Publications

Solutions for data integration in functional genomics: a critical assessment and case study

Abstract (Expand)

The torrent of data emerging from the application of new technologies to functional genomics and systems biology can no longer be contained within the traditional modes of data sharing and publication … with the consequence that data is being deposited in, distributed across and disseminated through an increasing number of databases. The resulting fragmentation poses serious problems for the model organism community which increasingly rely on data mining and computational approaches that require gathering of data from a range of sources. In the light of these problems, the European Commission has funded a coordination action, CASIMIR (coordination and sustainability of international mouse informatics resources), with a remit to assess the technical and social aspects of database interoperability that currently prevent the full realization of the potential of data integration in mouse functional genomics. In this article, we assess the current problems with interoperability, with particular reference to mouse functional genomics, and critically review the technologies that can be deployed to overcome them. We describe a typical use-case where an investigator wishes to gather data on variation, genomic context and metabolic pathway involvement for genes discovered in a genome-wide screen. We go on to develop an automated approach involving an in silico experimental workflow tool, Taverna, using web services, BioMart and MOLGENIS technologies for data retrieval. Finally, we focus on the current impediments to adopting such an approach in a wider context, and strategies to overcome them.

Authors: Damian Smedley, Morris A Swertz, Firstname Lastname, Glenn Proctor, Michael Zouberakis, Jonathan Bard, John M Hancock, Paul Schofield

Date Published: 30th Dec 2008

Publication Type: Not specified

A systematic strategy for large-scale analysis of genotype phenotype correlations: identification of candidate genes involved in African trypanosomiasis

Abstract (Expand)

It is increasingly common to combine Microarray and Quantitative Trait Loci data to aid the search for candidate genes responsible for phenotypic variation. Workflows provide a means of systematically … processing these large datasets and also represent a framework for the re-use and the explicit declaration of experimental methods. In this article, we highlight the issues facing the manual analysis of microarray and QTL data for the discovery of candidate genes underlying complex phenotypes. We show how automated approaches provide a systematic means to investigate genotype-phenotype correlations. This methodology was applied to a use case of resistance to African trypanosomiasis in the mouse. Pathways represented in the results identified Daxx as one of the candidate genes within the Tir1 QTL region. Subsequent re-sequencing in Daxx identified a deletion of an amino acid, identified in susceptible mouse strains, in the Daxx-p53 protein-binding region. This supports recent experimental evidence that apoptosis could be playing a role in the trypanosomiasis resistance phenotype. Workflows developed in this investigation, including a guide to loading and executing them with example data, are available at http://workflows.mygrid.org.uk/repository/myGrid/PaulFisher/.

Authors: Paul Fisher, Cornelia Hedeler, Firstname Lastname, Helen Hulme, Harry Noyes, Stephen Kemp, Robert Stevens, Andrew Brass

Date Published: 20th Aug 2007

Publication Type: Not specified

The dynamic architecture of the metabolic switch in Streptomyces coelicolor

Abstract (Expand)

BACKGROUND: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene … expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples. RESULTS: Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis. CONCLUSIONS: Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting.

Authors: Kay Nieselt, Florian Battke, Alexander Herbig, Per Bruheim, Alexander Wentzel, Øyvind M Jakobsen, Håvard Sletta, Mohammad T Alam, Maria E Merlo, Firstname Lastname, Firstname Lastname, Edward R Morrissey, Miguel A Juarez-Hermosillo, Antonio Rodríguez-García, Merle Nentwich, Louise Thomas, Mudassar Iqbal, Roxane Legaie, William H Gaze, Gregory L Challis, Ritsert C Jansen, Lubbert Dijkhuizen, David A Rand, David L Wild, Michael Bonin, Jens Reuther, Wolfgang Wohlleben, Margaret C M Smith, Nigel J Burroughs, Juan F Martín, David A Hodgson, Eriko Takano, Rainer Breitling, Trond E Ellingsen, Elizabeth M H Wellington

Date Published: 28th May 2009

Publication Type: Not specified

Storing and annotating of kinetic data

Abstract (Expand)

This paper briefly describes the SABIO-RK database model for the storage of reaction kinetics information and the guidelines followed within the SABIO-RK project to annotate the kinetic data. Such … annotations support the definition of cross links to other related databases and augment the semantics of the data stored in the database.

Authors: Firstname Lastname, Martin Golebiewski, Renate Kania, Firstname Lastname, Saqib Mir, Andreas Weidemann, Ulrike Wittig

Date Published: 14th Sep 2007

Publication Type: Not specified

Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry

Abstract (Expand)

This paper examines whether the in vivo behavior of yeast glycolysis can be understood in terms of the in vitro kinetic properties of the constituent enzymes. In nongrowing, anaerobic, compressed … Saccharomyces cerevisiae the values of the kinetic parameters of most glycolytic enzymes were determined. For the other enzymes appropriate literature values were collected. By inserting these values into a kinetic model for glycolysis, fluxes and metabolites were calculated. Under the same conditions fluxes and metabolite levels were measured. In our first model, branch reactions were ignored. This model failed to reach the stable steady state that was observed in the experimental flux measurements. Introduction of branches towards trehalose, glycogen, glycerol and succinate did allow such a steady state. The predictions of this branched model were compared with the empirical behavior. Half of the enzymes matched their predicted flux in vivo within a factor of 2. For the other enzymes it was calculated what deviation between in vivo and in vitro kinetic characteristics could explain the discrepancy between in vitro rate and in vivo flux.

