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91.
Dong Chil Koo So Yoon Baek Sang Hoon Jung Sang Hee Shim 《Biotechnology and Bioprocess Engineering》2013,18(5):926-931
Amethanolic extract of Dipsacus asper, having anti-diabetic activity, was examined as a possible aldose reductase (ALR2) inhibitor, a key enzyme involved in diabetic complications. Bioactivity guided fractionation led to the isolation of ten compounds, ursolic acid (1), oleanolic acid-3-O-α-L-arabinopyranoside (2), daucosterol (3), hederagenin-3-O-α-L-arabinopyranoside (4), sweroside(5), caffeic acid (6), esculetin (7), protocatechualdehyde (8), loganin (9), and vanilic acid (10) from the ethyl acetate fraction of D. asper methanol extract. Among them, compounds 4, 6, 7, and 8 exhibited inhibitory effects on aldose reductase, with IC50 values of 23.70, 16.71, 34.36, and 21.81 μM, respectively. This is the first report on the isolation of these compounds from D. asper, and the ALR2 inhibitory activity of hederagenin-3-O-α-L-arabinopyranoside. These results suggest the successful use of the extract of D. asper for ameliorating diabetic complications. 相似文献
92.
Lyndon D. Estes Hein Beukes Bethany A. Bradley Stephanie R. Debats Michael Oppenheimer Alex C. Ruane Roland Schulze Mark Tadross 《Global Change Biology》2013,19(12):3762-3774
Crop model‐specific biases are a key uncertainty affecting our understanding of climate change impacts to agriculture. There is increasing research focus on intermodel variation, but comparisons between mechanistic (MMs) and empirical models (EMs) are rare despite both being used widely in this field. We combined MMs and EMs to project future (2055) changes in the potential distribution (suitability) and productivity of maize and spring wheat in South Africa under 18 downscaled climate scenarios (9 models run under 2 emissions scenarios). EMs projected larger yield losses or smaller gains than MMs. The EMs’ median‐projected maize and wheat yield changes were ?3.6% and 6.2%, respectively, compared to 6.5% and 15.2% for the MM. The EM projected a 10% reduction in the potential maize growing area, where the MM projected a 9% gain. Both models showed increases in the potential spring wheat production region (EM = 48%, MM = 20%), but these results were more equivocal because both models (particularly the EM) substantially overestimated the extent of current suitability. The substantial water‐use efficiency gains simulated by the MMs under elevated CO2 accounted for much of the EM?MM difference, but EMs may have more accurately represented crop temperature sensitivities. Our results align with earlier studies showing that EMs may show larger climate change losses than MMs. Crop forecasting efforts should expand to include EM?MM comparisons to provide a fuller picture of crop–climate response uncertainties. 相似文献
93.
94.
Stephanie Schwalm Josef Pfeilschifter Andrea Huwiler 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(1):239-250
Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that acts either on G protein-coupled S1P receptors on the cell surface or via intracellular target sites. In addition to the well established effects of S1P in angiogenesis, carcinogenesis and immunity, evidence is now continuously accumulating which demonstrates that S1P is an important regulator of fibrosis. The contribution of S1P to fibrosis is of a Janus-faced nature as S1P exhibits both pro- and anti-fibrotic effects depending on its site of action. Extracellular S1P promotes fibrotic processes in a S1P receptor-dependent manner, whereas intracellular S1P has an opposite effect and dampens a fibrotic reaction by yet unidentified mechanisms. Fibrosis is a result of chronic irritation by various factors and is defined by an excess production of extracellular matrix leading to tissue scarring and organ dysfunction. In this review, we highlight the general effects of extracellular and intracellular S1P on the multistep cascade of pathological fibrogenesis including tissue injury, inflammation and the action of pro-fibrotic cytokines that stimulate ECM production and deposition. In a second part we summarize the current knowledge about the involvement of S1P signaling in the development of organ fibrosis of the lung, kidney, liver, heart and skin. Altogether, it is becoming clear that targeting the sphingosine kinase-1/S1P signaling pathway offers therapeutic potential in the treatment of various fibrotic processes. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. 相似文献
95.
