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91.
Jean-Marc Bielser Leon Kraus Orlando Burgos-Morales Hervé Broly Jonathan Souquet 《Biotechnology progress》2020,36(5):e3026
Media preparation for perfusion cell culture processes contributes significantly to operational costs and the footprint of continuous operations for therapeutic protein manufacturing. In this study, definitions are given for the use of a perfusion equivalent nutrient feed stream which, when used in combination with basal perfusion medium, supplements the culture with targeted compounds and increases the medium depth. Definitions to compare medium and feed depth are given in this article. Using a concentrated nutrient feed, a 1.8-fold medium consumption (MC) decrease and a 1.67-fold increase in volumetric productivity (PR) were achieved compared to the initial condition. Later, this strategy was used to push cell densities above 100 × 106 cells/ml while using a perfusion rate below 2 RV/day. In this example, MC was also decreased 1.8-fold compared to the initial condition, but due to the higher cell density, PR was increased 3.1-fold and to an average PR value of 1.36 g L−1 day−1 during a short stable phase, and versus 0.46 g L−1 day−1 in the initial condition. Overall, the performance improvements were aligned with the given definitions. This multiple feeding strategy can be applied to gain some flexibility during process development and also in a manufacturing set-up to enable better control on nutrient addition. 相似文献
92.
Iglika Djoumerska-Alexieva Lubka Roumenina Anastas Pashov Jordan Dimitrov Maya Hadzhieva Sandro Lindig Elisaveta Voynova Petya Dimitrova Nina Ivanovska Clemens Bockmeyer Zvetanka Stefanova Catherine Fitting Markus Bl?ss Ralf Claus Stephan von Gunten Srini Kaveri Jean-Marc Cavaillon Michael Bauer Tchavdar Vassilev 《Molecular medicine (Cambridge, Mass.)》2015,21(1):1002-1010
Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. 相似文献
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95.
Ten microsatellite loci were used to investigate the impact of human activity on the spatial and temporal genetic structure of Vitellaria paradoxa (Sapotaceae), a parkland tree species in agroforestry systems in southern Mali. Two stands (forest and fallow) and three cohorts (adults, juveniles and natural regeneration) in each stand were studied to: (i) compare their levels of genetic diversity (gene diversity, HE; allelic richness, Rs; and inbreeding, FIS); (ii) assess their genetic differentiation (FST); and (iii) compare their levels of spatial genetic structuring. Gene diversity parameters did not vary substantially among stands or cohorts, and tests for bottleneck events were nonsignificant. The inbreeding coefficients were not significantly different from zero in most cases (FIS = -0.025 in forest and 0.045 in fallow), suggesting that the species is probably outbreeding. There was a weak decrease in F(IS) with age, suggesting inbreeding depression. Differentiation of stands within each cohort was weak (FST = 0.026, 0.0005, 0.010 for adults, juveniles and regeneration, respectively), suggesting extensive gene flow. Cohorts within each stand were little differentiated (FST = -0.001 and 0.001 in forest and fallow, respectively). The spatial genetic structure was more pronounced in fallow than in forest where adults showed no spatial structuring. In conclusion, despite the huge influence of human activity on the life cycle of Vitellaria paradoxa growing in parkland systems, the impact on the pattern of genetic variation at microsatellite loci appears rather limited, possibly due to the buffering effect of extensive gene flow between unmanaged and managed populations. 相似文献
96.
Magali Lucia Jean-Marc Andre Patrice Gonzalez Magalie Baudrimont Karine Gontier Regine Maury-Brachet Stephane Davail 《Biometals》2009,22(5):843-853
The impact on palmiped Cairina moschata of two levels of dietary cadmium (Cd) contamination (C1: 1 mg kg−1 and C10: 10 mg kg−1) was investigated on liver gene expression by real-time PCR. Genes involved in mitochondrial metabolism, in antioxidant defences,
detoxification and in DNA damage repair were studied. Metallothionein (MT) protein levels and Cd bioaccumulation were also
investigated in liver, kidneys and muscle. Male ducks were subjected to three periods of exposure: 10, 20 and 40 days. Cd
was mainly bioaccumulated in kidneys first and in liver. The concentrations in liver and kidneys appeared to reach a stable
level at 20 days of contamination even if the concentrations in muscle still increased. Cd triggered the enhancement of mitochondrial
metabolism, the establishment of antioxidant defences (superoxide dismutase Mn and Cu/Zn; catalase) and of DNA repair from
20 days of contamination. Discrepancies were observed in liver between MT protein levels and MT gene up-regulation. MT gene
expression appeared to be a late hour biomarker. 相似文献
97.
