1,154 research outputs found

    Revisiting Happiness Economics through a Post-structuralist Lens

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    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

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    Deletion of the cruciform binding domain in CBP/14-3-3 displays reduced origin binding and initiation of DNA replication in budding yeast

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    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

    The Effect of Regulatory Sequence Elements upon the Initiation of DNA Replication of the Minute Virus of Mice

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    AbstractThe minute virus of mice (MVM) genome is a linear single-stranded length of approximately 5000 nucleotides of DNA with unique terminal palindromic sequences at both ends. The left (3′) hairpin is used to prime the initiation of DNA synthesis on parental single-strand DNA while the right (5′) hairpin or stem-plus-arms structure can also prime the initiation of DNA synthesis during synthesis of dimer and higher oligomers as well as synthesis of progeny single strands. Previous studies have shown that if viral duplex DNA was input into anin vitroDNA replication system using extracts from uninfected HeLa cells, the 5′ end of the molecule was able to form a hairpin and initiate DNA synthesis by DNA polymerase δ (Cossonset al.(1996),Virology216, 258–264). In this study, the effect of the deletion of knowncis-acting genetic elements upon the initiation of DNA replication was studied using a series of MVM mutants with deletions within the 5′ terminal region. Mutants containing deletions of elements A (nucleotides 4489–4636), B (nucleotides 4636–4695), and either one or both of the 65-bp repeats (nucleotides 4720–4785 and 4785–4849) were used as template in thein vitroDNA replication system. When element A was deleted, the efficiency of initiation decreased significantly. Subsequent removal of element B, leaving just the two 65-bp repeats, restored levels of initiation back to those seen in the wild-type genome. In the absence of either A or B both 65-bp repeats were necessary for efficient initiation, and removal of one of these repeats caused a decrease in efficiency. Thus, element B appeared to have a negative regulatory effect (in the absence of element A), and element A appeared to have a positive regulatory effect, at least in the presence of element B. These data demonstrate, for the first time, a complex interaction between thesecis-acting regulatory elements which can function as both positive or negative regulators in the initiation of MVM DNA replication

    Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

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    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

    O CURRĂŤCULO DE ENFERMAGEM DA UFBA E O SUS

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    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

    Universal architecture of bacterial chemoreceptor arrays

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    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
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