Quantitative proteomic analysis and functional studies reveal that nucleophosmin is involved in cell death in glioblastoma cell line transfected with siRNA

Previously, we reported that nucleophosmin (NPM) was increased in glioblastoma multiforme (GBM). NPM is a phosphoprotein related to apoptosis, ribosome biogenesis, mitosis, and DNA repair, but details about its function remain unclear. We treated U87MG and A172 cells with small interference RNA (siRNA) and obtained a reduction of 80% in NPM1 expression. Knockdown at the protein level was evident after the 4th day and was maintained until the 7th day of transfection that was investigated by quantitative proteomic analysis using isobaric tags. The comparison of proteomic analysis of NPM1-siRNA against controls allowed the identification of 14 proteins, two proteins showed increase and 12 presented a reduction of expression levels. Gene ontology assigned most of the hypoexpressed proteins to apoptosis regulation, including GRP78. NPM1 silencing did not impair cell proliferation until the 7th day after transfection, but sensitized U87MG cells to temozolomide (TMZ), culminating with an increase in cell death and provoking at a later period a reduction of colony formation. In a large data set of GBM patients, both GRP78 and NPM1 genes were upregulated and presented a tendency to shorter overall survival time. In conclusion, NPM proved to participate in the apoptotic process, sensitizing TMZ-treated U87MG and A172 cells to cell death, and in association with upregulation of GRP78 may be helpful as a predictive factor of poor prognosis in GBM patients.

Quantitative Chemical Profile and Multivariate Statistical Analysis of Alembic Distilled Sugarcane Spirit Fractions

Concentrations of 39 organic compounds were determined in three fractions (head, heart and tail) obtained from the pot still distillation of fermented sugarcane juice. The results were evaluated using analysis of variance (ANOVA), Tukey's test, principal component analysis (PCA), hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA). According to PCA and HCA, the experimental data lead to the formation of three clusters. The head fractions give rise to a more defined group. The heart and tail fractions showed some overlap consistent with its acid composition. The predictive ability of calibration and validation of the model generated by LDA for the three fractions classification were 90.5 and 100%, respectively. This model recognized as the heart twelve of the thirteen commercial cachacas (92.3%) with good sensory characteristics, thus showing potential for guiding the process of cuts.

Pre- and Posttransplant Monitoring of Alloantibodies by Complement-Dependent Cytotoxicity and Luminex Methodologies in Liver Transplantation

Background. This study evaluated the influence of circulating anti-HLA antibodies on outcomes of 97 liver allografts from deceased donors. Methods. Human leukocyte antigen (HLA) antibody screening was performed by both complement-dependent cytotoxicity (CDC) and multiparameter Luminex microsphere-based assays (Luminex assay). Results. The agreements between T- and B- cell CDC and Luminex assays were 67% and 77% for pre- and posttransplant specimens, respectively. Graft dysfunction was not associated with either positive pretransplant CDC or Luminex panel-reactive antibody (PRA) values. Likewise, positive posttransplant T- or B- cell CDC PRA values were not associated with graft dysfunction. In contrast, posttransplant Luminex PRA values were significantly higher among patients with graft dysfunction compared with subjects with good outcomes (P = .017). Conclusion. Posttransplant monitoring of HLA antibodies with Luminex methodology allowed identification of patients at high-risk for poor graft outcomes.

Quantitative chemical profile and multivariate statistical analysis of alembic distilled sugarcane spirit fractions

As concentrações de 39 compostos orgânicos foram determinadas em três frações (cabeça, coração e cauda) obtidas da destilação em alambique do caldo de cana fermentado. Os resultados foram avaliados utilizando-se análise de variância (ANOVA), teste de Tukey, análise de componentes principais (PCA), agrupamento hierárquico (HCA) e análise discriminante linear (LDA). De acordo com PCA e HCA, os dados experimentais conduzem à formação de três agrupamentos. As frações de cabeça deram origem a um grupo mais definido. As frações coração e cauda apresentaram alguma sobreposição coerente com sua composição em ácidos. As habilidades preditivas de calibração e validação dos modelos gerados pela LDA para a classificação das três frações foram de 90,5 e 100%, respectivamente. Este modelo reconheceu como coração doze de treze cachaças comerciais (92,3%) com boas características sensoriais, apresentando potencial para a orientação do processo de cortes.

