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61.
Felix Rückert Gihan Dawelbait Christof Winter Arndt Hartmann Axel Denz Ole Ammerpohl Michael Schroeder Hans Konrad Schackert Bence Sipos Günter Kl?ppel Holger Kalthoff Hans-Detlev Saeger Christian Pilarsky Robert Grützmann 《PloS one》2010,5(8)
Background
Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer death. Changes in apoptosis signaling in pancreatic cancer result in chemotherapy resistance and aggressive growth and metastasizing. The aim of this study was to characterize the apoptosis pathway in pancreatic cancer computationally by evaluation of experimental data from high-throughput technologies and public data bases. Therefore, gene expression analysis of microdissected pancreatic tumor tissue was implemented in a model of the apoptosis pathway obtained by computational protein interaction prediction.Methodology/Principal Findings
Apoptosis pathway related genes were assembled from electronic databases. To assess expression of these genes we constructed a virtual subarray from a whole genome analysis from microdissected native tumor tissue. To obtain a model of the apoptosis pathway, interactions of members of the apoptosis pathway were analysed using public databases and computational prediction of protein interactions. Gene expression data were implemented in the apoptosis pathway model. 19 genes were found differentially expressed and 12 genes had an already known pathophysiological role in PDAC, such as Survivin/BIRC5, BNIP3 and TNF-R1. Furthermore we validated differential expression of IL1R2 and Livin/BIRC7 by RT-PCR and immunohistochemistry. Implementation of the gene expression data in the apoptosis pathway map suggested two higher level defects of the pathway at the level of cell death receptors and within the intrinsic signaling cascade consistent with references on apoptosis in PDAC. Protein interaction prediction further showed possible new interactions between the single pathway members, which demonstrate the complexity of the apoptosis pathway.Conclusions/Significance
Our data shows that by computational evaluation of public accessible data an acceptable virtual image of the apoptosis pathway might be given. By this approach we could identify two higher level defects of the apoptosis pathway in PDAC. We could further for the first time identify IL1R2 as possible candidate gene in PDAC. 相似文献62.
Fox BM Natero R Richard K Connors R Roveto PM Beckmann H Haller K Golde J Xiao SH Kayser F 《Bioorganic & medicinal chemistry letters》2011,21(8):2460-2467
We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibition. Increasing the acidity of the amide proton by converting the benzamide in lead 1 to an anilide provided single digit nanomolar MCHR1 antagonists while replacing the dimethoxyphenyl ring of 1 with alkyl groups possessing increased polarity dramatically reduced the hERG inhibition. 相似文献
63.
Ummanni R Mundt F Pospisil H Venz S Scharf C Barett C Fälth M Köllermann J Walther R Schlomm T Sauter G Bokemeyer C Sültmann H Schuppert A Brümmendorf TH Balabanov S 《PloS one》2011,6(2):e16833
Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies. 相似文献
64.
Dynamics and functional relevance of ammonia-oxidizing archaea in two agricultural soils 总被引:4,自引:0,他引:4
Kristina Schauss reas Focks Sven Leininger Anja Kotzerke Holger Heuer Sören Thiele-Bruhn Shilpi Sharma Berndt-Michael Wilke Michael Matthies Kornelia Smalla Jean Charles Munch Wulf Amelung Martin Kaupenjohann Michael Schloter Christa Schleper 《Environmental microbiology》2009,11(2):446-456
Crucial steps in geochemical cycles are in many cases performed by more than one group of microorganisms, but the significance of this functional redundancy with respect to ecosystem functioning is poorly understood. Ammonia-oxidizing archaea (AOA) and their bacterial counterparts (AOB) are a perfect system to address this question: although performing the same transformation step, they belong to well-separated phylogenetic groups. Using pig manure amended with different concentrations of sulfadiazine (SDZ), an antibiotic that is frequently used in veterinary medicine, it was possible to affect AOB and AOA to different degrees. Addition of manure stimulated growth of AOB in both soils and, interestingly, also growth of AOA was considerably stimulated in one of the soils. The antibiotic treatments decreased the manure effect notably on AOB, whereas AOA were affected to a lower extent. Model calculations concerning the respective proportions of AOA and AOB in ammonia oxidation indicate a substantial contribution of AOA in one of the soils that further increased under the influence of SDZ, hence indicating functional redundancy between AOA and AOB. 相似文献
65.
66.
Philippe Fuchs Nils Rugen Chris Carrie Marlene Elssser Iris Finkemeier Jonas Giese Tatjana M. Hildebrandt Kristina Kühn Veronica G. Maurino Cristina Ruberti Mareike Schallenberg‐Rüdinger Janina Steinbeck Hans‐Peter Braun Holger Eubel Etienne H. Meyer Stefanie J. Müller‐Schüssele Markus Schwarzlnder 《The Plant journal : for cell and molecular biology》2020,101(2):420-441
67.
Studying global change through investigation of the plastic responses of xylem anatomy in tree rings 总被引:1,自引:0,他引:1
Patrick Fonti Georg von Arx Ignacio García-González Britta Eilmann Ute Sass-Klaassen Holger Gärtner Dieter Eckstein 《The New phytologist》2010,185(1):42-53
Variability in xylem anatomy is of interest to plant scientists because of the role water transport plays in plant performance and survival. Insights into plant adjustments to changing environmental conditions have mainly been obtained through structural and functional comparative studies between taxa or within taxa on contrasting sites or along environmental gradients. Yet, a gap exists regarding the study of hydraulic adjustments in response to environmental changes over the lifetimes of plants. In trees, dated tree-ring series are often exploited to reconstruct dynamics in ecological conditions, and recent work in which wood-anatomical variables have been used in dendrochronology has produced promising results. Environmental signals identified in water-conducting cells carry novel information reflecting changes in regional conditions and are mostly related to short, sub-annual intervals. Although the idea of investigating environmental signals through wood anatomical time series goes back to the 1960s, it is only recently that low-cost computerized image-analysis systems have enabled increased scientific output in this field. We believe that the study of tree-ring anatomy is emerging as a promising approach in tree biology and climate change research, particularly if complemented by physiological and ecological studies. This contribution presents the rationale, the potential, and the methodological challenges of this innovative approach. 相似文献
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