Authors: Firstname Lastname, J Passarge, C A Reijenga, E Esgalhado, C C van der Weijden, M Schepper, M C Walsh, B M Bakker, K van Dam, H V Westerhoff, Firstname Lastname

Date Published: 22nd Aug 2000

Publication Type: Not specified

Taverna: a tool for building and running workflows of services

Abstract (Expand)

Taverna is an application that eases the use and integration of the growing number of molecular biology tools and databases available on the web, especially web services. It allows bioinformaticians … to construct workflows or pipelines of services to perform a range of different analyses, such as sequence analysis and genome annotation. These high-level workflows can integrate many different resources into a single analysis. Taverna is available freely under the terms of the GNU Lesser General Public License (LGPL) from http://taverna.sourceforge.net/.

Authors: Duncan Hull, Firstname Lastname, Robert Stevens, Firstname Lastname, Mathew R Pocock, Peter Li, Tom Oinn

Date Published: 18th Jul 2006

Publication Type: Not specified

Is the glycolytic flux in Lactococcus lactis primarily controlled by the redox charge? Kinetics of NAD(+) and NADH pools determined in vivo by 13C NMR

Abstract (Expand)

The involvement of nicotinamide adenine nucleotides (NAD(+), NADH) in the regulation of glycolysis in Lactococcus lactis was investigated by using (13)C and (31)P NMR to monitor in vivo the kinetics … of the pools of NAD(+), NADH, ATP, inorganic phosphate (P(i)), glycolytic intermediates, and end products derived from a pulse of glucose. Nicotinic acid specifically labeled on carbon 5 was synthesized and used in the growth medium as a precursor of pyridine nucleotides to allow for in vivo detection of (13)C-labeled NAD(+) and NADH. The capacity of L. lactis MG1363 to regenerate NAD(+) was manipulated either by turning on NADH oxidase activity or by knocking out the gene encoding lactate dehydrogenase (LDH). An LDH(-) deficient strain was constructed by double crossover. Upon supply of glucose, NAD(+) was constant and maximal (approximately 5 mm) in the parent strain (MG1363) but decreased abruptly in the LDH(-) strain both under aerobic and anaerobic conditions. NADH in MG1363 was always below the detection limit as long as glucose was available. The rate of glucose consumption under anaerobic conditions was 7-fold lower in the LDH(-) strain and NADH reached high levels (2.5 mm), reflecting severe limitation in regenerating NAD(+). However, under aerobic conditions the glycolytic flux was nearly as high as in MG1363 despite the accumulation of NADH up to 1.5 mm. Glyceraldehyde-3-phosphate dehydrogenase was able to support a high flux even in the presence of NADH concentrations much higher than those of the parent strain. We interpret the data as showing that the glycolytic flux in wild type L. lactis is not primarily controlled at the level of glyceraldehyde-3-phosphate dehydrogenase by NADH. The ATP/ADP/P(i) content could play an important role.

Authors: Ana Rute Neves, Rita Ventura, Nahla Mansour, Claire Shearman, Michael J Gasson, Christopher Maycock, Ana Ramos, Helena Santos

Date Published: 13th May 2002

Publication Type: Not specified

Metabolic control analysis of glycerol synthesis in Saccharomyces cerevisiae

Abstract (Expand)

Glycerol, a major by-product of ethanol fermentation by Saccharomyces cerevisiae, is of significant importance to the wine, beer, and ethanol production industries. To gain a clearer understanding of … and to quantify the extent to which parameters of the pathway affect glycerol flux in S. cerevisiae, a kinetic model of the glycerol synthesis pathway has been constructed. Kinetic parameters were collected from published values. Maximal enzyme activities and intracellular effector concentrations were determined experimentally. The model was validated by comparing experimental results on the rate of glycerol production to the rate calculated by the model. Values calculated by the model agreed well with those measured in independent experiments. The model also mimics the changes in the rate of glycerol synthesis at different phases of growth. Metabolic control analysis values calculated by the model indicate that the NAD(+)-dependent glycerol 3-phosphate dehydrogenase-catalyzed reaction has a flux control coefficient (C(J)v1) of approximately 0.85 and exercises the majority of the control of flux through the pathway. Response coefficients of parameter metabolites indicate that flux through the pathway is most responsive to dihydroxyacetone phosphate concentration (R(J)DHAP= 0.48 to 0.69), followed by ATP concentration (R(J)ATP = -0.21 to -0.50). Interestingly, the pathway responds weakly to NADH concentration (R(J)NADH = 0.03 to 0.08). The model indicates that the best strategy to increase flux through the pathway is not to increase enzyme activity, substrate concentration, or coenzyme concentration alone but to increase all of these parameters in conjunction with each other.

