An Integrative Genomic and Transcriptomic Analysis Reveals Potential Targets Associated with Cell Proliferation in Uterine Leiomyomas

Background: Uterine Leiomyomas (ULs) are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs). Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs. Methodology: We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC) and gene expression microarrays (SAM). The CONEXIC algorithm was applied to integrate the data. Principal Findings: The integrated analysis identified the top 30 significant genes (P<0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively) and IGFBP5 (P = 0.0002 and P = 0.006, respectively) were up-regulated in the tumours when compared with the adjacent normal myometrium. Conclusions: The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs. © 2013 Cirilo et al.

Transporter protein genes are differentially expressed in Acidithiobacillus ferrooxidans LR maintained in contact with covellite

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sistemas de criação para o Acará-bandeira Pterophyllum scalare

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Adaptabilidade e estabilidade de clones de cana-de-açúcar no Estado de São Paulo

Pós-graduação em Agronomia - FEIS

Adaptabilidade e estabilidade de cultivares de milho para diferentes safras, espaçamentos e populações de plantas

Pós-graduação em Agronomia - FEIS

Adaptabilidade e estabilidade de clones de cana-de-açúcar

The objective of this study was to identify clones of sugarcane with good stability and adaptability in the State of São Paulo, Brazil, and also identifying locations most representative for selection and experimentation. Ten clones and two commercial checks of medium-late maturation were evaluated in the first-ratoon of experiments harvested in August 2009, using bissegmented regression and AMMI (Additive Main Effects and Multiplicative Interaction Analysis) methods. The results of two methods were compared and they evidenced that the clones RB975201, RB975157, RB975932, RB975242 and RB975162 are the most promising, showing higher production when compared to the checks, higher stability observed in one or both statistical methods and broader or more specific adaptability. The environment Tarumã presented higher stability and capacity to discriminate genotypes, allowing an ordering more reliable as compared to the overall mean of the environments tested.

Abordagem genética e multivariada na performance agronômica de genótipos de soja oriundos de diferentes genealogias

Pós-graduação em Agronomia (Genética e Melhoramento de Plantas) - FCAV

Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A dimensão dialógica e a prática educativa: reflexões a partir de Paulo Freire e Humberto Maturana

Ao observarmos o cotidiano nas escolas é possível constatar que nem sempre se reconhece e se valoriza a diferença e a singularidade que caracteriza cada sujeito envolvido, pois ocorrem situações de negação mútua entre alunos, entre alunos e professores e entre outras relações do espaço escolar que ferem a dignidade humana. Uma alternativa a essa realidade é a promoção de vivências dialógicas. Nesse sentido, objetivamos com este trabalho: Refletir sobre as contribuições teórico-conceituais desenvolvidas por Paulo Freire e por Humberto Maturana acerca da vivência do diálogo, suas possibilidades e impasses nas relações sociais e na relação educativa; e identificar, a partir de um estudo de caso realizado em uma escola da Rede Pública Estadual, as concepções dos educadores sobre a prática dialógica no cotidiano escolar. Para Freire, o diálogo é o encontro e a partilha de concepções de A com B e não de A sobre B ou vice versa, sendo que nesta relação é importante que ambos se disponham à escuta mútua reconhecendo a diversidade de concepções que estimula a curiosidade epistemológica. Para Maturana, a partir da Biologia, cada ser vivo se constitui como uma organização autopoiética, ou seja, tem a tarefa de produzir-se a si próprio, estabelecendo relações com o meio. Na existência humana, essas interações com o meio e entre os humanos se estabelecem num entrelaçamento de emoções e ações, que ele nomeia de conversação. A partir das reflexões pelos autores e o diálogo estabelecido com sujeitos da pesquisa destacamos: 1) As relações sociais se mantêm quando há aceitação do outro como legítimo outro na convivência, o que implica a aceitação de si próprio; 2) O diálogo cria um clima de aceitação para com a história e a diferença do outro, o que favorece relações de partilha de ideias e de releitura coletiva do mundo. Tanto Maturana e Freire, quanto os entrevistados valorizam o ...

Caracterização funcional e estrutural das proteínas RUV-1 e RUV-2 do fungo Neurospora crassa

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The interaction between atoms of Au and Cu with clean Si(111) surface: A study combining synchrotron radiation grazing incidence X-ray fluorescence analysis and theoretical calculations

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Differential gene expression by Paracoccidioides brasiliensis in host interaction conditions: Representational difference analysis identifies candidate genes associated with fungal pathogenesis

Paracoccidioides brasiliensis causes infection by the host inhalation of airborne propagules of the mycelia phase of the fungus. These particles reach the lungs, and disseminate to virtually all organs. Here we describe the identification of differentially expressed genes in studies of host-fungus interaction. We analyzed two cDNA populations of P. brasiliensis, one obtained from infected animals and the other an admixture of fungus and human blood thus mimicking the hematologic events of the fungal dissemination. Our analysis identified transcripts differentially expressed. Genes related to iron acquisition, melanin synthesis and cell defense were specially upregulated in the mouse model of infection. The upregulated transcripts of yeast cells during incubation with human blood were those predominantly related to cell wall remodeling/synthesis. The expression pattern of genes was independently confirmed in host conditions, revealing their potential role in the infection process. This work can facilitate functional studies of novel regulated genes that may be important for the survival and growth strategies of P. brasiliensis in humans. (c) 2006 Elsevier Masson SAS. All rights reserved.

Evaluation of the Interaction Between Sodium Hypochlorite and Several Formulations Containing Chlorhexidine and its Effect on the Radicular Dentin-SEM and Push-Out Bond Strength Analysis

The aim of the current study was to evaluate the presence of debris and smear layer after endodontic irrigation with different formulations of 2% chlorhexidine gluconate (CHX) and its effects on the push-out bond strength of an epoxy-based sealer on the radicular dentin. One hundred extracted human canines were prepared to F5 instrument and irrigated with 2.5% sodium hypochlorite and 17% ethylenediaminetetraacetic acid. Fifty teeth were divided into five groups (n=10), according to the final irrigation protocol with different 2% CHX formulations: G1 (control, no final rinse irrigation), G2 (CHX solution), G3 (CHX gel), G4 (Concepsis), and G5 (CHX Plus). In sequence, the specimens were submitted to scanning electron microscopy (SEM) analysis, in the cervical-medium and medium-apical segments, to evaluate the presence of debris and smear layer. The other 50 teeth were treated equally to a SEM study, but with the root canals filled with an epoxy-based endodontic sealer and submitted to a push-out bond strength test, in the cervical, middle, and apical thirds. G2, G3, G4, and G5 provided higher precipitation of the debris and smear layer than G1 (P<0.05), but these groups were similar to each other (P>0.05), in both segments. The values obtained in the push out test did not differ between groups, independent of the radicular third (P>0.05). The CHXs formulations caused precipitation of the debris and smear layer on the radicular dentin, but these residues did not interfere in the push-out bond strength of the epoxy-based sealer. Microsc. Res. Tech. 77:17-22, 2014. (c) 2013 Wiley Periodicals, Inc.

Computational analysis and physico-chemical characterization of an inclusion compound between praziquantel and methyl-beta-cyclodextrin for use as an alternative in the treatment of schistosomiasis

Schistosomiasis is still an endemic disease in many regions, with 250 million people infected with Schistosoma and about 500,000 deaths per year. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment, however it is classified as Class II in the Biopharmaceutics Classification System, as its low solubility hinders its performance in biological systems. The use of cyclodextrins is a useful tool to increase the solubility and bioavailability of drugs. The aim of this work was to prepare an inclusion compound of PZQ and methyl-beta-cyclodextrin (MeCD), perform its physico-chemical characterization, and explore its in vitro cytotoxicity. SEM showed a change of the morphological characteristics of PZQ:MeCD crystals, and IR data supported this finding, with changes after interaction with MeCD including effects on the C-H of the aromatic ring, observed at 758 cm(-1). Differential scanning calorimetry measurements revealed that complexation occurred in a 1:1 molar ratio, as evidenced by the lack of a PZQ transition temperature after inclusion into the MeCD cavity. In solution, the PZQ UV spectrum profile in the presence of MeCD was comparable to the PZQ spectrum in a hydrophobic solvent. Phase solubility diagrams showed that there was a 5.5-fold increase in PZQ solubility, and were indicative of a type A(L) isotherm, that was used to determine an association constant (K(a)) of 140.8 M(-1). No cytotoxicity of the PZQ:MeCD inclusion compound was observed in tests using 3T3 cells. The results suggest that the association of PZQ with MeCD could be a good alternative for the treatment of schistosomiasis.

Effects of plant density and proportion on the interaction between wheat with alexandergrass plants

A determinação das relações competitivas entre espécies de plantas requer delineamentos experimentais e métodos de análise apropriados. A hipótese da pesquisa foi que duas espécies crescendo em convivência têm comportamento de crescimento e desenvolvimento distintos em função da sua competitividade relativa. O objetivo desta pesquisa foi quantificar a competitividade relativa da cultura do trigo com o capim-marmelada através da medida dos efeitos da densidade e da proporção de plantas, usando experimentos em série substitutiva. Monoculturas foram cultivadas em densidades de 1, 3, 5, 10 e 15 plantas por caixa e analisadas por regressão dos dados de massa seca, em 2006. Experimento em mistura foi cultivado nas proporções trigo:capim-marmelada de 0:6, 1:5, 2:4, 3:3, 4:2, 5:1 e 6:0 plantas por caixa e analisado através de interpretação gráfica de características de crescimento e produção, em 2007. Ambos os experimentos foram realizados em delineamento completamente casualizado com quatro repetições. Capim-marmelada foi mais sensível que trigo à competição intraespecífica. Capim-marmelada foi levemente mais competitivo que trigo. Número e massa de espigas e número de afilhos foram as características do trigo mais afetadas pela interferência do capim-marmelada.