Ongoing and future developments at the Universal Protein Resource.

The primary mission of Universal Protein Resource (UniProt) is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 4 weeks and can be accessed online for searches or download at http://www.uniprot.org.

EUROCAT website data on prenatal detection rates of congenital anomalies.

The EUROCAT website www.eurocat-network.eu publishes prenatal detection rates for major congenital anomalies using data from European population-based congenital anomaly registers, covering 28% of the EU population as well as non-EU countries. Data are updated annually. This information can be useful for comparative purposes to clinicians and public health service managers involved in the antenatal care of pregnant women as well as those interested in perinatal epidemiology.

Cross-species and cross-platform gene expression studies with the Bioconductor-compliant R package 'annotationTools'.

Background: The variety of DNA microarray formats and datasets presently available offers an unprecedented opportunity to perform insightful comparisons of heterogeneous data. Cross-species studies, in particular, have the power of identifying conserved, functionally important molecular processes. Validation of discoveries can now often be performed in readily available public data which frequently requires cross-platform studies.Cross-platform and cross-species analyses require matching probes on different microarray formats. This can be achieved using the information in microarray annotations and additional molecular biology databases, such as orthology databases. Although annotations and other biological information are stored using modern database models ( e. g. relational), they are very often distributed and shared as tables in text files, i.e. flat file databases. This common flat database format thus provides a simple and robust solution to flexibly integrate various sources of information and a basis for the combined analysis of heterogeneous gene expression profiles.Results: We provide annotationTools, a Bioconductor-compliant R package to annotate microarray experiments and integrate heterogeneous gene expression profiles using annotation and other molecular biology information available as flat file databases. First, annotationTools contains a specialized set of functions for mining this widely used database format in a systematic manner. It thus offers a straightforward solution for annotating microarray experiments. Second, building on these basic functions and relying on the combination of information from several databases, it provides tools to easily perform cross-species analyses of gene expression data.Here, we present two example applications of annotationTools that are of direct relevance for the analysis of heterogeneous gene expression profiles, namely a cross-platform mapping of probes and a cross-species mapping of orthologous probes using different orthology databases. We also show how to perform an explorative comparison of disease-related transcriptional changes in human patients and in a genetic mouse model.Conclusion: The R package annotationTools provides a simple solution to handle microarray annotation and orthology tables, as well as other flat molecular biology databases. Thereby, it allows easy integration and analysis of heterogeneous microarray experiments across different technological platforms or species.

Improving blood pressure control through pharmacist interventions: a meta-analysis of randomized controlled trials.

BACKGROUND: Control of blood pressure (BP) remains a major challenge in primary care. Innovative interventions to improve BP control are therefore needed. By updating and combining data from 2 previous systematic reviews, we assess the effect of pharmacist interventions on BP and identify potential determinants of heterogeneity. METHODS AND RESULTS: Randomized controlled trials (RCTs) assessing the effect of pharmacist interventions on BP among outpatients with or without diabetes were identified from MEDLINE, EMBASE, CINAHL, and CENTRAL databases. Weighted mean differences in BP were estimated using random effect models. Prediction intervals (PI) were computed to better express uncertainties in the effect estimates. Thirty-nine RCTs were included with 14 224 patients. Pharmacist interventions mainly included patient education, feedback to physician, and medication management. Compared with usual care, pharmacist interventions showed greater reduction in systolic BP (-7.6 mm Hg, 95% CI: -9.0 to -6.3; I(2)=67%) and diastolic BP (-3.9 mm Hg, 95% CI: -5.1 to -2.8; I(2)=83%). The 95% PI ranged from -13.9 to -1.4 mm Hg for systolic BP and from -9.9 to +2.0 mm Hg for diastolic BP. The effect tended to be larger if the intervention was led by the pharmacist and was done at least monthly. CONCLUSIONS: Pharmacist interventions - alone or in collaboration with other healthcare professionals - improved BP management. Nevertheless, pharmacist interventions had differential effects on BP, from very large to modest or no effect; and determinants of heterogeneity could not be identified. Determining the most efficient, cost-effective, and least time-consuming intervention should be addressed with further research.