Authors: Garth R Cronwright, Johann M Rohwer, Bernard A Prior

Date Published: 30th Aug 2002

Publication Type: Not specified

Formate assay in body fluids: application in methanol poisoning

Abstract

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Authors: A B Makar, K E McMartin, M Palese, T R Tephly

Date Published: 1st Jun 1975

Publication Type: Not specified

SABIO-RK: Access to Biochemical Reaction Kinetics Data

Abstract

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Authors: Martin Golebiewski, Martin Golebiewski

Date Published: 7th Oct 2011

Publication Type: Not specified

Metal substitutions incarbonic anhydrase: a halide ion probe study

Abstract

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Authors: R J Smith, R G Bryant

Date Published: 27th Oct 1975

Publication Type: Not specified

Cypher, a striated muscle-restricted PDZ and LIM domain-containing protein, binds to alpha-actinin-2 and protein kinase C

Abstract (Expand)

We have cloned and characterized a novel striated muscle-restricted protein (Cypher) that has two mRNA splice variants, designated Cypher1 and Cypher2. Both proteins contain an amino-terminal PDZ domain. … Cypher1, but not Cypher2, contains three carboxyl-terminal LIM domains and an amino acid repeat sequence that exhibits homology to a repeat sequence found in the largest subunit of RNA polymerase II. cypher1 and cypher2 mRNAs exhibited identical expression patterns. Both are exclusively expressed in cardiac and striated muscle in embryonic and adult stages. By biochemical assays, we have demonstrated that Cypher1 and Cypher2 bind to alpha-actinin-2 via their PDZ domains. This interaction has been further confirmed by immunohistochemical studies that demonstrated co-localization of Cypher and alpha-actinin at the Z-lines of cardiac muscle. We have also found that Cypher1 binds to protein kinase C through its LIM domains. Phosphorylation of Cypher by protein kinase C has demonstrated the functional significance of this interaction. Together, our data suggest that Cypher1 may function as an adaptor in striated muscle to couple protein kinase C-mediated signaling, via its LIM domains, to the cytoskeleton (alpha-actinin-2) through its PDZ domain.

Authors: Q Zhou, P Ruiz-Lozano, M E Martone, J Chen

Date Published: 3rd Jul 1999

Publication Type: Not specified

[Ability of antilymphocyte sera to counteract the allogeneic inhibition of hematopoietic stem cells]

Abstract

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Author: I N Golovistikov

Date Published: 11th Aug 1975

Publication Type: Not specified

Phenomenon of hot-cold hemolysis: chelator-induced lysis of sphingomyelinase-treated erythrocytes

Abstract (Expand)

Staphylococcus aureus produces a phospholipase C specific for sphingomyelin (beta-hemolysin). Erythrocytes with approximately 50% sphingomyelin in their membranes, e.g., from sheep, have been shown to … have up to 60% of this phospholipid hydrolyzed by this enzyme at 37 C in isotonic buffered saline without hemolysis. Cooling of sphingomyelinase C-treated erythrocytes to 4 C causes complete lysis of the cells, a phenomenon known as hot-cold hemolysis. The addition of ethylenediaminetetraacetate (EDTA) to sheep erythrocytes preincubated with sphingomyelinase C was found to induce rapid hemolysis at 37 C. The treated cells became susceptible to chelator-induced hemolysis and to hot-cold hemolysis simultaneously, and the degree of lysis of both mechanisms increased equally with prolonged preincubation with sphingomyelinase C. Erythrocytes of species not readily susceptible to hot-cold hemolysis were equally insusceptible to chelator-induced lysis. Chelators of the EDTA series were the most effective, whereas chelators more specific for Ca2+, Zn2+, Fe2+, Cu2+, and Mg2+ were without effect. The rate of chelator-induced lysis was dependent on the preincubation period with beta-hemolysin and on the concentration of chelator added. The optimal concentration of EDTA was found to equal the amount of exogenously added Mg2+, a cation necessary for sphingomyelinase C activity. Hypotonicity increased the rate of chelator-induced hemolysis, whereas increasing the osmotic pressure to twice isotonic completely inhibited chelator-induced lysis. The data suggest that exogenously added and/or membrane-bound divalent cations are important for the stability of sphingomyelin-depleted membranes. The phenomenon of hot-cold hemolysis may be a consequence of the temperature dependence of divalent ion stabilization.

Authors: C J Smyth, R Möllby, T Wadström

Date Published: 1st Nov 1975

Publication Type: Not specified

[A case of allergic granulomatous angitis (author's transl)]

Abstract

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Authors: Y Yokoyama, T Kono, M Aoki

Date Published: 10th Jun 1975

Publication Type: Not specified

A Mechanistic, Model-Based Approach to Safety Assessment in Clinical Development

Abstract

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Editor:

Date Published: 2013

Publication Type: Not specified

The Taverna workflow suite: designing and executing workflows of Web Services on the desktop, web or in the cloud

Abstract

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Authors: K. Wolstencroft, R. Haines, D. Fellows, A. Williams, D. Withers, S. Owen, S. Soiland-Reyes, I. Dunlop, A. Nenadic, P. Fisher, J. Bhagat, K. Belhajjame, F. Bacall, A. Hardisty, A. Nieva de la Hidalga, M. P. Balcazar Vargas, S. Sufi, C. Goble

Date Published: 2nd May 2013

Publication Type: Not specified

The transcript catalogue of the short-lived fish Nothobranchius furzeri provides insights into age-dependent changes of mRNA levels

Abstract (Expand)

The African annual fish Nothobranchius furzeri has over recent years been established as a model species for ageing-related studies. This is mainly based on its exceptionally short lifespan and the … presence of typical characteristics of vertebrate ageing. To substantiate its role as an alternative vertebrate ageing model, a transcript catalogue is needed, which can serve e.g. as basis for identifying ageing-related genes.

