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21.
Aniket Nikam Jay V. Patankar Carolin Lackner Elisabeth Sch?ck Dagmar Kratky Kurt Zatloukal Peter M. Abuja 《PloS one》2013,8(6)
The formation of protein inclusions is frequently associated with chronic metabolic diseases. In mice, short-term intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) leads to hepatocellular damage indicated by elevated serum liver enzyme activities, whereas only minor morphological changes are observed. Conversely, chronic administration of DDC for several weeks results in severe morphological damage, characterized by hepatocellular ballooning, disruption of the intermediate filament cytoskeleton, and formation of Mallory-Denk bodies consisting predominantly of misfolded keratins, Sqstm1/p62, and heat shock proteins. To evaluate the mechanistic underpinnings for this dichotomy we dissected the time-course of DDC intoxication for up to 10 weeks. We determined body weight change, serum liver enzyme activities, morphologic alterations, induction of antioxidant response (heme oxygenase-1, HO-1), oxidative damage and ATP content in livers as well as respiration, oxidative damage and the presence and activity of HO-1 in endoplasmic reticulum and mitochondria (mtHO-1). Elevated serum liver enzyme activity and oxidative liver damage were already present at early intoxication stages without further subsequent increase. After 2 weeks of intoxication, mice had transiently lost 9% of their body weight, liver ATP-content was reduced to 58% of controls, succinate-driven respiration was uncoupled from ATP-production and antioxidant response was associated with the appearance of catalytically active mtHO-1. Oxidative damage was associated with both acute and chronic DDC toxicity whereas the onset of chronic intoxication was specifically associated with mitochondrial dysfunction which was maximal after 2 weeks of intoxication. At this transition stage, adaptive responses involving mtHO-1 were induced, indirectly leading to improved respiration and preventing further drop of ATP levels. Our observations clearly demonstrate principally different mechanisms for acute and chronic toxic damage. 相似文献
22.
Chanjuan Guo Judy Simon Rainer Gasche Pascale Sarah Naumann Carolin Bimüller Rodica Pena Andrea Polle Ingrid Kögel-Knabner Bernd Zeller Heinz Rennenberg Michael Dannenmann 《Plant and Soil》2013,369(1-2):657-668
Aims
Our aims were to characterize the fate of leaf-litter-derived nitrogen in the plant-soil-microbe system of a temperate beech forest of Southern Germany and to identify its importance for N nutrition of beech seedlings.Methods
15N-labelled leaf litter was traced in situ into abiotic and biotic N pools in mineral soil as well as into beech seedlings and mycorrhizal root tips over three growing seasons.Results
There was a rapid transfer of 15N into the mineral soil already 21 days after tracer application with soil microbial biomass initially representing the dominant litter-N sink. However, 15N recovery in non-extractable soil N pools strongly increased over time and subsequently became the dominant 15N sink. Recovery in plant biomass accounted for only 0.025 % of 15N excess after 876 days. After three growing seasons, 15N excess recovery was characterized by the following sequence: non-extractable soil N?>>?extractable soil N including microbial biomass?>>?plant biomass?>?ectomycorrhizal root tips.Conclusions
After quick vertical dislocation and cycling through microbial N pools, there was a rapid stabilization of leaf-litter-derived N in non-extractable N pools of the mineral soil. Very low 15N recovery in beech seedlings suggests a high importance of other N sources such as root litter for N nutrition of beech understorey. 相似文献23.
Carolin Rapp 《Ethnic and racial studies》2013,36(10):1779-1797
Immigration and the ways in which host societies receive newcomers pose challenges for modern civil societies. This article contributes to the ongoing discussion about how ethnic diversity influences tolerance towards immigrants. Compared to previous studies, we analyse tolerance as a sequential concept in order to uncover the effects of contextual diversity on attitudes towards immigrants and the granting of certain rights to this group. Moreover, we distinguish different shares of ethnic groups based on their ethnic and cultural origins both on the independent and dependent variable. The analysis relies on a subnational survey of sixty municipalities in Switzerland, revealing that only certain ethnic groups are seen as an economic and cultural threat. 相似文献
24.
Sandra Münder Susanne Tischer Maresa Grundhuber Nathalie Büchels Nadine Bruckmeier Stefanie Eckert Carolin A. Seefeldt Andrea Prexl Tina Käsbauer Angelika Böttger 《Developmental biology》2013
Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated. The molecular components of this organising region involve Wnt-signalling and β-catenin. However, it is not known how correct patterning of hypostome and tentacles are achieved in the hydra head and whether other signals in addition to HyWnt3 are needed for re-establishing the new organiser after head removal. Here we show that Notch-signalling is required for re-establishing the organiser during regeneration and that this is due to its role in restricting tentacle activation. Blocking Notch-signalling leads to the formation of irregular head structures characterised by excess tentacle tissue and aberrant expression of genes that mark the tentacle boundaries. This indicates a role for Notch-signalling in defining the tentacle pattern in the hydra head. Moreover, lateral inhibition by HvNotch and its target HyHes are required for head regeneration and without this the formation of the β-catenin/Wnt dependent head organiser is impaired. Work on prebilaterian model organisms has shown that the Wnt-pathway is important for setting up signalling centres for axial patterning in early multicellular animals. Our data suggest that the integration of Wnt-signalling with Notch-Delta activity was also involved in the evolution of defined body plans in animals. 相似文献
25.
