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61.
Sergej Tschernyschkow Sabine Herda Gerd Gruenert Volker Döring Dennis Görlich Antje Hofmeister Christian Hoischen Peter Dittrich Stephan Diekmann Bashar Ibrahim 《Progress in biophysics and molecular biology》2013
Background
Combinatorial complexity is a central problem when modeling biochemical reaction networks, since the association of a few components can give rise to a large variation of protein complexes. Available classical modeling approaches are often insufficient for the analysis of very large and complex networks in detail. Recently, we developed a new rule-based modeling approach that facilitates the analysis of spatial and combinatorially complex problems. Here, we explore for the first time how this approach can be applied to a specific biological system, the human kinetochore, which is a multi-protein complex involving over 100 proteins.Results
Applying our freely available SRSim software to a large data set on kinetochore proteins in human cells, we construct a spatial rule-based simulation model of the human inner kinetochore. The model generates an estimation of the probability distribution of the inner kinetochore 3D architecture and we show how to analyze this distribution using information theory. In our model, the formation of a bridge between CenpA and an H3 containing nucleosome only occurs efficiently for higher protein concentration realized during S-phase but may be not in G1. Above a certain nucleosome distance the protein bridge barely formed pointing towards the importance of chromatin structure for kinetochore complex formation. We define a metric for the distance between structures that allow us to identify structural clusters. Using this modeling technique, we explore different hypothetical chromatin layouts.Conclusions
Applying a rule-based network analysis to the spatial kinetochore complex geometry allowed us to integrate experimental data on kinetochore proteins, suggesting a 3D model of the human inner kinetochore architecture that is governed by a combinatorial algebraic reaction network. This reaction network can serve as bridge between multiple scales of modeling. Our approach can be applied to other systems beyond kinetochores. 相似文献62.
63.
Gerd H?rl Harald Froehlich Ulrika Ferstl Gerhard Ledinski Josepha Binder Gerhard Cvirn Tatjana Stojakovic Michael Trauner Christoph Koidl Erwin Tafeit Karin Amrein Hubert Scharnagl Günther Jürgens Seth Hallstr?m 《PloS one》2016,11(2)
We investigated a polyethylene glycol non-precipitable low-density lipoprotein (LDL) subfraction targeted by IgG and the influence of statin therapy on plasma levels of these small LDL-IgG-immune complexes (LDL-IgG-IC). LDL-subfractions were isolated from 6 atherosclerotic subjects and 3 healthy individuals utilizing iodixanol density gradient ultracentrifugation. Cholesterol, apoB and malondialdehyde (MDA) levels were determined in each fraction by enzymatic testing, dissociation-enhanced lanthanide fluorescence immunoassay and high-performance liquid chromatography, respectively. The levels of LDL-IgG-IC were quantified densitometrically following lipid electrophoresis, particle size distribution was assessed with dynamic light scattering and size exclusion chromatography. The influence of simvastatin (40 mg/day for three months) on small LDL-IgG-IC levels and their distribution among LDL-subfractions (salt gradient separation) were investigated in 11 patients with confirmed coronary artery disease (CAD). We demonstrate that the investigated LDL-IgG-IC are small particles present in atherosclerotic patients and healthy subjects. In vitro assembly of LDL-IgG-IC resulted in particle density shifts indicating a composition of one single molecule of IgG per LDL particle. Normalization on cholesterol levels revealed MDA values twice as high for LDL-subfractions rich in small LDL-IgG-IC if compared to dominant LDL-subfractions. Reactivity of affinity purified small LDL-IgG-IC to monoclonal antibody OB/04 indicates a high degree of modified apoB and oxidative modification. Simvastatin therapy studied in the CAD patients significantly lowered LDL levels and to an even higher extent, small LDL-IgG-IC levels without affecting their distribution. In conclusion simvastatin lowers levels of small LDL-IgG-IC more effectively than LDL-cholesterol and LDL-apoB levels in atherosclerotic patients. This antiatherogenic effect may additionally contribute to the known beneficial effects of this drug in the treatment of atherosclerosis. 相似文献
64.
Andrea Seim Gulzar Omurova Erlan Azisov Kanaat Musuraliev Kumar Aliev Timur Tulyaganov Lyutsian Nikolyai Evgeniy Botman Gerd Helle Isabel Dorado Li?an Sandra Jivcov Hans W. Linderholm 《PloS one》2016,11(4)
Assessments of climate change impacts on forests and their vitality are essential for semi-arid environments such as Central Asia, where the mountain regions belong to the globally important biodiversity hotspots. Alterations in species distribution or drought-induced tree mortality might not only result in a loss of biodiversity but also in a loss of other ecosystem services. Here, we evaluate spatial trends and patterns of the growth-climate relationship in a tree-ring network comprising 33 juniper sites from the northern Pamir-Alay and Tien Shan mountain ranges in eastern Uzbekistan and across Kyrgyzstan for the common period 1935–2011. Junipers growing at lower elevations are sensitive to summer drought, which has increased in intensity during the studied period. At higher elevations, juniper growth, previously favored by warm summer temperatures, has in the recent few decades become negatively affected by increasing summer aridity. Moreover, response shifts are observed during all seasons. Rising temperatures and alterations in precipitation patterns during the past eight decades can account for the observed increase in drought stress of junipers at all altitudes. The implications of our findings are vital for the application of adequate long-term measures of ecosystem conservation, but also for paleo-climatic approaches and coupled climate-vegetation model simulations for Central Asia. 相似文献
65.
