Biomedical subjects

Jacques Demongeot

Publications and source records attributed to Jacques Demongeot.

13 recordsLinked to original sources

PubMed2003

Genetic regulation networks: circuits, regulons and attractors.

We deal in this paper with the concept of genetic regulation network. The genes expression observed through the bio-array imaging allows the geneticist to obtain the intergenic interaction matrix W of the network. The interaction graph G associated to W presents in general interesting features like connected components, gardens of Eden, positive and negative circuits (or loops), and minimal components having 1 positive and 1 negative loop called regulons. Depending on parameters values like the connectivity coefficient K(W) and the mean inhibition weight I(W), the genetic regulation network can present several dynamical behaviours (fixed configuration, limit cycle of configurations) called attractors, when the observation time increases. We give some examples of such genetic regulation networks and analyse their dynamical properties and their biological consequences.

Animals↗

PubMed2003

Bio-array images processing and genetic networks modelling.

The new tools available for gene expression studies are essentially the bio-array methods using a large variety of physical detectors (isotopes, fluorescent markers, ultrasounds...). Here we present first rapidly an image-processing method independent of the detector type, dealing with the noise and with the peaks overlapping, the peaks revealing the detector activity (isotopic in the presented example), correlated with the gene expression. After this primary step of bio-array image processing, we can extract information about causal influence (activation or inhibition) a gene can exert on other genes, leading to clusters of genes co-expression in which we extract an interaction matrix M and an associated interaction graph G explaining the genetic regulatory dynamics correlated to the studied tissue function. We give two examples of such interaction matrices and graphs (the flowering genetic regulatory network of Arabidopsis thaliana and the lytic/lysogenic operon of the phage Mu) and after some theoretical rigorous results recently obtained concerning the asymptotic states generated by the genetic networks having a given interaction matrix and reciprocally concerning the minimal (in the sense of having a minimal number of non-zero coefficients) matrices having given stationary stable states.

Arabidopsis↗

PubMed2002

Quantitative and qualitative changes in V-J alpha rearrangements during mouse thymocytes differentiation: implication for a limited T cell receptor alpha chain repertoire.

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR alpha chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR alpha repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3' side than 5' end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR alpha repertoire size and suggest a scenario for V usage during differentiation.

Animals↗

PubMed2002

Positive and negative feedback: striking a balance between necessary antagonists.

Most biological regulation systems comprise feedback circuits as crucial components. Negative feedback circuits have been well understood for a very long time; indeed, their understanding has been the basis for the engineering of cybernetic machines exhibiting stable behaviour. The importance of positive feedback circuits, considered as "vicious circles", has however been underestimated. In this article, we give a demonstration based on degree theory for vector fields of the conjecture, made by René Thomas, that the presence of positive feedback circuits is a necessary condition for autonomous differential systems, covering a wide class of biologically relevant systems, to possess multiple steady states. We also show ways to derive constraints on the weights of positive and negative feedback circuits. These qualitative and quantitative results provide, respectively, structural constraints (i.e. related to the interaction graph) and numerical constraints (i.e. related to the magnitudes of the interactions) on systems exhibiting complex behaviours, and should make it easier to reverse-engineer the interaction networks animating those systems on the basis of partial, sometimes unreliable, experimental data. We illustrate these concepts on a model multistable switch, in the context of cellular differentiation, showing a requirement for sufficient cooperativity. Further developments are expected in the discovery and modelling of regulatory networks in general, and in the interpretation of bio-array hybridization and proteomics experiments in particular.

Animals↗

PubMed2002

Microtubule self-organisation and its gravity dependence.

