Jacques Demongeot

Quantitative and Qualitative Changes in V-J α Rearrangements During Mouse Thymocytes Differentiation Implication For a Limited T Cell Receptor α 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 α 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 α 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 α repertoire size and suggest a scenario for V usage during differentiation.

A model for the measurement of patient activity in a hospital suite

At the time of hospitalization, it is essential to evaluate the general health status of a patient and to follow up the trends during therapy. Our work is focused on a set of tools for the measurement of patient activity. In this paper, we propose a few indicators of the patient activities of daily living, such as mobility, agitation, repartitions of stays, and displacements. As a result of this work, a diagnostic system was developed that could lead to a deeper knowledge of human activity rhythms in normal situations

New trends in health smart homes

The concept of Health Smart House aims at giving an autonomous life, in their own home, to people who would normally be placed in institutions: patients suffering from a chronic disease, handicapped people, and also fragile elderly. We propose an overview of the researches on the concept. It then presents the main trends in each the technological fields of concern-Information systems, home automations, ubiquitous sensors, robotic assistance-meanwhile it indicates the standards efforts leaded by some large consortiums, and the ethical point of view.

Modelling malaria incidence with environmental dependency in a locality of Sudanese savannah area, Mali

BackgroundThe risk of Plasmodium falciparum infection is variable over space and time and this variability is related to environmental variability. Environmental factors affect the biological cycle of both vector and parasite. Despite this strong relationship, environmental effects have rarely been included in malaria transmission models.Remote sensing data on environment were incorporated into a temporal model of the transmission, to forecast the evolution of malaria epidemiology, in a locality of Sudanese savannah area.MethodsA dynamic cohort was constituted in June 1996 and followed up until June 2001 in the locality of Bancoumana, Mali. The 15-day composite vegetation index (NDVI), issued from satellite imagery series (NOAA) from July 1981 to December 2006, was used as remote sensing data.The statistical relationship between NDVI and incidence of P. falciparum infection was assessed by ARIMA analysis. ROC analysis provided an NDVI value for the prediction of an increase in incidence of parasitaemia.Malaria transmission was modelled using an SIRS-type model, adapted to Bancoumanas data. Environmental factors influenced vector mortality and aggressiveness, as well as length of the gonotrophic cycle. NDVI observations from 1981 to 2001 were used for the simulation of the extrinsic variable of a hidden Markov chain model. Observations from 2002 to 2006 served as external validation.ResultsThe seasonal pattern of P. falciparum incidence was significantly explained by NDVI, with a delay of 15 days (p = 0.001). An NDVI threshold of 0.361 (p = 0.007) provided a Diagnostic Odd Ratio (DOR) of 2.64 (CI95% [1.26;5.52]).The deterministic transmission model, with stochastic environmental factor, predicted an endemo-epidemic pattern of malaria infection. The incidences of parasitaemia were adequately modelled, using the observed NDVI as well as the NDVI simulations. Transmission pattern have been modelled and observed values were adequately predicted. The error parameters have shown the smallest values for a monthly model of environmental changes.ConclusionRemote-sensed data were coupled with field study data in order to drive a malaria transmission model. Several studies have shown that the NDVI presents significant correlations with climate variables, such as precipitations particularly in Sudanese savannah environments. Non-linear model combining environmental variables, predisposition factors and transmission pattern can be used for community level risk evaluation.

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.

BMP2 and BMP7 play antagonistic roles in feather induction.

Feathers, like hairs, first appear as primordia consisting of an epidermal placode associated with a dermal condensation that is necessary for the continuation of their differentiation. Previously, the BMPs have been proposed to inhibit skin appendage formation. We show that the function of specific BMPs during feather development is more complex. BMP2 and BMP7, which are expressed in both the epidermis and the dermis, are involved in an antagonistic fashion in regulating the formation of dermal condensations, and thus are both necessary for subsequent feather morphogenesis. BMP7 is expressed earlier and functions as a chemoattractant that recruits cells into the condensation, whereas BMP2 is expressed later, and leads to an arrest of cell migration, likely via its modulation of the EIIIA fibronectin domain and α4 integrin expression. Based on the observed cell proliferation, chemotaxis and the timing of BMP2 and BMP7 expression, we propose a mathematical model, a reaction-diffusion system, which not only simulates feather patterning, but which also can account for the negative effects of excess BMP2 or BMP7 on feather formation.

Cooperation of selection and meiotic mechanisms in the production of imbalances in reciprocal translocations

We have used data from chromosomally unbalanced offspring observed at birth, as well as data from sperm chromosome analysis, to study the meiotic segregation of reciprocal translocations. Using data from a total of 1,597 unbalanced children, we have observed an excess in maternal origin for all modes of imbalance. This excess is particularly marked for the 3:1 unbalanced mode, for which we have also observed a maternal age effect, indicating a close relationship with autosomal trisomies. In addition, a statistical analysis of data from 34 different published studies using sperm chromosome analysis has demonstrated that factors which, for reasons of viability, produce a predisposition for a particular mode of imbalance at birth also appear to favor meiotic production of this type of imbalance. Thus the production of unbalanced gametes of a particular type is influenced by the size of the imbalance.

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.

Cartographic study: breakpoints in 1574 families carrying human reciprocal translocations

Reciprocal translocations (rcp) are among the most common constitutional chromosomal aberrations in man. Using a European database of 1574 families carrying autosomal rep, a cartographic study was done on the breakpoints involved. The breakpoints are non-randomly distributed along the different chromosomes, indicating “hot spots”. Breakpoints of rep that result in descendants that are unbalanced chromosomally at birth are more frequent in a distal position on chromosomal arms, and 65% of them are localised in R-bands. Among the R-bands, bands rich in GC islands and poor in Alu repetitive sequences are more frequently the site of breakpoints, as well as bands that include a fragile site. This result suggests that the variation in degree of methylation in GC islands could be involved in chromosomal breakage and hence in chromosomal rearrangements.

Controlling posture using a plantar pressure-based, tongue-placed tactile biofeedback system

The present paper introduces an original biofeedback system for improving human balance control, whose underlying principle consists in providing additional sensory information related to foot sole pressure distribution to the user through a tongue-placed tactile output device. To assess the effect of this biofeedback system on postural control during quiet standing, ten young healthy adults were asked to stand as immobile as possible with their eyes closed in two conditions of No-biofeedback and Biofeedback. Centre of foot pressure (CoP) displacements were recorded using a force platform. Results showed reduced CoP displacements in the Biofeedback relative to the No-biofeedback condition. The present findings evidenced the ability of the central nervous system to efficiently integrate an artificial plantar-based, tongue-placed tactile biofeedback for controlling control posture during quiet standing.