Occupational class and cause specific mortality in middle aged men in 11 European countries: comparison of population based studies

Objectives: To compare countries in western Europe with respect to class differences in mortality from specific causes of death and to assess the contributions these causes make to class differences in total mortality.

Demographic and epidemiological determinants of healthcare costs in Netherlands: cost of illness study

Objectives: To determine the demands on healthcare resources caused by different types of illnesses and variation with age and sex.

Tight Asp-85–Thr-89 association during the pump switch of bacteriorhodopsin

Unidirectional proton transport in bacteriorhodopsin is enforced by the switching machinery of the active site. Threonine 89 is located in this region, with its O—H group forming a hydrogen bond with Asp-85, the acceptor for proton transfer from the Schiff base of the retinal chromophore. Previous IR spectroscopy of [3-18O]threonine-labeled bacteriorhodopsin showed that the hydrogen bond of the O—D group of Thr-89 in D2O is strengthened in the K photocycle intermediate. Here, we show that the strength and orientation of this hydrogen bond remains unchanged in the L intermediate and through the M intermediate. Furthermore, a strong interaction between Asp-85 and the O—H (O—D) group of Thr-89 in M is indicated by a shift in the C⩵O stretching vibration of the former because of 18O substitution in the latter. Thus, the strong hydrogen bond between Asp-85 and Thr-89 in K persists through M, contrary to structural models based on x-ray crystallography of the photocycle intermediates. We propose that, upon photoisomerization of the chromophore, Thr-89 forms a tight, persistent complex with one of the side-chain oxygens of Asp-85 and is thereby precluded from participating in the switching process. On the other hand, the loss of hydrogen bonding at the other oxygen of Asp-85 in M may be related to the switching event.

Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor

A common feature of many metabolic pathways is their control by retinoid X receptor (RXR) heterodimers. Dysregulation of such metabolic pathways can lead to the development of atherosclerosis, a disease influenced by both systemic and local factors. Here we analyzed the effects of activation of RXR and some of its heterodimers in apolipoprotein E −/− mice, a well established animal model of atherosclerosis. An RXR agonist drastically reduced the development of atherosclerosis. In addition, a ligand for the peroxisome proliferator-activated receptor (PPAR)γ and a dual agonist of both PPARα and PPARγ had moderate inhibitory effects. Both RXR and liver X receptor (LXR) agonists induced ATP-binding cassette protein 1 (ABC-1) expression and stimulated ABC-1-mediated cholesterol efflux from macrophages from wild-type, but not from LXRα and β double −/−, mice. Hence, activation of ABC-1-mediated cholesterol efflux by the RXR/LXR heterodimer might contribute to the beneficial effects of rexinoids on atherosclerosis and warrant further evaluation of RXR/LXR agonists in prevention and treatment of atherosclerosis.

Appetite of an epiphyte: Quantitative monitoring of bacterial sugar consumption in the phyllosphere

We report here the construction, characterization, and application of a bacterial bioreporter for fructose and sucrose that was designed to monitor the availability of these sugars to microbial colonizers of the phyllosphere. Plasmid pPfruB-gfp[AAV] carries the Escherichia coli fruB promoter upstream from the gfp[AAV] allele that codes for an unstable variant of green fluorescent protein (GFP). In Erwinia herbicola, this plasmid brings about the accumulation of GFP fluorescence in response to both fructose and sucrose. Cells of E. herbicola (pPfruB-gfp[AAV]) were sprayed onto bean plants, recovered from leaves at various time intervals after inoculation, and analyzed individually for GFP content by quantitative analysis of digital microscope images. We observed a positive correlation between single-cell GFP accumulation and ribosomal content as determined by fluorescence in situ hybridization, indicating that foliar growth of E. herbicola occurred at the expense of fructose and/or sucrose. One hour after inoculation, nearly all bioreporter cells appeared to be actively engaged in fructose consumption. This fraction dropped to approximately 11% after 7 h and to ≈1% a day after inoculation. This pattern suggests a highly heterogeneous availability of fructose to individual E. herbicola cells as they colonize the phyllosphere. We estimated that individual cells were exposed to local initial fructose abundances ranging from less than 0.15 pg fructose to more than 4.6 pg.

