Fulvestrant-Induced Cell Death and Proteasomal Degradation of Estrogen Receptor α Protein in MCF-7 Cells Require the CSK c-Src Tyrosine Kinase

Fulvestrant is a representative pure antiestrogen and a Selective Estrogen Receptor Down-regulator (SERD). In contrast to the Selective Estrogen Receptor Modulators (SERMs) such as 4-hydroxytamoxifen that bind to estrogen receptor α (ERα) as antagonists or partial agonists, fulvestrant causes proteasomal degradation of ERα protein, shutting down the estrogen signaling to induce proliferation arrest and apoptosis of estrogen-dependent breast cancer cells. We performed genome-wide RNAi knockdown screenings for protein kinases required for fulvestrant-induced apoptosis of the MCF-7 estrogen-dependent human breast caner cells and identified the c-Src tyrosine kinase (CSK), a negative regulator of the oncoprotein c-Src and related protein tyrosine kinases, as one of the necessary molecules. Whereas RNAi knockdown of CSK in MCF-7 cells by shRNA-expressing lentiviruses strongly suppressed fulvestrant-induced cell death, CSK knockdown did not affect cytocidal actions of 4-hydroxytamoxifen or paclitaxel, a chemotherapeutic agent. In the absence of CSK, fulvestrant-induced proteasomal degradation of ERα protein was suppressed in both MCF-7 and T47D estrogen-dependent breast cancer cells whereas the TP53-mutated T47D cells were resistant to the cytocidal action of fulvestrant in the presence or absence of CSK. MCF-7 cell sensitivities to fulvestrant-induced cell death or ERα protein degradation was not affected by small-molecular-weight inhibitors of the tyrosine kinase activity of c-Src, suggesting possible involvement of other signaling molecules in CSK-dependent MCF-7 cell death induced by fulvestrant. Our observations suggest the importance of CSK in the determination of cellular sensitivity to the cytocidal action of fulvestrant

Characterization of cover crops by NMR spectroscopy: impacts on soil carbon, nitrogen and phosphorus under tilage regimes.

The objective of this study was to investigate the chemical composition of cover crops by solid-state CPMAS 13C NMR spectroscopy and its effects on carbon, nitrogen and phosphorus in a Typic Acrustox. Cover crops (Crotalaria juncea, Canavalia brasiliensis, Cajanus cajan, Mucuna pruriens and Raphanus sativus) and natural fallow were studied in rotation with maize under conventional and no-tillage regimes. Tissues of Crotalaria juncea, Canavalia brasiliensis, Mucuna pruriens and Raphanus sativus were analyzed using CPMAS 13C NMR spectroscopy. Soil samples were collected at the end of the growing season of the cover crops (September 2002) and during the grain filling period in corn from 0-5 and 5-10 cm layers. Cajanus cajan presented the lowest content of polysaccharides and along with Mucuna pruriens presented the highest percentage of aromatic carbon compounds, reflecting the slow decomposition of highly lignified material. Carbon stocks were higher in the superficial soil layer and under no-tillage due to the accumulation and slower decomposition of plant tissues under these conditions. Increases in the C/N ratio of the soil with Mucuna pruriens and the C/P ratio with Cajanus cajan in the dry season were also related to slower rates of decomposition, caused by the large concentration of aromatic compounds in the tissues of these species. The higher C/P ratios found at 0-5 cm layer are due to higher values of P (Mehlich-1) at 5-10 cm (25 mg kg-1) layer and the higher concentration of carbon in the superficial soil layer as a result of the accumulation of plant residues

Emissão de N2O de um latossolo vermelho sob consórcio sorgo e braquiária no Cerrado.

O objetivo desse trabalho foi avaliar os fluxos de N2O em Latossolo Vermelho sob consórcio de sorgo (Sorghum bicolor) e braquiária piatã (Brachiaria brizantha cv. Piatã) em sucessão à soja em área de sequeiro, correlacionandoos com dados de precipitação, temperatura e umidade do solo. O experimento foi conduzido na Embrapa Cerrados em blocos ao acaso com duas repetições. Os tratamentos foram constituídos por: sistema de lavoura contínua sob plantio direto (1), lavoura contínua sob plantio convencional (2) e sistema de integração lavoura pecuária (3), tendo o Cerrado Nativo como referência. O plantio de sorgo foi realizado em consórcio com Piatã, após a colheita da soja. As amostras de N2O foram coletadas no período de 21/03/2014 a 04/07/2014 em câmaras do tipo estática fechada e analisadas em cromatógrafo gasoso. O fluxo de N2O foi maior logo após o plantio, a adubação de cobertura e precipitação para todos os sistemas de manejo avaliados. Os maiores fluxos foram verificados no sistema 2 com valores médios de 90,55 μg m-2 h-1, enquanto que nos sistemas 1 e 3 os fluxos médios foram 46,49 e 45,29 μg m-2 h-1, respectivamente

Nitrogênio mineral e fluxos de N2O em sistemas integrados no Cerrado.

