355 research outputs found

    Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

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    Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total

    Identifying Cognate Binding Pairs among a Large Set of Paralogs: The Case of PE/PPE Proteins of Mycobacterium tuberculosis

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    We consider the problem of how to detect cognate pairs of proteins that bind when each belongs to a large family of paralogs. To illustrate the problem, we have undertaken a genomewide analysis of interactions of members of the PE and PPE protein families of Mycobacterium tuberculosis. Our computational method uses structural information, operon organization, and protein coevolution to infer the interaction of PE and PPE proteins. Some 289 PE/PPE complexes were predicted out of a possible 5,590 PE/PPE pairs genomewide. Thirty-five of these predicted complexes were also found to have correlated mRNA expression, providing additional evidence for these interactions. We show that our method is applicable to other protein families, by analyzing interactions of the Esx family of proteins. Our resulting set of predictions is a starting point for genomewide experimental interaction screens of the PE and PPE families, and our method may be generally useful for detecting interactions of proteins within families having many paralogs

    AtPID: Arabidopsis thaliana protein interactome databaseβ€”an integrative platform for plant systems biology

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    Arabidopsis thaliana Protein Interactome Database (AtPID) is an object database that integrates data from several bioinformatics prediction methods and manually collected information from the literature. It contains data relevant to protein–protein interaction, protein subcellular location, ortholog maps, domain attributes and gene regulation. The predicted protein interaction data were obtained from ortholog interactome, microarray profiles, GO annotation, and conserved domain and genome contexts. This database holds 28 062 protein–protein interaction pairs with 23 396 pairs generated from prediction methods. Among the rest 4666 pairs, 3866 pairs of them involving 1875 proteins were manually curated from the literature and 800 pairs were from enzyme complexes in KEGG. In addition, subcellular location information of 5562 proteins is available. AtPID was built via an intuitive query interface that provides easy access to the important features of proteins. Through the incorporation of both experimental and computational methods, AtPID is a rich source of information for system-level understanding of gene function and biological processes in A. thaliana. Public access to the AtPID database is available at http://atpid.biosino.org/

    Using structural motif descriptors for sequence-based binding site prediction

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    All authors are with the Biotechnological Center, TU Dresden, Tatzberg 47-51, 01307 Dresden, Germany and -- Wan Kyu Kim is with the Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USABackground: Many protein sequences are still poorly annotated. Functional characterization of a protein is often improved by the identification of its interaction partners. Here, we aim to predict protein-protein interactions (PPI) and protein-ligand interactions (PLI) on sequence level using 3D information. To this end, we use machine learning to compile sequential segments that constitute structural features of an interaction site into one profile Hidden Markov Model descriptor. The resulting collection of descriptors can be used to screen sequence databases in order to predict functional sites. -- Results: We generate descriptors for 740 classified types of protein-protein binding sites and for more than 3,000 protein-ligand binding sites. Cross validation reveals that two thirds of the PPI descriptors are sufficiently conserved and significant enough to be used for binding site recognition. We further validate 230 PPIs that were extracted from the literature, where we additionally identify the interface residues. Finally we test ligand-binding descriptors for the case of ATP. From sequences with Swiss-Prot annotation "ATP-binding", we achieve a recall of 25% with a precision of 89%, whereas Prosite's P-loop motif recognizes an equal amount of hits at the expense of a much higher number of false positives (precision: 57%). Our method yields 771 hits with a precision of 96% that were not previously picked up by any Prosite-pattern. -- Conclusion: The automatically generated descriptors are a useful complement to known Prosite/InterPro motifs. They serve to predict protein-protein as well as protein-ligand interactions along with their binding site residues for proteins where merely sequence information is available.Institute for Cellular and Molecular [email protected]

    Performance of the CMS Cathode Strip Chambers with Cosmic Rays

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    The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

    Unilateral congenital elongation of the cervical part of the internal carotid artery with kinking and looping: two case reports and review of the literature

