The building of a global model of carcinogenesis is one of modern biology’s greatest challenges. The traditional somatic mutation theory is now supplemented by a new approach, called the Tissue Organization Field Theory. According to TOFT, the original source of cancer is loss of tissue organization rather than genetic mutations. In this paper, we study the argumentative strategy used by the advocates of TOFT to impose their view. In particular, we criticize their claim of incompatibility used to justify the necessity (...) to definitively reject SMT. First, we note that since it is difficult to build a non-ambiguous experimental demonstration of the superiority of TOFT, its partisans add epistemological and metaphysical arguments to the debate. This argumentative strategy allows them to defend the necessity of a paradigm shift, with TOFT superseding SMT. To do so, they introduce a notion of incompatibility, which they actually use as the Kuhnian notion of incommensurability. To justify this so-called incompatibility between the two theories of cancer, they move the debate to a metaphysical ground by assimilating the controversy to a fundamental opposition between reductionism and organicism. We show here that this argumentative strategy is specious, because it does not demonstrate clearly that TOFT is an organicist theory. Since it shares with SMT its vocabulary, its ontology and its methodology, it appears that a claim of incompatibility based on this metaphysical plan is not fully justified in the present state of the debate. We conclude that it is more cogent to argue that the two theories are compatible, both biologically and metaphysically. We propose to consider that TOFT and SMT describe two distinct and compatible causal pathways to carcinogenesis. This view is coherent with the existence of integrative approaches, and suggests that they have a higher epistemic value than the two theories taken separately. (shrink)

This paper is devoted to computer modelling of the development and regeneration of multicellular biological structures. Some species are able to regenerate parts of their body after amputation damage, but the global rules governing cooperative cell behaviour during morphogenesis are not known. Here, we consider a simplified model organism, which consists of tissues formed around special cells that can be interpreted as stem cells. We assume that stem cells communicate with each other by a set of signals, and that the (...) values of these signals depend on the distance between cells. Thus the signal distribution characterizes location of stem cells. If the signal distribution is changed, then the difference between the initial and the current signal distribution affects the behaviour of stem cells—e.g. as a result of an amputation of a part of tissue the signal distribution changes which stimulates stem cells to migrate to new locations, appropriate for regeneration of the proper pattern. Moreover, as stem cells divide and form tissues around them, they control the form and the size of regenerating tissues. This two-level organization of the model organism, with global regulation of stem cells and local regulation of tissues, allows its reproducible development and regeneration. (shrink)

The genetic code has evolved from its initial non-degenerate wobble version until reaching its present state of degeneracy. By using the stereochemical hypothesis, we revisit the problem of codon assignations to the synonymy classes of amino-acids. We obtain these classes with a simple classifier based on physico-chemical properties of nucleic bases, like hydrophobicity and molecular weight. Then we propose simple RNA ring structures that present, overlap included, one and only one codon by synonymy class as solutions of a combinatory variational (...) problem. We compare these solutions to sequences of present RNAs considered as relics, with a high interspecific invariance, like invariant parts of tRNAs and micro-RNAs. We conclude by emphasizing some optimal properties of the genetic code. (shrink)

Building a meaningful model of biological regulatory network is usually done by specifying the components and their interactions, by guessing the values of parameters, by comparing the predicted behaviors to the observed ones, and by modifying in a trial-error process both architecture and parameters in order to reach an optimal fitness. We propose here a different approach to construct and analyze biological models avoiding the trial-error part, where structure and dynamics are represented as formal constraints. We apply the method to (...) Hopfield-like networks, a formalism often used in both neural and regulatory networks modeling. The aim is to characterize automatically the set of all models consistent with all the available knowledge. The available knowledge is formalized into formal constraints. The latter are compiled into Boolean formula in conjunctive normal form and then submitted to a Boolean satisfiability solver. This approach allows to formulate a wide range of queries, expressed in a high level language, and possibly integrating formalized intuitions. In order to explore its potential, we use it to find cycles for 3-nodes networks and to determine the flower morphogenesis regulatory network of Arabidopsis thaliana. Applications of this technique are numerous and concern the building of models from data as well as the design of biological networks possessing specified behaviors. (shrink)

