Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma

Epidermal growth factor receptor (EGFR) and tumour growth factor alpha (TGFα) are frequently overexpressed in renal cell carcinoma (RCC) yet responses to single-agent EGFR inhibitors are uncommon. Although von Hippel–Lindau (VHL) mutations are predominant, RCC also develops in individuals with tuberous sclerosis (TSC). Tuberous sclerosis mutations activate mammalian target of rapamycin (mTOR) and biochemically resemble VHL alterations. We found that RCC cell lines expressed EGFR mRNA in the near-absence of other ErbB family members. Combined EGFR and mTOR inhibition synergistically impaired growth in a VHL-dependent manner. Iressa blocked ERK1/2 phosphorylation specifically in wt-VHL cells, whereas rapamycin inhibited phospho-RPS6 and 4E-BP1 irrespective of VHL. In contrast, phospho-AKT was resistant to these agents and MYC translation initiation (polysome binding) was similarly unaffected unless AKT was inhibited. Primary RCCs vs cell lines contained similar amounts of phospho-ERK1/2, much higher levels of ErbB-3, less phospho-AKT, and no evidence of phospho-RPS6, suggesting that mTOR activity was reduced. A subset of tumours and cell lines expressed elevated eIF4E in the absence of upstream activation. Despite similar amounts of EGFR mRNA, cell lines (vs tumours) overexpressed EGFR protein. In the paired cell lines, PRC3 and WT8, EGFR protein was elevated post-transcriptionally in the VHL mutant and EGF-stimulated phosphorylation was prolonged. We propose that combined EGFR and mTOR inhibitors may be useful in the subset of RCCs with wt-VHL. However, apparent differences between primary tumours and cell lines require further investigation

Efeitos de extratos de plantas na biologia de Spodoptera frugiperda (J. E. Smith, 1797) (Lepidoptera: Noctuidae) mantida em dieta artificial Effects of plant extracts on the biology of Spodoptera frugiperda (J. E. Smith, 1797) (Lepidoptera: Noctuidae) maintained under artificial diet

Avaliaram-se os efeitos dos extratos aquosos a 10% de folhas e ramos de arruda (Ruta graveolens L.), folhas e ramos de melão-de-são-caetano (Momordica charantia L.), folhas do alecrim-pimenta (Lippia sidoides Cham.) e fruto verde de mamona (Ricinus communis L.), sobre a biologia da lagarta-do-cartucho do milho (Spodoptera frugiperda), mantida em dieta artificial. Os parâmetros avaliados foram duração e viabilidade das fases larval e pupal, peso de pupa, fecundidade, fertilidade e longevidade de adultos. Larvas de S. frugiperda recém-eclodidas foram colocadas em tubos de ensaio com dieta artificial, contendo os extratos de cada material testado. O extrato aquoso do fruto verde de R. communis apresentou bioatividade, nos parâmetros duração larval e pupal e peso de pupa. O extrato aquoso de R. graveolens reduziu o peso de pupa. A dieta contendo extrato de folhas e ramos de M. charantia reduziu a viabilidade larval e o peso de pupa. O extrato aquoso de folhas de L. sidoides não afetou as fases larval e pupal, reduziu a postura e a viabilidade de ovos e aumentou a longevidade de adultos de S. frugiperda. A viabilidade de pupa não foi afetada pelos extratos testados.<br>The effects of aqueous extracts, at 10% concentration of leaves and branches of Ruta graveolens L., leaves and branches of Momordica charantia L., leaves of Lippia sidoides Cham. and green fruits of Ricinus communis L. were evaluated on the biology of fall armyworm (Spodoptera frugiperda) maintained under artificial diet. The evaluated parameters were: duration and viability of the larval and pupal phases, pupa weight, fecundity, fertility and longevity of adults. Just-hatched larvae of S. frugiperda was placed in test tube with artificial diet containing extracts of each tested material. The aqueous extract of the green fruits of R. communis presented bioactivity upon duration and weight of larval and pupal phases. The aqueous extract of R. graveolens reduced weight of pupa. The diet containing extract of M. charantia reduced larval viability and weight of pupa. The aqueous extract of L. sidoides did not affect larval and pupal phases, but reduced the posture and the viability of eggs and increased longevity of adults of S. frugiperda. The viability of pupa was not affected by the extracts

