GraphCombEx: A Software Tool for Exploration of Combinatorial Optimisation Properties of Large Graphs

We present a prototype of a software tool for exploration of multiple combinatorial optimisation problems in large real-world and synthetic complex networks. Our tool, called GraphCombEx (an acronym of Graph Combinatorial Explorer), provides a unified framework for scalable computation and presentation of high-quality suboptimal solutions and bounds for a number of widely studied combinatorial optimisation problems. Efficient representation and applicability to large-scale graphs and complex networks are particularly considered in its design. The problems currently supported include maximum clique, graph colouring, maximum independent set, minimum vertex clique covering, minimum dominating set, as well as the longest simple cycle problem. Suboptimal solutions and intervals for optimal objective values are estimated using scalable heuristics. The tool is designed with extensibility in mind, with the view of further problems and both new fast and high-performance heuristics to be added in the future. GraphCombEx has already been successfully used as a support tool in a number of recent research studies using combinatorial optimisation to analyse complex networks, indicating its promise as a research software tool

Prototyping the Semantics of a DSL using ASF+SDF: Link to Formal Verification of DSL Models

A formal definition of the semantics of a domain-specific language (DSL) is a key prerequisite for the verification of the correctness of models specified using such a DSL and of transformations applied to these models. For this reason, we implemented a prototype of the semantics of a DSL for the specification of systems consisting of concurrent, communicating objects. Using this prototype, models specified in the DSL can be transformed to labeled transition systems (LTS). This approach of transforming models to LTSs allows us to apply existing tools for visualization and verification to models with little or no further effort. The prototype is implemented using the ASF+SDF Meta-Environment, an IDE for the algebraic specification language ASF+SDF, which offers efficient execution of the transformation as well as the ability to read models and produce LTSs without any additional pre or post processing.Comment: In Proceedings AMMSE 2011, arXiv:1106.596

Revisited experimental comparison of node-link and matrix representations

Visualizing network data is applicable in domains such as biology, engineering, and social sciences. We report the results of a study comparing the effectiveness of the two primary techniques for showing network data: node-link diagrams and adjacency matrices. Specifically, an evaluation with a large number of online participants revealed statistically significant differences between the two visualizations. Our work adds to existing research in several ways. First, we explore a broad spectrum of network tasks, many of which had not been previously evaluated. Second, our study uses a large dataset, typical of many real-life networks not explored by previous studies. Third, we leverage crowdsourcing to evaluate many tasks with many participants

FYVE-Dependent Endosomal Targeting of an Arrestin-Related Protein in Amoeba

International audienceBACKGROUND: Visual and β-arrestins are scaffolding proteins involved in the regulation of receptor-dependent intracellular signaling and their trafficking. The arrestin superfamilly includes several arrestin domain-containing proteins and the structurally related protein Vps26. In Dictyostelium discoideum, the arrestin-domain containing proteins form a family of six members, namely AdcA to -F. In contrast to canonical arrestins, Dictyostelium Adc proteins show a more complex architecture, as they possess, in addition to the arrestin core, other domains, such as C2, FYVE, LIM, MIT and SAM, which potentially mediate selective interactions with either lipids or proteins. METHODOLOGY AND PRINCIPAL FINDINGS: A detailed analysis of AdcA has been performed. AdcA extends on both sides of the arrestin core, in particular by a FYVE domain which mediates selective interactions with PI(3)P, as disclosed by intrinsic fluorescence measurements and lipid overlay assays. Localization studies showed an enrichment of tagged- and endogenous AdcA on the rim of early macropinosomes and phagosomes. This vesicular distribution relies on a functional FYVE domain. Our data also show that the arrestin core binds the ADP-ribosylation factor ArfA, the unique amoebal Arf member, in its GDP-bound conformation. SIGNIFICANCE: This work describes one of the 6 arrestin domain-containing proteins of Dictyostelium, a novel and atypical member of the arrestin clan. It provides the basis for a better understanding of arrestin-related protein involvement in trafficking processes and for further studies on the expanding roles of arrestins in eukaryotes

APP controls the formation of PI(3,5)P2 vesicles through its binding of the PIKfyve complex

