Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells

The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-a (TNF-a). To evaluate the role of TNF-a in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-a -treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-a treatment. These results showed that TNF-a can promote epithelial-mesenchymal transition (EMT) of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB) inhibitor aspirin while not affected by the reactive oxygen species (ROS) scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBa also blocked the TNF-a-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-a-induced EMT. ROS caused by TNF-a seemed to play a minor role in the TNF-a-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-a - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

Nuclear calcium signaling: a cell within a cell

Calcium (Ca2+) is a versatile second messenger that regulates a wide range of cellular functions. Although it is not established how a single second messenger coordinates diverse effects within a cell, there is increasing evidence that the spatial patterns of Ca2+ signals may determine their specificity. Ca2+ signaling patterns can vary in different regions of the cell and Ca2+ signals in nuclear and cytoplasmic compartments have been reported to occur independently. No general paradigm has been established yet to explain whether, how, or when Ca2+ signals are initiated within the nucleus or their function. Here we highlight that receptor tyrosine kinases rapidly translocate to the nucleus. Ca2+ signals that are induced by growth factors result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. This novel signaling mechanism may be responsible for growth factor effects on cell proliferation.

Angiotensin II stimulates MCP-1 production in rat glomerular endothelial cells via NAD(P)H oxidase-dependent nuclear factor-kappa B signaling

Angiotensin II (Ang II) plays a crucial role in the pathogenesis of renal diseases. The objective of the present study was to investigate the possible inflammatory effect of Ang II on glomerular endothelial cells and the underlying mechanism. We isolated and characterized primary cultures of rat glomerular endothelial cells (GECs) and observed that Ang II induced the synthesis of monocyte chemoattractant protein-1 (MCP-1) in GECs as demonstrated by Western blot. Ang II stimulation, at concentrations ranging from 0.1 to 10 µm, of rat GECs induced a rapid increase in the generation of reactive oxygen species as indicated by laser fluoroscopy. The level of p47phox protein, an NAD(P)H oxidase subunit, was also increased by Ang II treatment. These effects of Ang II on GECs were all reduced by diphenyleneiodonium (1.0 µm), an NAD(P)H oxidase inhibitor. Ang II stimulation also promoted the activation of nuclear factor-kappa B (NF-κB). Telmisartan (1.0 µm), an AT1 receptor blocker, blocked all the effects of Ang II on rat GECs. These data suggest that the inhibition of NAD(P)H oxidase-dependent NF-κB signaling reduces the increase in MCP-1 production by GECs induced by Ang II. This may provide a mechanistic basis for the benefits of selective AT1 blockade in dealing with chronic renal disease.

Genetic and environmental influences on blood pressure and physical activity: a study of nuclear families from Muzambinho, Brazil

Blood pressure (BP) and physical activity (PA) levels are inversely associated. Since genetic factors account for the observed variation in each of these traits, it is possible that part of their association may be related to common genetic and/or environmental influences. Thus, this study was designed to estimate the genetic and environmental correlations of BP and PA phenotypes in nuclear families from Muzambinho, Brazil. Families including 236 offspring (6 to 24 years) and their 82 fathers and 122 mothers (24 to 65 years) were evaluated. BP was measured, and total PA (TPA) was assessed by an interview (commuting, occupational, leisure time, and school time PA). Quantitative genetic modeling was used to estimate maximal heritability (h²), and genetic and environmental correlations. Heritability was significant for all phenotypes (systolic BP: h² = 0.37 ± 0.10, P < 0.05; diastolic BP: h² = 0.39 ± 0.09, P < 0.05; TPA: h² = 0.24 ± 0.09, P < 0.05). Significant genetic (r g) and environmental (r e) correlations were detected between systolic and diastolic BP (r g = 0.67 ± 0.12 and r e = 0.48 ± 0.08, P < 0.05). Genetic correlations between BP and TPA were not significant, while a tendency to an environmental cross-trait correlation was found between diastolic BP and TPA (r e = -0.18 ± 0.09, P = 0.057). In conclusion, BP and PA are under genetic influences. Systolic and diastolic BP share common genes and environmental influences. Diastolic BP and TPA are probably under similar environmental influences.