Authors: Andreas Petzold, Kathrin Reichwald, Marco Groth, Stefan Taudien, Nils Hartmann, Steffen Priebe, Dmitry Shagin, Christoph Englert, Matthias Platzer

Date Published: 16th Mar 2013

Publication Type: Not specified

The transcript catalogue of the short-lived fish Nothobranchius furzeri provides insights into age-dependent changes of mRNA levels

Abstract (Expand)

The African annual fish Nothobranchius furzeri has over recent years been established as a model species for ageing-related studies. This is mainly based on its exceptionally short lifespan and the … presence of typical characteristics of vertebrate ageing. To substantiate its role as an alternative vertebrate ageing model, a transcript catalogue is needed, which can serve e.g. as basis for identifying ageing-related genes.

Authors: Andreas Petzold, Kathrin Reichwald, Marco Groth, Stefan Taudien, Nils Hartmann, Steffen Priebe, Dmitry Shagin, Christoph Englert, Matthias Platzer

Date Published: 16th Mar 2013

Publication Type: Not specified

Bridging the layers: towards integration of signal transduction, regulation and metabolism into mathematical models

Abstract (Expand)

Mathematical modelling is increasingly becoming an indispensable tool for the study of cellular processes, allowing their analysis in a systematic and comprehensive manner. In the vast majority of the … cases, models focus on specific subsystems, and in particular describe either metabolism, gene expression or signal transduction. Integrated models that are able to span and interconnect these layers are, by contrast, rare as their construction and analysis face multiple challenges. Such methods, however, would represent extremely useful tools to understand cell behaviour, with application in distinct fields of biological and medical research. In particular, they could be useful tools to study genotype-phenotype mappings, and the way they are affected by specific conditions or perturbations. Here, we review existing computational approaches that integrate signalling, gene regulation and/or metabolism. We describe existing challenges, available methods and point at potentially useful strategies.

Authors: Emanuel Gonçalves, Joachim Bucher, Anke Ryll, Jens Niklas, Klaus Mauch, Steffen Klamt, Miguel Rocha, Julio Saez-Rodriguez

Date Published: 4th Jun 2013

Publication Type: Not specified

Efficacy and Safety of Curcumin in Major Depressive Disorder: A Randomized Controlled Trial

Abstract (Expand)

Curcumin, an active ingredient of Curcuma longa Linn (Zingiberaceae), has shown potential antidepressant-like activity in animal studies. The objectives of this trial were to compare the efficacy and … safety of curcumin with fluoxetine in patients with major depressive disorder (MDD). Herein, 60 patients diagnosed with MDD were randomized in a 1:1:1 ratio for six weeks observer-masked treatment with fluoxetine (20 mg) and curcumin (1000 mg) individually or their combination. The primary efficacy variable was response rates according to Hamilton Depression Rating Scale, 17-item version (HAM-D17 ). The secondary efficacy variable was the mean change in HAM-D17 score after six weeks. We observed that curcumin was well tolerated by all the patients. The proportion of responders as measured by the HAM-D17 scale was higher in the combination group (77.8%) than in the fluoxetine (64.7%) and the curcumin (62.5%) groups; however, these data were not statistically significant (P = 0.58). Interestingly, the mean change in HAM-D17 score at the end of six weeks was comparable in all three groups (P = 0.77). This study provides first clinical evidence that curcumin may be used as an effective and safe modality for treatment in patients with MDD without concurrent suicidal ideation or other psychotic disorders. Copyright © 2013 John Wiley & Sons, Ltd.

Authors: Jayesh Sanmukhani, Vimal Satodia, Jaladhi Trivedi, Tejas Patel, Deepak Tiwari, Bharat Panchal, Ajay Goel, Chandra Bhanu Tripathi

Date Published: 9th Jul 2013

Publication Type: Not specified

The transcript catalogue of the short-lived fish Nothobranchius furzeri provides insights into age-dependent changes of mRNA levels

Abstract (Expand)

The African annual fish Nothobranchius furzeri has over recent years been established as a model species for ageing-related studies. This is mainly based on its exceptionally short lifespan and the … presence of typical characteristics of vertebrate ageing. To substantiate its role as an alternative vertebrate ageing model, a transcript catalogue is needed, which can serve e.g. as basis for identifying ageing-related genes.

Authors: Andreas Petzold, Kathrin Reichwald, Marco Groth, Stefan Taudien, Nils Hartmann, Steffen Priebe, Dmitry Shagin, Christoph Englert, Matthias Platzer

Date Published: 16th Mar 2013

Publication Type: Not specified

Annotation and merging of SBML models with semanticSBML

Abstract (Expand)

Systems Biology Markup Language (SBML) is the leading exchange format for mathematical models in Systems Biology. Semantic annotations link model elements with external knowledge via unique database … identifiers and ontology terms, enabling software to check and process models by their biochemical meaning. Such information is essential for model merging, one of the key steps towards the construction of large kinetic models. SemanticSBML is a tool that helps users to check and edit MIRIAM annotations and SBO terms in SBML models. Using a large collection of biochemical names and database identifiers, it supports modellers in finding the right annotations and in merging existing models. Initially, an element matching is derived from the MIRIAM annotations and conflicting element attributes are categorized and highlighted. Conflicts can then be resolved automatically or manually, allowing the user to control the merging process in detail.

