Altering Chemosensitivity by Modulating Translation Elongation

BACKGROUND: The process of translation occurs at a nexus point downstream of a number of signal pathways and developmental processes. Modeling activation of the PTEN/AKT/mTOR pathway in the Emu-Myc mouse is a valuable tool to study tumor genotype/chemosensitivity relationships in vivo. In this model, blocking translation initiation with silvestrol, an inhibitor of the ribosome recruitment step has been showed to modulate the sensitivity of the tumors to the effect of standard chemotherapy. However, inhibitors of translation elongation have been tested as potential anti-cancer therapeutic agents in vitro, but have not been extensively tested in genetically well-defined mouse tumor models or for potential synergy with standard of care agents. METHODOLOGY/PRINCIPAL FINDINGS: Here, we chose four structurally different chemical inhibitors of translation elongation: homoharringtonine, bruceantin, didemnin B and cycloheximide, and tested their ability to alter the chemoresistance of Emu-myc lymphomas harbouring lesions in Pten, Tsc2, Bcl-2, or eIF4E. We show that in some genetic settings, translation elongation inhibitors are able to synergize with doxorubicin by reinstating an apoptotic program in tumor cells. We attribute this effect to a reduction in levels of pro-oncogenic or pro-survival proteins having short half-lives, like Mcl-1, cyclin D1 or c-Myc. Using lymphomas cells grown ex vivo we reproduced the synergy observed in mice between chemotherapy and elongation inhibition and show that this is reversed by blocking protein degradation with a proteasome inhibitor. CONCLUSION/SIGNIFICANCE: Our results indicate that depleting short-lived pro-survival factors by inhibiting their synthesis could achieve a therapeutic response in tumors harboring PTEN/AKT/mTOR pathway mutations

Five Nuclear Loci Resolve the Polyploid History of Switchgrass (Panicum virgatum L.) and Relatives

Polyploidy poses challenges for phylogenetic reconstruction because of the need to identify and distinguish between homoeologous loci. This can be addressed by use of low copy nuclear markers. Panicum s.s. is a genus of about 100 species in the grass tribe Paniceae, subfamily Panicoideae, and is divided into five sections. Many of the species are known to be polyploids. The most well-known of the Panicum polyploids are switchgrass (Panicum virgatum) and common or Proso millet (P. miliaceum). Switchgrass is in section Virgata, along with P. tricholaenoides, P. amarum, and P. amarulum, whereas P. miliaceum is in sect. Panicum. We have generated sequence data from five low copy nuclear loci and two chloroplast loci and have clarified the origin of P. virgatum. We find that all members of sects. Virgata and Urvilleana are the result of diversification after a single allopolyploidy event. The closest diploid relatives of switchgrass are in sect. Rudgeana, native to Central and South America. Within sections Virgata and Urvilleana, P. tricholaenoides is sister to the remaining species. Panicum racemosum and P. urvilleanum form a clade, which may be sister to P. chloroleucum. Panicum amarum, P. amarulum, and the lowland and upland ecotypes of P. virgatum together form a clade, within which relationships are complex. Hexaploid and octoploid plants are likely allopolyploids, with P. amarum and P. amarulum sharing genomes with P. virgatum. Octoploid P. virgatum plants are formed via hybridization between disparate tetraploids. We show that polyploidy precedes diversification in a complex set of polyploids; our data thus suggest that polyploidy could provide the raw material for diversification. In addition, we show two rounds of allopolyploidization in the ancestry of switchgrass, and identify additional species that may be part of its broader gene pool. This may be relevant for development of the crop for biofuels

Prevalência e fatores associados à respiração oral em escolares participantes do projeto Santo Amaro-Recife,2005 Prevalence and factors related to mouth breathing in school children at the Santo Amaro project-Recife,2005

OBJETIVO: Determinar prevalência de crianças portadoras de respiração oral inscritas no Projeto Santo Amaro/ ESEF/ UPE e verificar as principais alterações faciais e comportamentais associadas. FORMA DE ESTUDO: Estudo transversal. MATERIAL E MÉTODO: Amostra de 150 crianças de 8 a 10 anos. Dados coletados mediante aplicação de questionário e exames clínicos. Para o diagnóstico da respiração foram feitos dois testes. Teste 1, observado no espelho, vapor decorrente da respiração, e teste 2, a permanência de água na boca com os lábios em contato pelo tempo de 3 minutos. RESULTADOS: Prevalência de respiração oral foi de 53,3%. Não se comprovou diferença significante entre gênero, faixa etária, tipo de respiração. As alterações faciais da respiração oral foram: selamento labial inadequado (58,8% x 5,7%), olhos caídos (40,0% x 1,4%), palato ogival (38,8% x 2,9%), mordida aberta anterior (60,0% x 30,0%), lábios hipotônicos (23,8% x 0,0%) e olheiras (97,5% x 77,1%). CONCLUSÃO: Prevalência de respiração oral elevada sem diferença estatística entre os gêneros, faixa etária e tipo de respiração oral. Não houve associação entre características comportamentais e o tipo de respiração. Houve diferença significante entre as características físicas e o padrão de respiração.<br>AIM: To determine the prevalence of mouth breathing children at the santo amaro project/ esef/ upe, and study their main facial and behavior alterations. STUDY DESIGN: transversal study. MATERIAL AND METHODS: there were 150 children in the sample, with ages ranging from 8 to 10 years. Data was collected by means of a questionnaire and clinical examinations. As for their breathing assessment, two tests were carried out: test 1- breath steam against a mirror; and test 2 -water remains in the mouth with lips closed for 3 minutes. RESULTS: mouth breathing prevalence was of 53.3%. There was no significant difference between gender, age and type of breathing. Facial alterations were:incomplete lip closure ( 58.8% X 5,7%), fallen eyes ( 40.0% X 1.4%), High palate ( 38.8% X 2.9%), Anterior open bite ( 60.0% Versus 30.0%), Hypotonic lips ( 3.8% X 0.0%), Circles under the eyes (97.5% Versus 77.1%). CONCLUSION: high mouth breathing prevalence without significant statistical difference between genders,age and type of mouth breathing. There was no association between behavior characteristics and type of breathing. There were significant differences between physical traits and breathing pattern