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Marc Becker

Publications and source records attributed to Marc Becker.

4 recordsLinked to original sources

Specific and redundant roles for NFAT transcription factors in the expression of mast cell-derived cytokines.

By virtue of their ability to express a plethora of biologically highly active mediators, mast cells (MC) are involved in both adaptive and innate immune responses. MC-derived Th2-type cytokines are thought to act as local amplifiers of Th2 reactions, including chronic inflammatory disorders such as allergic asthma, whereas MC-derived TNF-alpha is a critical initiator of antimicrobial defense. In this study, we demonstrate that the transcription factors NFATc1 and NFATc2 are part of a MC-specific signaling network that regulates the expression of TNF-alpha and IL-13, whereas NFATc3 is dispensable. Primary murine bone marrow-derived MC from NFATc2(-/-) mice, activated by either ionomycin or IgE/Ag cross-link, display a strong reduction in the production of these cytokines, compared with bone marrow-derived MC from wild-type mice. Detailed analyses of TNF-alpha and IL-13 expression using small interfering RNA-mediated knockdown reveals that both NFATc2 and NFATc1 are able to drive the expression of these cytokines, whereas neither degranulation nor the expression of IL-6 depends on NFAT activity. These results support the view that high NFAT activity is necessary for TNF-alpha and IL-13 promoter induction in MC, irrespective of whether NFATc2 or NFATc1 or a combination of both is present.

Animals↗

The telomerisation of 1,3-butadiene and carbon dioxide: process development and optimisation in a continuous miniplant.

The telomerisation of 1,3-butadiene and carbon dioxide is one of the first homogeneously catalyzed reactions using carbon dioxide as a C1-building block. In this article we describe the process development for a miniplant applying this telomerisation in a continuous scale. Through repeated optimisation of the plant setup combined with parallel laboratory batch experiments the overall space-time-yield of the plant was enhanced significantly.

Journal Article↗

p38 MAP kinase drives the expression of mast cell-derived IL-9 via activation of the transcription factor GATA-1.

Mast cells are able to produce a huge panel of mediators including the Th2-type cytokine IL-9, which is considered to be a key mediator for the pathogenesis of allergic asthma, but detailed information on the regulation of IL-9 transcription in mast cells has been scarce. Herein we provide evidence that the erythroid/myeloid transcription factor GATA-1, which is not expressed in Th2 cells, is a potent activator of IL-9 expression in murine bone marrow-derived mast cells (BMMC). Furthermore, in mast cells, but not in Th2 cells, production of IL-9 is sensitive to inhibition of p38 MAP kinase. As transactivation mediated by GATA-1 is also sensitive to inhibition of p38 MAP kinase, and GATA-1 is a target for p38 MAP kinase-mediated phosphorylation in vitro, we conclude that both signaling molecules represent a part of a mast cell-specific signaling network that regulates the expression of IL-9.

Animals↗

Local infusion therapy in the monkey brainstem: technical considerations.

This chapter assesses the safety of freehand placement of an infusion catheter (outer diameter, 0.3 mm) in brainstems of cynomolgus monkeys (Macaca fascicularis) for local infusion therapy. A posterior midline approach through the cerebellum and roof of the fourth ventricle was used to implant catheters into a pontine target area. Computer tomography (CT), magnetic resonance imaging (MRI), and histology were used to examine the position of the implants. The freehand placement of a catheter resulted in approximately 5-mm variations in anterior-posterior and dorsal-ventral locations of the targeted implantation site. No evidence of morbidity from the surgery, or from the infusion process was present. In conclusion, small-diameter catheters for chronic drug infusions can be implanted safely into the brainstem, an eloquent region that has been considered surgically inoperable. Infusion systems may offer a minimally invasive, generally applicable tool to provide chronic therapy for central nervous system (CNS) lesions.

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