Authors: Firstname Lastname, Jannis Uhlendorf, Timo Lubitz, Marvin Schulz, Edda Klipp, Wolfram Liebermeister

Date Published: 17th Nov 2009

Publication Type: Not specified

Inferring statin-induced gene regulatory relationships in primary human hepatocytes

Abstract (Expand)

MOTIVATION: Statins are the most widely used cholesterol-lowering drugs. The primary target of statins is HMG-CoA reductase, a key enzyme in cholesterol synthesis. However, statins elicit pleitropic … responses including beneficial as well as adverse effects in the liver or other organs. Today, the regulatory mechanisms that cause these pleiotropic effects are not sufficiently understood. RESULTS: In this work, genome-wide RNA expression changes in primary human hepatocytes of six individuals were measured at up to six time points upon atorvastatin treatment. A computational analysis workflow was applied to reconstruct regulatory mechanisms based on these drug-response data and available knowledge about transcription factor (TF) binding specificities and protein-drug interactions. Several previously unknown TFs were predicted to be involved in atorvastatin-responsive gene expression. The novel relationships of nuclear receptors NR2C2 and PPARA on CYP3A4 were successfully validated in wet-lab experiments. AVAILABILITY: Microarray data are available at the Gene Expression Omnibus (GEO) database at www.ncbi.nlm.nih.gov/geo/, under accession number GSE29868. CONTACT: andreas.zell@uni-tuebingen.de; adrian.schroeder@uni-tuebingen.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Authors: A. Schroder, J. Wollnik, C. Wrzodek, A. Drager, M. Bonin, O. Burk, M. Thomas, W. E. Thasler, U. M. Zanger, A. Zell

Date Published: 14th Jul 2011

Publication Type: Not specified

Inferring statin-induced gene regulatory relationships in primary human hepatocytes

Abstract

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Authors: A. Schroder, J. Wollnik, C. Wrzodek, A. Drager, M. Bonin, O. Burk, M. Thomas, W. E. Thasler, U. M. Zanger, A. Zell

Date Published: 14th Jul 2011

Publication Type: Not specified

Is health-related quality of life associated with upper and lower airway inflammation in asthmatics

Abstract (Expand)

Background. Allergic diseases impair health-related quality of life (HR-QoL). However, the relationship between airway inflammation and HR-QoL in patients with asthma and rhinitis has not been fully … investigated. We explored whether the inflammation of upper and lower airways is associated with HR-QoL. Methods. Twenty-two mild allergic asthmatics with concomitant rhinitis (10 males, 38 +/- 17 years) were recruited. The Rhinasthma was used to identify HR-QoL, and the Asthma Control Test (ACT) was used to assess asthma control. Subjects underwent lung function and exhaled nitric oxide (eNO) test, collection of exhaled breath condensate (EBC), and nasal wash. Results. The Rhinasthma Global Summary score (GS) was 25 +/- 11. No relationships were found between GS and markers of nasal allergic inflammation (% eosinophils: r = 0.34, P = 0.24; ECP: r = 0.06, P = 0.87) or bronchial inflammation (pH of the EBC: r = 0.12, P = 0.44; bronchial NO: r = 0.27, P = 0.22; alveolar NO: r = 0.38, P = 0.10). The mean ACT score was 18. When subjects were divided into controlled (ACT >/= 20) and uncontrolled (ACT < 20), the alveolar NO significantly correlated with GS in uncontrolled asthmatics (r = 0.60, P = 0.04). Conclusions. Upper and lower airways inflammation appears unrelated to HR-QoL associated with respiratory symptoms. These preliminary findings suggest that, in uncontrolled asthma, peripheral airway inflammation could be responsible for impaired HR-QoL.

Authors: N. Scichilone, F. Braido, S. Taormina, E. Pozzecco, A. Paterno, I. Baiardini, V. Casolaro, G. W. Canonica, V. Bellia

Date Published: 31st Aug 2013

Publication Type: Not specified

Semantic Data and Models Sharing in Systems Biology: The Just Enough Results Model and the SEEK Platform

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Editor:

Date Published: 2013

Publication Type: Not specified

Stealthy annotation of experimental biology by spreadsheets

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Authors: Firstname Lastname, Firstname Lastname, Matthew Horridge, Simon Jupp, Firstname Lastname, Firstname Lastname, Firstname Lastname, Wolfgang Mueller, Robert Stevens, Firstname Lastname

Date Published: 1st Feb 2013

Publication Type: Not specified

Identification and characterization of the PhhR regulon in Pseudomonas putida

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Authors: M. Carmen Herrera, Estrella Duque, José J. Rodríguez-Herva, Ana M. Fernández-Escamilla, Juan L. Ramos

Date Published: 2010

Publication Type: Not specified

Biggest challenges in bioinformatics

Abstract (Expand)

The third Heidelberg Unseminars in Bioinformatics (HUB) was held on 18th October 2012, at Heidelberg University, Germany. HUB brought together around 40 bioinformaticians from academia and industry to … discuss the 'Biggest Challenges in Bioinformatics' in a 'World Cafe' style event.