Stephanie Ringeissen Susan C. Connor H. Roger Brown Brian C. Sweatman Mark P. Hodson Steve P. Kenny 《Biomarkers》2013,18(3-4):240-271
This study identified two potential novel biomarkers of peroxisome proliferation in the rat. Three peroxisome proliferator-activated receptor (PPAR) ligands, chosen for their high selectivity towards the PPARα, -δ and -γ subtypes, were given to rats twice daily for 7 days at doses known to cause a pharmacological effect or peroxisome proliferation. Fenofibrate was used as a positive control. Daily treatment with the PPARα and -δ agonists produced peroxisome proliferation and liver hypertrophy. 1H nuclear magnetic resonance spectroscopy and multivariate statistical data analysis of urinary spectra from animals given the PPARα and -δ agonists identified two new potential biomarkers of peroxisome proliferation - N-methylnicotinamide (NMN) and N-methyl-4-pyridone-3-carboxamide (4PY) - both endproducts of the tryptophan-nicotinamide adenine dinucleotide (NAD+) pathway. After 7 days, excretion of NMN and 4PY increased 24- and three-fold, respectively, following high doses of fenofibrate. The correlation between total NMN excretion over 7 days and the peroxisome count was r=0.87 (r2=0.76). Plasma NMN, measured using a sensitive high performance liquid chromatography method, was increased up to 61-fold after 7 days' treatment with high doses of fenofibrate. Hepatic gene expression of aminocarboxymuconate-semialdehyde decarboxylase (EC 4.1.1.45) was downregulated following treatment with the PPARα and -δ agonists. The decrease was up to 11-fold compared with controls in the groups treated with high doses of fenofibrate. This supports the link between increased NMN and 4PY excretion and regulation of the tryptophan-NAD+ pathway in the liver. In conclusion, NMN, and possibly other metabolites in the pathway, are potential non-invasive surrogate biomarkers of peroxisome proliferation in the rat. 相似文献
96.
Susan C. Connor Mark P. Hodson Stephanie Ringeissen Brian C. Sweatman Paul J. Mcgill Catherine J. Waterfield 《Biomarkers》2013,18(4-5):364-385
A previous report of this work (Ringeissen et al. 2003) described the use of nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical data analysis (MVDA) to identify novel biomarkers of peroxisome proliferation (PP) in Wistar Han rats. Two potential biomarkers of peroxisome proliferation in the rat were described, N-methylnicotinamide (NMN) and N-methyl-4-pyridone-3-carboxamide (4PY). The inference from these results was that the tryptophan-nicotinamide adenine dinucleotide (NAD+) pathway was altered in correlation with peroxisome proliferation, a hypothesis subsequently confirmed by TaqMan® analysis of the relevant genes encoding two key enzymes in the pathway, aminocarboxymuconate-semialdehyde decarboxylase (EC 4.1.1.45) and quinolinate phosphoribosyltransferase (EC 2.4.2.19). The objective of the present study was to investigate these data further and identify other metabolites in the NMR spectrum correlating equally with PP. MVDA Partial Least Squares (PLS) models were constructed that provided a better prediction of PP in Wistar Han rats than levels of 4PY and NMN alone. The resulting Wistar Han rat predictive models were then used to predict PP in a test group of Sprague Dawley rats following administration of fenofibrate. The models predicted the presence or absence of PP (above on arbitrary threshold of >2-fold mean control) in all Sprague Dawley rats in the test group. 相似文献
97.
98.
Stephanie Brunet Nassim Shahrzad Djenann Saint‐Dic Hartley Dutczak Michael Sacher 《Traffic (Copenhagen, Denmark)》2013,14(10):1091-1104
TRAPP is a multisubunit complex that functions in membrane traffic. Mutations in the mammalian TRAPP protein C2 are linked to the skeletal disorder spondyloepiphyseal dysplasia tarda (SEDT) that is thought to arise from an inability to secrete procollagen from the endoplasmic reticulum. Here, we show that C2 binds to the SNARE protein Syntaxin 5 and this interaction is weakened by an SEDT‐causing missense mutation (D47Y). Interestingly, the equivalent mutation (D46Y) in the yeast C2 homolog Trs20p does not block anterograde traffic but did affect endocytosis. The trs20D46Y mutation interfered with the interaction between Trs20p and Trs85p (TRAPP III‐specific subunit), Trs120p and Trs130p (TRAPP II‐specific subunits). Size exclusion chromatography suggested that this yeast mutation destabilized the TRAPP III complex that is involved in autophagy. We further show that this mutation blocks both the selective cytosol‐to‐vacuole (cvt) pathway as well as non‐selective autophagy. We demonstrate that the apparent molecular size of the TRAPP III complex is dependent upon membranes, and that the presence of TRAPP III is dependent upon Atg9p. Finally, we demonstrate that lipidated Bet3p is enriched in TRAPP III and that lipidation increases the efficiency of autophagy. Our study suggests that Trs20p acts as an adaptor for Trs85p and Trs120p and reveals complexities in TRAPP III assembly and function. The implications of C2D47Y in SEDT are discussed . 相似文献
99.
Adam M. Siepielski Kiyoko M. Gotanda Michael B. Morrissey Sarah E. Diamond Joseph D. DiBattista Stephanie M. Carlson 《Ecology letters》2013,16(11):1382-1392
Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta‐analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. 相似文献
100.
Stephanie Korn Marisa Hübner Matthias Jung Maria Blettner Roland Buhl 《Respiratory research》2013,14(1):25