Genome-wide screen of genes required for caffeine tolerance in fission yeast

Background: An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to atoxic dose of this drug, and the relationship between caffeine and oxidative stress pathways.Methodology/Principal Findings: We searched for Schizosaccharomyces pombe mutants with inhibited growth on caffeinecontainingplates. We screened a collection of 2,700 haploid mutant cells, of which 98 were sensitive to caffeine. The genes mutated in these sensitive clones were involved in a number of cellular roles including the H2O2-induced Pap1 and Sty1 stress pathways, the integrity and calcineurin pathways, cell morphology and chromatin remodeling. We have investigated the role of the oxidative stress pathways in sensing and promoting survival to caffeine. The Pap1 and the Sty1 pathways are both required for normal tolerance to caffeine, but only the Sty1 pathway is activated by the drug. Cells lacking Pap1 aresensitive to caffeine due to the decreased expression of the efflux pump Hba2. Indeed, ?hba2 cells are sensitive to caffeine, and constitutive activation of the Pap1 pathway enhances resistance to caffeine in an Hba2-dependent manner. Conclusions/Significance: With our caffeine-sensitive, genome-wide screen of an S. pombe deletion collection, we havedemonstrated the importance of some oxidative stress pathway components on wild-type tolerance to the drug.

The peroxiredoxin Tpx1 is essential as a H202-scavenger during aerobic growth in fission yeast

Peroxiredoxins are known to interact with hydrogen peroxide (H2O2) and to participate in oxidant scavenging, redox signal transduction, and heat-shock responses. The two-cysteine peroxiredoxin Tpx1 of Schizosaccharomyces pombe has been characterized as the H2O2 sensor that transduces the redox signal to the transcription factor Pap1. Here, we show that Tpx1 is essential for aerobic, but not anaerobic, growth. We demonstrate that Tpx1 has an exquisite sensitivity for its substrate, which explains its participation in maintaining low steady-state levels of H2O2. We also show in vitro and in vivo that inactivation of Tpx1 by oxidation of its catalytic cysteine to a sulfinic acid is always preceded by a sulfinic acid form in a covalently linked dimer, which may be important for understanding the kinetics of Tpx1 inactivation. Furthermore, we provide evidence that a strain expressing Tpx1.C169S, lacking the resolving cysteine, can sustain aerobic growth, and we show that small reductants can modulate the activity of the mutant protein in vitro, probably by supplying a thiol group to substitute for cysteine 169.

Not the right job but a secure one : over-education and temporary employment in France, Italy and Spain

Resorting to four waves of the European Community Household Panel, this research explores the association between temporary employment and the likelihood of being over-educated. Such an association has been largely ignored by the literature explaining over-education, more inclined to attribute such a mismatch to the system of education. Selecting three similarly standarised and stratified systems of education (France, Italy and Spain) and controlling for many other variables likely to affect over-education, like gender, age, tenure, job change, firm size or sector, the paper demonstrates that such an association between temporary employment and over-education exists. Being a stepping stone towards a more stable and adjusted position in the labour market, holding a temporary employment may be associated to a higher likelihood of being over-educated. Such an association is more likely in Italy and France. Yet, the opposite sign prevails where permanent employment becomes such a valuable asset as to make individuals trade human capital by employment security. This is the case of Spain.

Cosmopolitan justice and minority rights: the case of minority nations (or Kant again, but different)

Global Justice has usually been understood to mean institutional and social justice (political and redistributive issues on a global scale). In contrast, issues involving different national and cultural identities, are usually marginal in reflections on global justice. This occurs despite the fact that human rights include political social and cultural rights. This paper links a conception of global justice, moral cosmopolitanism, with plurinational democracies. After giving a brief description of moral cosmopolitanism I go on to analyse notions of cosmopolitanism and patriotism in Kant's work and the political significance that the notion of "unsocial sociability" and the "Ideas of Pure Reason" of Kant's first Critique have for cosmopolitanism. Finally, I analyse the relationship between cosmopolitanism and minority nations based on the preceding sections. I postulate the need for a moral and institutional refinement of democracies and international society that is better able to accommodate national pluralism than has so far been achieved by traditional liberal constitutionalism and cosmopolitanism

Excuse me, but your accent is very unusual. The complexity of establishing third languages in Inglourious Basterds. Applying a model of translation analysis to dubbing

The growing multilingual trend in movie production comes with a challenge for dubbing translators since they are increasingly confronted with more than one source language. The main purpose of this master’s thesis is to provide a case study on how these third languages (see CORRIUS and ZABALBEASCOA 2011) are rendered. Another aim is to put a particular focus on their textual and narrative functions and detect possible shifts that might occur in translations. By applying a theoretical model for translation analysis (CORRIUS and ZABALBEASCOA 2011), this study describes how third languages are rendered in the German, Spanish, and Italian dubbed versions of the 2009 Tarantino movie Inglourious Basterds. A broad range of solution-types are thereby revealed and prevalent restrictions of the translation process identified. The target texts are brought in context with some sociohistorical aspects of dubbing in order to detect prevalent norms of the respective cultures andto discuss the acceptability of translations (TOURY 1995). The translatability potential of even highly complex multilingual audiovisual texts is demonstrated in this study. Moreover, proposals for further studies in multilingual audiovisual translation are outlined and the potential for future investigations in this field thereby emphasised.