Authors: J. C. Fuller, P. Khoueiry, H. Dinkel, K. Forslund, A. Stamatakis, J. Barry, A. Budd, T. G. Soldatos, K. Linssen, A. M. Rajput

Date Published: 15th Mar 2013

Publication Type: Not specified

Stealthy annotation of experimental biology by spreadsheets

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Authors: Katherine Wolstencroft, Stuart Owen, Matthew Horridge, Simon Jupp, Olga Krebs, Jacky Snoep, Franco du Preez, Wolfgang Mueller, Robert Stevens, Carole Goble

Date Published: 1st Feb 2013

Publication Type: Not specified

[Microenvironment of enzymes as 1 of the factors determining enzyme stability. Stabilization of soluble and immobilized horseradish peroxidase]

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Authors: I. V. Berezin, B. M. Kershengol'ts, N. N. Ugarova

Date Published: 11th Aug 1975

Publication Type: Not specified

Semantic Data and Models Sharing in Systems Biology: The Just Enough Results Model and the SEEK Platform

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Authors: Katherine Wolstencroft, Stuart Owen, Olga Krebs, Wolfgang Mueller, Quyen Nguyen, Jacky L. Snoep, Carole Goble

Date Published: 2013

Publication Type: Not specified

Construction and validation of a detailed kinetic model of glycolysis in Plasmodium falciparum

Abstract

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Authors: Gerald Penkler, Francois du Toit, Waldo Adams, Marina Rautenbach, Daniel C. Palm, David D. van Niekerk, Jacky L. Snoep

Date Published: 1st Apr 2015

Publication Type: Not specified

Toward Community Standards and Software for Whole-Cell Modeling.

Abstract

Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate comprehensive models of complex cells.

Authors: Dagmar Waltemath, Jonathan R Karr, Frank T Bergmann, Vijayalakshmi Chelliah, Michael Hucka, Marcus Krantz, Wolfram Liebermeister, Pedro Mendes, Chris J Myers, Pinar Pir, Begum Alaybeyoglu, Naveen K Aranganathan, Kambiz Baghalian, Arne T Bittig, Paulo E Pinto Burke, Matteo Cantarelli, Yin Hoon Chew, Rafael S Costa, Joseph Cursons, Tobias Czauderna, Arthur P Goldberg, Harold F Gomez, Jens Hahn, Tuure Hameri, Daniel F Hernandez Gardiol, Denis Kazakiewicz, Ilya Kiselev, Vincent Knight-Schrijver, Christian Knupfer, Matthias Konig, Daewon Lee, Audald Lloret-Villas, Nikita Mandrik, J Kyle Medley, Bertrand Moreau, Hojjat Naderi-Meshkin, Sucheendra K Palaniappan, Daniel Priego-Espinosa, Martin Scharm, Mahesh Sharma, Kieran Smallbone, Natalie J Stanford, Je-Hoon Song, Tom Theile, Milenko Tokic, Namrata Tomar, Vasundra Toure, Jannis Uhlendorf, Thawfeek M Varusai, Leandro H Watanabe, Florian Wendland, Markus Wolfien, James T Yurkovich, Yan Zhu, Argyris Zardilis, Anna Zhukova, Falk Schreiber

Date Published: 24th Sep 2016

Publication Type: Not specified

Semantic Data and Models Sharing in Systems Biology: The Just Enough Results Model and the SEEK Platform

Abstract

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Authors: Katherine Wolstencroft, Stuart Owen, Olga Krebs, Wolfgang Mueller, Quyen Nguyen, Jacky L. Snoep, Carole Goble

Date Published: 2013

Publication Type: Not specified

The FAIR Guiding Principles for scientific data management and stewardship

Abstract (Expand)

There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have … come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.

Author: Mark D. Wilkinson, Michel Dumontier, IJsbrand Jan Aalbersberg, Gabrielle Appleton, Myles Axton, Arie Baak, Niklas Blomberg, Jan-Willem Boiten, Luiz Bonino da Silva Santos, Philip E. Bourne, Jildau Bouwman, Anthony J. Brookes, Tim Clark, Mercè Crosas, Ingr Mons

Date Published: 15th Mar 2016

Publication Type: Not specified

Plasma Organochlorine Levels and the Risk of Breast Cancer

Abstract

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Authors: David J. Hunter, Susan E. Hankinson, Francine Laden, Graham A. Colditz, JoAnn E. Manson, Walter C. Willett, Frank E. Speizer, Mary S. Wolff

Date Published: 1997

Publication Type: Not specified

Data archiving is a good investment.

