Selective accumulation of differentiated FOXP3(+) CD4 (+) T cells in metastatic tumor lesions from melanoma patients compared to peripheral blood

Precise identification of regulatory T cells is crucial in the understanding of their role in human cancers. Here, we analyzed the frequency and phenotype of regulatory T cells (Tregs), in both healthy donors and melanoma patients, based on the expression of the transcription factor FOXP3, which, to date, is the most reliable marker for Tregs, at least in mice. We observed that FOXP3 expression is not confined to human CD25(+/high) CD4(+) T cells, and that these cells are not homogenously FOXP3(+). The circulating relative levels of FOXP3(+) CD4(+) T cells may fluctuate close to 2-fold over a short period of observation and are significantly higher in women than in men. Further, we showed that FOXP3(+) CD4(+) T cells are over-represented in peripheral blood of melanoma patients, as compared to healthy donors, and that they are even more enriched in tumor-infiltrated lymph nodes and at tumor sites, but not in normal lymph nodes. Interestingly, in melanoma patients, a significantly higher proportion of functional, antigen-experienced FOXP3(+) CD4(+) T was observed at tumor sites, compared to peripheral blood. Together, our data suggest that local accumulation and differentiation of Tregs is, at least in part, tumor-driven, and illustrate a reliable combination of markers for their monitoring in various clinical settings.

The Employment Precariousness Scale (EPRES): psychometric properties of a new tool for epidemiological studies among waged and salaried workers

Background: Despite the fact that labour market flexibility has resulted in an expansion of precarious employment in industrialized countries, to date there is limited empirical evidence about its health consequences. The Employment Precariousness Scale (EPRES) is a newly developed, theory-based, multidimensional questionnaire specifically devised for epidemiological studies among waged and salaried workers. Objective: To assess acceptability, reliability and construct validity of EPRES in a sample of waged and salaried workers in Spain. Methods: Cross-sectional study, using a sub-sample of 6.968 temporary and permanent workers from a population-based survey carried out in 2004-2005. The survey questionnaire was interviewer administered and included the six EPRES subscales, measures of the psychosocial work environment (COPSOQ ISTAS21), and perceived general and mental health (SF-36). Results: A high response rate to all EPRES items indicated good acceptability; Cronbach’s alpha coefficients, over 0.70 for all subscales and the global score, demonstrated good internal consistency reliability; exploratory factor analysis using principal axis analysis and varimax rotation confirmed the six-subscale structure and the theoretical allocation of all items. Patterns across known groups and correlation coefficients with psychosocial work environment measures and perceived health demonstrated the expected relations, providing evidence of construct validity. Conclusions: Our results provide evidence in support of the psychometric properties of EPRES, which appears to be a promising tool for the measurement of employment precariousness in public health research.

Analysis of epidermis- and mesophyll-specific transcript accumulation in powdery mildew-inoculated wheat leaves.

Powdery mildew is an important disease of wheat caused by the obligate biotrophic fungus Blumeria graminis f. sp. tritici. This pathogen invades exclusively epidermal cells after penetrating directly through the cell wall. Because powdery mildew colonizes exclusively epidermal cells, it is of importance not only to identify genes which are activated, but also to monitor tissue specificity of gene activation. Acquired resistance of wheat to powdery mildew can be induced by a previous inoculation with the non-host pathogen B. graminis f. sp. hordei, the causal agent of barley powdery mildew. The establishment of the resistant state is accompanied by the activation of genes. Here we report the tissue-specific cDNA-AFLP analysis and cloning of transcripts accumulating 6 and 24 h after the resistance-inducing inoculation with B. graminis f. sp. hordei. A total of 25,000 fragments estimated to represent about 17,000 transcripts were displayed. Out of these, 141 transcripts, were found to accumulate after Bgh inoculation using microarray hybridization analysis. Forty-four accumulated predominantly in the epidermis whereas 76 transcripts accumulated mostly in mesophyll tissue.

Main Street Messenger, Summer 2005

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Nuclear accumulation of the phytochrome A photoreceptor requires FHY1.

