miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer

Background: Prognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line. Materials and methods: To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR). Results: The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025). Conclusions: Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.

Upregulation of hsa-miR-125b in HTLV-1 asymptomatic carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis patients

The retrovirus human T lymphotropic virus type 1 (HTLV-1) promotes spastic paraparesis, adult T cell leukaemia and other diseases. Recently, some human microRNAs (miRNAs) have been described as important factors in host-virus interactions. This study compared miRNA expression in control individuals, asymptomatic HTLV-1 carriers and HTLV-1 associated myelopathy (HAM)/tropical spastic paraparesis patients. The proviral load and Tax protein expression were measured in order to characterize the patients. hsa-miR-125b expression was significantly higher in patients than in controls (p = 0.0285) or in the HAM group (p = 0.0312). Therefore, our findings suggest that miR-125b expression can be used to elucidate the mechanisms of viral replication and pathogenic processes.

MicroRNAs miR-146-5p and let-7f as prognostic tools for aggressive papillary thyroid carcinoma: a case report

Papillary thyroid cancer (PTC) is the most incident histotype of thyroid cancer. A certain fraction of PTC cases (5%) are irresponsive to conventional treatment, and refractory to radioiodine therapy. The current prognostic factors for aggressiveness are mainly based on tumor size, the presence of lymph node metastasis, extrathyroidal invasion and, more recently, the presence of the BRAFT(1799A) mutation. MicroRNAs (miRNAs) have been described as promising molecular markers for cancer as their deregulation is observed in a wide range of tumors. Recent studies indicate that the over-expression of miR-146b-5p is associated with aggressiveness and BRAFT(1799A) mutation. Furthermore, down-regulation of let-7f is observed in several types of tumors, including PTC. In this study, we evaluated the miR146b-5p and let-7f status in a young male patient with aggressive, BRAFT(1799A)-positive papillary thyroid carcinoma, with extensive lymph node metastases and short-time recurrence. The analysis of miR-146b-5p and let-7f expression revealed a distinct pattern from a cohort of PTC patients, suggesting caution in evaluating miRNA expression data as molecular markers of PTC diagnosis and prognosis. Arq Bras Endocrinol Metab. 2012;56(8):552-7

Mutual Information Rate and Bounds for It

The amount of information exchanged per unit of time between two nodes in a dynamical network or between two data sets is a powerful concept for analysing complex systems. This quantity, known as the mutual information rate (MIR), is calculated from the mutual information, which is rigorously defined only for random systems. Moreover, the definition of mutual information is based on probabilities of significant events. This work offers a simple alternative way to calculate the MIR in dynamical (deterministic) networks or between two time series (not fully deterministic), and to calculate its upper and lower bounds without having to calculate probabilities, but rather in terms of well known and well defined quantities in dynamical systems. As possible applications of our bounds, we study the relationship between synchronisation and the exchange of information in a system of two coupled maps and in experimental networks of coupled oscillators.

MicroRNA miR-146b-5p regulates signal transduction of TGF-beta by repressing SMAD4 in thyroid cancer

MicroRNAs (miRNA) are small non-coding RNAs involved in post-transcriptional gene regulation that have crucial roles in several types of tumors, including papillary thyroid carcinoma (PTC). miR-146b-5p is overexpressed in PTCs and is regarded as a relevant diagnostic marker for this type of cancer. A computational search revealed that miR-146b-5p putatively binds to the 3' untranslated region (UTR) of SMAD4, an important member of the transforming growth factor beta (TGF-beta) signaling pathway. The TGF-beta pathway is a negative regulator of thyroid follicular cell growth, and the mechanism by which thyroid cancer cells evade its inhibitory signal remains unclear. We questioned whether the modulation of the TGF-beta pathway by miR-146b-5p can contribute to thyroid tumorigenesis. Luciferase reporter assay confirmed the direct binding of miR-146b-5p on the SMAD4 3'UTR. Specific inhibition of miR-146b-5p with a locked nucleic acid-modified anti-miR-146b oligonucleotide significantly increased SMAD4 levels in the human papillary carcinoma cell lines, TPC-1 and BCPAP. Moreover, suppression of miR-146b-5p increased the cellular response to the TGF-beta anti-proliferative signal, significantly decreasing the proliferation rate. The overexpression of miR-146b-5p in normal rat follicular PCCL3 cells decreased SMAD4 levels and disrupted TGF-beta signal transduction. MiR-146b-5p overexpression in PCCL3 cells also significantly increased cell proliferation in the absence of thyroid-stimulating hormone and conferred resistance to TGF-beta-mediated cell-cycle arrest. Additionally, the activation of thyroid most common oncogenes RET/PTC3 and BRAF in PCCL3 cells upregulated miR-146b-5p expression. Our results confirm the oncogenic role of miR-146b-5p in thyroid follicular cells and contribute to knowledge regarding the modulation of TGF-beta signal transduction by miRNAs in PTCs. Oncogene (2012) 31, 1910-1922; doi:10.1038/onc.2011.381; published online 29 August 2011

miR-15a and 16-1 Are Downregulated in CD4(+) T Cells of Multiple Sclerosis Relapsing Patients