Phosphoinositides are signalling lipids that are crucial for major signalling events as well as established regulators of membrane trafficking. Control of endosomal sorting and endosomal homeostasis requires phosphatidylinositol-3-phosphate (PI(3)P) and phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), the latter a lipid of low abundance but significant physiological relevance. PI(3,5)P2 is formed by phosphorylation of PI(3)P by the PIKfyve complex which is crucial for maintaining endosomal homeostasis. Interestingly, loss of PIKfyve function results in dramatic neurodegeneration. Despite the significance of PIKfyve, its regulation is still poorly understood. Here we show that the Amyloid Precursor Protein (APP), a central molecule in Alzheimer’s disease, associates with the PIKfyve complex (consisting of Vac14, PIKfyve and Fig4) and that the APP intracellular domain directly binds purified Vac14. We also show that the closely related APP paralogues, APLP1 and 2 associate with the PIKfyve complex. Whether APP family proteins can additionally form direct protein–protein interaction with PIKfyve or Fig4 remains to be explored. We show that APP binding to the PIKfyve complex drives formation of PI(3,5)P2 positive vesicles and that APP gene family members are required for supporting PIKfyve function. Interestingly, the PIKfyve complex is required for APP trafficking, suggesting a feedback loop in which APP, by binding to and stimulating PI(3,5)P2 vesicle formation may control its own trafficking. These data suggest that altered APP processing, as observed in Alzheimer’s disease, may disrupt PI(3,5)P2 metabolism, endosomal sorting and homeostasis with important implications for our understanding of the mechanism of neurodegeneration in Alzheimer’s disease

TULIP 5

International audienceTulip is an information visualization framework dedicated to the analysis and visualization of relational data. Based on more than 16 years of research and development, Tulip is built on a suite of tools and techniques, that can be used to address a large variety of domain-specific problems. With \tulip, we aim to provide Python and/or C++ developers a complete library, supporting the design of interactive information visualization applications for relational data, that can be customized to address a wide range of visualization problems. In its current iteration, \tulip enables the development of algorithms, visual encodings, interaction techniques, data models, and domain-specific visualizations. This development pipeline makes the framework efficient for creating research prototypes as well as developing end-user applications. The recent addition of a complete Python programming layer wraps up Tulip as an ideal tool for fast prototyping and treatment automation, allowing to focus on problem solving, and as a great system for teaching purposes at all education levels

The SNX-PX-BAR Family in Macropinocytosis: The Regulation of Macropinosome Formation by SNX-PX-BAR Proteins

Background: Macropinocytosis is an actin-driven endocytic process, whereby membrane ruffles fold back onto the plasma membrane to form large (> 0.2 mu m in diameter) endocytic organelles called macropinosomes. Relative to other endocytic pathways, little is known about the molecular mechanisms involved in macropinocytosis. Recently, members of the Sorting Nexin (SNX) family have been localized to the cell surface and early macropinosomes, and implicated in macropinosome formation. SNX-PX-BAR proteins form a subset of the SNX family and their lipid-binding (PX) and membrane-curvature sensing (BAR) domain architecture further implicates their functional involvement in macropinosome formation

Membrane Protein Location-Dependent Regulation by PI3K (III) and Rabenosyn-5 in Drosophila Wing Cells

The class III phosphatidylinositol-3 kinase (PI3K (III)) regulates intracellular vesicular transport at multiple steps through the production of phosphatidylinositol-3-phosphate (PI(3)P). While the localization of proteins at distinct membrane domains are likely regulated in different ways, the roles of PI3K (III) and its effectors have not been extensively investigated in a polarized cell during tissue development. In this study, we examined in vivo functions of PI3K (III) and its effector candidate Rabenosyn-5 (Rbsn-5) in Drosophila wing primordial cells, which are polarized along the apical-basal axis. Knockdown of the PI3K (III) subunit Vps15 resulted in an accumulation of the apical junctional proteins DE-cadherin and Flamingo and also the basal membrane protein β-integrin in intracellular vesicles. By contrast, knockdown of PI3K (III) increased lateral membrane-localized Fasciclin III (Fas III). Importantly, loss-of-function mutation of Rbsn-5 recapitulated the aberrant localization phenotypes of β-integrin and Fas III, but not those of DE-cadherin and Flamingo. These results suggest that PI3K (III) differentially regulates localization of proteins at distinct membrane domains and that Rbsn-5 mediates only a part of the PI3K (III)-dependent processes

Two PI 3-Kinases and One PI 3-Phosphatase Together Establish the Cyclic Waves of Phagosomal PtdIns(3)P Critical for the Degradation of Apoptotic Cells

Cyclic oscillations in the level of phosphatidylinositol 3-phosphate in phagosomes, regulated by two phosphoinositide kinases and one phosphatase, are critical for phagosome maturation and degradation of apoptotic cells

Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria

The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous) modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL) – a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM) are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis