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961.
Birgit Kreiseder Yvonne M Holper-Schichl Barbara Muellauer Nico Jacobi Alexander Pretsch Johannes A. Schmid Rainer de Martin Harald Hundsberger Andreas Eger Christoph Wiesner 《PloS one》2015,10(3)
Melanoma is the most dangerous type of skin cancer accounting for 48,000 deaths worldwide each year and an average survival rate of about 6-10 months with conventional treatment. Tumor metastasis and chemoresistance of melanoma cells are reported as the main reasons for the insufficiency of currently available treatments for late stage melanoma. The cytoskeletal linker protein α-catulin (CTNNAL1) has been shown to be important in inflammation, apoptosis and cytoskeletal reorganization. Recently, we found an elevated expression of α-catulin in melanoma cells. Ectopic expression of α-catulin promoted melanoma progression and occurred concomitantly with the downregulation of E-cadherin and the upregulation of mesenchymal genes such as N-cadherin, Snail/Slug and the matrix metalloproteinases 2 and 9. In the current study we showed that α-catulin knockdown reduced NF-κB and AP-1 activity in malignant melanoma cells. Further, downregulation of α-catulin diminished ERK phosphorylation in malignant melanoma cells and sensitized them to treatment with chemotherapeutic drugs. In particular, cisplatin treatment led to decreased ERK-, JNK- and c-Jun phosphorylation in α-catulin knockdown melanoma cells, which was accompanied by enhanced apoptosis compared to control cells. Altogether, these results suggest that targeted inhibition of α-catulin may be used as a viable therapeutic strategy to chemosensitize melanoma cells to cisplatin by down-regulation of NF-κB and MAPK pathways. 相似文献
962.
963.
Independent force field validation is an essential practice to keep track of developments and for performing meaningful Molecular Dynamics simulations. In this work, atomistic force fields for intrinsically disordered proteins (IDP) are tested by simulating the archetypical IDP α-synuclein in solution for 2.5 μs. Four combinations of protein and water force fields were tested: ff19SB/OPC , ff19SB/TIP4P-D , ff03CMAP/TIP4P-D , and a99SB-disp/TIP4P-disp , with four independent repeat simulations for each combination. We compare our simulations to the results of a 73 μs simulation using the a99SB-disp/TIP4P-disp combination, provided by D. E. Shaw Research. From the trajectories, we predict a range of experimental observations of α-synuclein and compare them to literature data. This includes protein radius of gyration and hydration, intramolecular distances, NMR chemical shifts, and 3J-couplings. Both ff19SB/TIP4P-D and a99SB-disp/TIP4P-disp produce extended conformational ensembles of α-synuclein that agree well with experimental radius of gyration and intramolecular distances while a99SB-disp/TIP4P-disp reproduces a balanced α-synuclein secondary structure content. It was found that ff19SB/OPC and ff03CMAP/TIP4P-D produce overly compact conformational ensembles and show discrepancies in the secondary structure content compared to the experimental data. 相似文献
964.
Planktic foraminiferal assemblages are well known to vary in accordance with seasonal fluctuations in ocean properties, periodic reproduction cycles, and variations between water masses. Here we report that storms also can significantly influence foraminiferal assemblages. During the RV Meteor cruise 21 to the Northeast Atlantic Ocean (
area), from March to May 1992, planktic foraminifera were sampled using a multiple opening-closing net. While sampling, two storms with wind forces up to 12 Beaufort caused intensified surface layer mixing with shifts in the depth of the upper ocean mixed-layer from 20–40 m to 170–240 m. Subsequently, planktic foraminiferal growth rates increased, resulting in an elevated quantity of small (100–150 μm) tests (Phase 1). When the wind strength increased a second time, the mixed-layer deepened to a depth below the former position of the pycnocline, and again the abundance of small tests increased (Phase 2). During Phase 2, the weight of calcite in specimens of the productive zone reached its maximum. In the export zone, an associated increase in empty tests occurred with a lag time depending on the test sinking velocity. In the upper export zone, down to 700 m water depth, CaCO3 flux increased from 9.3 to 49.8 mg CaCO3 m−2 d−1 after the first storm and from 8.9 to 19.9 mg CaCO3 m−2d−1 after the second storm. In the 700 to 2500 m depth interval, the flux increased from 5.1 mg CaCO3 m−2 d−1 to about 9.2 mg CaCO, m−2 d−1. Thus, the standing stock of living foraminifera and export of empty tests from the productive zone increased after the storms, leading to pulses of CaCO3 exported from the surface to deep water. 相似文献
965.
Birgit M. Kräling Joyce Bischoff 《In vitro cellular & developmental biology. Animal》1998,34(4):308-315
Summary Human dermal microvascular endothelial cells are used to analyze the functions of microvascular endothelium in vitro. However, the low yield and short lifespan of these cells in culture has limited the types of analysis that could be performed.
Human microvascular endothelial cells are typically grown in media containing supplements such as dibutyryl cyclic AMP, hydrocortisone,
bovine brain extract, and antifungal agents, each of which increase the complexity of experimental design and interpretation
of results. In the present study, endothelial cells were transferred after Ulex europeus-I selection into a simplified medium consisting of Endothelial Basal Medium 131, 10% fetal bovine serum, and 2 ng/ml basic
fibroblast growth factor and analyzed over 3 mo. The human microvascular endothelial cells expressed the endothelial markers
von Willebrand factor, CD31, P-selectin, and E-selectin. In addition, the cells showed increased proliferation in the presence
of basic fibroblast growth factor (0.5 ng/ml) or vascular endothelial cell growth factor (10 ng/ml). Tumor necrosis factor-α-induced
expression of E-selectin was similar in cells at Passages 3, 6, and 12, indicating that the cells maintained responsiveness
to cytokines over several weeks. Furthermore, the endothelial cells attained a typical cobblestone morphology with increased
cellular density and also formed capillarylike tubes on Matrigel. In summary, the human dermal microvascular endothelial cells
display the expected endothelial characteristics when grown for several passages and, therefore, provide a valuable in vitro model for human microvascular endothelium. 相似文献
966.
