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1.
Wilfredo Mellado Neal F. Magri David G.I. Kingston Renee Garcia-Arenas George A. Orr Susan Band Horwitz 《Biochemical and biophysical research communications》1984,124(2):329-336
Synthesis and biological activity of 2′-acetyltaxol and 7-acetyltaxol are reported. Activity is measured by cytotoxicity toward the macrophage-like cell line J774.2, and by promotion of microtubule assembly in the absence of exogenous GTP. Addition of an acetyl moiety at C-2′ results in loss of activity but not cytotoxicity. The properties of 7-acetyltaxol are similar to those of taxol in its effects on cell replication and on microtubule polymerization. Therefore a free hydroxyl group at C-7 is not required for activity and this position is available for structural modifications. 相似文献
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Sailendra N. Nichenametla Dwight A. L. Mattocks Diana Cooke Vishal Midya Virginia L. Malloy Wilfredo Mansilla Bente
vreb Cheryl Turner Nasser
E. Bastani Jitka Sokolov Markta Pavlíkov John P. Richie Jr. Anna
K. Shoveller Helga Refsum Thomas Olsen Kathrine J. Vinknes Viktor Koich Gene P. Ables 《Aging cell》2022,21(12)
Decreasing the dietary intake of methionine exerts robust anti‐adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not methionine, suggesting that CR, but not MR, is responsible for the anti‐adiposity effects of SAAR. Whether this is true, and, if so, the underlying mechanisms are unknown. Using methionine‐ and cysteine‐titrated diets, we demonstrate that the anti‐adiposity effects of SAAR are due to CR. Data indicate that CR increases serinogenesis (serine biosynthesis from non‐glucose substrates) by diverting substrates from glyceroneogenesis, which is essential for fatty acid reesterification and triglyceride synthesis. Molecular data suggest that CR depletes hepatic glutathione and induces Nrf2 and its downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck‐M. In mice, the magnitude of SAAR‐induced changes in molecular markers depended on dietary fat concentration (60% fat >10% fat), sex (males > females), and age‐at‐onset (young > adult). Our findings are translationally relevant as we found negative and positive correlations of plasma serine and cysteine, respectively, with triglycerides and metabolic syndrome criteria in a cross‐sectional epidemiological study. Controlled feeding of low‐SAA, high‐polyunsaturated fatty acid diets increased plasma serine in humans. Serinogenesis might be a target for treating hypertriglyceridemia. 相似文献
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Arriesgado Dan M. Kurokochi Hiroyuki Nakajima Yuichi Matsuki Yu Uy Wilfredo H. Fortes Miguel D. Campos Wilfredo L. Nadaoka Kazuo Lian Chunlan 《Aquatic Ecology》2015,49(3):357-372
Aquatic Ecology - Persistence of populations at their distributional ranges relies on local population dynamics and the fitness of species with low dispersal potential. We analyzed the population... 相似文献
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de Beus MD Chung J Colón W 《Protein science : a publication of the Protein Society》2004,13(5):1347-1355
Cu/Zn superoxide dismutase (SOD) mutations are involved in about 20% of all cases of familial amyotrophic lateral sclerosis (FALS). Recently, it has been proposed that aberrant copper activity may be occurring within SOD at an alternative binding, and cysteine 111 has been identified as a potential copper ligand. Using a commercial source of human SOD isolated from erythrocytes, an anomalous absorbance at 325 nm was identified. This unusual property, which does not compromise SOD activity, had previously been shown to be consistent with a sulfhydryl modification at a cysteine residue. Here, we utilized limited trypsin proteolysis and mass spectrometry to show that the modification has a mass of 32 daltons and is located at cysteine 111. The reaction of SOD with sodium sulfide, which can react with cysteine to form a persulfide group, and with potassium cyanide, which can selectively remove persulfide bonds, confirmed the addition of a persulfide group at cysteine 111. Gel electrophoresis and glutaraldehyde cross-linking revealed that this modification makes the acid-induced denaturation of SOD fully irreversible. Furthermore, the modified protein exhibits a slower acid-induced unfolding, and is more resistant to oxidation-induced aggregation caused by copper and hydrogen peroxide. Thus, these results suggest that cysteine 111 can have a biochemical and biophysical impact on SOD, and suggest that it can interact with copper, potentially mediating the copper-induced oxidative damage of SOD. It will be of interest to study the role of cysteine 111 in the oxidative damage and aggregation of toxic SOD mutants. 相似文献
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Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro 总被引:16,自引:0,他引:16
Elevation of cAMP can overcome myelin inhibitors to encourage regeneration of the CNS. We show that a consequence of elevated cAMP is the synthesis of polyamines, resulting from an up-regulation of Arginase I, a key enzyme in their synthesis. Inhibiting polyamine synthesis blocks the cAMP effect on regeneration. Either over-expression of Arginase I or exogenous polyamines can overcome inhibition by MAG and by myelin in general. While MAG/myelin support the growth of young DRG neurons, they become inhibitory as DRGs mature. Endogenous Arginase I levels are high in young DRGs but drop spontaneously at an age that coincides with the switch from promotion to inhibition by MAG/myelin. Over-expressing Arginase I in maturing DRGs blocks that switch. Arginase I and polyamines are more specific targets than cAMP for intervention to encourage regeneration after CNS injury. 相似文献
