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61.
Michal Grzmil Brian A. Hemmings 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(7):1371-1380
Glioblastoma is the most common and aggressive brain tumor type, with a mean patient survival of approximately 1 year. Many previous analyses of the glioma kinome have identified key deregulated pathways that converge and activate mammalian target of rapamycin (mTOR). Following the identification and characterization of mTOR-promoting activity in gliomagenesis, data from preclinical studies suggested the targeting of mTOR by rapamycin or its analogs (rapalogs) as a promising therapeutic approach. However, clinical trials with rapalogs have shown very limited efficacy on glioma due to the development of resistance mechanisms. Analysis of rapalog-insensitive glioma cells has revealed increased activity of growth and survival pathways compensating for mTOR inhibition by rapalogs that are suitable for therapeutic intervention. In addition, recently developed mTOR inhibitors show high anti-glioma activity. In this review, we recapitulate the regulation of mTOR signaling and its involvement in gliomagenesis, discuss mechanisms resulting in resistance to rapalogs, and speculate on strategies to overcome resistance. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012). 相似文献
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Carmen García-Ibarbia Jesús Delgado-Calle Iñigo Casafont Javier Velasco Jana Arozamena María I. Pérez-Núñez María A. Alonso María T. Berciano Fernando Ortiz José L. Pérez-Castrillón Agustín F. Fernández Mario F. Fraga María T. Zarrabeitia José A. Riancho 《Gene》2013
We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic and epigenetic mechanisms involved. 相似文献
64.
植食性昆虫的天敌能够利用虫害诱导的挥发物进行有效的寄主或猎物定位。为了开发稻飞虱卵期天敌稻虱缨小蜂Anagrus nilaparvatae Pang et Wang的引诱剂,分别在室内和室外检测了多种褐飞虱诱导的水稻挥发物组分对褐飞虱卵期天敌稻虱缨小蜂的引诱作用。Y型嗅觉仪实验结果表明,5种单一化合物,Z-3-己烯乙酸酯,1-戊烯基-3-醇,Z-3-己烯醛,芳樟醇和水杨酸甲酯,以及3种混合物,水杨酸甲酯+Z-3-己烯醛,Z-3-己烯醛+Z-3-己烯乙酸酯+芳樟醇,水杨酸甲酯+Z-3-己烯醛+Z-3-己烯乙酸酯+芳樟醇,对稻虱缨小蜂具有明显引诱作用。田间试验表明,3种单一化合物,Z-3-己烯乙酸酯,Z-3-己烯醛和芳樟醇,以及一种混合物,水杨酸甲酯+Z-3-己烯醛+Z-3-己烯乙酸酯+芳樟醇,能明显提高稻虱缨小蜂对褐飞虱卵的寄生作用。这些结果对于改善褐飞虱治理具有重要的意义。 相似文献
65.
Dariusz Pańka Dariusz PiesikMałgorzata Jeske Anna Baturo-Cieśniewska 《Journal of plant physiology》2013
Grasses very often form symbiotic associations with Neotyphodium/Epichloë endophytic fungi. These endophytes often allow the host grass to be protected from different pathogens. However, there is little known about the mechanisms of such endophyte influence on the host. Thus, the purpose of this research was to examine the effect of the N. lolii endophyte on the total production of phenolic compounds, VOCs emission and the resistance of three perennial ryegrass genotypes infected by pathogenic Fusarium poae. Analyses of total phenolics content were performed in control (not inoculated) and inoculated plants after 1, 2, 3, 4, 5, and 6 days (DAI) and for VOCs after 0, 3, 6 and 12 DAI. The presence of endophytes significantly reduced the disease index in two of the three genotypes relative to that in E−. Plants infected by N. lolii exhibited higher production of phenolics relative to the E− plants. The highest amounts of phenolics were observed on the second and sixth DAI. Genotype Nl22 showed the strongest effect of the endophyte on the production of phenolics, which increased by over 61%. Both the endophyte infected and non-infected plants emitted most abundantly two GLVs ((Z)-3-hexenal, (Z)-3-hexen-1-yl acetate), three terpenes (linalool, (Z)-ocimene, β-caryophyllene) and three shikimic acid pathway derivatives (benzyl acetate, indole, and methyl salicylate). The endophyte presence and the intervals of VOCs detection were a highly significant source of variation for all emitted volatiles (P < 0.001). The genotype of the perennial ryegrass significantly affected only the emission of methyl salicylate (P < 0.05) and β-caryophyllene (P < 0.05). Most of the VOCs ((Z)-3-hexen-1-yl acetate, (Z)-3-hexenal, linalool and methyl salicylate) reached their highest levels of emission on the sixth DAI, when averaged over genotypes and endophyte status. The results highlight the role of Neotyphodium spp. in the mediation of quadro-trophic interactions among plants, symbiotic endophytes, invertebrate herbivores and plant pathogenic fungi. Our results also confirm the fact that symbiotic plants can activate a defense reaction faster than non-symbiotic plants after a pathogen attack. Thus, N. lolii can be involved in the defense of perennial ryegrass against pathogens and potentially could be central to the host plants’ protection. 相似文献
66.