The phytochrome family of red/far-red (R/FR)-responsive photoreceptors plays a key role throughout the life cycle of plants . Arabidopsis has five phytochromes, phyA-phyE, among which phyA and phyB play the most predominant functions . Light-regulated nuclear accumulation of the phytochromes is an important regulatory step of this pathway, but to this date no factor specifically required for this event has been identified . Among all phyA signaling mutants, fhy1 and fhy3 (far-red elongated hypocotyl 1 and 3) have the most severe hyposensitive phenotype, indicating that they play particularly important roles . FHY1 is a small plant-specific protein of unknown function localized both in the nucleus and the cytoplasm . Here we show that FHY1 is specifically required for the light-regulated nuclear accumulation of phyA but not phyB. Moreover, phyA accumulation is only slightly affected in fhy3, indicating that the diminished nuclear accumulation of phyA observed in fhy1 seedlings is not simply a general consequence of reduced phyA signaling. By in vitro pull-down and yeast two-hybrid analyses, we demonstrate that FHY1 physically interacts with phyA, preferentially in its active Pfr form. Furthermore, FHY1 and phyA colocalize in planta. We therefore identify the first component required for light-regulated phytochrome nuclear accumulation.

Accumulation of human immunodeficiency virus-specific cytotoxic T lymphocytes away from the predominant site of virus replication during primary infection.

Down-regulation of the initial burst of viremia during primary human immunodeficiency virus (HIV) infection is thought to be mediated predominantly by HIV-specific CD8+ cytotoxic T lymphocytes (CTL). This response is associated with major perturbations in the T cell receptor (TCR) repertoire. To investigate the failure of the cellular immune response to adequately control viral spread and replication and to prevent establishment of HIV infection, changes in the TCR repertoire and in the distribution of virus-specific CTL between blood and lymph node were analyzed in three patients with primary infection. By the combined use of clonotype-specific polymerase chain reaction and analysis of the frequency of in vivo activated HIV-specific CTL, it was shown that HIV-specific CTL clones preferentially accumulated in blood as opposed to lymph node. Accumulation of HIV-specific CTL in blood occurred prior to effective down-regulation of virus replication in both blood and lymph node. These findings should provide new insights into how HIV, and possibly other viruses, elude the immune response of the host during primary infection.

Rates of cultural change and patterns of cultural accumulation in stochastic models of social transmission.

Cultural variation in a population is affected by the rate of occurrence of cultural innovations, whether such innovations are preferred or eschewed, how they are transmitted between individuals in the population, and the size of the population. An innovation, such as a modification in an attribute of a handaxe, may be lost or may become a property of all handaxes, which we call "fixation of the innovation." Alternatively, several innovations may attain appreciable frequencies, in which case properties of the frequency distribution-for example, of handaxe measurements-is important. Here we apply the Moran model from the stochastic theory of population genetics to study the evolution of cultural innovations. We obtain the probability that an initially rare innovation becomes fixed, and the expected time this takes. When variation in cultural traits is due to recurrent innovation, copy error, and sampling from generation to generation, we describe properties of this variation, such as the level of heterogeneity expected in the population. For all of these, we determine the effect of the mode of social transmission: conformist, where there is a tendency for each naïve newborn to copy the most popular variant; pro-novelty bias, where the newborn prefers a specific variant if it exists among those it samples; one-to-many transmission, where the variant one individual carries is copied by all newborns while that individual remains alive. We compare our findings with those predicted by prevailing theories for rates of cultural change and the distribution of cultural variation.

Girona, capital jurisdiccional de la Catalunya convulsa dels anys 1630

El treball té per marc precís els anys 1635-37. El seu objecteés la transferència de Barcelona a Girona de la plana major deles institucions virregnals de Catalunya (la Reial Audiència, laBatllia General, l’ofici del mestre racional...) i el seu personal.

