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51.
Wojciech T. Markiewicz Gabriele Gröger Rudi Rösch Anna Zebrowska Hartmut Seliger 《Nucleosides, nucleotides & nucleic acids》2013,32(10):1703-1711
Abstract A new approach to the chemical synthesis of oligonucleotides bearing reporter functional groups based on the modification of cytosine residues during the final deprotection step is reported. The application of the fluorescently labelled primer for the automated DNA sequencing is shown. 相似文献
52.
Kurt Reifenberg Fei Cheng Laura Twardowski Ines Küpper Elena Wiese Franziska Bollmann Hartmut Kleinert Manfred Blessing Karl J. Lackner Michael Torzewski 《PloS one》2013,8(12)
Clinical data have indicated a negative correlation between plasma TGFß1 concentrations and the extent of atherosclerosis and have thus led to the hypothesis that the pleiotropic cytokine may have anti-atherogenic properties. T-cells are currently discussed to significantly participate in atherogenesis, but the precise role of adaptive immunity in atherogenesis remains to be elucidated. TGFß1 is known to strongly modulate the function of T-cells, however, inhibition of TGFß1 signalling in T-cells of atherosclerosis-prone knock-out mice failed to unequivocally clarify the role of the cytokine for the development of atherosclerosis. In the present study, we thus tried to specify the role of TGFß1 in atherogenesis by using the murine CD2-TGFß1 transgenic strain which represents a well characterized model of T-cell specific TGFß1 overexpression. The CD2-TGFß1 transgenic mice were crossed to ApoE knock-out mice and quantity and quality of atherosclerosis regarding number of macrophages, smooth muscle cells, CD3 positive T-cells and collagen was analyzed in CD2-TGFß1 ApoE double mutants as well as non-transgenic ApoE controls on both normal and atherogenic diet of a duration of 8, 16 or 24 weeks, respectively. In all experimental groups investigated, we failed to detect any influence of TGFß1 overexpression on disease. Total number of CD3-positive T-lymphocytes was not significantly different in atherosclerotic lesions of CD2-TGFß1 ApoE−/− females and isogenic ApoE−/− controls, even after 24 weeks on the atherogenic diet. The synopsis of these data and our previous study on TGFß1 overexpressing macrophages suggests that potential effects of TGFß1 on atherosclerosis are most probably mediated by macrophages rather than T-cells. 相似文献
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Dr. Johannes Richter Dr. Hartmut Kegler 《Archives Of Phytopathology And Plant Protection》2013,46(2):169-175
Morris, C. J. O. R.; Morris, P.: Separation methods in biochemistry. London, Sir Isaac Pitman & Sons Ltd., 1964, 887 S., 155 Abb., Leinen, £ 5, 15 s. Reviewed by H. Wolffgang. Neuman, M.: Vade-mecum des antibiotiques et agents chimiothérapiques anti-infectieun. Paris, Librairie Maloine G. Doin et Cie Editeurs, 1962, 410 S., 8 Abb.; 15 Tab., Karton. 40,00 NF. Reviewed by Thren. Umbreit, W. W.: Modern microbiology. San Francisco und London, W. H. Freeman and Company, 1962, 507 S., 307 Abb., Leinen, 48 s. Reviewed by H. J. Müller. Gold, V.: pH-Measurements. Their theory and practice. London, Methuen & Co. Ltd., 1963, 125 S., 11 Abb., Leinen, 10 s 6 d. Reviewed by H. Wolffgang. Horsfall, J. G. (Ed.): Annual review of phytopathology. Vol. 1, Palo Alto, Annual Reviews, Inc., 1963, 469 S., 6 Abb., Leinen, 9,00 $. Reviewed by M. Schmiedeknecht. Rubin, B. A.; Artsikhovskaya, Ye. V.: Biochemistry and physiology of plant immunity. Oxford, Pergamon Press, 1963, IX und 358 S., 68 Abb., Leinen, £ 5. Reviewed by H. Wolffgang. Nord, F. F. (Ed.): Advances in Enzymology. Vol. 24, New York und London, Interscience Publishers a division of John Wiley & Sons, 1962, 572 S., 23 Abb., Leinen, 120 s. Reviewed by H. Wolffgang. Nord, F. F. (Ed.): Advances in Enzymology. Vol. 25, New York und London, Interscience Publishers a division of John Wiley & Sons, 1963, 565 S., 56 Abb., Leinen, 115 s. Reviewed by H. Wolffgang. Forbes, J.: A laboratory manual for histology. 2. Aufl., New York, Fordham University Press, 1961, 132 S., 3 Abb., brosch., 3,00 $. Reviewed by J. H. Scharf. Guaoliumi, P.: Las Plagas de la Caña de Azucar en Venezuela. Bd. 1 und 2, Maracay/Yenezuela, Ministerio de Agricultura y Cria Centro de Investigaciones Agronoinicas, 1962, 850 S., 212 Abb., 14 ganzs. Farbtafeln, brosch., 8,00 $. Reviewed by G. Fröhlich. Clifton, C. E. (Ed.): Annual review of microbiology. Vol. 17, Palo Alto, Annual Reviews, Inc., 1963, 628 S., 19 Abb., Leinen, 9,00 $. Reviewed by K. Naumann. Ramschandran, G. N. (Ed.): Aspects of protein structure. Proceedings of a symposium held in Madras 14–18 January 1963 and organized by the University of Madras. London und New York, Academic Press, 1963, 380 S., 130 Abb., Leinen, 84 s. Reviewed by P. Hermann. 相似文献
56.