Genetics for clinicians: from candidate genes to whole genome scans (technological advances).

Human genetics has progressed at an unprecedented pace during the past 10 years. DNA microarrays currently allow screening of the entire human genome with high level of coverage and we are now entering the era of high-throughput sequencing. These remarkable technical advances are influencing the way medical research is conducted and have boosted our understanding of the structure of the human genome as well as of disease biology. In this context, it is crucial for clinicians to understand the main concepts and limitations of modern genetics. This review will describe key concepts in genetics, including the different types of genetic markers in the human genome, review current methods to detect DNA variation, describe major online public databases in genetics, explain key concepts in statistical genetics and finally present commonly used study designs in clinical and epidemiological research. This review will therefore concentrate on human genetic variation analysis.

DEL FESTIVAL A LA ACADEMIA. Informe sobre la institucionalización de una disciplina híbrida (arte digital)

Aquest document és un esborrany. Amb l'objectiu d'aprofundir en el procés d'institucionalització, vam dissenyar una investigació empírica que permetés visualitzar les tendències discursives i àmbits d'activitats de les pràctiques relacionades amb les interseccions entre l'art, la ciència i la tecnologia. La metodologia va consistir en la implementació de tres bases de dades que recullen l'activitat dels últims anys en relació a: 1) els congressos (i festivals associats) realitzats a nivell internacional 2) les publicacions acadèmiques i divulgatives centrades en aquest àmbit interdisciplinar 3) els programes acadèmics.

Decision-support tools to manage drug incompatibilities: evaluation by nurses

Introduction Preventing drug incompatibilities has a high impact onthe safety of drug therapy. Although there are no internationalguidelines to manage drug incompatibilities, different decision-supporttools such as handbooks, cross-tables and databases are available.In a previous study, two decision-support tools have been pre-selectedby pharmacists as fitting nurses' needs on the wards1. The objective ofthis study was to have these both tools evaluated by nurses todetermine which would be the most suitable for their daily practice.Materials & Methods Evaluated tools were:1. Cross-table of drug pairs (http://files.chuv.ch/internet-docs/pha/medicaments/pha_phatab_compatibilitessip.pdf)2. Colour-table (a colour for each drug according to the pH: red =acid; blue = basic; yellow = neutral; black = to be infused alone)2Tools were assessed by 48 nurses in 5 units (PICU, adult andgeriatric intensive care, surgery, onco-hematology) using a standardizedform1. The scientific accuracy of the tools was evaluated bydetermining the compatibility of five drugs pairs (rate of correctanswers according to the Trissel's Handbook on Injectable Drugs,chi-square test). Their ergonomics, design, reliability and applicabilitywere estimated using visual analogue scales (VAS 0-10; 0 =null, 10 = excellent). Results are expressed as the median and interquartilerange (IQR) for 25% and 75% (Wilcoxon rank sum test).Results The rate of correct answers was above 90% for both tools(cross-table 96.2% vs colour-table 92.5%, p[0.05).The ergonomics and the applicability were higher for the crosstable[7.1 (IQR25 4.0, IQR75 8.0) vs 5.0 (IQR25 2.7, IQR75 7.0), p =0.025 resp. 8.3 (IQR25 7.4, IQR75 9.2) vs 7.6 (IQR25 5.9, IQR75 8.8)p = 0.047].The design of the colour-table was judged better [4.6 (IQR25 2.9,IQR75 7.1) vs 7.1 (IQR25 5.4, IQR75 8.4) p = 0.002].No difference was observed in terms of reliability [7.3 (IQR25 6.5,IQR75 8.4) vs 6.7 (IQR25 5.0, IQR758.6) p[0.05].The cross-table was globally preferred by 65% of the nurses (27%colour-table, 8% undetermined) and 68% would like to have thisdecision-support tool available for their daily practice.Discussion & Conclusion Both tools showed the same accuracy toassess drug compatibility. In terms of ergonomics and applicabilitythe cross-table was better than the colour-table, and was preferred bythe nurses for their daily practice. The cross-table will be implementedin our hospital as decision-support tool to help nurses tomanage drug incompatibilities.

