c-Jun N-Terminal Kinase Phosphorylation Is a Biomarker of Plitidepsin Activity     

María J. Mu?oz-Alonso  Enrique álvarez  María José Guillén-Navarro  Marina Pollán  Pablo Avilés  Carlos M. Galmarini  Alberto Mu?oz 《Marine drugs》2013,11(5):1677-1692

Plitidepsin is an antitumor drug of marine origin currently in Phase III clinical trials in multiple myeloma. In cultured cells, plitidepsin induces cell cycle arrest or an acute apoptotic process in which sustained activation of c-Jun N-terminal kinase (JNK) plays a crucial role. With a view to optimizing clinical use of plitidepsin, we have therefore evaluated the possibility of using JNK activation as an in vivo biomarker of response. In this study, we show that administration of a single plitidepsin dose to mice xenografted with human cancer cells does indeed lead to increased phosphorylation of JNK in tumors at 4 to 12 h. By contrast, no changes were found in other in vitro plitidepsin targets such as the levels of phosphorylated-ERK, -p38MAPK or the protein p27^KIP1. Interestingly, plitidepsin also increased JNK phosphorylation in spleens from xenografted mice showing similar kinetics to those seen in tumors, thereby suggesting that normal tissues might be useful for predicting drug activity. Furthermore, plitidepsin administration to rats at plasma concentrations comparable to those achievable in patients also increased JNK phosphorylation in peripheral mononuclear blood cells. These findings suggest that changes in JNK activity provide a reliable biomarker for plitidepsin activity and this could be useful for designing clinical trials and maximizing the efficacy of plitidepsin.  相似文献   

Electrophysiological and behavioural responses of Pityophthorus pubescens (Coleoptera: Scolytinae) to (E,E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(−)‐verbenone in Pinus radiata (Pinaceae) stands in northern Spain     

Sergio López  Carmen Quero  Juan Carlos Iturrondobeitia  Ángel Guerrero  Arturo Goldarazena 《Pest management science》2013,69(1):40-47

BACKGROUND: Some twig beetles in the genus Pityophthorus (Coleoptera: Scolytinae) may vector pitch canker disease Fusarium circinatum (Niremberg & O'Donnell) of Pinus spp. (Pinaceae). Because Pityophthorus pubescens (Marsh.) has been found to be associated with F. circinatum in the Basque Country (northern Spain), various experiments were conducted to assess the beetle's behavioural responses to (E, E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(?)‐verbenone to develop a potential inhibitor to host attraction. These experiments comprise electroantennographic and double‐choice olfactometer tests, as well as field assays in Pinus radiata D. Don stands. RESULTS: Both sexes of P. pubescens showed similar electroantennographic responses to different doses (from 1 ng to 1 µg in decadic steps) of each individual compound, with depolarisations to (S)‐(‐)‐verbenone (100 ng) being similar to those of the aggregation pheromone (+)‐trans‐pityol. In olfactometer assays, both sexes were significantly attracted to (+)‐trans‐pityol, but the attraction was reduced when increasing amounts of the chemicals were added to the pheromone. Particularly relevant was the repellent effect induced by (S)‐(?)‐verbenone at 1 ng dose and higher. In the field, (E, E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(?)‐verbenone reduced significantly the number of beetles attracted to (+)‐trans‐pityol and racemic trans‐pityol, with (S)‐(?)‐verbenone being the most effective. CONCLUSIONS: (S)‐(?)‐Verbenone showed an interesting potential for use in the protection of P. radiata stands. A potentially effective strategy, which could be implemented in further, more in‐depth studies, could involve the use of this semiochemical as repellent and (+)‐trans‐pityol‐baited traps as attractant in a ‘push‐pull’ strategy. Copyright © 2012 Society of Chemical Industry  相似文献   

Genetic diversity and gene flow in six accessions of Meso-America teosintes     

Carlos Henry Loáisiga  Oscar Rocha  Agnese Kolodinska Brantestam  Björn Salomon  Arnulf Merker 《Genetic Resources and Crop Evolution》2012,59(1):95-111