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Authors: H. A. Piwowar, T. J. Vision, M. C. Whitlock

Date Published: 20th May 2011

Publication Type: Not specified

Minimal manual publication

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Editor:

Date Published: No date defined

Publication Type: Not specified

{Stable theories}

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Author: Saharon Shelah

Date Published: 1969

Publication Type: Not specified

Reconstruction of a high-quality metabolic model enables the identification of gene overexpression targets for enhanced antibiotic production in Streptomyces coelicolor A3(2)

Abstract

Not specified

Authors: Minsuk Kim, Jeong Sang Yi, Joonwon Kim, Ji-Nu Kim, Min Woo Kim, Byung-Gee Kim

Date Published: 1st Sep 2014

Publication Type: Not specified

[Inhibition effect of soybean isoflavones on the oxidative modification of low-density lipoprotein].

Abstract (Expand)

In order to investigate the effect of soybean isoflavones(SI) on the oxidative modification to low-density lipoprotein(LDL) and to differentiate the effect of SI and alpha-tocopherol, in vitro and in … vivo test were conducted. An in vitro model of LDL oxidative modification induced by copper-ion was established by monitoring the production of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes after SI or alpha-tocopherol was added. The in vivo test was conducted by feeding rats with a high fat diet supplemented with SI and measured the sensitivity of LDL oxidative modification mediated by Cu2+ in vitro. The results revealed that when SI was added into the in vitro LDL oxidation system, the content of TBARS or conjugated dienes in the system was much reduced with a dose-effect relationship, whether lipid oxidation being initiated or not by copper-ion at 37 degrees C. In comparison with SI, only a significant inhibiting effect on lipid oxidation while alpha-tocopherol was added before the initiation of oxidation. High fat diet induced a rising of LDL sensitivity of oxidative stress, and adding SI to the high fat diet could counteract the sensitivity of LDL oxidative modification significantly. It is concluded that SI is a valuable natural antioxidant different from alpha-tocopherol in inhibiting LDL oxidative modification both in vitro and inv vivo.

Authors: X. Yan, J. Gu, C. Sun, D. Liu

Date Published: No date defined

Publication Type: Not specified

Allosteric regulation of phosphofructokinase controls the emergence of glycolytic oscillations in isolated yeast cells.

Abstract (Expand)

UNLABELLED: Oscillations are widely distributed in nature and synchronization of oscillators has been described at the cellular level (e.g. heart cells) and at the population level (e.g. fireflies). … Yeast glycolysis is the best known oscillatory system, although it has been studied almost exclusively at the population level (i.e. limited to observations of average behaviour in synchronized cultures). We studied individual yeast cells that were positioned with optical tweezers in a microfluidic chamber to determine the precise conditions for autonomous glycolytic oscillations. Hopf bifurcation points were determined experimentally in individual cells as a function of glucose and cyanide concentrations. The experiments were analyzed in a detailed mathematical model and could be interpreted in terms of an oscillatory manifold in a three-dimensional state-space; crossing the boundaries of the manifold coincides with the onset of oscillations and positioning along the longitudinal axis of the volume sets the period. The oscillatory manifold could be approximated by allosteric control values of phosphofructokinase for ATP and AMP. DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.mib.ac.uk/webMathematica/UItester.jsp?modelName=gustavsson5. [Database section added 14 May 2014 after original online publication].

Authors: A. K. Gustavsson, D. D. van Niekerk, C. B. Adiels, B. Kooi, M. Goksor, J. L. Snoep

Date Published: No date defined

Publication Type: Not specified

I did this

Abstract

Not specified

Author: Alan Williams

Date Published: 16th Jan 2019

Publication Type: Not specified

Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution.

Abstract

Not specified

Authors: K. S. Bose, R. H. Sarma

Date Published: 27th Oct 1975

Publication Type: Not specified

From steady-state to synchronized yeast glycolytic oscillations II: model validation.

Abstract (Expand)

UNLABELLED: In an accompanying paper [du Preez et al., (2012) FEBS J279, 2810-2822], we adapt an existing kinetic model for steady-state yeast glycolysis to simulate limit-cycle oscillations. Here we … validate the model by testing its capacity to simulate a wide range of experiments on dynamics of yeast glycolysis. In addition to its description of the oscillations of glycolytic intermediates in intact cells and the rapid synchronization observed when mixing out-of-phase oscillatory cell populations (see accompanying paper), the model was able to predict the Hopf bifurcation diagram with glucose as the bifurcation parameter (and one of the bifurcation points with cyanide as the bifurcation parameter), the glucose- and acetaldehyde-driven forced oscillations, glucose and acetaldehyde quenching, and cell-free extract oscillations (including complex oscillations and mixed-mode oscillations). Thus, the model was compliant, at least qualitatively, with the majority of available experimental data for glycolytic oscillations in yeast. To our knowledge, this is the first time that a model for yeast glycolysis has been tested against such a wide variety of independent data sets. DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.