Satisfaction in choice as a function of the number of alternatives: When "goods satiate" but "bads escalate"

Whereas people are typically thought to be better off with more choices, studiesshow that they often prefer to choose from small as opposed to large sets of alternatives.We propose that satisfaction from choice is an inverted U-shaped function of thenumber of alternatives. This proposition is derived theoretically by considering thebenefits and costs of different numbers of alternatives and is supported by fourexperimental studies. We also manipulate the perceptual costs of information processingand demonstrate how this affects the resulting satisfaction function. We furtherindicate that satisfaction when choosing from a given set is diminished if people aremade aware of the existence of other choice sets. The role of individual differences insatisfaction from choice is documented by noting effects due to gender and culture. Weconclude by emphasizing the need to have an explicit rationale for knowing how muchchoice is enough.

Protectionist but globalised? Latin American custom duties and trade during the pre-1914 belle époque

While it is true that Latin American republics had no rival on maximising revenues from custom collection during the belle époque, this paper shows that Latin American countries were also generous importers, only behind the larger commercial countries of Western Europe in terms of imports per capita. Latin American citizens were much more linked to international trade than citizens of most regions of the world. Their relation to the world economy was tighter both via their imports and their exports relative to their population and income levels. This paper comes to show that there is no contradiction between the high custom collection by the Latin American republics and their high level of interaction with the global economy in the pre-1914 belle époque, although large country differences can be observed when descending from the regional to the national level.

Polymorphisms of pyrimidine pathway enzymes encoding genes and HLA-B*4001 carriage in stavudine-associated lipodystrophy in HIV-infected patients.

: To assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*4001 carriage with HIV lipodystrophy syndrome (HALS). 336 patients, 187 with HALS and 149 without HALS, and 72 controls were recruited. HALS was associated with the presence of a low expression, thymidylate synthase (TS) genotype polymorphism. Methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms and HLA-B*4001 carriage were not associated with HALS or d4T-TP intracellular levels. In conclusion HALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*4001 carriage.

Fluctuaciones cíclicas y raíces unitarias en la economia española, 1850-1990

En este artículo se analiza el grado de persistencia de las fluctuaciones cíclicas en la economía española. En concreto, se estudia si el PIB y el PIB por capita de esta economía presentan una raíz unitaria. Con el fin de evitar el sesgo a aceptar raíces unitarias cuando se producen cambios en la función de tendencia, como el originado por la Guerra Civil española (1936-1939), se han aplicado varios contrastes que tienen en cuenta los cambios en la función de tendencia. Los resultados obtenidos muestran que existe una importante evidencia en el sentido que el logaritmo del PIB presenta una raíz unitaria. La principal implicación de este resultado es que los shocks sobre el producto tienen efectos permanentes en el nivel del PIB de la economía española, aun cuando esta hipótesis es más difícil de aceptar por el PIB por capita vista la evidencia contradictoria encontrada a favor de la misma.

Fluctuaciones cíclicas y raíces unitarias en la economia española, 1850-1990

En este artículo se analiza el grado de persistencia de las fluctuaciones cíclicas en la economía española. En concreto, se estudia si el PIB y el PIB por capita de esta economía presentan una raíz unitaria. Con el fin de evitar el sesgo a aceptar raíces unitarias cuando se producen cambios en la función de tendencia, como el originado por la Guerra Civil española (1936-1939), se han aplicado varios contrastes que tienen en cuenta los cambios en la función de tendencia. Los resultados obtenidos muestran que existe una importante evidencia en el sentido que el logaritmo del PIB presenta una raíz unitaria. La principal implicación de este resultado es que los shocks sobre el producto tienen efectos permanentes en el nivel del PIB de la economía española, aun cuando esta hipótesis es más difícil de aceptar por el PIB por capita vista la evidencia contradictoria encontrada a favor de la misma.

Escape over a potential barrier driven by colored noise: Large but finite correlation times

The recent theory of Tsironis and Grigolini for the mean first-passage time from one metastable state to another of a bistable potential for long correlation times of the noise is extended to large but finite correlation times.