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.

The N-terminal 33 amino acid domain of Siva-1 is sufficient for nuclear localization

Siva-1 induces apoptosis in multiple pathological processes and plays an important role in the suppression of tumor metastasis, protein degradation, and other functions. Although many studies have demonstrated that Siva-1 functions in the cytoplasm, a few have found that Siva-1 can relocate to the nucleus. In this study, we found that the first 33 amino acid residues of Siva-1 are required for its nuclear localization. Further study demonstrated that the green fluorescent protein can be imported into the nucleus after fusion with these 33 amino acid residues. Other Siva-1 regions and domains showed less effect on Siva-1 nuclear localization. By site-mutagenesis of all of these 33 amino acid residues, we found that mutants of the first 1-18 amino acids affected Siva-1 nuclear compartmentalization but could not complete this localization independently. In summary, we demonstrated that the N-terminal 33 amino acid residues were sufficient for Siva-1 nuclear localization, but the mechanism of this translocation needs additional investigation.

Bolos simples elaborados com farinha da entrecasca de melancia (Citrullus vulgaris, sobral): avaliação química, fisica e sensorial

A farinha da entrecasca de melancia (FEM) foi obtida, sua composição determinada e utilizada em formulação de bolos. Elaboraram-se bolos sem a FEM (controle) e contendo 7 e 30% de FEM em substituição à farinha de trigo (experimentais). A composição química, características físicas, físico-químicas foram determinadas. Na avaliação sensorial, cem provadores não treinados receberam amostras em blocos balanceados e realizaram testes sensoriais, utilizando escala hedônica de 9 pontos e comparação múltipla. Os dados obtidos foram avaliados por estatísticas descritivas, ANOVA, testes de Tukey e Dunnet. Os resultados revelaram que 100 g da FEM continham 9,06 g de umidade, 12,72 g de cinzas, 0,7 g de lipídios, 1,20 g de proteínas, 31,01 g de fibras insolúveis, 45,21 g de glicídios totais e 192,75 kcal. Nos bolos experimentais, os pesos, alturas, diâmetros e rendimentos foram maiores e o índice de expansão menor, bem como, o volume aparente do bolo com 30% FEM foi menor. Os bolos experimentais apresentaram menor pH, maior acidez titulável, maiores teores de fibra e umidade, menores de glicídios totais e reduzido valor energético. Os bolos obtiveram boa aceitação e mais de 60% dos provadores comprariam os bolos. O bolo com 7% FEM foi ligeiramente melhor que o controle, diferindo no aroma e sabor do que continha 30% FEM. Portanto, o uso de FEM para produção de bolos, nas condições dessa pesquisa, é viável do ponto de vista tecnológico, nutricional e sensorial.

The role of nuclear and other conventional power plants in the flexible energy system

This thesis reviews the role of nuclear and conventional power plants in the future energy system. The review is done by utilizing freely accesible publications in addition to generating load duration and ramping curves for Nordic energy system. As the aim of the future energy system is to reduce GHG-emissions and avoid further global warming, the need for flexible power generation increases with the increased share of intermittent renewables. The goal of this thesis is to offer extensive understanding of possibilities and restrictions that nuclear power and conventional power plants have regarding flexible and sustainable generation. As a conclusion, nuclear power is the only technology that is able to provide large scale GHG-free power output variations with good ramping values. Most of the currently operating plants are able to take part in load following as the requirement to do so is already required to be included in the plant design. Load duration and ramping curves produced prove that nuclear power is able to cover most of the annual generation variation and ramping needs in the Nordic energy system. From the conventional power generation methods, only biomass combustion can be considered GHG-free because biomass is considered carbon neutral. CFB combusted biomass has good load follow capabilities in good ramping and turndown ratios. All the other conventional power generation technologies generate GHG-emissions and therefore the use of these technologies should be reduced.