The pathology of relapsing-remitting multiple sclerosis (RR-MS) is largely attributed to activated autoreactive effector T lymphocytes. The influence of microRNAs on the immune response has been shown to occur in different pathways of lymphocyte differentiation and function. Here, the expression of the miRNAs miR-15a/161 in PBMC, CD4(+), and CD8(+) from RR-MS patients has been investigated. BCL2, a known miR-15a/16-1 target, has also been analyzed. The results have shown that miR-15a/16-1 is downregulated in CD4(+) T cells, whereas BCL2 is highly expressed in RR-MS patients only. Our data suggest that miR-15a/16-1 can also modulate the BCL2 gene expression in CD4(+) T cells from RR-MS patients, thereby affecting apoptosis processes.

Neoproterozoic glacial deposits from the Aracuai orogen, Brazil: Age, provenance and correlations with the Sao Francisco craton and West Congo belt

Glacigenic diamictite successions of the Macaubas Group are widespread in the western domain of the Aracuai orogen, east of the Sao Francisco craton (Brazil). Diamictites also occur on this craton and in the African counterpart of the Aracuai orogen, the West Congo belt. Detrital zircon grains from the matrix of diamictites and sandstones from the Macaubas Group were dated by the U-Pb SHRIMP technique. The geochronological study sets the maximum depositional age of the glacial diamictites at 900 Ma, and indicates multiple sources for the Macaubas basin with ages ranging from 900 to 2800 Ma. Sm-Nd T-DM model ages, determined on whole rock samples, range from 1.8 Ga to 2.5 Ga and get older up-section. Comparison of our data with those from the cratonic area suggest that these glacial deposits can be correlated to the Jequitai and Carrancas diamictites in the Sao Francisco craton, and to the Lower Mixtite Formation of the West Congolian Group, exposed in Africa. The 900-1000 Ma source is most probably represented by the Zadinian-Mayumbian volcanic rocks and related granites from the West Congo belt. However, one of the most voluminous sources, with ages in the 1.1-1.3 Ga interval, has not been detected in the Sao Francisco-Congo craton. Possible sources for these grains could occur elsewhere in Africa, or possibly from within the Brasilia Belt in western central Brazil. (C) 2011 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Increased expression of miR-221 is associated with shorter overall survival in T-cell acute lymphoid leukemia

Background: CD56 expression has been associated with a poor prognosis in lymphoid neoplasms, including T-cell acute lymphoblastic leukemia (T-ALL). MicroRNAs (miRNAs) play an important role in lymphoid differentiation, and aberrant miRNA expression has been associated with treatment outcome in lymphoid malignancies. Here, we evaluated miRNA expression profiles in normal thymocytes, mature T-cells, and T-ALL samples with and without CD56 expression and correlated microRNA expression with treatment outcome. Methods: The gene expression profile of 164 miRNAs were compared for T-ALL/CD56+ (n=12) and T-ALL/CD56- (n=36) patients by Real-Time Quantitative PCR. Based on this analysis, we decided to evaluate miR-221 and miR-374 expression in individual leukemic and normal samples. Results: miR-221 and miR-374 were expressed at significantly higher levels in T-ALL/CD56+ than in T-ALL/CD56- cells and in leukemic blasts compared with normal thymocytes and peripheral blood (PB) T-cells. Age at diagnosis (15 or less vs grater than 15 years; HR: 2.19, 95% CI: 0.98-4.85; P=0.05), miR-221 expression level (median value as cut off in leukemic samples; HR: 3.17, 95% CI: 1.45-6.92; P=0.004), and the expression of CD56 (CD56- vs CD56+; HR: 2.99, 95% CI: 1.37-6.51; P=0.006) were predictive factors for shorter overall survival; whereas, only CD56 expression (HR: 2.73, 95% CI: 1.03-7.18; P=0.041) was associated with a shorter disease-free survival rate. Conclusions: miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis.

