Genome-Wide Analysis of Gene Expression during Early Arabidopsis Flower Development

Detailed information about stage-specific changes in gene expression is crucial for the understanding of the gene regulatory networks underlying development. Here, we describe the global gene expression dynamics during early flower development, a key process in the life cycle of a plant, during which floral patterning and the specification of floral organs is established. We used a novel floral induction system in Arabidopsis, which allows the isolation of a large number of synchronized floral buds, in conjunction with whole-genome microarray analysis to identify genes with differential expression at distinct stages of flower development. We found that the onset of flower formation is characterized by a massive downregulation of genes in incipient floral primordia, which is followed by a predominance of gene activation during the differentiation of floral organs. Among the genes we identified as differentially expressed in the experiment, we detected a significant enrichment of closely related members of gene families. The expression profiles of these related genes were often highly correlated, indicating similar temporal expression patterns. Moreover, we found that the majority of these genes is specifically up-regulated during certain developmental stages. Because co-expressed members of gene families in Arabidopsis frequently act in a redundant manner, these results suggest a high degree of functional redundancy during early flower development, but also that its extent may vary in a stage-specific manner

A Rapid and Sensitive HPLC–DAD Assay to Quantify Lamotrigine, Phenytoin and Its Main Metabolite in Samples of Cultured HepaRG Cells

A sensitive and fast high-performance liquid chromatography-diode-array detection assay was developed and validated for the simultaneous quantification of 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), phenytoin (PHT) and lamotrigine (LTG) in samples of cultured HepaRG cells. Chromatographic separation of analytes and internal standard (IS) was achieved in ∼15 min on a C18-column, at 35°C, using acetonitrile (6%), methanol (25%) and a mixture (69%) of water-triethylamine (99.7:0.3, v/v; pH 6.0), pumped at 1 mL/min. The analytes and IS were detected at 215 or 235 nm. Calibration curves were linear with regression coefficients >0.994 over the concentration ranges of 0.1-15 µg/mL for HPPH; 0.15-30 µg/mL for PHT and 0.2-20 µg/mL for LTG. The method showed to be accurate (bias value of ±10.5 or ±17.6% in the lower limit of quantification, LLOQ) and precise (coefficient variation ≤8.1 or ≤15.4% in the LLOQ), and the absolute recovery of the analytes ranged from 62.5 to 96.9%. HepaRG cells have emerged as a very promising in vitro model to evaluate metabolic, drug interaction and/or pharmacokinetic studies, and this methodology will be suitable to support subsequent studies involving the antiepileptic drugs PHT and LTG

Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats

Considering the potential of flavonoids in reversing the P-glycoprotein (P-gp)–mediated multidrug resistance, this work aimed to assess the combined effects of silymarin and (-)-epigallocatechin gallate (EPG) on the pharmacokinetics of the P-gp substrates oxcarbazepine (OXC) and licarbazepine (LIC). Rats were pre-treated intraperitoneally with silymarin (25 mg/kg), EPG (25 mg/kg), silymarin/EPG (12.5/12.5 mg/kg; 6.25/18.75 mg/kg; 18.75/6.25 mg/kg) or verapamil (25 mg/kg, reference P-gp inhibitor) before the intraperitoneal administration of OXC (50 mg/kg). Pre-treatment with dual silymarin/EPG combinations originated peak plasma concentrations of OXC and LIC (pharmacologically active metabolite of OXC) similar to those achieved in the presence of verapamil (positive control). Moreover, the effects promoted by silymarin/EPG combinations on the magnitude of systemic drug exposure to OXC and LIC were also reflected in the corresponding drug levels attained in the brain (biophase). These findings evidence the synergistic effect of silymarin and EPG in enhancing the degree of systemic exposure to OXC and LIC in rats, which occurred in a comparable extent to that observed with verapamil. Hence, our findings support the combination of flavonoid-type P-gp inhibitors and P-gp substrate antiepileptic drugs as a potential therapeutic strategy for the management of pharmacoresistant epilepsy.The authors are grateful to FCT - Foundation for Science and Technology (Lisbon, Portugal) for the PhD fellowship of Ana Ferreira (SFRH/BD/84936/2012). This work was also supported by FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalization in Axis I - Strengthening research, technological development and innovation (Project POCI-01-0145-FEDER-007491) and National Funds by FCT (Project UID/Multi/00709/2013)

