1,721,344 research outputs found
Analysis of the role of the secretory pathway Ca2+/Mn2+- ATPase, PMR1/ATP2C1, in calcium homeostasis: from oxidative stress to skin disease
Full text linkDuring my PhD, the genetically tractable Kluyveromyces lactis yeast has been used to study the molecular basis of Hailey–Hailey disease (HHD). This pathology, also known as familial benign chronic pemphigus, is a rare, chronic and recurrent blistering disorder, characterized by acantholysis. The genetics and pathophysiology of HHD have been linked to mutations in ATP2C1. The gene encodes for an adenosine triphosphate (ATP)-powered calcium channel pump and PMR1 is the yeast orthologue. Similarly to human HHD-cells, in yeast the loss of PMR1 promotes cellular toxicity caused by increased oxidative stress linked to the alteration of calcium homeostasis. By a functional suppression screening of yeast mutant with a cDNA library, we found that Glutathione S-transferase (GST), an important detoxifying enzyme, could be a candidate gene associated with Hailey-Hailey disease. Expression of mammalian GST in Klpmr1 alleviated several defects; these include oxidative-stress toxicity, calcium alteration and mitochondrial dysfunction. Additionally, the discoveries made in yeast were validated in HHD-derived cells. Indeed, HHD-lesional derived keratinocytes showed a decreased expression of GST gene when compared to non-lesional skin derived cells from the same patients.
In parallel to the genetic screening, a drug screen was performed to find compounds with potential therapeutic effects for HHD treatment. Indeed, currently, there is no reported cure for HHD. For this reason, 131 FDA-approved natural compounds were screened for their ability to alleviate the calcium alterations and the oxidative stress of Kluyveromyces lactis pmr1cells. The drug collection includes inhibitors, activators and antagonists acting on molecular targets involved in different signaling pathways. Initially, for the sake of simplicity, the initial screening system was based on the cell wall alterations of the pmr1∆ mutant, utilizing the chitin binding stilbene fluorescent brightener calcofluor white. In the first part of the screening 12 molecules resulted toxic, while 71% of the library molecules were ineffective and the remaining appeared to have a partial effect. Therefore, in a second round of the screening, these last compounds were evaluated at higher concentrations. Based on this, six molecules were selected for further analysis. Their effects on other defects of pmr1 mutant strain were also evaluated, ranging from alteration of Ca2+ homeostasis to sensitivity to the ROS-generator menadione, as well as the mitochondrial functionality
Contagion across Eurozone's sovereign spreads and the Core-Periphery divide
Full text linkThis paper investigates the causes of disproportionate increases of sovereign yields with respect to the interest rate on the 10 years German Bund within the Eurozone. Empirical evidence drawn from the Bank for International
Settlements dataset on banks’ portfolios shows that rapid financial integration, following the launch of the monetary union, resulted in excess exposure of Core countries’ banks in the Peripheral countries’ financial assets. In order to endogenize
the possibility of contagion effects, we conduct econometric estimates through a Global Vector Autoregressive model, where each country’s spread depends upon all Eurozone countries’ spreads. Results show that after the burst of the financial crisis
the Core countries’ sovereign yields are essentially determined by the international risk aversion, whereas the spreads of Peripheral countries mainly depend on fundamentals, namely the public debt/GDP ratio and the Real Effective Exchange Rate
values with respect to the Eurozone average. These results are supported by the estimate of an impulse response analysis. Macroeconomic failures in public finances and competitiveness seem to originate the exceptional increases in sovereign
spreads of the Periphery, through a contagion effect which is limited to this group of Eurozone countries
In situ U-Pb and Hf isotopes analyses on zircon from the Giglio Island pluton
Full text linkThe monzogranitic pluton of Giglio Island in the Tuscan Archipelago (Italy) is a relatively poorly
studied intrusion belonging to the Tuscan Magmatic Province (TMP), an association of intrusive
and effusive magmatic rocks formed between 14 and 0.3 Ma. New LAICPMS geochronological
UPb and Hf isotopic data were obtained from zircon grains separated from the two main tex
turally distinct units forming the intrusion: the outer, foliated Pietrabona facies (PBF), and the
inner porphyritic Arenella facies (ARF). We defined from UPb dating an emplacement age for
the Giglio intrusion of 5.448 ± 0.030 (2SE) Ma (weighted mean on 80 analyses, 206 Pb/ 238 U ages,
Th disequilibrium corrected), improving the previously published age. Although individual spot
ages are indistinguishable within error, the obtained weighted mean ages for the two facies are
different, 5.493 ± 0.034 (49 analyses) for PBF, and 5.309 ± 0.060 (31 analyses) for ARF, thus
suggesting that the pluton formed incrementally. We developed a robust method for the deter
mination of Hf isotopic composition in zircon by LAMCICPMS obtaining crustal values of ini
tial εHf comprised between 3.5 and 11.9 (2SE≈1). No differences between the two facies are
apparent, however each sample exhibits a large Hf isotopic heterogeneity that is statistically
significant compared to the repeatability obtained for reference zircons. Such variability suggests
that different crustallyderived magmas contributed to the magmatic evolution of the pluton,
advocating for a complex mechanism of melt production, ascent and final emplacement
Going to university? Family background and tertiary education enrolment in France and Italy
No full textDifferently from the presumption of standard economic theory, empirical evidence suggests that returns to education do not play the most relevant role in tertiary education enrolment. On the whole, the results of our investigation conducted on a probit regression model indicates that the cultural family background has a great influence on the young’s decision to go to university. The offspring’s own income is also very significant in all models, as the p-values are very good in both countries. The main difference between the two countries is that the influence of the father is much lower in France than in Italy, where the coefficient for the father’s education is relevant on average to the same extent than the mother’s education one
Wage inequality in Europe. The role of Labour Market and Redistributive Institutions
No full textThis paper aims at a deeper understanding of the determinants of wage inequality, the most important component of income inequality, in the European countries. We investigate on how wage inequality is affected by government regulation in the labour market and by the redistribution operated by the social protection system, also controlling for the impact of the effect of skillpremium related to technical change. To explain the continuously rising wage inequality in Europe, two regression models of wage inequality are employed each one using a different databases. In the last period, the overall degree of governance of the labour markets does not substantially change, but a different balance between decreasing labour market regulation and increasing redistribution manifest across Europe. While job and wage protection has been eased, income redistribution was strengthened, though its size differs across four clusters of European countries, depending on the majority voting preference for “risk insurance”. Overall, institutional substitution between labour market regulation and income redistribution seems to back the upward trend in wage inequalit
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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