The contribution of aging to the understanding of the dimensionality of executive functions.

It has been reported in the literature that executive functions may be fractioned into updating, shifting, and inhibition. The present study aimed to explore whether these executive sub-components can be identified in a more age-heterogeneous sample and see if they are prone to an age-related decline. We tested the performances of 81 individuals aged from 18 to 88 years old in each executive sub-component, working memory, fluid intelligence and processing speed. Correlation analysis revealed only a slight positive relationship between the two updating measures. A linear decrement with age was observed only for two complex executive tests. Tasks indexing working memory, processing speed and fluid intelligence showed a stronger linear decline with age than executive tasks. In conclusion, our results did not replicate the executive structure known from the literature, and revealed that decrement in executive function is not an unavoidable concomitant of aging but rather concerns specific executive tasks.

CD4+CD25-mTGFbeta+ T cells induced by nasal application of ovalbumin transfer tolerance in a therapeutic model of asthma.

Background: Intranasal administration of high amount of allergen was shown to induce tolerance and to reverse the allergic phenotype. However, mechanisms of tolerance induction via the mucosal route are still unclear. Objectives: To characterize the therapeutic effects of intranasal application of ovalbumin (OVA) in a mouse model of bronchial inflammation as well as the cellular and molecular mechanisms leading to protection upon re-exposure to allergen. Methods: After induction of bronchial inflammation, mice were treated intranasally with OVA and re-exposed to OVA aerosols 10 days later. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined. The respective role of CD4(+)CD25(+) and CD4(+)CD25(-) T cells in the induction of tolerance was analysed. Results: Intranasal treatment with OVA drastically reduced inflammatory cell recruitment into BALF and bronchial hyperresponsiveness upon re-exposure to allergen. Both OVA- specific-proliferation of T cells, T(h)1 and T(h)2 cytokine production from lung and bronchial lymph nodes were inhibited. Transfer of CD4(+)CD25(-) T cells, which strongly expressed membrane-bound transforming growth factor beta (mTGF beta), from tolerized mice protected asthmatic recipient mice from subsequent aerosol challenges. The presence of CD4(+)CD25(+)(Foxp3(+)) T cells during the process of tolerization was indispensable to CD4(+)CD25(-) T cells to acquire regulatory properties. Whereas the presence of IL-10 appeared dispensable in this model, the suppression of CD4(+)CD25(-)mTGF beta(+) T cells in transfer experiments significantly impaired the down-regulation of airways inflammation. Conclusion: Nasal application of OVA in established asthma led to the induction of CD4(+)CD25(-)mTGF beta(+) T cells with regulatory properties, able to confer protection upon allergen re-exposure.

Quetiapine dosage in bipolar disorder episodes and mixed states

OBJECTIVE: Although the maximal quetiapine doses in the published studies were restricted to 800 mg/day, higher quetiapine doses are not unusual in clinical practice. The aim of the present study was to evaluate the effectiveness, tolerability and clinical reasons associated to the use of high dosage of quetiapine (>800 mg), when used under routine clinical conditions, in a sample of bipolar disorder and schizoaffective bipolar inpatients. METHODS: Charts of all bipolar and schizoaffective adult inpatients, who had received quetiapine for a mood episode between 1999 and 2005 were retrospectively reviewed. These charts also included the assessment of manic and depressive symptoms on admission and at discharge using the Beck-Rafaelsen Mania Scale (MAS) and the Montgomery Asberg depression rating scale (MADRS), respectively. RESULTS: Data of 50 patients were analyzed. The overall F in repeated measures ANOVA revealed a significant MAS scores reduction between admission and discharge. MAS scores reduction did not differ between the high and low quetiapine groups. Similarly, a significant MADRS reduction was found. Again, no differences between the high and the low dose group were found. Logistic regression analysis of the 50 patients revealed only mixed episodes predicted high quetiapine dosage. CONCLUSIONS: The present study confirms quetiapine efficiency and tolerability in the treatment of bipolar episodes, even in doses > to 800 mg and found a link between quetiapine doses and mixed episodes

La ironía en el transfer intercultural : aproximación pragmática en la traducción al castellano de relatos satíricos de Mijaíl Zoschenko y Mijaíl Bulgákov