Efeito de extratos aquosos de Azadirachta indica, Melia azedarach e Aspidosperma pyrifolium no desenvolvimento e oviposição de Plutella xylostella Effect of aqueous extracts of Azadirachta indica (A. Juss), Melia azedarach (L.) and Aspidosperma pyrifolium (Mart.) on the development and oviposition of Plutella xylostella (L.) (Lepidoptera: Plutellidae)

Foram avaliados a CL50 e o efeito de extratos aquosos de plantas na biologia, oviposição e período embrionário de Plutella xylostella L. (Lepidoptera: Plutellidae). Para determinação da CL50 foram utilizadas concentrações entre 0,03 e 0,8 % para amêndoas de Azadirachta indica (A. Juss.) 0,5 e 7,0 % para casca de Aspidosperma pyrifolium (Mart.) e 0,5 e 12,5 % para frutos de Melia azedarach (L.), obtendo-se as CL50 de 0,06; 2,17 e 2,90%, respectivamente. Verificou-se que os extratos aquosos de todas as espécies vegetais afetaram o desenvolvimento do inseto, principalmente na fase larval. Na fase de pupa, os extratos reduziram a massa e a viabilidade. Houve deformação de adultos para os extratos de A. pyrifolium e M. azedarach e o de A. indica causou maior porcentagem. Todos os extratos possuem efeito tóxico para ovos de P. xylostella, sendo dependente do aumento da concentração. Nos extratos da casca de A. pyrifolium, do fruto de M. azedarach e da amêndoa de A. indica observa-se ação ovicida quando usados na concentração letal de lagartas de primeiro ínstar da praga. Em observações do ovo de P. xylostella com auxílio de um microscópio eletrônico de varredura, verificou-se a existência de microporos onde pode ocorrer a penetração do produto ovicida, além da constatação da textura rugosa da casca do ovo que pode reter ou fixar os extratos.<br>The effects of aqueous extracts of plants on the biology, preference for oviposition and embryonic period of Plutella xylostella were evaluated. Concentrations between 0.03 and 0.8 % for kernel of Azadirachta indica, 0.5 and 7.0% for peel of Aspidosperma pyrifolium and 0.5 and 12.5% for fruits of Melia azedarach were used, with LC50 values of 0.06; 2.17 and 2.90%, respectively, being obtained. It was verified that the aqueous extracts of all of the appraised vegetable species affected the development of the insect, mainly in the larval phase. In the pupae phase, the extracts reduced the weight and the viability. There was adults' deformation for the extracts of A. pyrifolium and M. azedarach, being it of A. indica what caused larger percentage. Toxics effects on the eggs of P. xylostella were observed for all extracts. The extracts from A. pyrifolium (peel); M. azedarach (fruit) and A. indica (kernel) presented ovicide action in the lethal concentration of caterpillars at first instar of the pest. Observations of P. xylostella eggs with the aid of an electronic microscope showed presence of microspore, revealing ovicide action, besides wrinkled texture of the eggs peel retaining the extracts

Analysis of ill-structured problem solving, mentoring functions, and perceptions of practicum teachers and mentors toward online mentoring in a field-based practicum

This article describes an exploratory study of question prompts and online mentoring (specifically a lateral or peer mentoring experience) in a field-based practicum that focused on teaching ill-structured problem solving of classroom discipline. Data were gathered on 26 in-service practicum teachers through online observations, online journal reports, questionnaires, and reflection logs. Results showed that the practicum teachers were successful in using the approach to plan and implement effective interventions for their students and that they perceived the online mentoring approach as being very beneficial in supporting their learning. A more detail analysis of seven practicum teachers and their mentors indicated that their mentors engaged in eight types of online mentoring functions; the most frequently used were asking practicum teachers to elaborate, and valuing the practicum teachers' contributions. The influence of the mentoring functions on the seven practicum teachers' ill-structured problem solving is also discussed. The study offers evidence that asynchronous online mentoring and question prompts can enhance the professional development of both practicum teachers and mentors by helping them learn about and apply intervention strategies in solving real-world teaching problems. © Springer Science+Business Media, Inc. 2007.link_to_subscribed_fulltex