1,446 research outputs found
Modelling time varying volatility spillovers and conditional correlations across commodity metal futures
This paper examines how the most prevalent stochastic properties of key metal futures returns have been affected by the recent financial crisis using both mapped and unmapped data. Our results suggest that copper and gold futures returns exhibit time-varying persistence in their corresponding conditional volatilities over the crisis period; in particular,such persistence increases during periods of high volatility compared with low volatility. The estimation of a bivariate GARCH model further shows the existence of time-varying volatility spillovers between these returns during the different stages of such a crisis. Our results, which are broadly the same in relation to the use of mapped or unmapped data, suggest that the volatilities of copper and gold are inherently linked, although these metals have very different applications
Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice
We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio
Revisiting Happiness Economics through a Post-structuralist Lens
Despite the substantial growth in interest and publications in recent decades, Happiness Economics (henceforth HE) remains a largely problematic scholarly field as is evidenced by the field’s failure to accumulate a considerable corpus of consensual knowledge. To the contrary, methodological approaches abound and conclusions often contradict one another. It is this project’s contention that these mixed results should not be attributed to either simple methodological errors or to the interdisciplinarity of the field, as it has been suggested. Rather, while clear patterns of significant methodological flaws are, indeed, identified, the author makes the case that they are owed to the precarious theoretical framework that underlies HE, something which explains both their ubiquity and persistence. More specifically, the source of problems is traced in flawed assumptions that pertain, on the one hand, to problematic understandings of meaning and subjectivity and, on the other, to epistemology, broadly construed. The former concerns an unwarranted treatment of both meaning and subjectivity as stable, fixed, and universal, while the latter refers to an ill-conceived positivist framework that is not fit for purpose. Through a categorisation and analysis of the literature, post-structuralism emerges as a uniquely positioned theoretical toolbox to illuminate these difficulties and to clear the ground for a HE that addresses them effectively. In addition, the author proposes neo-pragmatism as the appropriate theoretical backdrop for any future HE projects. It is illustrated that not only is neo-pragmatism congruent with the post-structuralist critique levelled against HE but it also avoids the pitfalls of epistemic nihilism by embracing the sociological character of meaning and knowledge as well as its entailed contingencies. Finally, this project considers the general methodological implications of this intervention, how the quality of already existing literature may be improved, and explores a small number of broad policy implications
Universal architecture of bacterial chemoreceptor arrays
Chemoreceptors are key components of the high-performance signal transduction system that controls bacterial chemotaxis. Chemoreceptors are typically localized in a cluster at the cell pole, where interactions among the receptors in the cluster are thought to contribute to the high sensitivity, wide dynamic range, and precise adaptation of the signaling system. Previous structural and genomic studies have produced conflicting models, however, for the arrangement of the chemoreceptors in the clusters. Using whole-cell electron cryo-tomography, here we show that chemoreceptors of different classes and in many different species representing several major bacterial phyla are all arranged into a highly conserved, 12-nm hexagonal array consistent with the proposed “trimer of dimers” organization. The various observed lengths of the receptors confirm current models for the methylation, flexible bundle, signaling, and linker sub-domains in vivo. Our results suggest that the basic mechanism and function of receptor clustering is universal among bacterial species and was thus conserved during evolution
Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice
10.1038/srep03754Scientific Reports4
Deletion of the cruciform binding domain in CBP/14-3-3 displays reduced origin binding and initiation of DNA replication in budding yeast
BACKGROUND: Initiation of eukaryotic DNA replication involves many protein-protein and protein-DNA interactions. We have previously shown that 14-3-3 proteins bind cruciform DNA and associate with mammalian and yeast replication origins in a cell cycle dependent manner. RESULTS: By expressing the human 14-3-3ε, as the sole member of 14-3-3 proteins family in Saccharomyces cerevisiae, we show that 14-3-3ε complements the S. cerevisiae Bmh1/Bmh2 double knockout, conserves its cruciform binding activity, and associates in vivo with the yeast replication origins ARS307. Deletion of the α5-helix, the potential cruciform binding domain of 14-3-3, decreased the cruciform binding activity of the protein as well as its association with the yeast replication origins ARS307 and ARS1. Furthermore, the mutant cells had a reduced ability to stably maintain plasmids bearing one or multiple origins. CONCLUSION: 14-3-3, a cruciform DNA binding protein, associates with yeast origins of replication and functions as an initiator of DNA replication, presumably through binding to cruciform DNA forming at yeast replicators
O CURRÍCULO DE ENFERMAGEM DA UFBA E O SUS
A construção do Sistema Único de Saúde como proposto pelo movimento da Reforma Sanitária Brasileira implica em mudança do modelo médico-assistencial, até então hegemônico, para um modelo voltado para o enfrentamento dos problemas e atendimento das necessidades de saúde da população. Tais mudanças requerem novas práticas profissionais e processos de formação profissional direcionados para o novo modelo de atenção, o que levou à indagação sobre a direcionalidade do currículo da Escola de Enfermagem da Universidade Federal da Bahia (EEUFBA). Esse estudo tem como objetivo analisar o conteúdo e a estrutura do currículo da EEUFBA, no período de 2002 a 2007. Trata-se de um estudo de caso com abordagem quantiqualitativa, assumindo como dimensões de análise o conteúdo curricular e a estrutura curricular. As fontes de dados foram as grades curriculares e as ementas das disciplinas do período considerado. Os achados permitem afirmar que, até o ano de 2007, a EEUFBA mantinha o conteúdo, a estrutura e a organização do seu currículo seguindo o modelo biologicista e centrado na doença, impedindo a compreensão do ser humano na sua integralidade, isto é, a direcionalidade do currículo é para a formação de profissionais para a reprodução do modelo médico assistencial hegemônico na saúde, contrariando, inclusive, as indicações das novas diretrizes curriculares
Increased origin activity in transformed versus normal cells: identification of novel protein players involved in DNA replication and cellular transformation
Using libraries of replication origins generated previously, we identified three clones that supported the autonomous replication of their respective plasmids in transformed, but not in normal cells. Assessment of their in vivo replication activity by in situ chromosomal DNA replication assays revealed that the chromosomal loci corresponding to these clones coincided with chromosomal replication origins in all cell lines, which were more active by 2–3-fold in the transformed by comparison to the normal cells. Evaluation of pre-replication complex (pre-RC) protein abundance at these origins in transformed and normal cells by chromatin immunoprecipitation assays, using anti-ORC2, -cdc6 and -cdt1 antibodies, showed that they were bound by these pre-RC proteins in all cell lines, but a 2–3-fold higher abundance was observed in the transformed by comparison to the normal cells. Electrophoretic mobility shift assays (EMSAs) performed on the most efficiently replicating clone, using nuclear extracts from the transformed and normal cells, revealed the presence of a DNA replication complex in transformed cells, which was barely detectable in normal cells. Subsequent supershift EMSAs suggested the presence of transformation-specific complexes. Mass spectrometric analysis of these complexes revealed potential new protein players involved in DNA replication that appear to correlate with cellular transformation
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