Ulrich Grädler Daniel Schwarz Verena Dresing Djordje Musil Jörg Bomke Matthias Frech Hartmut Greiner Stefan Jäkel Thomas Rysiok Dirk Müller-Pompalla Ansgar Wegener 《Journal of molecular biology》2013,425(2):309-333
Syk is an essential non-receptor tyrosine kinase in intracellular immunological signaling, and the control of Syk kinase function is considered as a valuable target for pharmacological intervention in autoimmune or inflammation diseases. Upon immune receptor stimulation, the kinase activity of Syk is regulated by binding of phosphorylated immune receptor tyrosine-based activating motifs (pITAMs) to the N-terminal tandem Src homology 2 (tSH2) domain and by autophosphorylation with consequences for the molecular structure of the Syk protein. Here, we present the first crystal structures of full-length Syk (fl-Syk) as wild type and as Y348F,Y352F mutant forms in complex with AMP-PNP revealing an autoinhibited conformation. The comparison with the crystal structure of the truncated Syk kinase domain in complex with AMP-PNP taken together with ligand binding studies by surface plasmon resonance (SPR) suggests conformational differences in the ATP sites of autoinhibited and activated Syk forms. This hypothesis was corroborated by studying the thermodynamic and kinetic interaction of three published Syk inhibitors with isothermal titration calorimetry and SPR, respectively. We further demonstrate the modulation of inhibitor binding affinities in the presence of pITAM and discuss the observed differences of thermodynamic and kinetic signatures. The functional relevance of pITAM binding to fl-Syk was confirmed by a strong stimulation of in vitro autophosphorylation. A structural feedback mechanism on the kinase domain upon pITAM binding to the tSH2 domain is discussed in analogy of the related family kinase ZAP-70 (Zeta-chain-associated protein kinase 70). Surprisingly, we observed distinct conformations of the tSH2 domain and the activation switch including Tyr348 and Tyr352 in the interdomain linker of Syk in comparison to ZAP-70. 相似文献
57.
Bacterial growth under oxygen‐limited (microaerobic) conditions is often accompanied by phenomena of great interest for fundamental research and industrial application. The microaerobic lifestyle of anoxygenic photosynthetic bacteria like Rhodospirillum rubrum harbors such a phenomenon, as it allows the formation of photosynthetic membranes and related interesting products without light. However, due to the technical difficulties in process control of microaerobic cultivations and the limited sensitivity of available oxygen sensors, the analysis of microaerobic growth and physiology is still underrepresented in current research. The main focus of the present study was to establish an experimental set‐up for the systematic study of physiological processes, associated with the growth of R. rubrum under microaerobic conditions in the dark. For this purpose, we introduce a robust and reliable microaerobic process control strategy, which applies the culture redox potential (CRP) for assessing different degrees of oxygen limitation in bioreactor cultivations. To describe the microaerobic growth behavior of R. rubrum cultures for each of these defined CRP reduction steps, basic growth parameters were experimentally determined. Flux variability analysis provided an insight into the metabolic activity of the TCA cycle and implied its connection to the respiratory capacity of the cells. In this context, our results suggest that microaerobic growth of R. rubrum can be described as an oxygen‐activated cooperative mechanism. The present study thus contributes to the investigation of metabolic and regulatory events responsible for the redox‐sensitive formation of photosynthetic membranes in facultative photosynthetic bacteria. Furthermore, the introduced microaerobic cultivation setup should be generally applicable for any microbial system of interest which can be cultivated in common stirred‐tank bioreactors. Biotechnol. Bioeng. 2013; 110: 573–585. © 2012 Wiley Periodicals, Inc. 相似文献
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Martin Neumann Ebru Coskun Lars Fransecky Liliana H. Mochmann Isabelle Bartram Nasrin Farhadi Sartangi Sandra Heesch Nicola G?kbuget Stefan Schwartz Christian Brandts Cornelia Schlee Rainer Haas Ulrich Dührsen Martin Griesshammer Hartmut D?hner Gerhard Ehninger Thomas Burmeister Olga Blau Eckhard Thiel Dieter Hoelzer Wolf-Karsten Hofmann Claudia D. Baldus 《PloS one》2013,8(1)
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup. 相似文献
60.
Analysis of monosomy‐3 in immunomagnetically isolated circulating melanoma cells in uveal melanoma patients 下载免费PDF全文
Aysegül Tura Hartmut Merz Mihaela Reinsberg Matthias Lüke Martine J. Jager Salvatore Grisanti Julia Lüke 《Pigment cell & melanoma research》2016,29(5):583-589
Monosomy‐3 in primary uveal melanoma (UM) is associated with a high risk of metastasis and mortality. Although circulating melanoma cells (CMC) can be found in most UM patients, only approximately 50% of the patients develop metastases. We utilized a novel immuno‐FISH assay to detect chromosome‐3 in intact CMC isolated by dual immunomagnetic enrichment. Circulating melanoma cells were detected in 91% of the patients (n = 44) with primary non‐metastatic UM, of which 58% were positive for monosomy‐3. The monosomy‐3 status of CMC corresponded to the monosomy‐3 status of the primary tumor in 10 of the 11 patients where this could be tested. Monosomy‐3 in the CMC was associated with an advanced tumor stage (P = 0.046) and was detected in all four patients who developed metastasis within the follow‐up period of 4 yr. This non‐invasive technique may enable the identification of UM patients at risk for metastasis particularly when a primary tumor specimen is unavailable. 相似文献