The genus Zea (teosinte) has a native distribution from Mexico to Nicaragua (Meso-America region) and studies on teosinte species may help improve our understanding of maize genetics, population genetics, genome evolution and crop evolution. Moreover, since F1 hybrids between teosinte and maize are fertile, all teosinte species can potentially contribute to maize breeding in the form of traits such as resistance or tolerance to heavy metals in the soil and other adverse environmental conditions. Gene flow between maize and teosinte occurs in Mexico and Central America. This study analysed the genetic diversity of teosintes by using the microsatellite technique on a total of 120 individuals from six different species and 21 Simple Sequence Repeats (SSR). A total of 109 alleles were found and the number of alleles per locus ranged from 2 to 7. The genetic diversity varied between all species from 0.514 to 0.572, with a mean value of 0.548 (Nei index). Rare and unique alleles were detected in all species, with the highest frequencies found in Zea diploperennis Iltis, Doebley et Guzman, Zea perennis (Hitchc.) Reeves et Mangelsdorf and Zea nicaraguensis Iltis et Benz, which had more than seven rare alleles each. Analysis of molecular variance revealed that 19.87% of the variation between species was statistically significant (P < 0.001). When the different species were compared with the Wright (Fst) value, genetic variation between species was confirmed. The data also revealed a moderate rate gene flow between the species. Genetic diversity was found to be somewhat higher in Central America than in Mexico.  相似文献   

Molecular characterization of a novel waxy allele (Wx-A u 1a) from Triticum urartu Thum. ex Gandil.     

Carlos Guzmán  Juan B. Alvarez 《Genetic Resources and Crop Evolution》2012,59(6):971-979

Granule Bound Starch Synthase I, or waxy protein, is the sole enzyme responsible for the accumulation of amylose during the development of starch granules in wheat. The full coding region of the waxy (Wx) gene was sequenced in Triticum urartu, (a wild diploid species) and is related to the A genome of polyploid wheats. The Wx gene of T. urartu (Wx-A ^u 1) showed a homology of ~88.0?% with Wx-A1 from polyploid wheats. A greater homology was found with Wx-A ^m 1 from the diploid cultivated wheat einkorn. Most of the differences were found in introns although several changes were also detected in exons that led to amino acid changes in the transit peptide and mature protein. These results show the potential of T. urartu as a source of new alleles that could be used in the breeding of durum and common wheat in order to synthesize starches with different properties.  相似文献   

Comparison of accelerated methods for the extraction of phenolic compounds from different vine-shoot cultivars     

Delgado-Torre MP  Ferreiro-Vera C  Priego-Capote F  Pérez-Juan PM  Luque de Castro MD 《Journal of agricultural and food chemistry》2012,60(12):3051-3060

Most research on the extraction of high-priced compounds from vineyard/wine byproducts has traditionally been focused on grape seeds and skins as raw materials. Vine-shoots can represent an additional source to those materials, the characteristics of which could depend on the cultivar. A comparative study of hydroalcoholic extracts from 18 different vineyard cultivars obtained by superheated liquid extraction (SHLE), microwave-assisted extraction (MAE), and ultrasound-assisted extraction (USAE) is here presented. The optimal working conditions for each type of extraction have been investigated by using multivariate experimental designs to maximize the yield of total phenolic compounds, measured by the Folin-Ciocalteu method, and control hydroxymethylfurfural because of the organoleptic properties of furanic derivatives and toxicity at given levels. The best values found for the influential variables on each extraction method were 80% (v/v) aqueous ethanol at pH 3, 180 °C, and 60 min for SHLE; 140 W and 5 min microwave irradiation for MAE; and 280 W, 50% duty cycle, and 7.5 min extraction for USAE. SHLE reported better extraction efficiencies as compared to the other two approaches, supporting the utility of SHLE for scaling-up the process. The extracts were dried in a rotary evaporator, reconstituted in 5 mL of methanol, and finally subjected to liquid-liquid extraction with n-hexane to remove nonpolar compounds that could complicate chromatographic separation. The methanolic fractions were analyzed by both LC-DAD and LC-TOF/MS, and the differences in composition according to the extraction conditions were studied. Compounds usually present in commercial wood extracts (mainly benzoic and hydroxycinnamic acids and aldehydes) were detected in vine-shoot extracts.  相似文献   

A dietary resveratrol-rich grape extract prevents the developing of atherosclerotic lesions in the aorta of pigs fed an atherogenic diet     