Background
Two-component signal transduction systems are one means of bacteria to respond to external stimuli. The LiaFSR two-component system of Bacillus subtilis consists of a regular two-component system LiaRS comprising the core Histidine Kinase (HK) LiaS and the Response Regulator (RR) LiaR and additionally the accessory protein LiaF, which acts as a negative regulator of LiaRS-dependent signal transduction. The complete LiaFSR system was shown to respond to various peptide antibiotics interfering with cell wall biosynthesis, including bacitracin.Methodology and Principal Findings
Here we study the response of the LiaFSR system to various concentrations of the peptide antibiotic bacitracin. Using quantitative fluorescence microscopy, we performed a whole population study analyzed on the single cell level. We investigated switching from the non-induced ‘OFF’ state into the bacitracin-induced ‘ON’ state by monitoring gene expression of a fluorescent reporter from the RR-regulated liaI promoter. We found that switching into the ‘ON’ state occurred within less than 20 min in a well-defined switching window, independent of the bacitracin concentration. The switching rate and the basal expression rate decreased at low bacitracin concentrations, establishing clear heterogeneity 60 min after bacitracin induction. Finally, we performed time-lapse microscopy of single cells confirming the quantitative response as obtained in the whole population analysis for high bacitracin concentrations.Conclusion
The LiaFSR system exhibits an immediate, heterogeneous and graded response to the inducer bacitracin in the exponential growth phase. 相似文献26.
Zeinab Mokhtari Franziska Mech Carolin Zitzmann Mike Hasenberg Matthias Gunzer Marc Thilo Figge 《PloS one》2013,8(12)
Cell migration is the driving force behind the dynamics of many diverse biological processes. Even though microscopy experiments are routinely performed today by which populations of cells are visualized in space and time, valuable information contained in image data is often disregarded because statistical analyses are performed at the level of cell populations rather than at the single-cell level. Image-based systems biology is a modern approach that aims at quantitatively analyzing and modeling biological processes by developing novel strategies and tools for the interpretation of image data. In this study, we take first steps towards a fully automated characterization and parameter-free classification of cell track data that can be generally applied to tracked objects as obtained from image data. The requirements to achieve this aim include: (i) combination of different measures for single cell tracks, such as the confinement ratio and the asphericity of the track volume, and (ii) computation of these measures in a staggered fashion to retrieve local information from all possible combinations of track segments. We demonstrate for a population of synthetic cell tracks as well as for in vitro neutrophil tracks obtained from microscopy experiment that the information contained in the track data is fully exploited in this way and does not require any prior knowledge, which keeps the analysis unbiased and general. The identification of cells that show the same type of migration behavior within the population of all cells is achieved via agglomerative hierarchical clustering of cell tracks in the parameter space of the staggered measures. The recognition of characteristic patterns is highly desired to advance our knowledge about the dynamics of biological processes. 相似文献
27.
Lithium Fluoride Based Electron Contacts for High Efficiency n‐Type Crystalline Silicon Solar Cells
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James Bullock Peiting Zheng Quentin Jeangros Mahmut Tosun Mark Hettick Carolin M. Sutter‐Fella Yimao Wan Thomas Allen Di Yan Daniel Macdonald Stefaan De Wolf Aïcha Hessler‐Wyser Andres Cuevas Ali Javey 《Liver Transplantation》2016,6(14)
Low‐resistance contact to lightly doped n‐type crystalline silicon (c‐Si) has long been recognized as technologically challenging due to the pervasive Fermi‐level pinning effect. This has hindered the development of certain devices such as n‐type c‐Si solar cells made with partial rear contacts (PRC) directly to the lowly doped c‐Si wafer. Here, a simple and robust process is demonstrated for achieving mΩ cm2 scale contact resistivities on lightly doped n‐type c‐Si via a lithium fluoride/aluminum contact. The realization of this low‐resistance contact enables the fabrication of a first‐of‐its‐kind high‐efficiency n‐type PRC solar cell. The electron contact of this cell is made to less than 1% of the rear surface area, reducing the impact of contact recombination and optical losses, permitting a power conversion efficiency of greater than 20% in the initial proof‐of‐concept stage. The implementation of the LiFx/Al contact mitigates the need for the costly high‐temperature phosphorus diffusion, typically implemented in such a cell design to nullify the issue of Fermi level pinning at the electron contact. The timing of this demonstration is significant, given the ongoing transition from p‐type to n‐type c‐Si solar cell architectures, together with the increased adoption of advanced PRC device structures within the c‐Si photovoltaic industry. 相似文献
28.
Anna-Lena Volckmar Chung Ting Han Carolin Pütter Stefan Haas Carla I. G. Vogel Nadja Knoll Christoph Struve Maria G?bel Katharina Haas Nikolas Herrfurth Ivonne Jarick Harald Grallert Annette Schürmann Hadi Al-Hasani Johannes Hebebrand Sascha Sauer Anke Hinney 《PloS one》2016,11(2)
Introduction
Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing.Methods
We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) ≥ 99th percentile and 176 lean adults (BMI ≤ 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults.Results and Conclusion
We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (pTDT = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted. 相似文献29.
30.
In vivo and in vitro requirements for the formation of cytochrome b(6) were examined to analyze the mechanisms of transmembrane b-type cytochrome formation. After heterologous expression of spinach cytochrome b(6), formation of the holo-cytochrome was observed within the E. coli inner membrane. The transmembrane orientation of cytochrome b(6) appeared not to be critical for heme binding and holo-cytochrome formation. Furthermore, in vitro reconstitution of cytochrome b(6) was possible under oxidizing as well as under reducing conditions. Taken together these observations strongly indicate that transmembrane b-type cytochromes can spontaneously assemble in vitro as well as in a membrane. 相似文献