Vision substitution by electro-stimulation has been studied since the 60s beginning with P. Bach-y-Rita. Camera pictures or movies encoded in gray levels are displayed using an electro-stimulation display device on the surface of a body part, such as the skin or the tongue. Medical-technical devices have been developed on this principle to compensate for sensory-motor disabilities such as blindness or loss of balance, or to guide specific actions, such as surgery. However, the electrical signals of stationary or moving slowly moving (...) objects, displayed on a Tongue display unit , are quickly lost due to saturation of receptors undergoing electrostimulation. We propose to add random saccades or sparkle to the displayed visual scene to increase the quality of pattern recognition by the subjects. In the present experimental trimodal study , we show that the presence of a moderate sparkle level enhances the perception of the direction of lines drawn on a TDU and reduces the response time. (shrink)

In this article we present a new kind of computing device that uses biochemical reactions networks as building blocks to implement logic gates. The architecture of a computing machine relies on these generic and composable building blocks, computation units, that can be used in multiple instances to perform complex boolean functions. Standard logical operations are implemented by biochemical networks, encapsulated and insulated within synthetic vesicles called protocells. These protocells are capable of exchanging energy and information with each other through transmembrane (...) electron transfer. In the paradigm of computation we propose, protoputing, a machine can solve only one problem and therefore has to be built specifically. Thus, the programming phase in the standard computing paradigm is represented in our approach by the set of assembly instructions that directs the wiring of the protocells that constitute the machine itself. To demonstrate the computing power of protocellular machines, we apply it to solve a NP-complete problem, known to be very demanding in computing power, the 3-SAT problem. We show how to program the assembly of a machine that can verify the satisfiability of a given boolean formula. Then we show how to use the massive parallelism of these machines to verify in less than 20 min all the valuations of the input variables and output a fluorescent signal when the formula is satisfiable or no signal at all otherwise. (shrink)

The Enzymatic control reactions model was presented within the scope of fractional calculus. In order to accommodate the usual initial conditions, the fractional derivative used is in Caputo sense. The methodologies of the three analytical methods were used to derive approximate solution of the fractional nonlinear system of differential equations. Two methods use integral operator and the other one uses just an integral. Numerical results obtained exhibit biological behavior of real world problem.

Various threshold Boolean networks, a formalism used to model different types of biological networks, can produce similar dynamics, i.e. share same behaviors. Among them, some are complex, others not. By computing both structural and behavioral complexities, we show that most TBNs are structurally complex, even those having simple behaviors. For this purpose, we developed a new method to compute the structural complexity of a TBN based on estimates of the sizes of equivalence classes of the threshold Boolean functions composing the (...) TBN. (shrink)

The field of synthetic biology is looking forward engineering framework for safely designing reliable de-novo biological functions. In this undertaking, Computer-Aided-Design environments should play a central role for facilitating the design. Although, CAD environment is widely used to engineer artificial systems the application in synthetic biology is still in its infancy. In this article we address the problem of the design of a high level language which at the core of CAD environment. More specifically the Gubs language is a specification (...) language used to describe the observations of the expected behaviour. The compiler appropriately selects components such that the observation of the synthetic biological function resulting to their assembly complies to the programmed behaviour. (shrink)