Petrology of Gameleira potassic lamprophyres, São Francisco Craton

Gameleira lamprophyres are dykes and mafic microgranular enclaves associated with the shoshonitic Gameleira monzonite. This association belongs to the Paleoproterozoic alkaline magmatism from Serrinha nucleus, northeast Brazil. The liquidus paragenesis is diopside, pargasite, apatite and mica. Reverse zoning was identified in the groundmass alkali feldspar and was related to the undercooling of lamprophyric magma during the emplacement, with high growth rate of pargasite/edenite inducing disequilibrium between feldspars and liquid. Chemical data indicate that the lamprophyres are basic rocks (SiO2 < 48 wt%), with alkaline character (Na2O + K2O > 3 wt%) and potassic signature (K2O/Na2O ≈ 2). High contents of MgO and Cr are consistent with a signature of a primary liquid, and such concentrations, as well as Al, K, P, Ba, Ni- and light rare earth elements, are consistent with an olivine-free metasomatic mantle source enriched in amphibole, clinopyroxene and apatite. By contrast, the ultrapotassic lamprophyres from Morro do Afonso, contemporaneous alkaline ultrapotassic magmatism in Serrinha nucleus, were probably produced by melting of a clinopyroxene-phlogopite-apatite enriched-source. The identification of different mineral paragenesis in the source of potassic and ultrapotassic lamprophyres from Serrinha nucleus can contribute to the understanding of the mantle heterogeneities and tectonic evolution of this region.

Water transfer from São Francisco river to semiarid northeast of Brazil: technical data, environmental impacts, survey of opinion about the amount to be transferred

The transposition of the São Francisco River is considered one of the greatest engineering works in Brazil of all time since it will cross an extensive agricultural region of continental dimensions, involving environmental impacts, water, soil, irrigation, water payment and other multidisciplinary themes. Taking into account its importance, this subject was incorporated into a discipline of UFSCar (Federal University of São Carlos - Brazil) named "Pollution and Environmental Impacts". It was noted strong reaction against the project, even before the presentation. To allow a critical analysis, the first objective was to compile the main technical data and environmental impacts. The second objective was to detect the three most important aspects that cause reaction, concluding for the following reasons: assumption that the volume of water to be transferred was much greater than it actually is proposed in the project; lack of knowledge about similar project already done in Brazil; the idea that the artificial canal to be built was much broader than that proposed by the project. The participants' opinion about "volume to be transferred" was raised quantitatively four times: 2-undergraduate students; 1-graduate; 1-outside community. The average resulted 14 times larger than that proposed in the project, significant according to t-test. It was concluded that the reaction to water transfer project is due in part to the ignorance combined with a preconceived idea that tend to overestimate the magnitude of environmental impacts.

400 anos do De Legibus de Francisco SUAREZ (1548-1617)

O artigo destaca a importância da contribuição de Francisco SUAREZ (1548- 1617) para a evolução do direito internacional, com ênfase nas questões práticas que este teve de enfrentar para formular soluções legais – o dado central da obra é a afirmação da unidade intrínseca da humanidade, em comunidade internacional formando um todo, apesar de dividida em povos e reinos. Observa o caráter de continuidade histórica entre o legado medieval e o Direito Internacional moderno, do qual o tratado Das leis e Deus legislador (1612) foi marco relevante.

Reflexões sobre a formação do acervo da Academia de Direito do Largo de São Francisco: do século XIX aos nossos dias

O trabalho apresenta algumas reflexões sobre a história da formação do acervo acadêmico dos cursos jurídicos do Brasil criados no século XIX, especificamente da Faculdade de Direito da Universidade de São Paulo. A primeira Biblioteca Pública de São Paulo, fundada em 1825, exerceu forte influência para que o Convento dos frades franciscanos recebesse a escola de direito criada por Decreto Imperial, em razão de seu fundo bibliográfico de 5.000 mil livros, preponderantemente de cunho eclesiástico, e considerável para os padrões culturais do Brasil à época. Atualmente configura-se como uma importante biblioteca jurídica acadêmica da América Latina e, ao longo da sua história tem sido uma instituição de depósito moral, isto é, recebe doações das mais diversas localidades do país, encaminhadas espontaneamente pelos autores para ter sua obra disponibilizada no acervo do primeiro e um dos mais tradicionais cursos de Direito do Brasil. Atualmente, este acervo está estimado em aproximadamente 400 mil itens, com doações de personalidades brasileiras. Outro ponto estudado refere-se ao estabelecimento de critérios para seleção de material – corpo editorial, autores de renome, relevância nos temas abordados etc. – em razão do boom editorial ocorrido na década de 1990, concomitante com o aumento de escolas de Direito no país. Chama-se à reflexão de quem atua na seara jurídica para atentar a pontos relevantes no momento da seleção para não incorrer no erro de avaliar com preconceito, modernidade, ideológico, interesse de estudo pessoal ou embasado apenas na data de publicação da obra. As ciências humanas, diferentemente de outras áreas, têm sua obsolescência mais lenta ou inexistente, decorrendo em grave erro para o Direito julgar exclusivamente pela data de publicação, o que torna premente aos profissionais bibliotecários dominarem conceitos básicos na área de atuação para que as bibliotecas sejam depositárias de material bibliográfico de qualidade.