Authors: F. B. du Preez, D. D. van Niekerk, J. L. Snoep

Date Published: 13th Jun 2012

Publication Type: Not specified

The NOVA project: maximizing beam time efficiency through synergistic analyses of SRμCT data

Abstract

Not specified

Authors: Sebastian Schmelzle, Thomas van de Kamp, Michael Heethoff, Vincent Heuveline, Philipp Lösel, Jürgen Becker, Felix Beckmann, Frank Schluenzen, Jörg U. Hammel, Andreas Kopmann, Wolfgang Mexner, Matthias Vogelgesang, Nicholas T. Jerome, Oliver Betz, Rolf Beutel, Benjamin Wipfler, Alexander Blanke, Steffen Harzsch, Marie Hörnig, Tilo Baumbach

Date Published: 7th Sep 2017

Publication Type: Not specified

Semantic Author Name Disambiguation with Word Embeddings

Abstract

Not specified

Author: Mark-Christoph Müller

Date Published: 2017

Publication Type: Not specified

Prediction with Confidence Based on a Random Forest Classifier

Abstract

Not specified

Authors: Dmitry Devetyarov, Ilia Nouretdinov

Date Published: 2010

Publication Type: Not specified

Peptides binding to the dimer interface of thymidylate synthase for the treatment of cancer” United States Patent No.: US 8,916,679 B2

Abstract

Not specified

Authors: Costi MP, Marverti G, Cardinale D, Venturelli A, Ferrari S, Ponterini G (Univ. Modena), Henrich S, Salo-Ahen O, Wade R. (HITS)

Date Published: No date defined

Publication Type: Not specified

<title>LUCIFER control software: an OO approach using CORBA technology</title>

Abstract

Not specified

Authors: Marcus J’tte, Kai Polsterer, Michael Lehmitz, Ralf-J’rgen Dettmar

Date Published: 13th Dec 2002

Publication Type: Not specified

Harmonizing semantic annotations for computational models in biology.

Abstract (Expand)

Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability … and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol. Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current annotation practices among the COmputational Modeling in BIology NEtwork community and provide a set of recommendations for building a consensus approach to semantic annotation.

Authors: M. L. Neal, M. Konig, D. Nickerson, G. Misirli, R. Kalbasi, A. Drager, K. Atalag, V. Chelliah, M. T. Cooling, D. L. Cook, S. Crook, M. de Alba, S. H. Friedman, A. Garny, J. H. Gennari, P. Gleeson, M. Golebiewski, M. Hucka, N. Juty, C. Myers, B. G. Olivier, H. M. Sauro, M. Scharm, J. L. Snoep, V. Toure, A. Wipat, O. Wolkenhauer, D. Waltemath

Date Published: 22nd Mar 2019

Publication Type: InBook

Harmonizing semantic annotations for computational models in biology.

Abstract (Expand)

Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability … and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol. Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current annotation practices among the COmputational Modeling in BIology NEtwork community and provide a set of recommendations for building a consensus approach to semantic annotation.

Authors: M. L. Neal, M. Konig, D. Nickerson, G. Misirli, R. Kalbasi, A. Drager, K. Atalag, V. Chelliah, M. T. Cooling, D. L. Cook, S. Crook, M. de Alba, S. H. Friedman, A. Garny, J. H. Gennari, P. Gleeson, M. Golebiewski, M. Hucka, N. Juty, C. Myers, B. G. Olivier, H. M. Sauro, M. Scharm, J. L. Snoep, V. Toure, A. Wipat, O. Wolkenhauer, D. Waltemath

Date Published: 22nd Mar 2019

Publication Type: Booklet

Promoting Coordinated Development of Community-Based Information Standards for Modeling in Biology: The COMBINE Initiative

Abstract

Not specified

Authors: Michael Hucka, David P. Nickerson, Gary D. Bader, Frank T. Bergmann, Jonathan Cooper, Emek Demir, Alan Garny, Martin Golebiewski, Chris J. Myers, Falk Schreiber, Dagmar Waltemath, Nicolas Le Novère

Date Published: 24th Feb 2015

Publication Type: InBook

Properties of optically selected BL Lacertae candidates from the SDSS

Abstract

Not specified

Authors: S. D. Kügler, K. Nilsson, J. Heidt, J. Esser, T. Schultz

Date Published: 30th Sep 2014

Publication Type: Journal

FAIR Computational Workflows

Abstract (Expand)

ional workflows describe the complex multi-step methods that are used for data collection, data preparation, analytics, predictive modelling, and simulation that lead to new data products. They can … inherently contribute to the FAIR data principles: by processing data according to established metadata; by creating metadata themselves during the processing of data; and by tracking and recording data provenance. These properties aid data quality assessment and contribute to secondary data usage. Moreover, workflows are digital objects in their own right. This paper argues that FAIR principles for workflows need to address their specific nature in terms of their composition of executable software steps, their provenance, and their development.

Authors: Carole Goble, Sarah Cohen-Boulakia, Stian Soiland-Reyes, Daniel Garijo, Yolanda Gil, Michael R. Crusoe, Kristian Peters, Daniel Schober

Date Published: 2020

Publication Type: Journal

Issue Cover (September 2017)

Abstract

Not specified

Editor:

Date Published: 1st Sep 2017

Publication Type: Journal

Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in pink1 − / − zebrafish

Abstract

Not specified

Authors: Smijin Soman, Marcus Keatinge, Mahsa Moein, Marc Da Costa, Heather Mortiboys, Alexander Skupin, Sreedevi Sugunan, Michal Bazala, Jacek Kuznicki, Oliver Bandmann

Date Published: 24th Nov 2016

Publication Type: Journal

Modeling and Predicting Spatio-Temporal Dynamics of PM$_{2.5}$ Concentrations Through Time-Evolving Covariance Models

Abstract

Not specified

Authors: Ghulam A. Qadir, Ying Sun

Date Published: 2025

Publication Type: Journal

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