NQL, Natural Query Language

Desarrollo de un sistema capaz de procesar consultas en lenguaje natural introducidas por el usuario mediante el teclado. El sistema es capaz de responder a consultas en castellano, relacionadas con un dominio de aplicación representado mediante una base de datos relacional.

Genometric analyses of the organization of circular chromosomes: a universal pressure determines the direction of ribosomal RNA genes transcription relative to chromosome replication.

Selective pressures related to gene function and chromosomal architecture are acting on genome sequences and can be revealed, for instance, by appropriate genometric methods. Cumulative nucleotide skew analyses, i.e., GC, TA, and ORF orientation skews, predict the location of the origin of DNA replication for 88 out of 100 completely sequenced bacterial chromosomes. These methods appear fully reliable for proteobacteria, Gram-positives, and spirochetes as well as for euryarchaeotes. Based on this genome architecture information, coorientation analyses reveal that in prokaryotes, ribosomal RNA (rRNA) genes encoding the small and large ribosomal subunits are all transcribed in the same direction as DNA replication; that is, they are located along the leading strand. This result offers a simple and reliable method for circumscribing the region containing the origin of the DNA replication and reveals a strong selective pressure acting on the orientation of rRNA genes similar to the weaker one acting on the orientation of ORFs. Rate of coorientation of transfer RNA (tRNA) genes with DNA replication appears to be taxon-specific. Analyzing nucleotide biases such as GC and TA skews of genes and plotting one against the other reveals a taxonomic clusterization of species. All ribosomal RNA genes are enriched in Gs and depleted in Cs, the only so far known exception being the rRNA genes of deuterostomian mitochondria. However, this exception can be explained by the fact that in the chromosome of the human mitochondrion, the model of the deuterostomian organelle genome, DNA replication, and rRNA transcription proceed in opposite directions. A general rule is deduced from prokaryotic and mitochondrial genomes: ribosomal RNA genes that are transcribed in the same direction as the DNA replication are enriched in Gs, and those transcribed in the opposite direction are depleted in Gs.

Diseño e implementación de una base de datos relacional para la gestión sanitaria

El ejercicio que se nos plantea es desarrollar una base de datos para la gestión integral del sistema sanitario. Además, también tendremos que crear un almacén de datos para facilitar el análisis de la situación del sistema.

Impact of pharmacist care in the management of cardiovascular disease risk factors: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Pharmacists may improve the clinical management of major risk factors for cardiovascular disease (CVD) prevention. A systematic review was conducted to determine the impact of pharmacist care on the management of CVD risk factors among outpatients. METHODS: The MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials that involved pharmacist care interventions among outpatients with CVD risk factors. Two reviewers independently abstracted data and classified pharmacists' interventions. Mean changes in blood pressure, total cholesterol, low-density lipoprotein cholesterol, and proportion of smokers were estimated using random effects models. RESULTS: Thirty randomized controlled trials (11 765 patients) were identified. Pharmacist interventions exclusively conducted by a pharmacist or implemented in collaboration with physicians or nurses included patient educational interventions, patient-reminder systems, measurement of CVD risk factors, medication management and feedback to physician, or educational intervention to health care professionals. Pharmacist care was associated with significant reductions in systolic/diastolic blood pressure (19 studies [10 479 patients]; -8.1 mm Hg [95% confidence interval {CI}, -10.2 to -5.9]/-3.8 mm Hg [95% CI,-5.3 to -2.3]); total cholesterol (9 studies [1121 patients]; -17.4 mg/L [95% CI,-25.5 to -9.2]), low-density lipoprotein cholesterol (7 studies [924 patients]; -13.4 mg/L [95% CI,-23.0 to -3.8]), and a reduction in the risk of smoking (2 studies [196 patients]; relative risk, 0.77 [95% CI, 0.67 to 0.89]). While most studies tended to favor pharmacist care compared with usual care, a substantial heterogeneity was observed. CONCLUSION: Pharmacist-directed care or in collaboration with physicians or nurses improve the management of major CVD risk factors in outpatients.