Azorín-Ortuño M  Yañéz-Gascón MJ  Pallarés FJ  Rivera J  González-Sarrías A  Larrosa M  Vallejo F  García-Conesa MT  Tomás-Barberán F  Espín JC 《Journal of agricultural and food chemistry》2012,60(22):5609-5620

The presence of grape and wine polyphenol resveratrol (RES) in the diet is negligible. Therefore, the cardiovascular benefits of this molecule, in a dietary context, remain to be established. We aimed to investigate, through dietary intervention, the effects of a resveratrol-rich grape extract (GE-RES) on the prevention of early aortic lesions in pigs fed an atherogenic diet (AD). These effects were compared with those produced by a grape extract lacking RES (GE) or RES alone. Pigs fed the AD for 4 months showed early atherosclerotic lesions in the thoracic aorta: degeneration and fragmentation of elastic fibers, increase of intima thickness, subendothelial fibrosis, and accumulation of fatty cells and anion superoxide radicals. GE-RES was the most effective treatment and prevented the disruption of aortic elastic fibers, decreased their alteration (57%), and reduced the intima thickness (33%) and the accumulation of fatty cells (42%) and O(2)(?-) (38%) in aortic tissue. In addition, GE-RES moderately downregulated the expression of the suppressors of cytokine signaling 1 (SOCS1) and 3 (SOCS3), key regulators of vascular cell responses, in peripheral mononuclear blood cells. Our results suggest that the consumption of this GE-RES nutraceutical, in a dietary prevention context, could prevent early atherosclerotic events. The presence of RES in the grape extract strengthened these effects.  相似文献   

Distribution of hydroxytyrosol and hydroxytyrosol acetate in olive oil emulsions and their antioxidant efficiency     

Lisete-Torres P  Losada-Barreiro S  Albuquerque H  Sánchez-Paz V  Paiva-Martins F  Bravo-Díaz C 《Journal of agricultural and food chemistry》2012,60(29):7318-7325

We employed a kinetic method to determine the distributions of the antioxidants hydroxytyrosol (HT) and hydroxytyrosol acetate (HTA) between the oil, aqueous, and interfacial regions of a model food emulsion composed of stripped olive oil, acidic water, and a blend of Tween 80 and Span 80 [hydrophilic–lipophilic balance (HLB) = 8.05] as an emulsifier. HT is oil-insoluble, but HTA is both oil- and water-soluble (partition constant P(O)(W) = 0.61). Results indicate that, at a given emulsifier volume fraction Φ(I), the fraction of HTA in the interfacial region is higher than that of HT. The percentage of both antioxidants increases with an increasing Φ(I), so that % HT > 40% at Φ(I) = 0.005 and % HT > 80% at Φ(I) = 0.04. HTA appears to be a better antioxidant than HT, as shown by an accelerated oxidative test (Schaal oven method). A correlation between their distribution in the emulsion and their efficiency was established.  相似文献   

Habitat structure,soil properties,and food availability do not predict terrestrial flatworms occurrence in Araucaria Forest sites     

Michelle Antunes  Ana Maria Leal-Zanchet  Carlos Roberto Fonseca 《Pedobiologia》2012,55(1):25-31

Flatworm community structure responds strongly to large-scale habitat alteration, with low diversity in disturbed environments. However, the ecological factors influencing small-scale distribution of flatworms are poorly understood. The aim of this study is to test if the occurrence of land planarians is influenced by microhabitat traits. The study was developed in two Araucaria Forest sites located in the São Francisco de Paula National Forest, southern Brazil. In each site, a 0.5 ha grid subdivided in 10 m² plots, was established. In 100 randomly selected plots, the occurrence and abundance of each land planarian species were recorded. For each plot, we also recorded information on six habitat structural traits, 21 soils properties, and 15 prey availability parameters. Sixty-six specimens were recorded, belonging to 21 species of land planarians. Although the two areas differed in relation to 17 ecological factors analyzed, mean flatworm density did not significantly differ between the two studied areas. The pattern of their abundance followed a Poisson distribution, suggesting that flatworms were randomly distributed throughout the study area. Simple logistic regressions and a multiple logistic regression, controlled for spatial autocorrelation, showed no evidence that the occurrence of terrestrial flatworms is controlled by habitat structure, prey availability or soil properties. In addition, a Principal Component Analysis, controlled for spatial autocorrelation, generated three main axes that represented 40.7% of the variation of the 42 ecological traits. This analysis showed very similar distribution of plots with and without flatworms along these three axes. The results suggest that land flatworms exhibit no pronounced microhabitat preferences inside undisturbed Araucaria Forest sites.  相似文献   