The molecular processes by which gravity affects biological systems are poorly, if at all, understood. Under equilibrium conditions, chemical and biochemical reactions do not depend upon gravity. It has been proposed that biological systems might depend on gravity by way of the bifurcation properties of certain types of non-linear chemical reactions that are far-from-equilibrium. In such reactions, the initially homogenous solution spontaneously self-organises by way of a combination of reaction and diffusion. Theoreticians have predicted that the presence or absence of an external field, such as gravity, at a critical moment early in the self-organising process may determine the morphology that subsequently develops. We have found that the formation in vitro of microtubules, a major element of the cellular skeleton, shows this type of behaviour. The microtubule preparations spontaneously self-organise by way of reaction and diffusion, and the morphology of the state that forms depends upon gravity at a critical bifurcation time early in the process. Experiments carried out under low gravity conditions show that the presence of gravity at the bifurcation time actually triggers the self-organising process. This is an experimental demonstration of how a very simple biochemical system, containing only two molecules, can be gravity sensitive. At a microscopic level the behaviour results from an interaction of gravity with the concentration and density fluctuations that arise from processes of microtubule shortening and elongation. We have developed a numerical reaction-diffusion scheme, based on the chemical dynamics of a population of microtubules, that simulate self-organisation. These simulations provide insight into how self-organisation occurs at a microscopic level and how gravity triggers this process. Recent experiments on cell lines cultured in space suggest that microtubule organisation may not occur properly under low gravity conditions. As microtubule organisation is essential to cellular function, it is quite plausible that the type of processes described in this article provide an underlying explanation for the gravity dependence of living systems at a cellular level.

Diffusion↗

PubMed2002

Comparison of reaction-diffusion simulations with experiment in self-organised microtubule solutions.

This article deals with the physical chemical processes underlying biological self-organization by which an initially homogenous solution of reacting chemicals spontaneously self-organizes so as to give rise to a preparation of macroscopic order and form. Theoreticians have predicted that self-organization can arise from a coupling of reactive processes with molecular diffusion. In addition, the presence or absence of an external field, such as gravity, at a critical moment early in the self-organizing process may determine the morphology that subsequently develops. We have found that the formation in vitro of microtubules, a major element of the cellular skeleton, show this type of behaviour. The microtubule preparations spontaneously self-organise by way of reaction and diffusion, and the morphology of the state that forms depends on the presence of gravity at a critical moment early in the process. We have developed a numerical reaction-diffusion scheme, based on the chemical dynamics of a population of microtubules, which simulates the experimental self-organisation. In this article we outline the main features of these simulations and discuss the manner by which a permanent dialogue with experiment has helped develop a microscopic understanding of the collective behaviour.

Algorithms↗

PubMed2002

[Multi-compartmental modelling and experimental design for glucose transport studies in insulin-resistant rats].

Many pathologies are associated with abnormalities of glucose metabolism or with perturbations of its transport (type 2 diabetes or insulin-resistance). The pre-diabetic state is characterised by a state of insulin-resistance, in others words a defect of glucose transport in insulin-sensible tissues, such as muscles and adipose tissues. The mathematical modelling of experimental data can be an excellent method to explore the mechanisms implied in the studied biological phenomenon. Thus, starting from a symbolic formulation like the compartmental modelling, it can be possible to develop a theoretical basis for the observation and to consider the best-adapted experiments for the study. We showed with mathematical models that [123I]-6-deoxy-6-iodo-D-glucose (6-DIG), shown as a tracer of glucose transport in vitro, could point out this transport abnormality. To quantify the insulin resistance, we estimated the fractional transfer coefficients of 6-DIG from the blood to the organs. We realised many studies to lead to a satisfying model; special attention has been paid to the precision of the parameter to select the best model. The results showed that by associating experimental data obtained with 6-DIG activities and an adapted mathematical model, discriminating parameters (in and out fractional transfer coefficients) between the two groups (control and insulin-resistant rats) could be pointed out.

Animals↗

PubMed2002

A differential geometry approach for biomedical image processing.

We show in this paper how simple considerations about bio-arrays images lead to a peak segmentation allowing the genes activity analysis. Bio-arrays images have a particular structure and the aim of the paper is to present a mathematical method allowing their automatic processing. The differential geometry approach used here can be also employed for other types of images presenting grey level peaks corresponding to a functional activity or to a chemical concentration. The mathematical method is based on elementary techniques of differential geometry and dynamical systems theory and provides a simple efficient algorithm when the peaks to segment are isolated.