Climate Change and "historical responsibilities"

The historical responsibility of countries listed in the Annex I of the Convention on Climate Change has been used extensively as a justification for the lack of action of countries not included in Annex I to reduce their greenhouse gas emissions. We analyzed the contribution of non-Annex I countries to the CO2 emissions in the period 1850 - 2006 to assess their relative contribution to total CO2 emissions. In the period 1980 - 2006 non-Annex I countries represented 44% of the total but this contribution increased in the period 1990 - 2006 to 48%. If we extrapolate present trends to 2020 they will represent 56% in the period 1990 - 2020. The "historical responsibility" of Annex I countries is therefore decreasing. If we take 1990 as the starting year in which the Climate Convention recognized clearly that greenhouse gases are interfering dangerously with the climate system, it becomes very difficult to attribute "blame" and "guilt" to Annex I for their historical contributions. It becomes also quite clear the need of non-Annex I countries to engage with Annex I countries in the effort to reduce emissions. The Copenhagen Accord has no mention of "historical responsibilities".

Physical education and quality of life: reflections and perspectives

The study of the quality of life of individuals has become a prominent issue for contemporary society. However, research involving quality of life should consider that this is a complex issue that involves objective and subjective aspects, living conditions, lifestyles and multidimensional factors. There is a widespread idea in society that physical activity, exercise, sports and related activities can have a positive impact on improving the quality of life of the population. However, in several studies, this relationship is examined from the biological point of view, which considers only health indicators. Such practices are being studied in the area of Physical Education in various perspectives, such as biological, psychological, social, and cultural. Therefore, Physical Education should seek to produce knowledge that meets the scientific principles, and look for evidence that effectively clarifies the dynamics of this relationship. In this sense, methodological rigor, particularly the conceptual definition, is essential for a better understanding of the results and of which generalizations are actually likely to e proved. In addition, it is necessary to identify the possibilities and limitations of quantitative evaluations, qualitative evaluations and possible combinations.

Matrix Support in Mental Health: Achievements and Limits in Primary Health Care

Changes in mental health care in the city of Fortaleza (Northeastern Brazil) have a recent historical and political process. Compared to other municipalities of the State of Ceara, which in the early 1990s were already pioneers in the process, Fortaleza has not implemented the changes due to the interests of psychiatric hospitals, of psychiatric outpatient clinics of the public network, and because of the difficulty in managing the new mental health devices and equipment present in Primary Care. In the municipality, the reorganization of mental health actions and services has required that the Primary Care Network faces the challenge of assisting mental health problems with the implementation of Matrix Support. In light of this context, we aimed to evaluate Matrix Support in mental health in Primary Care Units and to identify achievements and limitations in the Primary Care Units with Matrix Support. This study used a qualitative approach and was carried out by means of a case study. We interviewed twelve professionals from the Family Health Teams of four Units with implemented Matrix Support. The analysis of the information reveals that access, decision making, participation and the challenges of implementing Matrix Support are elements that are, in a dialectic way, weak and strong in the reorganization of services and practices. The presence of Matrix Support in Primary Care highlights the proposal of dealing with mental health within the network in the municipality. The process has not ended. Mobilization, awareness-raising and qualification of Primary Care have to be enhanced constantly, but implementation has enabled, to the service and professionals, greater acceptance of mental health in Primary Care.

Multiple Quaternary Refugia in the Eastern Guiana Shield Revealed by Comparative Phylogeography of 12 Frog Species

The Guiana Shield (GS) is one of the most pristine regions of Amazonia and biologically one of the richest areas on Earth. How and when this massive diversity arose remains the subject of considerable debate. The prevailing hypothesis of Quaternary glacial refugia suggests that a part of the eastern GS, among other areas in Amazonia, served as stable forested refugia during periods of aridity. However, the recently proposed disturbance-vicariance hypothesis proposes that fluctuations in temperature on orbital timescales, with some associated aridity, have driven Neotropical diversification. The expectations of the temporal and spatial organization of biodiversity differ between these two hypotheses. Here, we compare the genetic structure of 12 leaf-litter inhabiting frog species from the GS lowlands using a combination of mitochondrial and nuclear sequences in an integrative analytical approach that includes phylogenetic reconstructions, molecular dating, and Geographic Information System methods. This comparative and integrated approach overcomes the well-known limitations of phylogeographic inference based on single species and single loci. All of the focal species exhibit distinct phylogeographic patterns highlighting taxon-specific historical distributions, ecological tolerances to climatic disturbance, and dispersal abilities. Nevertheless, all but one species exhibit a history of fragmentation/isolation within the eastern GS during the Quaternary with spatial and temporal concordance among species. The signature of isolation in northern French Guiana (FG) during the early Pleistocene is particularly clear. Approximate Bayesian Computation supports the synchrony of the divergence between northern FG and other GS lineages. Substructure observed throughout the GS suggests further Quaternary fragmentation and a role for rivers. Our findings support fragmentation of moist tropical forest in the eastern GS during this period when the refuge hypothesis would have the region serving as a contiguous wet-forest refuge.