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141.
142.
U Hofmann S Michaelis T Winckler J Wegener KH Feller 《Biosensors & bioelectronics》2013,39(1):156-162
This study presents the time-resolved detection of chemically induced stress upon intracellular signaling cascades by using genetically modified sensor cells based on the human keratinocyte cell line HaCaT. The cells were stably transfected with a HSP72-GFP reporter gene construct to create an optical sensor cell line expressing a stress-inducible reporter protein. The time- and dose-dependent performance of the sensor cells is demonstrated and discussed in comparison to a label-free impedimetric monitoring approach (electric cell-substrate impedance sensing, ECIS). Moreover, a microfluidic platform was established based on μSlidesI(0,4)Luer to allow for a convenient, sterile and incubator-independent time-lapse microscopic observation of the sensor cells. Cell growth was successfully achieved in this microfluidic setup and the cellular response to a cytotoxic substance could be followed in real-time and in a non-invasive, sensitive manner. This study paves the way for the development of micro-total analysis systems that combine optical and impedimetric readouts to enable an overall quantitative characterization of changes in cell metabolism and morphology as a response to toxin exposure. By recording multiple parameters, a detailed discrimination between competing stress- or growth-related mechanisms is possible, thereby presenting an entirely new in vitro alternative to skin irritation tests. 相似文献
143.
An evidence-based consensus for the classification of arbuscular mycorrhizal fungi (Glomeromycota) 总被引:1,自引:0,他引:1
Dirk Redecker Arthur Schüßler Herbert Stockinger Sidney L. Stürmer Joseph B. Morton Christopher Walker 《Mycorrhiza》2013,23(7):515-531
The publication of a large number of taxon names at all levels within the arbuscular mycorrhizal fungi (Glomeromycota) has resulted in conflicting systematic schemes and generated considerable confusion among biologists working with these important plant symbionts. A group of biologists with more than a century of collective experience in the systematics of Glomeromycota examined all available molecular–phylogenetic evidence within the framework of phylogenetic hypotheses, incorporating morphological characters when they were congruent. This study is the outcome, wherein the classification of Glomeromycota is revised by rejecting some new names on the grounds that they are founded in error and by synonymizing others that, while validly published, are not evidence-based. The proposed “consensus” will provide a framework for additional original research aimed at clarifying the evolutionary history of this important group of symbiotic fungi. 相似文献
144.
Seied Mojtaba Valiahdi Alexander E. Egger Walter Miklos Ute Jungwirth Kristof Meelich Petra Nock Walter Berger Christian G. Hartinger Markus Galanski Michael A. Jakupec Bernhard K. Keppler 《Journal of biological inorganic chemistry》2013,18(2):249-260
Extracellular acidity is a frequent pathophysiological condition of solid tumors offering possibilities for improving the tumor selectivity of molecular therapy. This might be accomplished by prodrugs with low systemic toxicity, attaining their full antitumor potency only under acidic conditions, such as bis(2-aminoalcoholato-κ²N,O)platinum(II) complexes that are activated by protonation of alcoholato oxygen, resulting in cleavage of platinum–oxygen bonds. In this work, we examined whether the pH dependency of such compounds is reflected in differential biological activity in vitro. In particular, the pH dependence of cytotoxicity, cellular accumulation, DNA platination, GMP binding, effects on DNA secondary structure, cell cycle alterations, and induction of apoptosis was investigated. Enhanced cytotoxicity of five of these complexes in non-small-cell lung cancer (A549) and colon carcinoma (HT-29) cells at pH 6.0 in comparison with pH 7.4 was confirmed: 50 % growth inhibition concentrations ranged from 42 to 214 μM in A549 cells and from 35 to 87 μM in HT-29 cells at pH 7.4 and decreased at pH 6.0 to 11–50 and 7.3–25 μM, respectively. The effects induced by all five pH-sensitive compounds involve increased 5′-GMP binding, cellular accumulation, and DNA platination as well as stronger effects on DNA secondary structure at pH 6.0 than at pH 7.4. As exemplified by treatment of A549 cells with a 2-amino-4-methyl-1-pentanolato complex, induction of apoptosis is enhanced at pH 6.5. These results confirm the increased reactivity and in vitro activity of these compounds under slightly acidic conditions, encouraging further evaluation of ring-closed aminoalcoholatoplatinum(II) derivatives in solid tumors in vivo. 相似文献
145.