Heparin attenuates TNF-alpha induced inflammatory response through a CD11b dependent mechanism

Background In addition to its anticoagulant properties, heparin has anti-inflammatory effects, the molecular and mechanistic bases of which are incompletely defined. AIMS The current studies were designed to test the hypothesis that heparin abrogates the expression or function of leucocyte-endothelial adherence molecules which are fundamental to the acute inflammatory response. Methods The effects of heparin on tumour necrosis factor alpha (TNF-¿) induced leucocyte rolling, adhesion, and migration as well as vascular permeability were assessed in rat mesenteric venules using intravital microscopy. Expression of adhesion molecules was quantitated using a double radiolabelled monoclonal antibody (mAb) binding technique in vivo (P-selectin, intercellular cell adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1)) or flow cytometry (CD11a, CD11b, and L-selectin). Ex vivo binding of heparin to neutrophils was assessed by flow cytometry. RESULTS TNF-alpha induced a significant increase in leucocyte rolling, adhesion, and migration, and vascular permeability, coincident with a significant increase in expression of P-selectin, ICAM-1, and VCAM-1. Ex vivo assessment of blood neutrophils showed significant upregulation of CD11a and CD11b and significant downregulation of L-selectin within five hours of TNF-¿ administration. Heparin pretreatment significantly attenuated leucocyte rolling, adhesion, and migration but did not affect expression of cell adhesion molecules or vascular permeability elicited by TNF-¿ administration. Binding of heparin was significantly increased on blood neutrophils obtained five hours after TNF-¿ administration. Preincubation with an anti-CD11b mAb but not with an anti-CD11a or anti-L-selectin antibody significantly diminished heparin binding ex vivo.

In vitro susceptibility to pentavalent antimony in Leishmania infantum strains is not modified during in vitro or in vivo passages but is modified after host treatment with meglumine antimoniate

Background: Leishmaniasis is a common parasitic disease in Southern Europe, caused by Leishmania infantum. The failures of current treatment with pentavalent antimonials are partially attributable to the emergence of antimony-resistant Leishmania strains. This study analyses the in vitro susceptibility to pentavalent antimony of intracellular amastigotes from a range of L. infantum strains, derived from the same infected animal, during in vitro and in vivo passages and after host treatment with meglumine antimoniate. Results: SbV-IC50 values for strains from two distinct isolates from the same host and one stock after two years of culture in NNN medium and posterior passage to hamster were similar (5.0 ± 0.2; 4.9 ± 0.2 and 4.4 ± 0.1 mgSbV/L, respectively). In contrast, a significant difference (P < 0.01, t test) was observed between the mean SbV-IC50 values in the stocks obtained before and after treatment of hosts with meglumine antimoniate (4.7 ± 0.4 mgSbV/L vs. 7.7 ± 1.5 mgSbV/L). Drug-resistance after drug pressure in experimentally infected dogs increased over repeated drug administration (6.4 ± 0.5 mgSbV/L after first treatment vs. 8.6 ± 1.4 mgSbV/L after the second) (P < 0.01, t test). Conclusions: These results confirm previous observations on strains from Leishmania/HIV co-infected patients and indicate the effect of the increasing use of antimony derivatives for treatment of canine leishmaniasis in endemic areas on the emergence of Leishmania antimony-resistant strains.

Intestinal and hepatic nitrogen balance in the rat after the administration of an oral protein load

The fate of a small oral dose of protein given to overnight-starved rats was studied. After 3 h, 62 per cent of the protein amino acids had been absorbed. Most of the absorbed N went into the bloodstream through the portal in the form of amino acids, but urea and ammonia were also present. About one-quarter of all absorbed N was carried as lymph amino acids. The liver was able to take all portal free ammonia and a large proportion of portal amino acids, releasing urea. The hepatic N balance was negative, indicating active proteolysis and net loss of liver protein.

Troballa d'un palet de riera pintat a la cova del Filador (Margalef de Montsant, Priorat, Tarragona)

Aquesta nota vol ser la primera notícia de la troballa d'un palet de riera pintat durant els treballs d'excavació de l'abric del Filador (Margalef de Montsant, Priorat, Tarragona) l'estiu de 1982. Volem que Pyrenae, la revista del nostre Institut d'Arqueología i Prehistoria, organisme que d'altra banda inclou la nostra tasca de camp dins de la seva programació, sigui la primera en tenir aquesta nova. Si bé una primera fotografía ja ha aparegut al cataleg de l'exposició "L'Arqueologia catalana, avui" (pag. 30), aixo no resta actualitat a les dades ínicials que oferirem.