Juan A. Pajares Gonzalo Álvarez David R. Hall Paul Douglas Felix Centeno Nieves Ibarra Martin Schroeder Stephen A. Teale Zhiying Wang Shanchun Yan Jocelyn G. Millar Lawrence M. Hanks 《Entomologia Experimentalis et Applicata》2013,149(2):118-127
The small white‐marmorated longicorn beetle, Monochamus sutor (L.) (Coleoptera: Cerambycidae), is widely distributed throughout Europe and Asia. It is a potential vector of the pine wood nematode, Bursaphelenchus xylophilus (Steiner et Buhrer) Nickle, the causal agent of the devastating pine wilt disease. Volatiles were collected from both male and female beetles after maturation feeding. In analyses of these collections using gas chromatography (GC) coupled to mass spectrometry, a single male‐specific compound was detected and identified as 2‐(undecyloxy)‐ethanol. In analyses by GC coupled to electroantennography the only consistent responses from both female and male antennae were to this compound. Trapping tests were carried out in Spain, Sweden, and China. 2‐(Undecyloxy)‐ethanol was attractive to both male and female M. sutor beetles. A blend of the bark beetle pheromones ipsenol, ipsdienol, and 2‐methyl‐3‐buten‐2‐ol was also attractive to both sexes in Spain and Sweden, and further increased the attractiveness of the 2‐(undecyloxy)‐ethanol. The host plant volatiles α‐pinene, 3‐carene, and ethanol were weakly attractive, if at all, in all three countries and did not significantly increase the attractiveness of the blend of 2‐(undecyloxy)‐ethanol and bark beetle pheromones. 2‐(Undecyloxy)‐ethanol is thus proposed to be the major, if not only, component of the male‐produced aggregation pheromone of M. sutor, and its role is discussed. This compound has been reported as a pheromone of several other Monochamus species and is another example of the parsimony that seems to exist among the pheromones of many of the Cerambycidae. Traps baited with 2‐(undecyloxy)‐ethanol and bark beetle pheromones should be useful for monitoring and control of pine wilt disease, should M. sutor be proven to be a vector of the nematode. 相似文献
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Shawn A. Christensen Andriy Nemchenko Eli Borrego Ian Murray Islam S. Sobhy Liz Bosak Stacy DeBlasio Matthias Erb Christelle A.M. Robert Kathy A. Vaughn Cornelia Herrfurth Jim Tumlinson Ivo Feussner David Jackson Ted C.J. Turlings Jurgen Engelberth Christian Nansen Robert Meeley Michael V. Kolomiets 《The Plant journal : for cell and molecular biology》2013,74(1):59-73
Fatty acid derivatives are of central importance for plant immunity against insect herbivores; however, major regulatory genes and the signals that modulate these defense metabolites are vastly understudied, especially in important agro‐economic monocot species. Here we show that products and signals derived from a single Zea mays (maize) lipoxygenase (LOX), ZmLOX10, are critical for both direct and indirect defenses to herbivory. We provide genetic evidence that two 13‐LOXs, ZmLOX10 and ZmLOX8, specialize in providing substrate for the green leaf volatile (GLV) and jasmonate (JA) biosynthesis pathways, respectively. Supporting the specialization of these LOX isoforms, LOX8 and LOX10 are localized to two distinct cellular compartments, indicating that the JA and GLV biosynthesis pathways are physically separated in maize. Reduced expression of JA biosynthesis genes and diminished levels of JA in lox10 mutants indicate that LOX10‐derived signaling is required for LOX8‐mediated JA. The possible role of GLVs in JA signaling is supported by their ability to partially restore wound‐induced JA levels in lox10 mutants. The impaired ability of lox10 mutants to produce GLVs and JA led to dramatic reductions in herbivore‐induced plant volatiles (HIPVs) and attractiveness to parasitoid wasps. Because LOX10 is under circadian rhythm regulation, this study provides a mechanistic link to the diurnal regulation of GLVs and HIPVs. GLV‐, JA‐ and HIPV‐deficient lox10 mutants display compromised resistance to insect feeding, both under laboratory and field conditions, which is strong evidence that LOX10‐dependent metabolites confer immunity against insect attack. Hence, this comprehensive gene to agro‐ecosystem study reveals the broad implications of a single LOX isoform in herbivore defense. 相似文献
69.
Cornelis A. Hordijk Harry R. Harhangi Jeroen J. Jansen A. Sankara Reddy Jeffrey A. Harvey Louise E. M. Vet Nicole M. van Dam 《Molecular ecology》2013,22(24):6179-6196
Upon herbivore feeding, plants emit complex bouquets of induced volatiles that may repel insect herbivores as well as attract parasitoids or predators. Due to differences in the temporal dynamics of individual components, the composition of the herbivore‐induced plant volatile (HIPV) blend changes with time. Consequently, the response of insects associated with plants is not constant either. Using Brassica juncea as the model plant and generalist Spodoptera spp. larvae as the inducing herbivore, we investigated herbivore and parasitoid preference as well as the molecular mechanisms behind the temporal dynamics in HIPV emissions at 24, 48 and 72 h after damage. In choice tests, Spodoptera litura moth preferred undamaged plants, whereas its parasitoid Cotesia marginiventris favoured plants induced for 48 h. In contrast, the specialist Plutella xylostella and its parasitoid C. vestalis preferred plants induced for 72 h. These preferences matched the dynamic changes in HIPV blends over time. Gene expression analysis suggested that the induced response after Spodoptera feeding is mainly controlled by the jasmonic acid pathway in both damaged and systemic leaves. Several genes involved in sulphide and green leaf volatile synthesis were clearly up‐regulated. This study thus shows that HIPV blends vary considerably over a short period of time, and these changes are actively regulated at the gene expression level. Moreover, temporal changes in HIPVs elicit differential preferences of herbivores and their natural enemies. We argue that the temporal dynamics of HIPVs may play a key role in shaping the response of insects associated with plants. 相似文献
70.