KnotProt: a database of proteins with knots and slipknots.

The protein topology database KnotProt, http://knotprot.cent.uw.edu.pl/, collects information about protein structures with open polypeptide chains forming knots or slipknots. The knotting complexity of the cataloged proteins is presented in the form of a matrix diagram that shows users the knot type of the entire polypeptide chain and of each of its subchains. The pattern visible in the matrix gives the knotting fingerprint of a given protein and permits users to determine, for example, the minimal length of the knotted regions (knot's core size) or the depth of a knot, i.e. how many amino acids can be removed from either end of the cataloged protein structure before converting it from a knot to a different type of knot. In addition, the database presents extensive information about the biological functions, families and fold types of proteins with non-trivial knotting. As an additional feature, the KnotProt database enables users to submit protein or polymer chains and generate their knotting fingerprints.

Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature.

Enzyme replacement therapy (ERT) has been used to treat Fabry disease - a progressive lysosomal storage disorder - since 2001. Two preparations of the enzyme alpha-galactosidase A are available in Europe: agalsidase alpha, produced in a human cell line, and agalsidase beta, produced in Chinese hamster ovary cells. To review critically the published evidence for the clinical efficacy of these two enzyme preparations. A systematic literature search was undertaken to identify open or randomised controlled trials published on Fabry disease since 2001. Eleven trials fulfilled the criteria for inclusion in this review, of a total of 586 references on Fabry disease. To date, no direct comparisons exists between the two available enzyme preparations. Significant clinical benefits compared with placebo, however, have been demonstrated with ERT, with positive effects on the heart, kidneys, nervous system and quality of life. The quality of most of these publications was less than optimal. Further prospective studies are required to confirm the long-term clinical benefits of ERT. More studies are also needed on the effects of ERT in women and on the use of ERT early in the course of Fabry disease, to prevent organ damage. Large national and international outcomes databases will also be invaluable in evaluating treatment effects and safety.

Use of the frc gene as a molecular marker to characterize oxalate-oxidizing bacterial abundance and diversity structure in soil.

Oxalate catabolism, which can have both medical and environmental implications, is performed by phylogenetically diverse bacteria. The formyl-CoA-transferase gene was chosen as a molecular marker of the oxalotrophic function. Degenerated primers were deduced from an alignment of frc gene sequences available in databases. The specificity of primers was tested on a variety of frc-containing and frc-lacking bacteria. The frc-primers were then used to develop PCR-DGGE and real-time SybrGreen PCR assays in soils containing various amounts of oxalate. Some PCR products from pure cultures and from soil samples were cloned and sequenced. Data were used to generate a phylogenetic tree showing that environmental PCR products belonged to the target physiological group. The extent of diversity visualised on DGGE pattern was higher for soil samples containing carbonate resulting from oxalate catabolism. Moreover, the amount of frc gene copies in the investigated soils was detected in the range of 1.64x10(7) to 1.75x10(8)/g of dry soil under oxalogenic tree (representing 0.5 to 1.2% of total 16S rRNA gene copies), whereas the number of frc gene copies in the reference soil was 6.4x10(6) (or 0.2% of 16S rRNA gene copies). This indicates that oxalotrophic bacteria are numerous and widespread in soils and that a relationship exists between the presence of the oxalogenic trees Milicia excelsa and Afzelia africana and the relative abundance of oxalotrophic guilds in the total bacterial communities. This is obviously related to the accomplishment of the oxalate-carbonate pathway, which explains the alkalinization and calcium carbonate accumulation occurring below these trees in an otherwise acidic soil. The molecular tools developed in this study will allow in-depth understanding of the functional implication of these bacteria on carbonate accumulation as a way of atmospheric CO(2) sequestration.

Human synthetic lethal inference as potential anti-cancer target gene detection

Background: Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results: In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates.Conclusions: Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.