Erawan Borkham-Kamphorst Eddy van de Leur Henning W. Zimmermann Karlin Raja Karlmark Lidia Tihaa Ute Haas Frank Tacke Thorsten Berger Tak W. Mak Ralf Weiskirchen 《生物化学与生物物理学报:疾病的分子基础》2013,1832(5):660-673
Lipocalin-2 is expressed under pernicious conditions such as intoxication, infection, inflammation and other forms of cellular stress. Experimental liver injury induces rapid and sustained LCN2 production by injured hepatocytes. However, the precise biological function of LCN2 in liver is still unknown. In this study, LCN2?/? mice were exposed to short term application of CCl4, lipopolysaccharide and Concanavalin A, or subjected to bile duct ligation. Subsequent injuries were assessed by liver function analysis, qRT-PCR for chemokine and cytokine expression, liver tissue Western blot, histology and TUNEL assay. Serum LCN2 levels from patients suffering from liver disease were assessed and evaluated. Acute CCl4 intoxication showed increased liver damage in LCN2?/? mice indicated by higher levels of aminotransferases, and increased expression of inflammatory cytokines and chemokines such as IL-1β, IL-6, TNF-α and MCP-1/CCL2, resulting in sustained activation of STAT1, STAT3 and JNK pathways. Hepatocytes of LCN2?/? mice showed lipid droplet accumulation and increased apoptosis. Hepatocyte apoptosis was confirmed in the Concanavalin A and lipopolysaccharide models. In chronic models (4 weeks bile duct ligation or 8 weeks CCl4 application), LCN2?/? mice showed slightly increased fibrosis compared to controls. Interestingly, serum LCN2 levels in diseased human livers were significantly higher compared to controls, but no differences were observed between cirrhotic and non-cirrhotic patients. Upregulation of LCN2 is a reliable indicator of liver damage and has significant hepato-protective effect in acute liver injury. LCN2 levels provide no correlation to the degree of liver fibrosis but show significant positive correlation to inflammation instead. 相似文献
146.
Lutz?HamannEmail author Alexander?Koch Saubashya?Sur Nadja?Hoefer Christiane?Glaeser Susanne?Schulz Michael?Gross Andre?Franke Ute?N?thlings Kai?Zacharowski Ralf?R?Schumann 《Immunity & ageing : I & A》2013,10(1):43
Background
The pro-inflammatory status of the elderly triggers most of the age-related diseases such as cancer and atherosclerosis. Atherosclerosis, the leading cause world wide of morbidity and death, is an inflammatory disease influenced by life-style and genetic host factors. Stimuli such as oxLDL or microbial ligands have been proposed to trigger inflammation leading to atherosclerosis. It has recently been shown that oxLDL activates immune cells via the Toll-like receptor (TLR) 4/6 complex. Several common single nucleotide polymorphisms (SNPs) of the TLR system have been associated with atherosclerosis. To investigate the role of TLR-6 we analyzed the association of the TLR-6 SNP Pro249Ser with atherogenesis.Results
Genotyping of two independent groups with CAD, as well as of healthy controls revealed a significant association of the homozygous genotype with a reduced risk for atherosclerosis (odds ratio: 0.69, 95% CI 0.51-0.95, P?=?0.02). In addition, we found a trend towards an association with the risk of restenosis after transluminal coronary angioplasty (odds ratio: 0.53, 95% CI 0.24-1.16, P?=?0.12). In addition, first evidence is presented that the frequency of this protective genotype increases in a healthy population with age. Taken together, our results define a role for TLR-6 and its genetic variations in modulating the inflammatory response leading to atherosclerosis.Conclusions
These results may lead to a better risk stratification, and potentially to an improved prophylactic treatment of high-risk populations. Furthermore, the protective effect of this polymorphism may lead to an increase of this genotype in the healthy elderly and may therefore be a novel genetic marker for the well-being during aging.147.