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Wilhelm Salzberger Wilfredo F. Garcia-Beltran Haley Dugan Supreetha Gubbala Camille Simoneau Simon B. Gressens Stephanie Jost Marcus Altfeld 《PloS one》2015,10(12)
Viral infections can affect the glycosylation pattern of glycoproteins involved in antiviral immunity. Given the importance of protein glycosylation for immune function, we investigated the effect that modulation of the highly conserved HLA class I N-glycan has on KIR:HLA interactions and NK cell function. We focused on HLA-B*57:01 and its interaction with KIR3DL1, which has been shown to play a critical role in determining the progression of a number of human diseases, including human immunodeficiency virus-1 infection. 721.221 cells stably expressing HLA-B*57:01 were treated with a panel of glycosylation enzyme inhibitors, and HLA class I expression and KIR3DL1 binding was quantified. In addition, the functional outcomes of HLA-B*57:01 N-glycan disruption/modulation on KIR3DL1ζ+ Jurkat reporter cells and primary human KIR3DL1+ NK cells was assessed. Different glycosylation enzyme inhibitors had varying effects on HLA-B*57:01 expression and KIR3DL1-Fc binding. The most remarkable effect was that of tunicamycin, an inhibitor of the first step of N-glycosylation, which resulted in significantly reduced KIR3DL1-Fc binding despite sustained expression of HLA-B*57:01 on 721.221 cells. This effect was paralleled by decreased activation of KIR3DL1ζ+ Jurkat reporter cells, as well as increased degranulation of primary human KIR3DL1+ NK cell clones when encountering HLA-B*57:01-expressing 721.221 cells that were pre-treated with tunicamycin. Overall, these results demonstrate that N-glycosylation of HLA class I is important for KIR:HLA binding and has an impact on NK cell function. 相似文献
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Alfredo Saldaña Christopher H. Lusk Wilfredo L. Gonzáles Ernesto Gianoli 《Evolutionary ecology》2007,21(5):651-662
Unlike other species of the genus Blechnum, the fern Blechnum chilense occurs in a wide range of habitats in Chilean temperate rainforest, from shaded forest understories to abandoned clearings
and large gaps. We asked if contrasting light environments can exert differential selection on ecophysiological traits of
B. chilense. We measured phenotypic selection on functional traits related to carbon gain: photosynthetic capacity (A
max), dark respiration rate (R
d), water use efficiency (WUE), leaf size and leaf thickness in populations growing in gaps and understorey environments. We
assessed survival until reproductive stage and fecundity (sporangia production) as fitness components. In order to determine
the potential evolutionary response of traits under selection, we estimated the genetic variation of these traits from clonally
propagated individuals in common garden experiments. In gaps, survival of B. chilense was positively correlated with WUE and negatively correlated with leaf size. In contrast, survival in shaded understories
was positively correlated with leaf size. We found positive directional fecundity selection on WUE in gaps population. In
understories, ferns of lower R
d and greater leaf size showed greater fecundity. Thus, whereas control of water loss was optimized in gaps, light capture
and net carbon balance were optimized in shaded understories. We found a significant genetic component of variation in WUE,
R
d and leaf size. This study shows the potential for evolutionary responses to heterogeneous light environments in functional
traits of B. chilense, a unique fern species able to occupy a broad successional niche in Chilean temperate rainforest. 相似文献
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Most studies on the fitness advantage of outbreeding in host–parasite systems have been assessed from the host rather than
the parasite perspective. Here, we performed experimental pollination treatments to evaluate the consequences of outbreeding
on fitness-related traits in the holoparasitic mistletoe Tristerix aphyllus in a 2-year field study. Results indicate that self-pollinated plants had a lower fruit production than outcrossed plants
(20.4% and 29.5% reduction in 2002 and 2003, respectively), and resulting inbred fruits were smaller than outcrossed fruits
in both years. No effect was detected for seed mass. The percentage of germination of inbred seeds was 15.1% and 6.0% lower
than outcrossed seeds in 2002 and 2003, respectively. Inbred seedlings had shorter radicles, which translated to a 71.6% and
60.0% reduction in infection success compared with outcrossed plants in 2002 and 2003, respectively. Overall, our results
revealed significant inbreeding depression on almost every trait that was examined. Although the mean value of traits varied
from a year to another, the magnitude of inbreeding depression did not change significantly between years. Our findings constitute
the first evidence that outcrossing increases infection success and probably virulence in parasitic plant populations. 相似文献