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111.
Homeostasis implies constant operational defence mechanisms, against both external and internal threats. Infectious agents are prominent among such threats. During infection, the host elicits the release of a vast array of molecules and numerous cell-cell interactions are triggered. These pleiomorphic mediators and cellular effects are of prime importance in the defence of the host, both in the systemic circulation and at sites of tissue injury, for example, the blood-brain barrier (BBB). Here, we focus on the interactions between the endothelium, astrocytes, and the molecules they release. Our review addresses these interactions during infectious neurological diseases of various origins, especially cerebral malaria (CM). Two novel elements of the interplay between endothelium and astrocytes, microparticles and the kynurenine pathway, will also be discussed. 相似文献
112.
Biochemical properties and regulation of cathepsin K activity 总被引:1,自引:0,他引:1
Cysteine cathepsins (11 in humans) are mostly located in the acidic compartments of cells. They have been known for decades to be involved in intracellular protein degradation as housekeeping proteases. However, the discovery of new cathepsins, including cathepsins K, V and F, has provided strong evidence that they also participate in specific biological events. This review focuses on the current knowledge of cathepsin K, the major bone cysteine protease, which is a drug target of clinical interest. Nevertheless, we will not discuss recent developments in cathepsin K inhibitor design since they have been extensively detailed elsewhere. We will cover features of cathepsin K structure, cellular and tissue distribution, substrate specificity, and regulation (pH, propeptide, glycosaminoglycans, oxidants), and its putative roles in physiological or pathophysiological processes. Finally, we will review the kinetic data of its inhibition by natural endogenous inhibitors (stefin B, cystatin C, H- and L-kininogens). 相似文献
113.
Minimal cut sets in biochemical reaction networks 总被引:3,自引:0,他引:3
MOTIVATION: Structural studies of metabolic networks yield deeper insight into topology, functionality and capabilities of the metabolisms of different organisms. Here, we address the analysis of potential failure modes in metabolic networks whose occurrence will render the network structurally incapable of performing certain functions. Such studies will help to identify crucial parts in the network structure and to find suitable targets for repressing undesired metabolic functions. RESULTS: We introduce the concept of minimal cut sets for biochemical networks. A minimal cut set (MCS) is a minimal (irreducible) set of reactions in the network whose inactivation will definitely lead to a failure in certain network functions. We present an algorithm which enables the computation of the MCSs in a given network related to user-defined objective reactions. This algorithm operates on elementary modes. A number of potential applications are outlined, including network verifications, phenotype predictions, assessing structural robustness and fragility, metabolic flux analysis and target identification in drug discovery. Applications are illustrated by the MCSs in the central metabolism of Escherichia coli for growth on different substrates. AVAILABILITY: Computation and analysis of MCSs is an additional feature of the FluxAnalyzer (freely available for academic users upon request, special contracts for industrial companies; see web page below). Supplementary information: http://www.mpi-magdeburg.mpg.de/projects/fluxanalyzer 相似文献
114.
Bérangère Farges Céline Laroche Jean‐François Cornet Claude‐Gilles Dussap 《Biotechnology progress》2009,25(1):151-162
The ability to cultivate the cyanobacterium Arhtrospira platensis in artificially lightened photobioreactors using high energetic efficiency (quasi‐monochromatic) red LED was investigated. To reach the same maximal productivities as with the polychromatic lightening control conditions (red + blue, P/2e? = 1.275), the need to work with an optimal range of wavelength around 620 nm was first established on batch and continuous cultures. The long‐term physiological and kinetic behavior was then verified in a continuous photobioreactor illuminated only with red (620 nm) LED, showing that the maximum productivities can be maintained over 30 residence times with only minor changes in the pigment content of the cells corresponding to a well‐known adaptation mechanism of the photosystems, but without any effect on growth and stoichiometry. For both poly and monochromatic incident light inputs, a predictive spectral knowledge model was proposed and validated for the first time, allowing the calculation of the kinetics and stoichiometry observed in any photobioreactor cultivating A. platensis, or other cyanobacteria if the parameters were updated. It is shown that the photon flux (with a specified wavelength) must be used instead of light energy flux as a relevant control variable for the growth. The experimental and theoretical results obtained in this study demonstrate that it is possible to save the energy consumed by the lightening device of photobioreactors using red LED, the spectral range of which is defined according to the action spectrum of photosynthesis. This appears to be crucial information for applications in which the energy must be rationalized, as it is the case for life support systems in closed environments like a permanent spatial base or a submarine. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 相似文献
115.