An Arxula adeninivorans vector element has been identified that provides multicopy integration in an atrp1 host strain. The element consists of the ATRP1 selection marker fused to a newly generated truncated ALEU2 promoter of 53 bp. In the described example eight copies of an amyA expression vector encoding heterologous alpha-amylase from Bacillus amyloliquefaciens are integrated in the genome of the recombinant strain instead of a single copy observed when using the ATRP1 element with the complete promoter. The high copy number results in strains of superior productivity for a secreted recombinant alpha-amylase. The vector design enables the integration of a small vector fragment that consists of yeast DNA only providing high transformation frequencies and a high mitotic stability. 相似文献
66.
Zsuzsanna Wolf Evelyn Orsó Tobias Werner Hans H Klünemann Gerd Schmitz 《Cytometry. Part A》2007,71(7):486-494
BACKGROUND: Lipid membrane microdomains are involved in the regulation of biological functions of monocyte membrane proteins. These microdomains show a relative resistance to non-ionic detergents providing an easy analytical tool to study them. METHODS: Here, we applied a rapid detergent-based flow cytometric assay to investigate microdomain association of proteins on monocytes from whole blood samples. The association of known surface antigens with detergent resistant fraction of membranes (DRMs) was compared using monocytes from healthy blood donors, patients with genetic disorders affecting cellular cholesterol traffic and patients with systemic inflammatory response. RESULTS: All investigated surface antigens of Niemann-Pick type C (NPC)-mutant monocytes with impaired cholesterol influx and defective late endosome cholesterol trafficking, presented a strongly increased DRM-association. Though, membrane antigens of ATP binding cassette transporter A1 (ABCA1)-mutant monocytes with impaired cholesterol efflux did not show alterations in DRM-association. Differential CD14-dependent receptor clustering within microdomains was also investigated in response to in vivo lipopolysaccharide (LPS) and/or atherogenic lipoprotein activation. Increased DRM-association of the GPI-anchored proteins CD14, CD55, the Fcgamma receptor CD64, the scavenger receptors CD36, CD91 and CD163, the integrin CD11a, and complement receptor 3 complex CD11b/CD18 were observed from patients with systemic inflammatory response syndrome (SIRS)/sepsis or coronary artery disease (CAD)/myocardial infarction. Interestingly, the tetraspanin CD81 presented increased DRM-association in SIRS/sepsis patients, but not in CAD patients. Moreover, the pentaspanin CD47 and the Fcgamma RIII CD16 showed an increased DRM partition in CAD patients but disassembled from DRMs in SIRS/sepsis patients. CONCLUSIONS: Our results demonstrate that flow cytometric analysis of short time in situ detergent extraction provides a powerful tool for rapid screening of blood monocyte DRMs to preselect patients with potential raft/microdomain abnormalities for more detailed analysis. 相似文献
67.
68.
Amino Acids - It is known for almost 25 years that the corpora cardiaca (neurosecretory glands) of cicadas synthesize two isobaric peptides with hypertrehalosaemic activity denominated... 相似文献
69.
Alice Y Cheung Daniel J Cosgrove Ikuko Hara-Nishimura Gerd Jürgens Clive Lloyd David G Robinson L Andrew Staehelin Dolf Weijers 《The Plant cell》2022,34(1):53
The field of plant cell biology has a rich history of discovery, going back to Robert Hooke’s discovery of cells themselves. The development of microscopes and preparation techniques has allowed for the visualization of subcellular structures, and the use of protein biochemistry, genetics, and molecular biology has enabled the identification of proteins and mechanisms that regulate key cellular processes. In this review, seven senior plant cell biologists reflect on the development of this research field in the past decades, including the foundational contributions that their teams have made to our rich, current insights into cell biology. Topics covered include signaling and cell morphogenesis, membrane trafficking, cytokinesis, cytoskeletal regulation, and cell wall biology. In addition, these scientists illustrate the pathways to discovery in this exciting research field.Seven senior plant cell biologists reflect on foundational contributions to a variety of topics, including pollen tube signaling, cell morphogenesis, membrane trafficking, cytokinesis, cytoskeletal regulation, and cell wall biology. 相似文献
70.
Tobias Ruck Stefanie Bock Steffen Pfeuffer Christina B.Schroeter Derya Cengiz Paul Marciniak Maren Lindner Alexander Herrmann Marie Liebmann Stjepana Kovac Lukas Gola Leoni Rolfes Marc Pawlitzki Nils Opel Tim Hahn Udo Dannlowski Thomas Pap Felix Luessi Julian A.Schreiber Bernhard Wünsch Tanja Kuhlmann Guiscard Seebohm Bjrn Tackenberg Patricia Seja Frank Dring Erhard Wischmeyer Achmet Imam Chasan Johannes Roth Luisa Klotz Gerd Meyer zu Hrste Heinz Wiendl Tobias Marschall Stefan Floess Jochen Huehn Thomas Budde Tobias Bopp Stefan Bittner Sven G.Meuth 《Cell research》2022,32(1):72-88
It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that driv... 相似文献