Biomedical Technology↗

PubMed2002

Multi-sensors acquisition, data fusion, knowledge mining and alarm triggering in health smart homes for elderly people.

We deal in this paper with the concept of health smart home (HSH) designed to follow dependent people at home in order to avoid the hospitalisation, limiting hospital sojourns to short acute care or fast specific diagnostic investigations. For elderly people the project of such a HSH has been called AISLE (Apartment with Intelligent Sensors for Longevity Effectiveness). For this purpose, system having three levels of automatic measuring (1) the circadian activity, (2) the vegetative state, and (3) some state variables specific of certain organs involved in precise diseases, has been developed within the framework of a 'Health Integrated Smart Home Information System' (HIS2). HIS2 is an experimental platform for technologic development and clinical evaluation, in order to ensure the medical security and quality of life for patients who need home based medical monitoring. Location sensors are placed in each room of the HIS2, allowing the monitoring of patient's successive daily activity phases within the patient's home environment. We proceed with a sampling in an hourly schedule to detect weak variations of the nycthemeral rhythms. Based on numerous measurements, we establish a mean value with confidence limits of activity variables in normal behaviour permitting to detect for example a sudden abnormal event (like a fall) as well as a chronic pathologic activity (like a pollakiuria), allowing us to define a canonical domain within which the patient's activity is qualified to be 'predictable'. Alerts are set off if the patient's activity deviates from a predictable canonical domain. Moreover, we can follow the cardio-respiratory state by measuring the intensity of the respiratory sinusal arrhythmia in order to quantify the integrity of the bulbar vegetative system, and we finally propose to carefully watch abnormal symptoms like arterial pressure or presence of plasma proteins in the expired air flow for early detecting respectively hypertension or pulmonary oedema.

Aged↗

PubMed2002

Roles of positive and negative feedback in biological systems.

We discuss the influence of positive and negative feedback on the stability of a system, which is not clear-cut, and involves complex, mathematical problems. We show in particular that positive feedback can have a stabilising effect on some systems. We also point out the role that positive feedback plays in the digital treatment of signals required by cellular signalling, drawing on analogies from electronics, and the role that negative feedback plays in making a system robust against alteration of its parameters. Both positive and negative feedback can be seen as important enhancers of the properties of biological systems.

Animals↗

PubMed2002

Numerical simulations of microtubule self-organisation by reaction and diffusion.

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.

Animals↗

PubMed2002

Health "Smart" home: information technology for patients at home.

This article reviews the emerging concept of health "Smart" homes (HSH) and its potential through the use of telemedical information systems and communication technologies. HSH systems provide health care services for people with special needs who wish to remain independent and living in their own home. The large diversity of needs in a home-based patient population requires complex technology. Meeting these needs technically requires the use of a distributed approach and the combination of many hardware and software techniques. We also describe the wide scope of new information, communication, and data-acquisition technologies used in home health care. We offer an introduction to the HSH concept in terms of technical, economic, and human requirements. Examples of HSH projects are presented, including a short description of our own smart home and telehealthcare information system project.

Aged↗

PubMed2002

A system for automatic measurement of circadian activity deviations in telemedicine.

A system for the automatic measurement of the circadian activity deviations in telemedicine has been developed within the framework of a "Health Integrated Smart Home Information System" (HIS2). HIS2 is an experimental platform for the evaluation and the development of technologies in order to ensure the security and quality of life for patients who need home based medical monitoring. Location sensors are placed in each room of the HIS2, allowing the monitoring of patient's successive activity phases within the patient's home environment. We proceeded with a sampling in an hourly schedule to detect weak rhythmic variations. Based on numerous measurements, we established a mean value with confidence limits. These also allowed us to define a zone within which the patient's activity is qualified to be "predictable." Alerts are set off if the patient's activity deviates from this zone.

Activities of Daily Living↗