17 research outputs found

    A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis

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    Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P-S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia

    Schrift- und vernunft-mäßige Abhandlung der zwölf Ursachen, warum Jesus Christus des Kreuzes-Todes hat sterben wollen

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    SCHRIFT- UND VERNUNFT-MÄSSIGE ABHANDLUNG DER ZWÖLF URSACHEN, WARUM JESUS CHRISTUS DES KREUZES-TODES HAT STERBEN WOLLEN Schrift- und vernunft-mäßige Abhandlung der zwölf Ursachen, warum Jesus Christus des Kreuzes-Todes hat sterben wollen ([1]) Titelseite ([1]) Widmung ([3]) Vorrede an den geneigten Leser ([7]) Vorbereitung ([9]) Cap. I. Die erste Ursache (13) Cap. II. Die andere Ursache (17) Cap. III. Die dritte Ursache (19) Cap. IV. Die vierte, fünfte, sechste und siebende Ursache (20) Cap. V. Die achte Ursache (23) Cap. VI, Die neunte Ursache (25) Cap. VII. Die zehente Ursache (26) Cap. VIII. Die eilfte Ursache (27) Cap. IX. Die zwölfte Ursache (29

    Transcription of sialic acid catabolism genes in Corynebacterium glutamicum is subject to catabolite repression and control by the transcriptional repressor NanR

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    Uhde A, Brühl N, Goldbeck O, et al. Transcription of sialic acid catabolism genes in Corynebacterium glutamicum is subject to catabolite repression and control by the transcriptional repressor NanR. J Bacteriol. 2016;198(16):2204-2218

    Chassis organism from Corynebacterium glutamicum – Genome reduction as a tool toward improved strains for synthetic biology and industrial biotechnology

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    Baumgart M, Unthan S, Radek A, et al. Chassis organism from Corynebacterium glutamicum – Genome reduction as a tool toward improved strains for synthetic biology and industrial biotechnology. In: New Biotechnology. New Biotechnology. Vol 33. Elsevier BV; 2016

    Corynebacterium glutamicum chassis C1*: Building and testing a novel platform host for synthetic biology and industrial biotechnology

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    Baumgart M, Unthan S, Kloss R, et al. Corynebacterium glutamicum chassis C1*: Building and testing a novel platform host for synthetic biology and industrial biotechnology. ACS Synthetic Biology. 2018;7(1):132–144.Targeted top-down strategies for genome reduction are considered to have a high potential for providing robust basic strains for synthetic biology and industrial biotechnology. Recently, we created a library of 26 genome-reduced strains of Corynebacterium glutamicum carrying broad deletions in single gene clusters and showing wild-type-like biological fitness. Here, we proceeded with combinatorial deletions of these irrelevant gene clusters in two parallel orders and the resulting library of 28 strains was characterized under various environmental conditions. The final chassis strain C1* carries a genome reduction of 13.4% (412 deleted genes) and shows wild-type-like growth behavior in defined medium with D-glucose as carbon and energy source. Moreover, C1* proves to be robust against several stresses (including oxygen limitation) and shows long-term growth stability under defined and complex medium conditions. In addition to providing a novel prokaryotic chassis strain, our results comprise a large strain library and a revised genome annotation list, which will be valuable sources for future systemic studies of C. glutamicum
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