Hannah Deußer Dorothee Rogoll Wolfgang Scheppach Antje Volk Ralph Melcher Prof. Dr. Elke Richling 《Biotechnology journal》2013,8(3):363-370
Polyphenols contained in food have various positive effects on human health. The absorption and metabolism of polyphenols in the intestinal tract needs to be studied to estimate these effects. The Ussing chamber technique was used to investigate the transport behavior of apple polyphenols through pig small intestinal mucosa, which served as a model for human gastrointestinal mucosa. The identities and concentrations of polyphenols and their metabolites in the half-chambers (luminal and basolateral) within an incubation period of 4 h were determined by HPLC–MS/MS and HPLC–DAD (DAD = diode-array detection). Flux values were also measured. It was found that 5-caffeoylquinic acid and caffeic acid were absorbed and translocated to the basolateral side (1.9 and 3.7%, respectively), but other compounds, including glycosides of phloretin and quercetin, were observed without translocation. A Ussing chamber utilizing pig small intestinal mucosa is a suitable model for assessing the effect of apple polyphenols on mucosal integrity and nutrition absorption across porcine mucosa. 相似文献
148.
Background
Predicting protein subnuclear localization is a challenging problem. Some previous works based on non-sequence information including Gene Ontology annotations and kernel fusion have respective limitations. The aim of this work is twofold: one is to propose a novel individual feature extraction method; another is to develop an ensemble method to improve prediction performance using comprehensive information represented in the form of high dimensional feature vector obtained by 11 feature extraction methods.Methodology/Principal Findings
A novel two-stage multiclass support vector machine is proposed to predict protein subnuclear localizations. It only considers those feature extraction methods based on amino acid classifications and physicochemical properties. In order to speed up our system, an automatic search method for the kernel parameter is used. The prediction performance of our method is evaluated on four datasets: Lei dataset, multi-localization dataset, SNL9 dataset and a new independent dataset. The overall accuracy of prediction for 6 localizations on Lei dataset is 75.2% and that for 9 localizations on SNL9 dataset is 72.1% in the leave-one-out cross validation, 71.7% for the multi-localization dataset and 69.8% for the new independent dataset, respectively. Comparisons with those existing methods show that our method performs better for both single-localization and multi-localization proteins and achieves more balanced sensitivities and specificities on large-size and small-size subcellular localizations. The overall accuracy improvements are 4.0% and 4.7% for single-localization proteins and 6.5% for multi-localization proteins. The reliability and stability of our classification model are further confirmed by permutation analysis.Conclusions
It can be concluded that our method is effective and valuable for predicting protein subnuclear localizations. A web server has been designed to implement the proposed method. It is freely available at http://bioinformatics.awowshop.com/snlpred_page.php. 相似文献149.
Thi My Lien Do Anh Vu Truong Thi Nga Vo Travis G. Pinnock Lawrence M. Pratt Dominique Guillaume Kim Phi Phung Nguyen 《Phytochemistry letters》2013,6(4):544-551
Boerhaavia diffusa L. is used in the traditional medicine of several Asian countries. The isolation and identification of five new compounds, together with 11 known compounds, from the ethyl acetate extract of the aerial part of B. diffusa grown Vietnam is reported. The structure of the new compounds was established by 1D and 2D NMR spectroscopy, and high resolution ESI-MS analysis. New compounds are two rotenoids: 9,11-dihydroxy-6,10-dimethoxy[1]benzopyrano[3,4-b][1]benzopyran-12(6H)-one (boeravinone P, 3) and 3-[2-(β-d-glucopyranosyloxy)-3-hydroxyphenyl]-5-hydroxy-2-hydroxymethyl-7-methoxy-6-methyl-4H-1-benzopyran-4-one (boeravinone Q, 9), an atropisomeric mixture of two rotenoid glycosides (3′,5-dihydroxy-2-hydroxymethyl-7-methoxy-6-methylisoflavone 2′-O-β-d-glucopyranoside, 11), a sesquiterpene lactone (4,10-dihydroxy-8-methoxyguai-7(11)-en-8,12-olide, 5) and a new phenylpropanoid glycoside (boerhaavic acid, 15). 相似文献
150.
John T. Heiker Matthias Kern Joanna Kosacka Gesine Flehmig Michael Stumvoll Edward Shang Tobias Lohmann Miriam Dreßler Peter Kovacs Matthias Blüher Nora Klöting 《Obesity (Silver Spring, Md.)》2013,21(3):529-534