El presente estudio está dedicado a analizar la traducción de la ironía en una obra de ficción literaria, más concretamente en los relatos satíricos de Mijaíl Zoschenko y Mijaíl Bulgákov en su versión castellana. Metodológicamente, el estudio presenta un enfoque pragmático, y se inscribe en las aportaciones pragmáticas de la segunda mitad del siglo XX, que permiten analizar el texto literario como un acto de comunicación y un discurso dialógico, inscribiéndolo en un contexto extralingúístico relevante. Abordaremos el análisis de lo "no dicho": el subtexto irónico que subyace como un significado implícito no-deducible de los medios lingüísticos en sí mismos, y donde cobran una gran importancia los factores comunicativos: la situación, la intención del hablante, el principio cooperativo (según Paul Grice) y toda una serie de presupuestos que pueden o no compartir los interlocutores. Partiendo del supuesto de la existencia de diferentes tipos textuales en toda traducción, la ficción literaria se abordará como un tipo de texto que presenta características particupares. En este sentido, el relato satírico de la época soviética se contempla como un género específico que implica, a su vez, una estrategia específica de traducción. Como es sabido, en los textos humorísticos predomina el efecto perlocutivo. Así pues, dependerá del tradutor que el texto transferido a otra cultura, y a menudo a otra época, consiga el mismo efecto humorístico, o similar, al que tuvo el original en su contexto histórico-cultural.

Conjugative Transfer of Chromosomal Genes between Fluorescent Pseudomonads in the Rhizosphere of Wheat.

Bacteria released in large numbers for biocontrol or bioremediation purposes might exchange genes with other microorganisms. Two model systems were designed to investigate the likelihood of such an exchange and some factors which govern the conjugative exchange of chromosomal genes between root-colonizing pseudomonads in the rhizosphere of wheat. The first model consisted of the biocontrol strain CHA0 of Pseudomonas fluorescens and transposon-facilitated recombination (Tfr). A conjugative IncP plasmid loaded with transposon Tn5, in a CHA0 derivative carrying a chromosomal Tn5 insertion, promoted chromosome transfer to auxotrophic CHA0 recipients in vitro. A chromosomal marker (pro) was transferred at a frequency of about 10(sup-6) per donor on wheat roots under gnotobiotic conditions, provided that the Tfr donor and recipient populations each contained 10(sup6) to 10(sup7) CFU per g of root. In contrast, no conjugative gene transfer was detected in soil, illustrating that the root surface stimulates conjugation. The second model system was based on the genetically well-characterized strain PAO of Pseudomonas aeruginosa and the chromosome mobilizing IncP plasmid R68.45. Although originally isolated from a human wound, strain PAO1 was found to be an excellent root colonizer, even under natural, nonsterile conditions. Matings between an auxotrophic R68.45 donor and auxotrophic recipients produced prototrophic chromosomal recombinants at 10(sup-4) to 10(sup-5) per donor on wheat roots in artificial soil under gnotobiotic conditions and at about 10(sup-6) per donor on wheat roots in natural, nonsterile soil microcosms after 2 weeks of incubation. The frequencies of chromosomal recombinants were as high as or higher than the frequencies of R68.45 transconjugants, reflecting mainly the selective growth advantage of the prototrophic recombinants over the auxotrophic parental strains in the rhizosphere. Although under field conditions the formation of chromosomal recombinants is expected to be reduced by several factors, we conclude that chromosomal genes, whether present naturally or introduced by genetic modification, may be transmissible between rhizosphere bacteria.

Theory of mind tasks and executive functions: A systematic review of group studies in neurology.

A growing number of studies have been addressing the relationship between theory of mind (TOM) and executive functions (EF) in patients with acquired neurological pathology. In order to provide a global overview on the main findings, we conducted a systematic review on group studies where we aimed to (1) evaluate the patterns of impaired and preserved abilities of both TOM and EF in groups of patients with acquired neurological pathology and (2) investigate the existence of particular relations between different EF domains and TOM tasks. The search was conducted in Pubmed/Medline. A total of 24 articles met the inclusion criteria. We considered for analysis classical clinically accepted TOM tasks (first- and second-order false belief stories, the Faux Pas test, Happe's stories, the Mind in the Eyes task, and Cartoon's tasks) and EF domains (updating, shifting, inhibition, and access). The review suggests that (1) EF and TOM appear tightly associated. However, the few dissociations observed suggest they cannot be reduced to a single function; (2) no executive subprocess could be specifically associated with TOM performances; (3) the first-order false belief task and the Happe's story task seem to be less sensitive to neurological pathologies and less associated to EF. Even though the analysis of the reviewed studies demonstrates a close relationship between TOM and EF in patients with acquired neurological pathology, the nature of this relationship must be further investigated. Studies investigating ecological consequences of TOM and EF deficits, and intervention researches may bring further contributions to this question.

Superatomic Boolean algebras constructed from strongly unbounded functions

"Vegeu el resum a l'inici del document del fitxer adjunt."

Optimum in vitro expansion of human antigen-specific CD8 T cells for adoptive transfer therapy.