This article addresses the physical chemical processes underlying biological self-organisation by which a homogenous solution of reacting chemicals spontaneously self-organises. Theoreticians have predicted that self-organisation can arise from a coupling of reactive processes with molecular diffusion. In addition, the presence of an external field, such as gravity, at a critical moment early in the process may determine the morphology that subsequently develops. The formation, in-vitro, of microtubules, a constituent of the cellular skeleton, shows this type of behaviour. The preparations spontaneously (...) self-organise by reaction-diffusion and the morphology that develops depends upon the presence of gravity at a critical bifurcation time early in the process. Here, we present numerical simulations of a population of microtubules that reproduce this behaviour. Microtubules can grow from one end whilst shrinking from the other. The shrinking end leaves behind a chemical trail of high tubulin concentration. Neighbouring microtubules preferentially grow into these regions, whilst avoiding regions of low tubulin concentration. The chemical trails produced by individual microtubules thus activate and inhibit the formation of neighbouring microtubules and this progressively leads to self-organisation. Gravity acts by way of its directional interaction with the macroscopic density fluctuations present in the solution arising from microtubule disassembly. (shrink)

Microtubules, major elements of the cell skeleton are, most of the time, well organized in vivo, but they can also show self-organizing behaviors in time and/or space in purified solutions in vitro. Theoretical studies and models based on the concepts of collective dynamics in complex systems, reaction–diffusion processes and emergent phenomena were proposed to explain some of these behaviors. In the particular case of microtubule spatial self-organization, it has been advanced that microtubules could behave like ants, self-organizing by ‘talking to (...) each other’ by way of hypothetic concentrated chemical trails of tubulin that are expected to be released by their disassembling ends. Deterministic models based on this idea yielded indeed like-looking spatio-temporal self-organizing behaviors. Nevertheless the question remains of whether microscopic tubulin trails produced by individual or bundles of several microtubules are intense enough to allow microtubule self-organization at a macroscopic level. In the present work, by simulating the diffusion of tubulin in microtubule solutions at the microscopic scale, we measure the shape and intensity of tubulin trails and discuss about the assumption of microtubule self-organization due to the production of chemical trails by disassembling microtubules. We show that the tubulin trails produced by individual microtubules or small microtubule arrays are very weak and not elongated even at very high reactive rates. Although the variations of concentration due to such trails are not significant compared to natural fluctuations of the concentration of tubuline in the chemical environment, the study shows that heterogeneities of biochemical composition can form due to microtubule disassembly. They could become significant when produced by numerous microtubule ends located in the same place. Their possible formation could play a role in certain conditions of reaction. In particular, it gives a mesoscopic basis to explain the collective dynamics observed in excitable microtubule solutions showing the propagation of concentration waves of microtubules at the millimeter scale, although we doubt that individual microtubules or bundles can behave like molecular ants. (shrink)

Large sets of elements interacting locally and producing specific architectures reliably form a category that transcends the usual dividing line between biological and engineered systems. We propose to call them morphogenetically architected complex systems. While taking the emergence of properties seriously, the notion of MACS enables at the same time the design of operational means that allow controlling and even, paradoxically, programming this emergence. To demonstrate our claim, we first show that among all the self-organized systems studied in the field (...) of Artificial Life, the specificity of MACS essentially lies in the close relation between their emergent properties and functional properties. Second, we argue that to be a MACS a system does not need to display more than weak emergent properties. Third, since the notion of weak emergence is based on the possibility of simulation, whether computational or mechanistic via machines, we see MACS as good candidates to help design artificial self-architected systems but also harness and redesign living ones. (shrink)

The classic model of blood pressure regulation by Guyton et al. set a new standard for quantitative exploration of physiological function and led to important new insights, some of which still remain the focus of debate, such as whether the kidney plays the primary role in the genesis of hypertension. Key to the success of this model was the fact that the authors made the computer code freely available and eventually provided a convivial user interface for exploration of model behavior (...) on early microcomputers. Ikeda et al. developed an offshoot of the Guyton model targeting especially the regulation of body fluids and acid–base balance; their model provides extended renal and respiratory functions and would be a good basis for further extensions. In the interest of providing a simple, useable version of Ikeda et al.’s model and to facilitate further such extensions, we present a practical implementation of the model of Ikeda et al., using the ODE solver Berkeley Madonna. (shrink)