with COPD was similar to that in well-nourished control subjects and cachectic cancer patients. In COPD patients, there was only a transient decrease in leg exchange values of 3MeH with administration of TPN. COPD patients demonstrated a reduction (p less than .01) in urinary 3MeH excretion and an increase in nitrogen balance (p less than .01) with TPN compared with period B. The decrease in muscle protein degradation with administration of TPN accounts for about 50% of the increase in nitrogen retention in patients with COPD. These data suggest that in severely malnourished patients with COPD the weight loss is not dependent on increased rates of skeletal muscle protein degradation; nevertheless, degradation rates attenuate with a positive nitrogen balance during nutrition repletion.

[Tibial hyperostosis and Propionibacterium acnes]. / Hyperostose tibiale et Propionibacterium acnes.

In a 39-year-old patient with tibial productive osteitis, Propionibacterium acnes was identified in a surgical specimen of the bone lesion. Similar cases have been reported by others. The possibility that P. acnes may play in a pathogenic role in the SAPHO syndrome by causing inflammatory or infectious changes is discussed.

[Late diagnosis of mucoviscidosis based on the association of bronchiectasis and sterility]. / Mucoviscidose diagnostiquée tardivement devant l'association bronchectasies-stérilité.

We report a case of a man aged 36, in whom a diagnosis of mucoviscidosis was diagnosed based on the association of diffuse bronchiectasis and obstructive azoospermia. We discussed some clinical and biological aspects leading to the diagnosis of mucoviscidosis in the adult.