Social capital and cognitive attainment

We review the different meanings that researchers have given to theconcept of social capital, differentiate four types – bridging, bonding,linking, and overheads –, and discuss their different functions as public,club, and common goods.For each form of social capital we distinguish its productivity (acollective characteristic) from the factors that account for individual’sdifferential access to its returns, and propose alternative ways formeasuring each.We show the utility of our theoretical and measuring approach byanalyzing the impact of the each form of social capital on 15 year-oldstudents’ cognitive attainment across OECD countries, using 2006 PISAdata.The results show that students’ cognitive attainments are a direct functionof the richness or productivity of each form of social capital and ofstudents’ degree of access to each.

Capital cities of federations. On the way to analysing the normative base of their asymmetrical status

Federal Capitals often have special statutes. Compared with member states, they often enjoy a lower degree of self-government and a lesser share in the governing of the federation. Why do actors choose such devices, and how can they be justified in a liberal democracy? Surprisingly, the burgeoning literature on asymmetric federalism (to which our research group has contributed significantly) has overlooked this important feature of a de iure asymmetry, perhaps because political theory up to now has concentrated on cases of multicultural and plurinational federations. However, comparative literature is also rare. This paper is the first step to filling in this gap by comparing some federal capitals. The Federal District model (Washington) is compared to capitals organized as member-states (Berlin and Brussels), and capitals that are cities belonging to a single member state (Ottawa in Ontario). The different features of de iure asymmetry will thereby be highlighted. Some light will be shed on the possible motives, reasons and justifications for the choice of each respective status. The paper opens the door to further research on such status questions by analysing public and parliamentary debates, for example. It paves the way for more thorough research. Sicne the author has been awarded a grant by the Institut d’Estudis Autonòmics, this research will be carried out soon.

Main Street Messenger, Winter 2006

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La Fuga de capital humà : una sortida sense retorn

Cert és que l’economia actual està sent transformada per la globalització, la integració econòmica i un increment en l’ús de les noves tecnologies. Una de les conseqüències d’aquest fenòmen és que la força de treball formada està adquirint cada vegada més mobilitat entre països industrialitzats. És precisament aquest el subjecte d’estudi del treball: la fuga de capital humà en el sector de la recerca i el desenvolupament. El nostre treball fa un recorregut per variables com la despesa en R+D, atur en el sector, personal que es dedica a investigació, entre altres. L’objectiu de les quals és arribar a extreure un rànquing de països emissors i receptors de capital humà a nivell europeu. No hem pogut obviar estudiar com ha estat l’evolució de la inversió espanyola a nivell públic i privat. Hem trobat interessant també, afegir el cas d’Estats Units, donat que és el país receptor per excel·lència.Per tenir-ne una visió més directe hem realitzat un pla d’enquestes a estudiants dedoctorats i màsters de la nostra universitat, per tal de veure, entre altres coses, si vertaderament la fuga de capital humà és una sortida sense retorn.

Deleterious mutation accumulation in asexual Timema stick insects.

Sexual reproduction is extremely widespread in spite of its presumed costs relative to asexual reproduction, indicating that it must provide significant advantages. One postulated benefit of sex and recombination is that they facilitate the purging of mildly deleterious mutations, which would accumulate in asexual lineages and contribute to their short evolutionary life span. To test this prediction, we estimated the accumulation rate of coding (nonsynonymous) mutations, which are expected to be deleterious, in parts of one mitochondrial (COI) and two nuclear (Actin and Hsp70) genes in six independently derived asexual lineages and related sexual species of Timema stick insects. We found signatures of increased coding mutation accumulation in all six asexual Timema and for each of the three analyzed genes, with 3.6- to 13.4-fold higher rates in the asexuals as compared with the sexuals. In addition, because coding mutations in the asexuals often resulted in considerable hydrophobicity changes at the concerned amino acid positions, coding mutations in the asexuals are likely associated with more strongly deleterious effects than in the sexuals. Our results demonstrate that deleterious mutation accumulation can differentially affect sexual and asexual lineages and support the idea that deleterious mutation accumulation plays an important role in limiting the long-term persistence of all-female lineages.

Main Street Messenger, Spring 2006

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