Kinetics and Adsorption Isotherms of Bisphenol A, Estrone, 17β-Estradiol, and 17α-Ethinylestradiol in Tropical Sediment Samples     

Bruno B. Cunha  Wander Gustavo Botero  Luciana Camargo Oliveira  Viviane M. Carlos  Marcelo L. M. Pompêo  Leonardo F. Fraceto  André H. Rosa 《Water, air, and soil pollution》2012,223(1):329-336

The sorption of four endocrine disruptors, bisphenol A (BPA), estrone (E1), 17β-estradiol (E2), and 17α-ethinylestradiol (EE2) in tropical sediment samples was studied in batch mode under different conditions of pH, time, and sediment amount. Data obtained from sorption experiments using the endocrine disruptors (EDs) and sediments containing different amounts of organic matter showed that there was a greater interaction between the EDs and organic matter (OM) present in the sediment, particularly at lower pH values. The pseudosecond order kinetics model successfully explained the interaction between the EDs and the sediment samples. The theoretical and experimentally obtained q _e values were similar, and k values were smaller for higher SOM contents. The k _F values, obtained from the Freundlich isotherms, varied in the ranges 4.2–7.4 × 10⁻² (higher OM sediment sample, S₂) and 1.7 × 10⁻³–3.1 × 10⁻² (lower OM sediment sample, S₁), the latter case indicating an interaction with the sediment that increased in the order: EE2 > > E2 > E1 > BPA. These results demonstrate that the availability of endocrine disruptors may be directly related to the presence of organic material in sediment samples. Studies of this kind provide an important means of understanding the mobility, transport, and/or reactivity of this type of emergent contaminant in aquatic systems.  相似文献   

Natural Biofilms in Freshwater Ecosystem: Indicators of the Presence of Polycyclic Aromatic Hydrocarbons     

Sandro Froehner  Karina Scurupa Machado  Luiz Fernando Dombroski  Anderson Correa Nunes  Regina Tiemy Kishi  Tobias Bleninger  Juan Sanez 《Water, air, and soil pollution》2012,223(7):3965-3973

Hydrophobic organic compounds are common in the environment, especially in water bodies like rivers and lakes. Generally, due to their physico-chemical characteristics, mainly to hydrophobicity, these compounds are adsorbed by suspended material or other compartments which provide compatibility. Thus, compounds such as polycyclic aromatic hydrocarbons (PAHs) are rapidly adsorbed onto suspended material or even naturally occurring biofilms in water bodies. Biofilms can be defined as complex structures with cells and aggregates of cells. The extracellular polymers present empty spaces that can be filled by water. The biofilm is a sessile microbial community with several kinds of organisms such as bacteria, protozoa, fungi, algae, and extracellular polymeric substances, which may be found on almost any surface exposed to water. Here, biofilms were used to monitor the presence of PAHs in the Barigui River in Curitiba, Brazil. For the measurements and collection of representative microcoenoses, a biofilm sampling device was designed consisting of six glass plates installed in an open polyvinyl chloride pipe of 30?cm diameter and 60?cm length. The sampling device was exposed in the Barigui River for 2?weeks campaigns. The formed biofilm was treated and chemical analysis was performed for PAHs determination. The results showed that biofilms can trap most of the PAHs, especially those with high K _ow values (octanol?Cwater partition coefficient). Four campaigns were conducted. The total PAHs concentration ranged from 11,204.34?±?560.12 to 45,846.90?±?2,290.45?ng/g. According to the isomers ratio, the main source of PAHs in the first and second campaign was of pyrolytic origin, in other words, the PAHs were by-products from burning of light-refined oil products (gasoline and diesel oil). Meanwhile, the other campaigns revealed that the main source is of petrogenic origin. However, the possibility of both sources is not discarded considering the scenario studied and the records of sediments samples. Most of the investigations carried out focused on the loading of river sediments and suspended solids, but the biofilms might detect the amount that could be taken up by benthic organisms, for instance.  相似文献