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    Unilateral and bilateral variation in the course and elongation of the cervical (extracranial) part of the internal carotid artery (ICA) leading to its tortuosity, kinking and coiling or looping is not a rare condition, which could be caused by both embryological and acquired factors. Patients with such variations may be asymptomatic in some cases; in others, they can develop cerebrovascular symptoms due to carotid stenosis affecting cerebral circulation. The risk of transient ischemic attacks in patients with carotid stenosis is high and its surgical correction is indicated for the prevention of ischemic stroke. Detection of developmental variations of the ICA and evaluation of its stenotic areas is very important for surgical interventions and involves specific diagnostic imaging techniques for vascular lesions including contrast arteriography, duplex ultrasonography and magnetic resonance angiography. Examination of obtained images in cases of unusual and complicated variations of vascular pattern of the ICA may lead to confusion in interpretation of data. Awareness about details and topographic anatomy of variations of the ICA may serve as a useful guide for both radiologists and vascular surgeons. It may help to prevent diagnostic errors, influence surgical tactics and interventional procedures and avoid complications during the head and neck surgery. Our present study was conducted with a purpose of updating data about developmental variations of the ICA. Dissections of the main neurovascular bundle of the head and neck were performed on a total 14 human adult cadavers (10 – Africans: 7 males & 3 females and 4 – East Indians: all males). Two cases of unilateral congenital elongation of the cervical part of the ICA with kinking and looping and carotid stenoses were found only in African males. Here we present their detailed case reports with review of the literature

    Predicting the protein-protein interactions using primary structures with predicted protein surface

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    <p>Abstract</p> <p>Background</p> <p>Many biological functions involve various protein-protein interactions (PPIs). Elucidating such interactions is crucial for understanding general principles of cellular systems. Previous studies have shown the potential of predicting PPIs based on only sequence information. Compared to approaches that require other auxiliary information, these sequence-based approaches can be applied to a broader range of applications.</p> <p>Results</p> <p>This study presents a novel sequence-based method based on the assumption that protein-protein interactions are more related to amino acids at the surface than those at the core. The present method considers surface information and maintains the advantage of relying on only sequence data by including an accessible surface area (ASA) predictor recently proposed by the authors. This study also reports the experiments conducted to evaluate a) the performance of PPI prediction achieved by including the predicted surface and b) the quality of the predicted surface in comparison with the surface obtained from structures. The experimental results show that surface information helps to predict interacting protein pairs. Furthermore, the prediction performance achieved by using the surface estimated with the ASA predictor is close to that using the surface obtained from protein structures.</p> <p>Conclusion</p> <p>This work presents a sequence-based method that takes into account surface information for predicting PPIs. The proposed procedure of surface identification improves the prediction performance with an <it>F-measure </it>of 5.1%. The extracted surfaces are also valuable in other biomedical applications that require similar information.</p

    Prediction of Protein Modification Sites of Pyrrolidone Carboxylic Acid Using mRMR Feature Selection and Analysis

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    Pyrrolidone carboxylic acid (PCA) is formed during a common post-translational modification (PTM) of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR) and incremental feature selection (IFS). We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations

    Genetic and Computational Identification of a Conserved Bacterial Metabolic Module

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    We have experimentally and computationally defined a set of genes that form a conserved metabolic module in the Ξ±-proteobacterium Caulobacter crescentus and used this module to illustrate a schema for the propagation of pathway-level annotation across bacterial genera. Applying comprehensive forward and reverse genetic methods and genome-wide transcriptional analysis, we (1) confirmed the presence of genes involved in catabolism of the abundant environmental sugar myo-inositol, (2) defined an operon encoding an ABC-family myo-inositol transmembrane transporter, and (3) identified a novel myo-inositol regulator protein and cis-acting regulatory motif that control expression of genes in this metabolic module. Despite being encoded from non-contiguous loci on the C. crescentus chromosome, these myo-inositol catabolic enzymes and transporter proteins form a tightly linked functional group in a computationally inferred network of protein associations. Primary sequence comparison was not sufficient to confidently extend annotation of all components of this novel metabolic module to related bacterial genera. Consequently, we implemented the Graemlin multiple-network alignment algorithm to generate cross-species predictions of genes involved in myo-inositol transport and catabolism in other Ξ±-proteobacteria. Although the chromosomal organization of genes in this functional module varied between species, the upstream regions of genes in this aligned network were enriched for the same palindromic cis-regulatory motif identified experimentally in C. crescentus. Transposon disruption of the operon encoding the computationally predicted ABC myo-inositol transporter of Sinorhizobium meliloti abolished growth on myo-inositol as the sole carbon source, confirming our cross-genera functional prediction. Thus, we have defined regulatory, transport, and catabolic genes and a cis-acting regulatory sequence that form a conserved module required for myo-inositol metabolism in select Ξ±-proteobacteria. Moreover, this study describes a forward validation of gene-network alignment, and illustrates a strategy for reliably transferring pathway-level annotation across bacterial species
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