Avaliação da perda da tolerância à dessecação e da quantidade de dna nuclear em sementes de Peltophorum dubium (spreng.) taubert durante e após a germinação

O presente trabalho teve por objetivo a avaliação da perda da tolerância à dessecação (TD) em sementes de Peltophorum dubium durante e após a germinação. As sementes foram colocadas para germinar e, ao atingirem 1, 3 e 5 mm de raiz primária (68% de umidade), foram desidratadas em sílica gel, até atingirem o grau de umidade inicial (8%), sendo em seguida reidratadas e avaliadas quanto à sobrevivência (retomada do crescimento e formação de plântulas normais). Procedimento semelhante foi adotado para os ensaios realizados durante a embebição, onde foram amostradas 100 sementes divididas em quatro repetições de 25 para cada um dos seguintes tempos de embebição: 12, 24, 48, 60 e 72 horas. Em seguida, foram selecionados diferentes pontos de interesse (12, 48 e 60 horas de embebição e raízes primárias com 1 mm de comprimento) para determinação da quantidade de DNA nuclear, afim de analisar possível correlação entre início do ciclo celular e perda da TD. Com relação ao comportamento de sementes germinadas submetidas à secagem e reidratação, para os três comprimentos de raízes primárias amostradas, não houve sobrevivência. Foi observada queda progressiva na sobrevivência de sementes de Peltophorum dubium relacionada ao tempo de embebição, e posterior secagem e reidratação, sugerindo que a perda da TD desta espécie acontece nos estágios iniciais da germinação, antes da protrusão da radícula. Sementes embebidas por 12 h, 24 h, 48 h, 60 h, 72 h e aquelas germinadas, com 1 mm de comprimento radicular, apresentaram índices iguais a 98%, 93%, 83%, 35%, 17% e 0% de sobrevivência respectivamente. Os estudos relacionados ao conteúdo de DNA nuclear não demonstram correlação entre retomada do ciclo celular e perda da TD.

Development of laboratory exercises for basic nuclear thermal hydraulics measurements

The thesis focuses on light water reactors (pressurized water reactors, boiling water reactors) and measurement techniques for basic thermal hydraulics parameters that are used in a nuclear power plant. The goal of this work is a development of laboratory exercises for basic nuclear thermal hydraulics measurements.

Failure modes of passive decay heat removing safety systems of modern nuclear power plants

The purpose of this master’s thesis is to gain an understanding of passive safety systems’ role in modern nuclear reactors projects and to research the failure modes of passive decay heat removal safety systems which use phenomenon of natural circulation. Another purpose is to identify the main physical principles and phenomena which are used to establish passive safety tools in nuclear power plants. The work describes passive decay heat removal systems used in AES-2006 project and focuses on the behavior of SPOT PG system. The descriptions of the main large-scale research facilities of the passive safety systems of the AES-2006 power plant are also included. The work contains the calculations of the SPOT PG system, which was modeled with thermal-hydraulic system code TRACE. The dimensions of the calculation model are set according to the dimensions of the real SPOT PG system. In these calculations three parameters are investigated as a function of decay heat power: the pressure of the system, the natural circulation mass flow rate around the closed loop, and the level of liquid in the downcomer. The purpose of the calculations is to test the ability of the SPOT PG system to remove the decay heat from the primary side of the nuclear reactor in case of failure of one, two, or three loops out of four. The calculations show that three loops of the SPOT PG system have adequate capacity to provide the necessary level of safety. In conclusion, the work supports the view that passive systems could be widely spread in modern nuclear projects.