Flavonoid compounds as reversing agents of the P-glycoprotein-mediated multidrug resistance: An in vitro evaluation with focus on antiepileptic drugs

The pharmacoresistance to antiepileptic drugs (AEDs) remains a major unsolved therapeutic need. The overexpression of multidrug transporters, as the P-glycoprotein (P-gp), at the level of the blood-brain barrier of epileptic patients has been suggested as a key mechanism underlying the refractory epilepsy. Thus, efforts have been made to search for therapeutically useful P-gp inhibitors. Herein, the strategy of flavonoid/AED combined therapy was exploited as a possible approach to overcome the P-gp-mediated pharmacoresistance. For this purpose, several in vitro studies were performed using Madin-Darby canine kidney II (MDCK II) cells and those transfected with the human multidrug resistance-1 (MDR1) gene, overexpressing the P-gp (MDCK-MDR1). Overall, the results showed that baicalein, (−)-epigallocatechin gallate, kaempferol, quercetin and silymarin, at 200 μM, produced a marked increase on the intracellular accumulation of rhodamine 123 in MDCK-MDR1 cells, potentially through inhibiting the P-gp activity. In addition, with the exception of lamotrigine, all other AEDs tested (phenytoin, carbamazepine and oxcarbazepine) and their active metabolites (carbamazepine-10,11-epoxide and licarbazepine) demonstrated to be P-gp substrates. Furthermore, the most promising flavonoids as Pgp inhibitors promoted a significant increase on the intracellular accumulation of the AEDs (excluding lamotrigine) and their active metabolites in MDCK-MDR1 cells, evidencing to be important drug candidates to reverse the AED-resistance. Thus, the co-administration of AEDs with baicalein, (−)-epigallocatechin gallate, kaempferol, quercetin and silymarin should continue to be explored as adjuvant therapy for refractory epilepsy

A disciplina de matemática financeira nas matrizes curriculares dos cursos de licenciaturas em matemática no Brasil

Nesta pesquisa, objetivamos compreender de que maneira a disciplina de Matemática Financeira está estruturada nos Projetos Pedagógicos dos Cursos (PPCs) das licenciaturas em Matemática e adequada à futura prática do professor. Adotamos como metodologia, uma abordagem qualitativa do tipo documental, cujo corpus foi constituído por 182 PPCs de cursos, de todas as regiões geográficas do Brasil. A análise dos dados foi realizada por meio da Análise de Conteúdo, a qual possibilitou a constituição de duas categorias de análise. Debatendo as categorias, evidenciamos a necessidade de as licenciaturas em Matemática tomem para si a responsabilidade de formar professores capacitados, contemplando saberes associados ao desenvolvimento do processo de educação escolar básica. Esperamos que este estudo possa contribuir com o debate do currículo da formação inicial de professores e que transcenda o ensino, meramente técnico, o qual supervaloriza o ensino numa perspectiva transmissiva de conceitos em detrimento da construção do conhecimento científico

Tratamento cirúrgico do exoftalmo endócrino por remoção da gordura orbitária: experiência clínica

PURPOSE: To report a series of 73 patients with endocrine exophthalmos treated by removal of orbital fat using the transpalpebral approach during the period 1989 to 1999. METHODS: The operation was performed according to the technique described by Olivari. Aesthetic analysis was done preoperatively and postoperatively (more than 6 months after surgery). The number of complications was also observed. RESULTS: The average volume of resected fat was approximately 7.6 mL per orbit. No major complication was observed. In 9 patients with epiphora, all improved. One patient developed postoperative diplopia and 5 complained of temporary diplopia. Appearance improved in 62 patients (85%). CONCLUSION: Surgical removal of orbital fat associated with endocrine exophthalmos provides consistent improvement in appearance with a low rate of complications. Additional procedures may be indicated to improve the cosmetic outcome.OBJETIVO: Apresentamos uma série de 73 pacientes com exoftalmo endócrino tratados pela Divisão de Cirurgia Plástica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, através da remoção da gordura orbitária usando acesso transpalpebral, durante o período de 1989 a 1999. MÉTODOS: A avaliação foi realizada através de análise estética, no pré e no pós-operatório (maior do que seis meses). O número de complicações também foi mensurado. Nove pacientes apresentaram epífora, todos com melhora espontânea. Um paciente desenvolveu diplopia no pós-operatório, e cinco apresentaram diplopia temporária. A aparência melhorou em 62 pacientes (85%). Uma retroposição média de 2,74 mm foi observada, apesar de o método não ser mais considerado relevante para avaliação de exoftalmo. CONCLUSÃO: Esta abordagem, ainda não usada rotineiramente no Brasil, constitui uma nova via de acesso para o tratamento do exoftalmo endócrino. Os resultados foram consistentes, com baixo índice de complicações. Outros procedimentos devem sempre ser realizados, visando à melhora dos resultados estéticos