98.
Hyvelin JM O'Connor C McLoughlin P 《American journal of physiology. Lung cellular and molecular physiology》2004,287(4):L673-L684
Pulmonary arteries (PA) are resistant to the vasodilator effects of extracellular acidosis in systemic vessels; the mechanism underlying this difference between systemic and pulmonary circulations has not been elucidated. We hypothesized that RhoA/Rho-kinase-mediated Ca2+ sensitization pathway played a greater role in tension development in pulmonary than in systemic vascular smooth muscle and that this pathway was insensitive to acidosis. In arterial rings contracted with the alpha1-agonist phenylephrine (PE), the Rho-kinase inhibitor Y-27632 (< or =3 microM) induced greater relaxation in precontracted PA rings than in aortic rings. In PA rings stimulated by PE, the activation of RhoA was greater than in aorta. Normocapnic acidosis (NA) induced a smaller relaxation in precontracted PA than in aorta. However, in the presence of nifedipine and thapsigargin, when PE-induced contraction was predominantly mediated by Rho-kinase, the relaxant effect of NA was reduced and similar in both vessel types. Furthermore, in the presence of Y-27632, NA induced a greater relaxation in both PA and aorta, which was similar in both vessels. Finally, in alpha-toxin-permeabilized smooth muscle, PE-induced contraction at constant Ca2+ activity was inhibited by Y-27632 and unaffected by acidosis. These results indicate that Ca2+ sensitization induced by the RhoA/Rho-kinase pathway played a greater role in agonist-induced vascular smooth muscle contraction in PA than in aorta and that tension mediated by this pathway was insensitive to acidosis. The predominant role of the RhoA/Rho-kinase pathway in the pulmonary vasculature may account for the resistance of this circulation to the vasodilator effect of acidosis observed in the systemic circulation. 相似文献
99.
Yueh-Hsin Ping Chia-ying Chu Hong Cao Jean-Marc Jacque Mario Stevenson Tariq M Rana 《Retrovirology》2004,1(1):1-13
Background
Dendritic cell (DC) transmission of human immunodeficiency virus (HIV) to CD4+ T cells occurs across a point of cell-cell contact referred to as the infectious synapse. The relationship between the infectious synapse and the classically defined immunological synapse is not currently understood. We have recently demonstrated that human B cells expressing exogenous DC-SIGN, DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin, efficiently transmit captured HIV type 1 (HIV-1) to CD4+ T cells. K562, another human cell line of hematopoietic origin that has been extensively used in functional analyses of DC-SIGN and related molecules, lacks the principal molecules involved in the formation of immunological synaptic junctions, namely major histocompatibility complex (MHC) class II molecules and leukocyte function-associated antigen-1 (LFA-1). We thus examined whether K562 erythroleukemic cells could recapitulate efficient DC-SIGN-mediated HIV-1 transmission (DMHT).Results
Here we demonstrate that DMHT requires cell-cell contact. Despite similar expression of functional DC-SIGN, K562/DC-SIGN cells were inefficient in the transmission of HIV-1 to CD4+ T cells when compared with Raji/DC-SIGN cells. Expression of MHC class II molecules or LFA-1 on K562/DC-SIGN cells was insufficient to rescue HIV-1 transmission efficiency. Strikingly, we observed that co-culture of K562 cells with Raji/DC-SIGN cells impaired DMHT to CD4+ T cells. The K562 cell inhibition of transmission was not directly exerted on the CD4+ T cell targets and required contact between K562 and Raji/DC-SIGN cells.Conclusions
DMHT is cell type dependent and requires cell-cell contact. We also find that the cellular milieu can negatively regulate DC-SIGN transmission of HIV-1 in trans. 相似文献100.
Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals 总被引:3,自引:0,他引:3
Jean-Marc Moulis 《Biometals》2010,23(5):877-896