Birgit Fuhrberg Ivonne Balzer Rüdiger Hardeland Astrid Werner Klaus Lüning 《Planta》1996,200(1):125-131
Melatonin, a methoxylated indoleamine, plays a role as a mediator of darkness in animals as well as in the unicellular alga Gonyaulax polyedra Stein and was recently detected in higher plants. We report on the first finding of melatonin in a multicellular alga, the brown alga Pterygophora californica Rupr. Melatonin was identified in juvenile sporophytes of P. californica by two independent methods, reverse-phase high-performance liquid chromatography (HPLC) with electrochemical detection, and radioimmunoassay. Another indolic metabolite, 5-methoxytryptophol, was also indentified by HPLC. The rapid decline of growth rate upon the onset of darkness in P. californica is mimicked by melatonin in the light, with increasing efficiency from 5 × 10–5M to 5 × 10–4M, while no effect was obtained at 10–5M.Abbreviations ANOVA
analysis of variance
- DMSO
dimethyl sulfoxide
- LD
light-dark cycle
K.L. and A.W. thank Petra Kadel for help with algal cultivation and evaluation of the experiments. 相似文献
967.
Funkhouser Edward A.; Gewitz Hans-Siegfied; Vennesland Birgit 《Plant & cell physiology》1983,24(8):1565-1568
During induction of nitrate reductase in Chlorella vulgaris,synthesis of the precursor, demolybdo cytochrome c reductase,exceeds the synthesis of active enzyme. Evidence is also presentedwhich shows that the purification procedure of Funkhouser etal. [(1980) Plant Physiol. 65: 939] separates demolybdo cytochromec reductase from active nitrate reductase.
1Supported in part by a grant to B. V. from the Deutsche Forschungsgemeinschaftand a contribution of the Texas Agricultural Experiment Station. (Received July 27, 1983; Accepted September 13, 1983) 相似文献
968.
A simple, rapid method for the preparation of pure microvillus membrane vesicles from pig small intestine is described. The method is based on the ability of agarose beads to adsorb selectively the impurities, mainly basolateral membrane fragments, from a microvillus vesicle preparation isolated by hypotonic lysis, Mg2+ aggregation of contaminants and differential centrifugation. 相似文献
969.
From various oxic or anoxic habitats anaerobic enrichment cultures were set up which completely oxidized aromatic amino acids to CO2 with nitrate as electron acceptor. Tyrosine and tryptophan at first were degraded to phenol and indole, respectively, prior to utilization of the aromatic ring; with phenylalanine no intermediates were detected. Attempts to isolate denitrifying bacteria able to completely degrade aromatic amino acids were unsuccessful. Starting with these enrichments several strains of denitrifying bacteria were anaerobically enriched and isolated with known fermentation products of amino acids (phenylacetate, 4-OH-phenylacetate, 2-OH-benzoate) plus nitrate as sole sources of carbon and energy.Three strains were characterized further. They grew well in defined mineral salts medium, were gram-negative and facultatively anaerobic with strictly oxidative metabolism; molecular oxygen, nitrate or nitrite served as electron acceptors. The isolates were tentatively identified as pseudomonads, but could not be aligned to known species. They oxidized a variety of aromatic compounds completely to CO2 anaerobically and, with some exceptions, also aerobically. The substrates included among others: (4-OH)-phenylacetate, (4-OH)-phenylglyoxylate, benzoate, 2-aminobenzoate, phenol, OH-benzoates, indole and notably toluene. Reduced alicyclic compounds were not utilized. During anaerobic degradation of (4-OH)-phenylacetate transient accumulation of (4-OH)-phenylglyoxylate was observed.It is proposed that anaerobic -oxidation of the-CH2–COOH side chain to -CO–COOH initiates anaerobic degradation of (4-OH)-phenylacetate. This implies a novel type of anaerobic -hydroxylation with water as the oxygen donor.
Abbreviation. Hydroxyl groups were abbreviated as OH 相似文献
970.
Riet J. Schocher Birgit Seyfried Francisco Vazquez Josef Zeyer 《Archives of microbiology》1991,157(1):7-12
Several denitrifying Pseudomonas spp., isolated with various aromatic compounds, were tested for the ability to degrade toluene in the absence of molecular oxygen. Four out of seven strains were able to degrade toluene in the presence of N2O. More than 50% of the 14C from ring-labelled toluene was released as CO2, and up to 37% was assimilated into cell material. Furthermore it was demonstrated for two strains that they were able to grow on toluene as the sole carbon and energy source in the presence of N2O. Suspensions of cells pre-grown on toluene degraded toluene, benzaldehyde or benzoate without a lag phase and without accumulation of intermediates. p-Cresol, p-hydroxybenzylalcohol, p-hydroxybenzaldehyde or p-hydroxybenzoate was degraded much slower or only after distinct lag times. In the presence of fluoroacetate [14C]toluene was transformed to [14C]benzoate, which suggests that anaerobic toluene degradation proceeds through oxidation of the methyl side chain to benzoate. 相似文献