Allo-network drugs: Extension of the allosteric drug concept to protein-protein interaction and signaling networks

Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design

Reclaiming human machine nature

Extending and modifying his domain of life by artifact production is one of the main characteristics of humankind. From the first hominid, who used a wood stick or a stone for extending his upper limbs and augmenting his gesture strength, to current systems engineers who used technologies for augmenting human cognition, perception and action, extending human body capabilities remains a big issue. From more than fifty years cybernetics, computer and cognitive sciences have imposed only one reductionist model of human machine systems: cognitive systems. Inspired by philosophy, behaviorist psychology and the information treatment metaphor, the cognitive system paradigm requires a function view and a functional analysis in human systems design process. According that design approach, human have been reduced to his metaphysical and functional properties in a new dualism. Human body requirements have been left to physical ergonomics or "physiology". With multidisciplinary convergence, the issues of "human-machine" systems and "human artifacts" evolve. The loss of biological and social boundaries between human organisms and interactive and informational physical artifact questions the current engineering methods and ergonomic design of cognitive systems. New developpment of human machine systems for intensive care, human space activities or bio-engineering sytems requires grounding human systems design on a renewed epistemological framework for future human systems model and evidence based "bio-engineering". In that context, reclaiming human factors, augmented human and human machine nature is a necessityComment: Published in HCI International 2014, Heraklion : Greece (2014

Revealing networks from dynamics: an introduction

What can we learn from the collective dynamics of a complex network about its interaction topology? Taking the perspective from nonlinear dynamics, we briefly review recent progress on how to infer structural connectivity (direct interactions) from accessing the dynamics of the units. Potential applications range from interaction networks in physics, to chemical and metabolic reactions, protein and gene regulatory networks as well as neural circuits in biology and electric power grids or wireless sensor networks in engineering. Moreover, we briefly mention some standard ways of inferring effective or functional connectivity.Comment: Topical review, 48 pages, 7 figure

Strategies for synthesis of yardsticks and abaci for nanometre distance measurements by pulsed EPR

Silvia Valera is grateful for support by EPSRC and Bela E. Bode acknowledges support by EastCHEM.Pulsed electron paramagnetic resonance (EPR) techniques have been found to be an efficient tool for elucidation of structure in complex biological systems as they give access to distances in the nanometre range. These measurements can provide additional structural information such as relative orientations, structural flexibility or aggregation states. A wide variety of model systems for calibration and optimisation of pulsed experiments has been synthesised. Their design is based on mimicking biological systems or materials in specific properties such as the distances themselves and the distance distributions. Here, we review selected approaches to the synthesis of chemical systems bearing two or more spin centres, such as nitroxide or trityl radicals, metal ions or combinations thereof and sketch their application in pulsed EPR distance measurements.Publisher PDFPeer reviewe

Simulation of Electric Vehicles Combining Structural and Functional Approaches

In this paper the construction of a model that represents the behavior of an Electric Vehicle is described. Both the mechanical and the electric traction systems are represented using Multi-Bond Graph structural approach suited to model large scale physical systems. Then the model of the controllers, represented with a functional approach, is included giving rise to an integrated model which exploits the advantages of both approaches. Simulation and experimental results are aimed to illustrate the electromechanical interaction and to validate the proposal.Fil: Silva, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Ingeniería. Grupo de Electronica Aplicada; ArgentinaFil: Magallán, Guillermo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Ingeniería. Grupo de Electronica Aplicada; ArgentinaFil: de la Barrera, Pablo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Ingeniería. Grupo de Electronica Aplicada; ArgentinaFil: de Angelo, Cristian Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Ingeniería. Grupo de Electronica Aplicada; ArgentinaFil: Garcia, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Ingeniería. Grupo de Electronica Aplicada; Argentin

Graph Theory and Networks in Biology

In this paper, we present a survey of the use of graph theoretical techniques in Biology. In particular, we discuss recent work on identifying and modelling the structure of bio-molecular networks, as well as the application of centrality measures to interaction networks and research on the hierarchical structure of such networks and network motifs. Work on the link between structural network properties and dynamics is also described, with emphasis on synchronization and disease propagation.Comment: 52 pages, 5 figures, Survey Pape