Serotonin Transporter Gene Polymorphism and Myocardial Infarction - Etude Cas-te'moins de L'Infarctus du Myocarde (ECTIM)

Background— Depression is a risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors reduce this risk. The site of action is the serotonin transporter (SLC6A4), which is expressed in brain and blood cells. A functional polymorphism in the promoter region of the SLC6A4 gene has been described. This polymorphism may be associated with the risk of MI. Methods and Results— The SLC6A4 polymorphism has been investigated by polymerase chain reaction in 671 male patients with MI and in 688 controls from the Etude Cas-Témoins de l’Infarctus du Myocarde (ECTIM) multicentric study. Percentages for LL, LS, and SS genotypes were 35.5%, 45.4%, and 19.1%, respectively, for cases versus 28.1%, 49.1%, and 22.8%, respectively, for controls. S allele frequency was 41.8% and 47.4% for cases and controls, respectively. After adjustment for age and center by using multivariable logistic regression, the odds ratio for MI associated with the LL genotype was 1.40 (95% CI 1.11 to 1.76, P=0.0047). Conclusions— The LL genotype of the SLC6A4 polymorphism is associated with a higher risk of MI. This could be attributable to the effect of the polymorphism on serotonin-mediated platelet activation or smooth muscle cell proliferation or on other risk factors, such as depression or response to stress

ULTRACAM photometry of the eclipsing cataclysmic variables GY Cnc, IR Com and HT Cas

We present high-speed, three-colour photometry of the eclipsing cataclysmic variables GY Cnc, IR Com and HT Cas. We find that the sharp eclipses in GY Cnc and IR Com are due to eclipses of the white dwarf. There is some evidence for a bright-spot on the edge of the accretion disc in GY Cnc, but not in IR Com. Eclipse mapping of HT Cas is presented which shows changes in the structure of the quiescent accretion disc. Observations in 2002 show the accretion disc to be invisible except for the presence of a bright-spot at the disc edge. 2003 observations, however, clearly show a bright inner disc and the bright-spot to be much fainter than in 2002. Although no outburst was associated with either set of quiescent observations, the system was similar to 0.6 mJy brighter in 2003, mainly due to the enhanced emission from the inner disc. We propose that these changes are due to variations in the mass-transfer rate from the secondary star and through the disc. The disc colours indicate that it is optically thin in both its inner and outer regions. We estimate the white dwarf temperature of HT Cas to be 15 000 +/- 1000 K in 2002 and 14 000 +/- 1000 K in 2003.

Ist patriotischer Nationalstolz wünschenswert? Eine differenzierte Analyse seiner psychologischen Bedeutung

Previous studies found that patriotic national pride (e.g., pride in democracy) - as opposed to nationalistic national pride (e.g., pride in being German) - has an attenuating effect on ethnocentrism, which is desirable from a democratic standpoint. Here it is hypothesized (1) that patriotic pride can be ascribed to the three components national identification, importance of democratic aspects of Germany, and belief in existence of democratic aspects of Germany, and (2) that these components exert in part conflicting effects on ethnocentrism and other variables. In two questionnaire studies (N-1 = 121, N-2 = 150) it is shown that (1) the three components do predict patriotic national pride and (2) the democratically desirable effects of patriotic pride trace back primarily to the importance of democratic aspects. In conclusion, from a democratic standpoint, it is positive valuation of democratic aspects and not patriotic pride that should be nurtured.

Combination of CFD and DOE to analyse solid particle erosion in elbows

Solid particle erosion is a major concern in the engineering industry, particularly where transport of slurry flow is involved. Such flow regimes are characteristic of those in alumina refinement plants. The entrainment of particulate matter, for example sand, in the Bayer liquor can cause severe erosion in pipe fittings, especially in those which redirect the flow. The considerable costs involved in the maintenance and replacement of these eroded components led to an interest in research into erosion prediction by numerical methods at Rusal Aughinish alumina refinery, Limerick, Ireland, and the University of Limerick. The first stage of this study focused on the use of computational fluid dynamics (CFD) to simulate solid particle erosion in elbows. Subsequently an analysis of the factors that affect erosion of elbows was performed using design of experiments (DOE) techniques. Combining CFD with DOE harnesses the computational power of CFD in the most efficient manner for prediction of elbow erosion. An analysis of the factors that affect the erosion of elbows was undertaken with the intention of producing an erosion prediction model. © 2009 Taylor & Francis.