O N2O, dentre os gases de efeito estufa, é o que possui maior importância para o setor agropecuário devido às suas emissões estarem relacionadas com a dinâmica e disponibilidade de nitrogênio (N) do solo nos agroecossistemas. O objetivo desse trabalho foi avaliar as taxas de nitrogênio mineral em solo e os fluxos de N2O sob Integração Lavoura-Pecuária (ILP), Integração Lavoura-Pecuária-Floresta (ILPF), Cerradão e Sistema Agroflorestal (SAF), relacionando-os com precipitação pluviométrica, temperatura e umidade do solo. As coletas de N2O e de solo para o SAF foram realizadas em dois períodos, entre 19/03/2014 a 07/04/2014 e de 22/07/2014 à 24/07/2014 e para os outros sistemas integrados coletou-se no mesmo período do ano de 2013, em Planaltina, DF, correspondente à transição chuva-seca e da estação seca respectivamente. Os fluxos de N2O para os sistemas integrados tiveram uma grande variação, e o Cerradão e o SAF apresentaram menores valores de fluxos de N2O. Os teores de N-NH4+ foram maiores no SAF e Cerradão. O solo sob ILP e ILPF apresentam maiores teores de N-NO3-, consequentemente, fluxos de N2O

Universal scaling of the logarithmic negativity in massive quantum field theory

We consider the logarithmic negativity, a measure of bipartite entanglement, in a general unitary 1 + 1-dimensional massive quantum field theory, not necessarily integrable. We compute the negativity between a finite region of length r and an adjacent semi-infinite region, and that between two semi-infinite regions separated by a distance r. We show that the former saturates to a finite value, and that the latter tends to zero, as r -> ∞. We show that in both cases, the leading corrections are exponential decays in r (described by modified Bessel functions) that are solely controlled by the mass spectrum of the model, independently of its scattering matrix. This implies that, like the entanglement entropy (EE), the logarithmic negativity displays a very high level of universality, allowing one to extract information about the mass spectrum. Further, a study of sub-leading terms shows that, unlike the EE, a large-r analysis of the negativity allows for the detection of bound states

A contour for the entanglement entropies in harmonic lattices

We construct a contour function for the entanglement entropies in generic harmonic lattices. In one spatial dimension, numerical analysis are performed by considering harmonic chains with either periodic or Dirichlet boundary conditions. In the massless regime and for some configurations where the subsystem is a single interval, the numerical results for the contour function are compared to the inverse of the local weight function which multiplies the energy-momentum tensor in the corresponding entanglement hamiltonian, found through conformal field theory methods, and a good agreement is observed. A numerical analysis of the contour function for the entanglement entropy is performed also in a massless harmonic chain for a subsystem made by two disjoint intervals

Dose-Related Estrogen Effects on Gene Expression in Fetal Mouse Prostate Mesenchymal Cells

Developmental exposure of mouse fetuses to estrogens results in dose-dependent permanent effects on prostate morphology and function. Fetal prostatic mesenchyme cells express estrogen receptor alpha (ERα) and androgen receptors and convert stimuli from circulating estrogens and androgens into paracrine signaling to regulate epithelial cell proliferation and differentiation. To obtain mechanistic insight into the role of different doses of estradiol (E2) in regulating mesenchymal cells, we examined E2-induced transcriptomal changes in primary cultures of fetal mouse prostate mesenchymal cells. Urogenital sinus mesenchyme cells were obtained from male mouse fetuses at gestation day 17 and exposed to 10 pM, 100 pM or 100 nM E2 in the presence of a physiological concentration of dihydrotestosterone (0.69 nM) for four days. Gene ontology studies suggested that low doses of E2 (10 pM and 100 pM) induce genes involved in morphological tissue development and sterol biosynthesis but suppress genes involved in growth factor signaling. Genes involved in cell adhesion were enriched among both up-regulated and down-regulated genes. Genes showing inverted-U-shape dose responses (enhanced by E2 at 10 pM E2 but suppressed at 100 pM) were enriched in the glycolytic pathway. At the highest dose (100 nM), E2 induced genes enriched for cell adhesion, steroid hormone signaling and metabolism, cytokines and their receptors, cell-to-cell communication, Wnt signaling, and TGF- β signaling. These results suggest that prostate mesenchymal cells may regulate epithelial cells through direct cell contacts when estrogen level is low whereas secreted growth factors and cytokines might play significant roles when estrogen level is high

Composição química de plantas de cobertura como indicador de emissão de N2O.

A versão atual do Guia para Elaboração de Inventários Nacionais de Emissões de Gases de Efeito Estufa do IPCC adicionou a quantificação da contribuição de emissões de N2O em decorrência da decomposição de resíduos vegetais no cálculo do fator de emissão de óxido nitroso. Assim, este trabalho teve como objetivo analisar parâmetros (lignina, celulose, hemiceluloses, N) relacionados ao processo de decomposição de plantas de cobertura indicadores do potencial de emissão de N2O em sistema plantio direto no Cerrado. As seguintes espécies vegetais foram analisadas quanto aos teores de lignina, FDA, FDN, N total e conteúdo de N: Canavalia brasiliensis; Cajanus cajan; Mucuna aterrima; Crotalaria juncea; Pennisetum glaucum; Sorgum bicholor; Brachiaria ruziziensis;Triticum aestivum, Raphanus sativus e vegetação espontânea. Os menores teores de lignina foram observados em tecido vegetal de Brachiaria ruziziensis, Pennisetum glaucum e Canavalia brasiliensis e os conteúdos de N mais elevados em Canavalia brasiliensis. Porém, o tecido vegetal de Pennisetum glaucum possui maior C:N. Assim, a qualidade dos resíduos vegetais de Brachiaria ruziziensis e Canavalia brasiliensis, que apresentam decomposição acelerada e elevada concentração de N, pode favorecer mineralização de nitrogênio, consequentemente, as emissões de N2O para atmosfera