Increasing evidence suggests that adoptive transfer of antigen-specific CD8(+) T cells could represent an effective strategy in the fight against chronic viral infections and malignancies such as melanoma. None the less, a major limitation in the implementation of such therapy resides in the difficulties associated with achieving rapid and efficient expansion of functional T cells in culture necessary to obtain the large numbers required for intravenous infusion. Recently, the critical role of the cytokines interleukin (IL)-2, IL-7 and IL-15 in driving T cell proliferation has been emphasized, thus suggesting their use in the optimization of expansion protocols. We have used major histocompatibility complex (MHC) class I/peptide multimers to monitor the expansion of antigen-specific CD8 T lymphocytes from whole blood, exploring the effect of antigenic peptide dose, IL-2, IL-7 and IL-15 concentrations on the magnitude and functional characteristics of the antigen-specific CD8(+) T cells generated. We show here that significant expansions of antigen-specific T cells, up to 50% of the CD8(+) T cell population, can be obtained after a single round of antigen/cytokine (IL-2 or IL-15) stimulation, and that these cells display good cytolytic and interferon (IFN)-gamma secretion capabilities. Our results provide an important basis for the rapid in vitro expansion of autologous T cells from the circulating lymphocyte pool using a simple procedure, which is necessary for the development of adoptive transfer therapies.

Endogenous Mergers of Complements with Mixed Bundling

This paper studies endogenous mergers of complements with mixed bundling, by allowing both for joint and separate consumption. After merger, partner fi…rms decrease the price of the bundled system. Besides, when markets for individual components are suffi…ciently important, partner …firms raise prices of stand-alone products, exploiting their monopoly power in local markets and making substitute 'mix-and-match' composite products less attractive to consumers. Even though these effects favor the pro…fitability of mergers, merging is not always an equilibrium outcome. The reason is that outsiders respond by cutting their prices to retain their market share, and mergers can be unprofitable when competition is intense. From a welfare analysis, we observe that the number of mergers observed in equilibrium may be either excessive (when markets for individual components are important) or suboptimal (when markets for individual components are less important). Keywords: complements; merger; mixed bundling; separate consumption JEL classi…fication: L13; L41; D43

Group strategy-proof social choice functions with binary ranges and arbitrary domains: characterization results

We define different concepts of group strategy-proofness for social choice functions. We discuss the connections between the defined concepts under different assumptions on their domains of definition. We characterize the social choice functions that satisfy each one of them and whose ranges consist of two alternatives, in terms of two types of basic properties.

The debate over the effector function of eosinophils in helminth infection: new evidence from studies on the regulation of vaccine immunity by IL-12

The production of Th1-type cytokines is associated with strong cell-mediated immunity while Th2-type cytokines are typically involved in the generation of humoral immune responses. In mice vaccinated a single time (1X) with attenuated cercariae of Schistosoma mansoni, the immunity induced is highly dependent on CD4+ T cells and IFN-gamma. In contrast, mice vaccinated multiple times (3X) have decreased IFN-gamma expression, develop a more dominant Th2-type cytokine response as well as protective antibodies which can passively transfer immunity to naive recipients. Previously, we demonstrated the ability of IL-12, a potent IFN-gamma-inducing cytokine to enhance (1X) schistosome cell-mediated immunity when administered during the period of immunization. More recently, we asked what effects IL-12 would have on the development humoral-based immunity. While multiply-immunized/saline-treated mice demonstrated a 70-80% reduction in parasite burden, 3X/IL-12-vaccinated animals displayed an even more striking >90% reduction in challenge infection, with many mice in the later group demonstrating complete protection. Analysis of pulmonary cytokine mRNA responses demonstrated that control challenged mice elicited a dominant Th2-type response, 3X/saline-vaccinated produced a mixed Th1/Th2-type cytokine response, while 3X/IL-12-immunized animals displayed a dominant Th1-type response. The IL-12-treated group also showed a marked reduction in total serum IgE and tissue eosinophilia while SWAP-specific IgG2a and IgG2b Abs were elevated. Interestingly, animals vaccinated with IL-12 also showed a highly significant increase in total Ig titers specific for IrV-5, a known protective antigen. More importantly, 3X/IL-12 serum alone, when transferred to naive mice reduced worm burdens by over 60% while 3X/saline serum transferred significantly less protection. Nevertheless, animals vaccinated in the presence of IL-12 also develop macrophages with enhanced nitric oxide dependent killing activity against the parasites. Together, these observations suggest that IL-12, initially described as an adjuvant for cell-mediated immunity, may also be used as an adjuvant for promoting both humoral and cell-mediated protective responses.

Study of Staphylococcus aureus pathogenic genes by transfer and expression in the less virulent organism Streptococcus gordonii.