Identification of two focal adhesion targeting sequences in the adapter molecule p130(Cas)

The adapter molecule CAS is localized primarily within focal adhesions in fibroblasts. Because many of the cellular functions attributed to CAS are likely to be dependent on its presence in focal adhesions, this study was undertaken to identify regions of the protein that are involved in its localization. The SH3 domain of CAS, when expressed in isolation from the rest of the protein, was able to target to focal adhesions, whereas a variant containing a point mutation that rendered the SH3 domain unable to associate with FAK remained cytoplasmic. However, in the context of full-length CAS, this mutation did not prevent CAS localization to focal adhesions. Two other variants of CAS that contained deletions of either the SH3 domain alone, or the SH3 domain together with an adjoining proline-rich region, also retained the capacity to localize to focal adhesions. A second focal adhesion targeting region was mapped to the extreme carboxy terminus of CAS. The identification of this second focal adhesion targeting domain in CAS ascribes a previously unknown function to the highly conserved C terminus of CAS. The regulated targeting of CAS to focal adhesions by two independent domains may reflect the important role of CAS within this subcellular compartment.

Regulation of c-SRC activity and function by the adapter protein CAS

SRC family kinases play essential roles in a variety of cellular functions, including proliferation, survival, differentiation, and apoptosis. The activities of these kinases are regulated by intramolecular interactions and by heterologous binding partners that modulate the transition between active and inactive structural conformations. p130(CAS) (CAS) binds directly to both the SH2 and SH3 domains of c-SRC and therefore has the potential to structurally alter and activate this kinase. In this report, we demonstrate that overexpression of full-length CAS in COS-1 cells induces c-SRC-dependent tyrosine phosphorylation of multiple endogenous cellular proteins. A carboxy-terminal fragment of CAS (CAS-CT), which contains the c-SRC binding site, was sufficient to induce c-SRC-dependent protein tyrosine kinase activity, as measured by tyrosine phosphorylation of cortactin, paxillin, and, to a lesser extent, focal adhesion kinase. A single amino acid substitution located in the binding site for the SRC SH3 domain of CAS-CT disrupted CAS-CT's interaction with c-SRC and inhibited its ability to induce tyrosine phosphorylation of cortactin and paxillin. Murine C3H10T1/2 fibroblasts that expressed elevated levels of tyrosine phosphorylated CAS and c-SRC-CAS complexes exhibited an enhanced ability to form colonies in soft agar and to proliferate in the absence of serum or growth factors. CAS-CT fully substituted for CAS in mediating growth in soft agar but was less effective in promoting serum-independent growth. These data suggest that CAS plays an important role in regulating specific signaling pathways governing cell growth and/or survival, in part through its ability to interact with and modulate the activity of c-SRC.

The role of SRC-CAS interactions in cellular transformation:ectopic expression of the carboxy terminus of CAS inhibits SRC-CAS interaction but has no effect on cellular transformation

Several lines of evidence indicate that the adapter molecule p130CAS (crk-associated substrate (CAS)) is required for src-mediated cellular transformation. CAS has been shown to be heavily tyrosine-phosphorylated in src-transformed cells, and genetic variants of src that are deficient in CAS binding are also unable to mediate cellular transformation. In this report, we investigated whether CAS phosphorylation and/or its association with src are required elements of the transformation process. Expression of the carboxy-terminal src binding domain of CAS in Rat 1 fibroblasts expressing a temperature-sensitive allele of v-src inhibited the formation of src-CAS complexes and also inhibited tyrosine phosphorylation of CAS. However, expression of this protein had no effect on morphological transformation, src-mediated actin rearrangements, or anchorage-independent growth of these cells when grown at the src-permissive temperature. Thus, the ability of activated src to mediate cellular transformation is either largely independent of endogenous CAS phosphorylation and/or its association with CAS or, alternatively, the carboxy-terminus of CAS may substitute for endogenous CAS in the process of src-mediated transformation.

L'indicateur EU2020 de suivi de la pauvreté et de l'exclusion: une analyse critique

The reduction of poverty and social exclusion is one of the targets of the European Union's 2020 strategy. The appropriateness and success of such a policy require the choice of relevant indicators that not only highlight poverty gaps between countries but also identify the groups of individuals in each country that need particular attention from social policies. The target retained in the European strategy combines three criteria: people living in households below the monetary poverty threshold, poor people “in terms of standard of living” who live in a situation of severe material deprivation, and those who live in households with very low or zero work intensity. We first show that neither the combination nor the intersection of these three criteria produces an adequate measure of the fight against poverty, or an objective for it. We therefore propose an alternative concept, that of “consistent poverty”, which targets people who simultaneously live below the monetary poverty threshold and above a certain level of material deprivation. The special material deprivation module of the EU-SILC 2009 database allows us to examine two versions of this notion of deprivation: the measurement of “severe” deprivation currently used by the European Union, which adopts a threshold with four items, and an alternative measure of “elementary” material deprivation with a three-item threshold. The intersection between our three-item elementary deprivation criterion and the monetary poverty criterion produces more satisfactory results than those obtained by the European Union approach, in terms of both coherency and profile of the population identified.