Gilles Curien Olivier Bastien Mylène Robert‐Genthon Athel Cornish‐Bowden María Luz Cárdenas Renaud Dumas 《Molecular systems biology》2009,5(1)
The aspartate‐derived amino‐acid pathway from plants is well suited for analysing the function of the allosteric network of interactions in branched pathways. For this purpose, a detailed kinetic model of the system in the plant model Arabidopsis was constructed on the basis of in vitro kinetic measurements. The data, assembled into a mathematical model, reproduce in vivo measurements and also provide non‐intuitive predictions. A crucial result is the identification of allosteric interactions whose function is not to couple demand and supply but to maintain a high independence between fluxes in competing pathways. In addition, the model shows that enzyme isoforms are not functionally redundant, because they contribute unequally to the flux and its regulation. Another result is the identification of the threonine concentration as the most sensitive variable in the system, suggesting a regulatory role for threonine at a higher level of integration. 相似文献
116.
Fran?oise Lazarini Marc-André Mouthon Gilles Gheusi Fabrice de Chaumont Jean-Christophe Olivo-Marin Stéphanie Lamarque Djoher Nora Abrous Fran?ois D. Boussin Pierre-Marie Lledo 《PloS one》2009,4(9)
Background
In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear.Methodology/Principal Findings
In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation.Conclusion/Significance
These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces. 相似文献117.
Paweł Zajdel Gilles Subra Pascal Verdie Ewa Gabzdyl Andrzej J. Bojarski Beata Duszyńska Jean Martinez Maciej Pawłowski 《Bioorganic & medicinal chemistry letters》2009,19(16):4827-4831
A series of arylsulfonamides containing guanidine incorporated in the structure of secondary amines (piperidine, piperazine) was synthesized on SynPhase Lanterns and evaluated for 5-HT1A, 5-HT2A, and 5-HT7 receptors. The results demonstrated that N-alkyl-N′-dialkylguanidines displayed good 5-HT7/5-HT1A selectivity and may be regarded as promising structural core for development of 5-HT7 ligands. 相似文献
118.
Benjamin Gilles Frank Kolo Christophe Nadia Magnenat-Thalmann Christoph D. Becker Sylvain R. Duc Jacques Menetrey Pierre Hoffmeyer 《Journal of biomechanics》2009,42(9):1201-1205
To better understand movement limitations and, to some extent, the pathogenesis of osteoarthritis, it is important to quantitatively measure femoroacetabular translations to assess if any joint subluxation occurs. In this paper, we aim at measuring hip joint displacements from magnetic resonance images (MRI) based on a surface registration technique. Because this measurement is related to the location of the hip joint center (HJC), we investigate and compare different HJC estimation approaches based on patient-specific 3D bone models. We estimate the HJC based on a simulated circumduction while minimizing inter-articular distance changes. Measurements of femoroacetabular translations during low amplitude abductions ( samples) and extreme flexions ( samples) in female professional dancers, which is a population potentially exposed to femoroactebaluar impingements, do not show any significant subluxation. 相似文献
119.
Guillaume Sarrabayrouse Christine Pich Rapha?l Moriez Virginie Armand-Labit Philippe Rochaix Gilles Favre Anne-Fran?oise Tilkin-Mariamé 《PloS one》2010,5(2)
Background
Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I) and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298) stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1].Methodology/Principal Findings
In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL), we demonstrated that in vitro treatment with hIFN-γ and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC) revealed that modifications induced by hIFN-γ and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-γ and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i) activation of CD8 T lymphocytes (CD8+/CD69+); ii) proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+); iii) secretion of hIFN-γ; and iv) anti-melanoma specific cytotoxic cells.Conclusions/Significance
These data indicate that pharmacological treatment of melanoma cell lines with IFN-γ and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells. 相似文献120.
Peyre M Commo F Dantas-Barbosa C Andreiuolo F Puget S Lacroix L Drusch F Scott V Varlet P Mauguen A Dessen P Lazar V Vassal G Grill J 《PloS one》2010,5(9):e12932