Meneco, a Topology-Based Gap-Filling Tool Applicable to Degraded Genome-Wide Metabolic Networks

International audienceIncreasing amounts of sequence data are becoming available for a wide range of non-model organisms. Investigating and modelling the metabolic behaviour of those organisms is highly relevant to understand their biology and ecology. As sequences are often incomplete and poorly annotated, draft networks of their metabolism largely suffer from incompleteness. Appropriate gap-filling methods to identify and add missing reactions are therefore required to address this issue. However, current tools rely on phenotypic or taxonomic information, or are very sensitive to the stoichiometric balance of metabolic reactions, especially concerning the co-factors. This type of information is often not available or at least prone to errors for newly-explored organisms. Here we introduce Meneco, a tool dedicated to the topological gap-filling of genome-scale draft metabolic networks. Meneco reformulates gap-filling as a qualitative combinatorial optimization problem, omitting constraints raised by the stoichiometry of a metabolic network considered in other methods, and solves this problem using Answer Set Programming. Run on several artificial test sets gathering 10,800 degraded Escherichia coli networks Meneco was able to efficiently identify essential reactions missing in networks at high degradation rates, outperforming the stoichiometry-based tools in scalability. To demonstrate the utility of Meneco we applied it to two case studies. Its application to recent metabolic networks reconstructed for the brown algal model Ectocarpus siliculosus and an associated bacterium Candidatus Phaeomarinobacter ectocarpi revealed several candidate metabolic pathways for algal-bacterial interactions. Then Meneco was used to reconstruct, from transcriptomic and metabolomic data, the first metabolic network for the microalga Euglena mutabilis. These two case studies show that Meneco is a versatile tool to complete draft genome-scale metabolic networks produced from heterogeneous data, and to suggest relevant reactions that explain the metabolic capacity of a biological system

Cow's milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren's syndrome

INTRODUCTION: Patients with primary Sjögren's syndrome (pSS) are reported to have a variety of gastrointestinal symptoms partly attributed to an overrepresentation of celiac disease. We have observed that irritable bowel syndrome (IBS)-like symptoms are frequent complaints in this patient group. Allergic manifestations to various drugs are also common in pSS. A role of food allergy in IBS has been proposed. OBJECTIVE: This study is aimed at evaluating the mucosal response to rectal challenge with cow's milk protein (CM) in patients with pSS and relates possible CM reactivity to their intestinal symptoms. Methods: A rectal challenge with CM was performed in 21 patients with pSS and 18 healthy controls. Fifteen hours after challenge the mucosal production of nitric oxide (NO) and the release of myeloperoxidase (MPO) as signs of mucosal inflammatory reaction were measured using the mucosal patch technique. RESULTS: Eight out of 21 patients with pSS had a definite increase of mucosal NO synthesis and the luminal release of MPO after rectal CM challenge. This sign of milk sensitivity was not linked to IgG/IgA antibodies to milk proteins. The symptoms for IBS according to Rome III criteria were fulfilled in 13 patients. All patients who were CM sensitive suffered from IBS. In a small open study, patients reactive to CM reported an improvement of intestinal symptoms on a CM-free diet. CONCLUSION: A rectal mucosal inflammatory response after CM challenge is seen in 38% of patients with pSS as a sign of CM sensitivity. IBS-like symptoms were common in pSS, linked to CM sensitivity.</p

Preparing DARIAH

In this paper, a preparatory project for an integrated European research infrastructure in the humanities is presented. This project, Preparing for the construction of the Digital Research Infrastructure for the Arts and Humanities - or Preparing DARIAH for short, is part of the ESFRI e-infrastructures programme and supports the emergence of a new collaborative framework in which researchers are able to maximise the impact of their work on the international stage and aims at providing the foundations for the timely construction of the infrastructure requisite for the arts, humanities and cultural heritage communities in the digital age. DARIAH uses an interdisciplinary approach and involves tackling a number of interrelated issues such as strategic, organisational, financial, technical and conceptual in order to facilitate long-term access to and use of all European humanities and cultural heritage information for the purposes of enhancing and expanding research, thereby increasing our knowledge and understanding of our histories, heritage, languages and cultures. The DARIAH network will act as a place where the incubation of new ideas and ways of working can be facilitated and developed, and then transitioned into established organisations thus ensuring long-term sustainability and stability and the integration of these methods and techniques into everyday research practice. DARIAH will support research practitioners at all stages in the research process, and at differing levels of sophistication, from beginners through to those employing advanced techniques and methodologies

