Expression and function of chemokine receptors on airway smooth muscle cells

Asthma is a respiratory disease that affects 2.5-3 million Canadians. This condition is characterized by a Th2-driven immune response that implicates the infiltration of eosinophils and remodelling of the airways. In the last decade, airway smooth muscle cells (ASMC) have became the subject of intense research in the field of inflammatory lung diseases including asthma. It is known that ASMC respond to a wide variety of inflammatory mediators such as cytokines and chemokines. Function of ASMC in the context of asthma has extended beyond its traditional role of a structural cell. Indeed, it is believed that they can participate in the initiation and the perpetuation of the inflammatory response that takes place in the airway of asthmatic subjects. The general aim of this work was to investigate the role of ASMC in the pathogenesis of asthma. More specifically, we studied the expression of two C-C chemokine receptors, CCR3 and CCR1 in the context of asthma.For the first time, this work describes the expression of chemokine receptors by ASMC. We have shown that eotaxin, an important chemokine in asthma, induces migration of ASMC through the activation of CCR3. Although CCR3 expression is not regulated by Th2 cytokines in vitro, ASMC isolated from asthmatic patients expressed intrinsically higher levels of the surface receptor when compared to controls. We also describe the expression of CCR1 by ASMC, a receptor involved in airway remodelling in an animal model of asthma. We reported the expression of CCR1 mRNA in biopsies obtained from mild, moderate and severe asthmatics and showed that mild group express the highest level of CCR1. We also confirmed that ASMC express the receptor in vivo and showed that stimulation of this receptor with its ligands induces intra-cellular calcium mobilization, which confirms its functionality. Regulation of CCR1 on ASMC was also assessed using proinflammatory, Th1 and Th2 cytokines. We found that TNF-alpha and to a lesser extent, IFN-gamma, upregulated CCR1 mRNA and protein expression, while Th2 cytokines had no effect. The effect of these two cytokines was totally suppressed by either dexamethasone or mithramycin.Collectively, our results demonstrate the expression of functional C-C chemokine receptors by ASMC. Interestingly, we have shown that CCR3 activation mediates ASMC migration and provides a new possible mechanism for the increased smooth muscle mass observed in asthmatic patients. Although the exact function of the CCR1 expressed by ASMC is unknown, our results suggest an involvement in asthma pathogenesis, possibly through airway remodelling

SPAM : a multiprocessor execution driven simulation Kernel

Trace driven simulation is a well known technique for performance evaluation of single processor computers. However, trace driven simulation introduces distortions when used to simulate multiprocessor architectures. Execution driven simulation is the only technique that gives accurate simulation results for multiprocessor architectures though it is difficult to implement. Thisd paper presents SPAM, a simulation kernel that simplifies the construction of execution driven simulators for shared memory multiprocessors. The kernel provides a tracing tool and a set of primitives which allow the execution, tracing and simulation of shared memory parallel applications on a single processor computer. The performance of the kernel allows the simulation of real sized parallel applications in a reasonnable time

Un déterminant de l'innovation technique en agriculture : les coordinations sur le travail dans la production bananière

Working Paper MOISASumary The growth of the international market of the horticultural products is made possible by the globalization of an intensive mode of production in synthetic products which mobilizes salaried workers. In the Antilles changes in technological trajectories enables the consideration of other modes of production. This article brings to light how the technical innovation allowing a decrease in the necessity to use pesticides is dependent on an adaptation of the coordination in the mobilization of the salaried work. For this purpose we compare two systems of the use of manual labour between Martinique and Guadeloupe by widening on certain aspects in the transnational. The comparison is based on the characterization of these systems in which manual labour is used and the indicators of performance of the sectors of banana as well as on the adaptation of the technical changes.Résumé La croissance du marché international des produits horticoles se réalise par la globalisation d'un mode de production intensif en produits de synthèses qui mobilise une main d'œuvre salariée. Dans les Antilles des changements de trajectoires technologiques permettent d'envisager d'autres modes de production. Cet article met en évidence comment l'innovation technique permettant de diminuer le recours aux pesticides est tributaire d'une adaptation des coordinations dans la mobilisation du travail salarié. Pour cela nous caractérisons les systèmes d'emploi de la main d'œuvre salarié entre différentes origines et leurs impact sur des indicateurs de performance des filières de banane et d'adaptation des changements techniques

Un déterminant de l'innovation technique en agriculture : les coordinations sur le travail dans la production bananière

Résumé La croissance du marché international des produits horticoles se réalise par la globalisation d'un mode de production intensif en produits de synthèses qui mobilise une main d'œuvre salariée. Dans les Antilles des changements de trajectoires technologiques permettent d'envisager d'autres modes de production. Cet article met en évidence comment l'innovation technique permettant de diminuer le recours aux pesticides est tributaire d'une adaptation des coordinations dans la mobilisation du travail salarié. Pour cela nous caractérisons les systèmes d'emploi de la main d'œuvre salarié entre différentes origines et leurs impact sur des indicateurs de performance des filières de banane et d'adaptation des changements techniques.Mots clés : Banane, Travail, Pesticides, Innovation, Filière, Guadeloupe, Martinique

Effect of 5-azacytidine and galectin-1 on growth and differentiation of the human b lymphoma cell line bl36

BACKGROUND: 5-AzaCytidine (AzaC) is a DNA demethylating drugs that has been shown to inhibit cell growth and to induce apoptosis in certain cancer cells. Induced expression of the galectin1 (Gal1) protein, a galactoside-binding protein distributed widely in immune cells, has been described in cultured hepatoma-derived cells treated with AzaC and this event may have a role in the effect of the drug. According to this hypothesis, we investigated the effect of AzaC and Gal1 on human lymphoid B cells phenotype. METHODS: The effect of AzaC and Gal1 on cell growth and phenotype was determined on the Burkitt lymphoma cell line BL36. An immunocytochemical analysis for detection of Gal1 protein expression was performed in AzaC-treated cells. To investigate the direct effects of Gal1, recombinant Gal1 was added to cells. RESULTS: Treatment of lymphoid B cells with AzaC results in: i) a decrease in cell growth with an arrest of the cell cycle at G0/G1 phase, ii) phenotypic changes consistent with a differentiated phenotype, and iii) the expression of p16, a tumor-suppressor gene whose expression was dependent of its promoter demethylation, and of Gal1. A targeting of Gal 1 to the plasma membrane follows its cytosolic expression. To determine which of the effects of AzaC might be secondary to the induction of Gal1, recombinant Gal1 was added to BL36 cells. Treated cells displayed growth inhibition and phenotypic changes consistent with a commitment toward differentiation. CONCLUSIONS: Altered cell growth and expression of the cell surface plasma cell antigen, CD138 are detectable in BL36 cells treated by AzaC as well as by Gal1. It seems that AzaC-induced Gal1 expression and consequent binding of Gal1 on its cell membrane receptor may be, in part, involved in AzaC-induced plasmacytic differentiation

Communicating processes and fault tolerance : a shared memory multiprocessor experience

The concept of backward recovery is now well established as a means of restoring a consistent state of a fault tolerant system should some faults occur. In this paper, we consider a system of communicating processes mapped onto a multilevel execution support. A shared memory multiprocessor machine is assumed. Our interest is in tolerating the hardware faults that may occur during the execution of a concurrent computation. The machine provides a hardware backard recovery protocol based on a specialized memory device which tracks dependencies between the processors accessing shared data residing in memory. The transparency provided by the protocol is discussed considering successively the models of computation at the various levels of abstraction of the execution support

Cinéma et musée : nouvelles temporalités

Les contributions qui suivent partaient d’un constat apparemment indiscutable et admis d’avance, soit qu’on l’admette pour s’en réjouir, soit qu’on l’estime décadent : toutes les formes possibles de cinéma, archaïques ou actuelles, commerciales ou expérimentales, dessinées ou enregistrées, sont aujourd’hui présentes au musée. Or, cela ne va pas de soi. Cette évidence d’époque n’est peut-être ni évidente ni propre à notre temps. Rapprocher musée et cinéma n’a tout d’abord rien d’évident parce ..

A microfluidic biochip for the nanoporation of living cells

International audienceThis paper deals with the development of a microfluidic biochip for the exposure of living cells to nanosecond pulsed electric fields (nsPEF). When exposed to ultra short electric pulses (typical duration of 3-10ns), disturbances on the plasma membrane and on the intra cellular components occur, modifying the behavioral response of cells exposed to drugs or transgene vectors. This phenomenon permits to envision promising therapies. The presented biochip is composed of thick gold electrodes that are designed to deliver a maximum of energy to the biological medium containing cells. The temporal and spectral distributions of the nsPEF are considered for the design of the chip. In order to validate the fabricated biochip ability to orient the pulse towards the cells flowing within the exposition channels, a frequency analysis is provided. High voltage measurements in the time domain are performed to characterize the amplitude and the shape of the nsPEF within the exposition channels and compared to numerical simulations achieved with a 3D Finite-Difference Time-Domain code. We demonstrate that the biochip is adapted for 3 ns and 10 ns pulses and that the nsPEF are homogenously applied to the biological cells regardless their position along the microfluidic channel. Furthermore, biological tests performed on the developed microfluidic biochip permit to prove its capability to permeabilize living cells with nanopulses. To the best of our knowledge, we report here the first successful use of a microfluidic device optimized for the achievement and real time observation of the nanoporation of living cells