Incidência de Diatraea em genótipos de sorgo sacarino em diferentes épocas de plantio

A field experiment was conducted at the Experimental Station of Campos, Rio de Janeiro, Brazil, with the objective of determining the incidence of Diatraea spp. (LEP. - Pyralidae) in sorghum (Sorghum bicolor (L.) Moench). The genotypes CMS XS 623, BR 501 and BR 505, were utilized in various planting dates (September, October and November, 1983). There were no statistical difference among the studied genotypes in relation to the incidence of Diatraea spp. However the genotype BR 505 showed the tendency of resistance to the borer infestation. The first planting date was significantly the one who presented the least infestation compared to the others. Foi conduzido na Estação Experimental de Campos, RJ, um experimento com o objetivo de determinar a incidência de Diatraea spp. (LEP., Pyralidae) em sorgo sacarino (Sorghum bicolor (L.) Moench). Foram utilizados os genótipos BR 501, BR 505 e CMS XS 623, em três plantios sucessivos (setembro, outubro e novembro, 1983), em parcelas subdivididas com três repetições. Apesar de os genótipos estudados não terem diferido estatisticamente entre si, com relação à infestação, o BR 505 apresentou indicações de resistência. A primeira época de plantio (setembro) foi significativamente a de menor infestação em relação às outras duas épocas, que foram estatisticamente iguais

The homeotic protein AGAMOUS controls microsporogenesis by regulation of SPOROCYTELESS

The Arabidopsis homeotic gene AGAMOUS (AG) is necessary for the specification of reproductive organs (stamens and carpels) during the early steps of flower development. AG encodes a transcription factor of the MADS-box family that is expressed in stamen and carpel primordia. At later stages of development, AG is expressed in distinct regions of the reproductive organs. This suggests that AG might function during the maturation of stamens and carpels, as well as in their early development. However, the developmental processes that AG might control during organogenesis and the genes that are regulated by this factor are largely unknown. Here we show that microsporogenesis, the process leading to pollen formation, is induced by AG through activation of the SPOROCYTELESS gene (SPL, also known as NOZZLE,NZZ), a regulator of sporogenesis. Furthermore, we demonstrate that SPL can induce microsporogenesis in the absence of AG function, suggesting that AG controls a specific process during organogenesis by activating another regulator that performs a subset of its functions

AUTO EFICÁCIA PROFISSIONAL E BARREIRAS DO MERCADO: UMA AVALIAÇÃO DAS DIFICULDADES ENCONTRADAS POR EGRESSOS DA UNIPAMPA, CAMPUS DOM PEDRITO/RS

A economia brasileira passa por diversas mudanças e os reflexos no mercado de trabalho são visíveis para jovens recém formados que estão prestes a ingressar no mesmo. As competências e habilidades pessoais são critérios importantes para a contratação de recém formados, visto que o mercado está cada vez mais exigente, ou seja, em busca de profissionais atualizados e com habilidades pessoais para bom desempenho de suas funções. Nesse sentido, este estudo buscou descrever e analisar se as habilidades pessoais são problemáticas maiores do que as barreiras encontradas no mercado de trabalho. Para isto, realizou-se uma survey com a participação de cem egressos formados na Universidade Federal do Pampa Campus Dom Pedrito/ RS. Após análise estatística dos dados por meio do Teste-T, constatou-se que as barreiras de mercados são uma problemática maior do que as habilidades pessoais. O estudo também constatou que pouco mais da metade dos egressos não está atuando em sua área de formação

Phenolic profiling, biological activities and in silico studies of Acacia tortilis (Forssk.) Hayne ssp. raddiana extracts

The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). L. Barros and R. C. Calhelha thank the national funding by the FCT, P.I., through the institutional scientific employment program-contract for their contracts. M. Carocho also thanks the project ValorNatural for his research contract. The authors are also grateful to the FEDER-Interreg España- Portugal programme for financial support through the project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio