173 research outputs found
Design and Implementation of the UniProt Website
The UniProt consortium is the main provider of protein sequence and annotation data for much of the life sciences community. The "www.uniprot.org":http://www.uniprot.org website is the primary access point to this data and to documentation and basic tools for the data. This paper discusses the design and implementation of the new website, which was released in July 2008, and shows how it improves data access for users with different levels of experience, as well as to machines for programmatic access
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MexAB-OprM Efflux Pump Interaction with the Peptidoglycan of Escherichia coli and Pseudomonas aeruginosa.
One of the major families of membrane proteins found in prokaryote genome corresponds to the transporters. Among them, the resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one of the most problematic mechanisms used by bacteria to resist to antibiotics, i.e., the active efflux of drugs. In Gram-negative bacteria, these proteins are inserted in the inner membrane and form a tripartite assembly with an outer membrane factor and a periplasmic linker in order to cross the two membranes to expulse molecules outside of the cell. A lot of information has been collected to understand the functional mechanism of these pumps, especially with AcrAB-TolC from Escherichia coli, but one missing piece from all the suggested models is the role of peptidoglycan in the assembly. Here, by pull-down experiments with purified peptidoglycans, we precise the MexAB-OprM interaction with the peptidoglycan from Escherichia coli and Pseudomonas aeruginosa, highlighting a role of the peptidoglycan in stabilizing the MexA-OprM complex and also differences between the two Gram-negative bacteria peptidoglycans
Functional Mechanism of the Efflux Pumps Transcription Regulators From Pseudomonas aeruginosa Based on 3D Structures
Bacterial antibiotic resistance is a worldwide health problem that deserves important research attention in order to develop new therapeutic strategies. Recently, the World Health Organization (WHO) classified Pseudomonas aeruginosa as one of the priority bacteria for which new antibiotics are urgently needed. In this opportunistic pathogen, antibiotics efflux is one of the most prevalent mechanisms where the drug is efficiently expulsed through the cell-wall. This resistance mechanism is highly correlated to the expression level of efflux pumps of the resistance-nodulation-cell division (RND) family, which is finely tuned by gene regulators. Thus, it is worthwhile considering the efflux pump regulators of P. aeruginosa as promising therapeutical targets alternative. Several families of regulators have been identified, including activators and repressors that control the genetic expression of the pumps in response to an extracellular signal, such as the presence of the antibiotic or other environmental modifications. In this review, based on different crystallographic structures solved from archetypal bacteria, we will first focus on the molecular mechanism of the regulator families involved in the RND efflux pump expression in P. aeruginosa, which are TetR, LysR, MarR, AraC, and the two-components system (TCS). Finally, the regulators of known structure from P. aeruginosa will be presented
Infrastructure for the life sciences: design and implementation of the UniProt website
<p>Abstract</p> <p>Background</p> <p>The UniProt consortium was formed in 2002 by groups from the Swiss Institute of Bioinformatics (SIB), the European Bioinformatics Institute (EBI) and the Protein Information Resource (PIR) at Georgetown University, and soon afterwards the website <url>http://www.uniprot.org</url> was set up as a central entry point to UniProt resources. Requests to this address were redirected to one of the three organisations' websites. While these sites shared a set of static pages with general information about UniProt, their pages for searching and viewing data were different. To provide users with a consistent view and to cut the cost of maintaining three separate sites, the consortium decided to develop a common website for UniProt. Following several years of intense development and a year of public beta testing, the <url>http://www.uniprot.org</url> domain was switched to the newly developed site described in this paper in July 2008.</p> <p>Description</p> <p>The UniProt consortium is the main provider of protein sequence and annotation data for much of the life sciences community. The <url>http://www.uniprot.org</url> website is the primary access point to this data and to documentation and basic tools for the data. These tools include full text and field-based text search, similarity search, multiple sequence alignment, batch retrieval and database identifier mapping. This paper discusses the design and implementation of the new website, which was released in July 2008, and shows how it improves data access for users with different levels of experience, as well as to machines for programmatic access.</p> <p><url>http://www.uniprot.org/</url> is open for both academic and commercial use. The site was built with open source tools and libraries. Feedback is very welcome and should be sent to <email>[email protected]</email>.</p> <p>Conclusion</p> <p>The new UniProt website makes accessing and understanding UniProt easier than ever. The two main lessons learned are that getting the basics right for such a data provider website has huge benefits, but is not trivial and easy to underestimate, and that there is no substitute for using empirical data throughout the development process to decide on what is and what is not working for your users.</p
The Proteome Analysis database: a tool for the in silico analysis of whole proteomes
The Proteome Analysis database (http://www.ebi.ac.uk/proteome/) has been developed by the Sequence Database Group at EBI utilizing existing resources and providing comparative analysis of the predicted protein coding sequences of the complete genomes of bacteria, archeae and eukaryotes. Three main projects are used, InterPro, CluSTr and GO Slim, to give an overview on families, domains, sites, and functions of the proteins from each of the complete genomes. Complete proteome analysis is available for a total of 89 proteome sets. A specifically designed application enables InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the databas
VLTI status update: a decade of operations and beyond
We present the latest update of the European Southern Observatory's Very
Large Telescope interferometer (VLTI). The operations of VLTI have greatly
improved in the past years: reduction of the execution time; better offering of
telescopes configurations; improvements on AMBER limiting magnitudes; study of
polarization effects and control for single mode fibres; fringe tracking real
time data, etc. We present some of these improvements and also quantify the
operational improvements using a performance metric. We take the opportunity of
the first decade of operations to reflect on the VLTI community which is
analyzed quantitatively and qualitatively. Finally, we present briefly the
preparatory work for the arrival of the second generation instruments GRAVITY
and MATISSE.Comment: 10 pages, 7 figures, Proceedings of the SPIE, 9146-1
Integr8 and Genome Reviews: integrated views of complete genomes and proteomes
Integr8 is a new web portal for exploring the biology of organisms with completely deciphered genomes. For over 190 species, Integr8 provides access to general information, recent publications, and a detailed statistical overview of the genome and proteome of the organism. The preparation of this analysis is supported through Genome Reviews, a new database of bacterial and archaeal DNA sequences in which annotation has been upgraded (compared to the original submission) through the integration of data from many sources, including the EMBL Nucleotide Sequence Database, the UniProt Knowledgebase, InterPro, CluSTr, GOA and HOGENOM. Integr8 also allows the users to customize their own interactive analysis, and to download both customized and prepared datasets for their own use. Integr8 is available at http://www.ebi.ac.uk/integr8
Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.
peer reviewedBackground: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease-modifying treatments (DMTs). Methods: A retrospective, observational study was carried out. All patients (n = 45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon-beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium-enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25-Foot Walk Test and on the Timed 100-Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment. Results: Sixty-two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse-mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients. Conclusions: These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs
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