XTraQue: traceability for product line systems

Product line engineering has been increasingly used to support the development and deployment of software systems that share a common set of features and are developed based on the reuse of core assets. The large number and heterogeneity of documents generated during the development of product line systems may cause difficulties to identify common and variable aspects among applications, and to reuse core assets that are available under the product line. In this paper, we present a traceability approach for product line systems. Traceability has been recognised as an important task in in software system development. Traceability relations can improve the quality of the product being developed and reduce development time and cost. We present a rule-based approach to support automatic generation of traceability relations between feature-based object-oriented documents. The traceability rules used in our work are classified into two groups namely (a) direct rules, which support the creation of traceability relations that do not depend on the existence of other relations, and (b) indirect rules, which require the existence of previously generated relations. The documents are represented in XML and the rules are represented in an extension of XQuery. A prototype tool called XTraQue has been implemented. This tool, together with a mobile phone product line case study, has been used to demonstrate and evaluate our work in various experiments. The results of these experiments are encouraging and comparable with other approaches that support automatic generation of traceability relations

Immediate post-operative effects of tracheotomy on respiratory function during mechanical ventilation

INTRODUCTION: Tracheotomy is widely performed in the intensive care unit after long-term oral intubation. The present study investigates the immediate influence of tracheotomy on respiratory mechanics and blood gases during mechanical ventilation. METHODS: Tracheotomy was performed in 32 orally intubated patients for 10.5 +/- 4.66 days (all results are means +/- standard deviations). Airway pressure, flow and arterial blood gases were recorded immediately before tracheotomy and half an hour afterwards. Respiratory system elastance (Ers), resistance (Rrs) and end-expiratory pressure (EEP) were evaluated by multiple linear regression. Respiratory system reactance (Xrs), impedance (Zrs) and phase angle (phirs) were calculated from Ers and Rrs. Comparisons of the mechanical parameters, blood gases and pH were performed with the aid of the Wilcoxon signed-rank test (P = 0.05). RESULTS: Ers increased (7 +/- 11.3%, P = 0.001), whereas Rrs (-16 +/- 18.4%, P = 0.0003), Xrs (-6 +/- 11.6%, P = 0.006) and phi rs (-14.3 +/- 16.8%, P = <0.001) decreased immediately after tracheotomy. EEP, Zrs, blood gases and pH did not change significantly. CONCLUSION: Lower Rrs but also higher Ers were noted immediately after tracheotomy. The net effect is a non-significant change in the overall Rrs (impedance) and the effectiveness of respiratory function. The extra dose of anaesthetics (beyond that used for sedation at the beginning of the procedure) or a higher FiO2 (fraction of inspired oxygen) during tracheotomy or aspiration could be related to the immediate elastance increase.Crit Car

Early Neurodegeneration Progresses Independently of Microglial Activation by Heparan Sulfate in the Brain of Mucopolysaccharidosis IIIB Mice

BACKGROUND: In mucopolysaccharidosis type IIIB, a lysosomal storage disease causing early onset mental retardation in children, the production of abnormal oligosaccharidic fragments of heparan sulfate is associated with severe neuropathology and chronic brain inflammation. We addressed causative links between the biochemical, pathological and inflammatory disorders in a mouse model of this disease. METHODOLOGY/PRINCIPAL FINDINGS: In cell culture, heparan sulfate oligosaccharides activated microglial cells by signaling through the Toll-like receptor 4 and the adaptor protein MyD88. CD11b positive microglial cells and three-fold increased expression of mRNAs coding for the chemokine MIP1alpha were observed at 10 days in the brain cortex of MPSIIIB mice, but not in MPSIIIB mice deleted for the expression of Toll-like receptor 4 or the adaptor protein MyD88, indicating early priming of microglial cells by heparan sulfate oligosaccharides in the MPSIIIB mouse brain. Whereas the onset of brain inflammation was delayed for several months in doubly mutant versus MPSIIIB mice, the onset of disease markers expression was unchanged, indicating similar progression of the neurodegenerative process in the absence of microglial cell priming by heparan sulfate oligosaccharides. In contrast to younger mice, inflammation in aged MPSIIIB mice was not affected by TLR4/MyD88 deficiency. CONCLUSIONS/SIGNIFICANCE: These results indicate priming of microglia by HS oligosaccharides through the TLR4/MyD88 pathway. Although intrinsic to the disease, this phenomenon is not a major determinant of the neurodegenerative process. Inflammation may still contribute to neurodegeneration in late stages of the disease, albeit independent of TLR4/MyD88. The results support the view that neurodegeneration is primarily cell autonomous in this pediatric disease

Neuropathology in Mouse Models of Mucopolysaccharidosis Type I, IIIA and IIIB

Mucopolysaccharide diseases (MPS) are caused by deficiency of glycosaminoglycan (GAG) degrading enzymes, leading to GAG accumulation. Neurodegenerative MPS diseases exhibit cognitive decline, behavioural problems and shortened lifespan. We have characterised neuropathological changes in mouse models of MPSI, IIIA and IIIB to provide a better understanding of these events