Decision-making theory applied to India's explosion of a nuclear device in May, 1974

This essay reviews the decision-making process that led to India exploding a nuclear device in May, 1974. An examination of the Analytic, Cybernetic and Cognitive Theories of decision, will enable a greater understanding of the events that led up to the 1974 test. While each theory is seen to be only partially useful, it is only by synthesising the three theories that a comprehensive account of the 1974 test can be given. To achieve this analysis, literature on decision-making in national security issues is reviewed, as well as the domestic and international environment in which involved decisionmakers operated. Finally, the rationale for the test in 1974 is examined. The conclusion revealed is that the explosion of a nuclear device by India in 1974 was primarily related to improving Indian international prestige among Third World countries and uniting a rapidly disintegrating Indian societal consensus. In themselves, individual decision-making theories were found to be of little use, but a combination of the various elements allowed a greater comprehension of the events leading up to the test than might otherwise have been the case.

Gypsy moths (Lymantria dispar) in the Niagara Region : population density variation, introduction of an entomopathogenic fungus (Entomophaga maimaiga) and occurrence of nuclear polyhedrosis virus

The gypsy moth, Lymantria dispar, a major defoliator of broad leaf trees, was accidentally introduced into North America in 1869. Much interest has been generated regarding the potential of using natural pathogens for biological control of this insect. One of these pathogens, a highly specific fungus, Entomophaga maimaiga, was accredited with causing major epizootics in populations of gypsy moth across the north-eastern United States in 1989 and 1990 and is thought to be spreading northwards into Canada. This study examined gypsy moth population densities in the Niagara Region. The fungus, .E.. maimaiga, was artificially introduced into one site and the resulting mortality in host populations was noted over two years. The relationship between fungal mortality, host population density and occurrence of another pathogen, the nuclear polyhedrosis virus (NPV), was assessed. Gypsy moth population density was assessed by counting egg masses in 0.01 hectare (ha) study plots in six areas, namely Louth, Queenston, Niagara-on-the-Lake, Shorthills Provincial Park, Chippawa Creek and Willoughby Marsh. High variability in density was seen among sites. Willoughby Marsh and Chippawa Creek, the sites with the greatest variability, were selected for more intensive study. The pathogenicity of E. maimaiga was established in laboratory trials. Fungal-infected gypsy moth larvae were then released into experimental plots of varying host density in Willoughby Marsh in 1992. These larvae served as the inoculum to infect field larvae. Other larvae were injected with culture medium only and released into control plots also of varying host density. Later, field larvae were collected and assessed for the presence of .E.. maimaiga and NPV. A greater proportion of larvae were infected from experimental plots than from control plots indicating that the experimental augmentation had been successful. There was no relationship between host density and the proportion of infected larvae in either experimental or control plots. In 1992, 86% of larvae were positive for NPV. Presence and intensity of NPV infection was independent of fungal presence, plot type or interaction of these two factors. Sampling was carried out in the summer of 1993, the year after the introduction, to evaluate the persistence of the pathogen in the environment. Almost 50% of all larvae were infected with the fungus. There was no difference between control and experimental plots. Data collected from Willoughby Marsh indicated that there was no correlation between the proportion of larvae infected with the fungus and host population density in either experimental or control plots. About 10% of larvae collected from a nearby site, Chippawa Creek, were also positive for .E.. maimaiga suggesting that low levels of .E.. maimaiga probably occurred naturally in the area. In 1993, 9.6% of larvae were positive for NPV. Again, presence or absence of NPV infection was independent of fungal presence plot type or interaction of these two factors. In conclusion, gypsy moth population densities were highly variable between and within sites in the Niagara Region. The introduction of the pathogenic fungus, .E.. maimaiga, into Willoughby Marsh in 1992 was successful and the fungus was again evident in 1993. There was no evidence for existence of a relationship between fungal mortality and gypsy moth density or occurrence of NPV. The results from this study are discussed with respect to the use of .E.. maimaiga in gypsy moth management programs.