Because Staphylococcus aureus strains contain multiple virulence factors, studying their pathogenic role by single-gene inactivation generated equivocal results. To circumvent this problem, we have expressed specific S. aureus genes in the less virulent organism Streptococcus gordonii and tested the recombinants for a gain of function both in vitro and in vivo. Clumping factor A (ClfA) and coagulase were investigated. Both gene products were expressed functionally and with similar kinetics during growth by streptococci and staphylococci. ClfA-positive S. gordonii was more adherent to platelet-fibrin clots mimicking cardiac vegetations in vitro and more infective in rats with experimental endocarditis (P < 0.05). Moreover, deleting clfA from clfA-positive streptococcal transformants restored both the low in vitro adherence and the low in vivo infectivity of the parent. Coagulase-positive transformants, on the other hand, were neither more adherent nor more infective than the parent. Furthermore, coagulase did not increase the pathogenicity of clfA-positive streptococci when both clfA and coa genes were simultaneously expressed in an artificial minioperon in streptococci. These results definitively attribute a role for ClfA, but not coagulase, in S. aureus endovascular infections. This gain-of-function strategy might help solve the role of individual factors in the complex the S. aureus-host relationship.

Divergent functions of three Candida albicans zinc-cluster transcription factors (CTA4, ASG1 and CTF1) complementing pleiotropic drug resistance in Saccharomyces cerevisiae.

One of the mediators of pleiotropic drug resistance in Saccharomyces cerevisiae is the ABC-transporter gene PDR5. This gene is regulated by at least two transcription factors with Zn(2)-Cys(6) finger DNA-binding motifs, Pdr1p and Pdr3p. In this work, we searched for functional homologues of these transcription factors in Candida albicans. A C. albicans gene library was screened in a S. cerevisiae mutant lacking PDR1 and PDR3 and clones resistant to azole antifungals were isolated. From these clones, three genes responsible for azole resistance were identified. These genes (CTA4, ASG1 and CTF1) encode proteins with Zn(2)-Cys(6)-type zinc finger motifs in their N-terminal domains. The C. albicans genes expressed in S. cerevisiae could activate the transcription of a PDR5-lacZ reporter system and this reporter activity was PDRE-dependent. They could also confer resistance to azoles in a S. cerevisiae strain lacking PDR1, PDR3 and PDR5, suggesting that CTA4-, ASG1- and CTF1-dependent azole resistance can be caused by genes other than PDR5 in S. cerevisiae. Deletion of CTA4, ASG1 and CTF1 in C. albicans had no effect on fluconazole susceptibility and did not alter the expression of the ABC-transporter genes CDR1 and CDR2 or the major facilitator gene MDR1, which encode multidrug transporters known as mediators of azole resistance in C. albicans. However, additional phenotypic screening tests on the C. albicans mutants revealed that the presence of ASG1 was necessary to sustain growth on non-fermentative carbon sources (sodium acetate, acetic acid, ethanol). In conclusion, C. albicans possesses functional homologues of the S. cerevisiae Pdr1p and Pdr3p transcription factors; however, their properties in C. albicans have been rewired to other functions.

Endothelial nitric oxide synthase gene transfer restores endothelium-dependent relaxations and attenuates lesion formation in carotid arteries in apolipoprotein E-deficient mice.

Nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1) exert partly opposing effects in vascular biology. NO plays pleiotropic vasoprotective roles including vasodilation and inhibition of platelet aggregation, smooth muscle cell proliferation, and endothelial monocyte adhesion, the last effect being mediated by MCP-1 downregulation. Early stages of arteriosclerosis are associated with reduced NO bioactivity and enhanced MCP-1 expression. We have evaluated adenovirus-mediated gene transfer of human endothelial NO synthase (eNOS) and of a N-terminal deletion (8ND) mutant of the MCP-1 gene that acts as a MCP-1 inhibitor in arteriosclerosis-prone, apolipoprotein E-deficient (ApoE(-/-)) mice. Endothelium-dependent relaxations were impaired in carotid arteries instilled with a noncoding adenoviral vector but were restored by eNOS gene transfer (p < 0.01). A perivascular collar was placed around the common carotid artery to accelerate lesion formation. eNOS gene transfer reduced lesion surface areas, intima/media ratios, and macrophage contents in the media at 5-week follow-up (p < 0.05). In contrast, 8ND-MCP-1 gene transfer did not prevent lesion formation. In conclusion, eNOS gene transfer restores endothelium-dependent vasodilation and inhibits lesion formation in ApoE(-/-) mouse carotids. Further studies are needed to assess whether vasoprotection is maintained at later disease stages and to evaluate the long-term efficacy of eNOS gene therapy for primary arteriosclerosis.