Characterization of Syntenin, a Syndecan-binding PDZ Protein, as a Component of Cell Adhesion Sites and Microfilaments

Syntenin is a PDZ protein that binds the cytoplasmic C-terminal FYA motif of the syndecans. Syntenin is widely expressed. In cell fractionation experiments, syntenin partitions between the cytosol and microsomes. Immunofluorescence microscopy localizes endogenous and epitope-tagged syntenin to cell adhesion sites, microfilaments, and the nucleus. Syntenin is composed of at least three domains. Both PDZ domains of syntenin are necessary to target reporter tags to the plasma membrane. The addition of a segment of 10 amino acids from the N-terminal domain of syntenin to these PDZ domains increases the localization of the tags to stress fibers and induces the formation of long, branching plasma membrane extensions. The addition of the complete N-terminal region, in contrast, reduces the localization of the tags to plasma membrane/adhesion sites and stress fibers, and reduces the morphotypical effects. Recombinant domains of syntenin with the highest plasma membrane localization display the lowest nuclear localization. Syndecan-1, E-cadherin, β-catenin, and α-catenin colocalize with syntenin at cell-cell contacts in epithelial cells, and coimmunoprecipitate with syntenin from extracts of these cells. These results suggest a role for syntenin in the composition of adherens junctions and the regulation of plasma membrane dynamics, and imply a potential role for syntenin in nuclear processes.

Involvement of the Octadecanoid Pathway and Protein Phosphorylation in Fungal Elicitor-Induced Expression of Terpenoid Indole Alkaloid Biosynthetic Genes in Catharanthus roseus

Two key genes in terpenoid indole alkaloid biosynthesis, Tdc and Str, encoding tryptophan decarboxylase and strictosidine synthase, respectively, are coordinately induced by fungal elicitors in suspension-cultured Catharanthus roseus cells. We have studied the roles of the jasmonate biosynthetic pathway and of protein phosphorylation in signal transduction initiated by a partially purified elicitor from yeast extract. In addition to activating Tdc and Str gene expression, the elicitor also induced the biosynthesis of jasmonic acid. The jasmonate precursor α-linolenic acid or methyl jasmonate (MeJA) itself induced Tdc and Str gene expression when added exogenously . Diethyldithiocarbamic acid, an inhibitor of jasmonate biosynthesis, blocked both the elicitor-induced formation of jasmonic acid and the activation of terpenoid indole alkaloid biosynthetic genes. The protein kinase inhibitor K-252a abolished both elicitor-induced jasmonate biosynthesis and MeJA-induced Tdc and Str gene expression. Analysis of the expression of Str promoter/gusA fusions in transgenic C. roseus cells showed that the elicitor and MeJA act at the transcriptional level. These results demonstrate that the jasmonate biosynthetic pathway is an integral part of the elicitor-triggered signal transduction pathway that results in the coordinate expression of the Tdc and Str genes and that protein kinases act both upstream and downstream of jasmonates.

A Selaginella lepidophylla Trehalose-6-Phosphate Synthase Complements Growth and Stress-Tolerance Defects in a Yeast tps1 Mutant1

The accumulation of the disaccharide trehalose in anhydrobiotic organisms allows them to survive severe environmental stress. A plant cDNA, SlTPS1, encoding a 109-kD protein, was isolated from the resurrection plant Selaginella lepidophylla, which accumulates high levels of trehalose. Protein-sequence comparison showed that SlTPS1 shares high similarity to trehalose-6-phosphate synthase genes from prokaryotes and eukaryotes. SlTPS1 mRNA was constitutively expressed in S. lepidophylla. DNA gel-blot analysis indicated that SlTPS1 is present as a single-copy gene. Transformation of a Saccharomyces cerevisiae tps1Δ mutant disrupted in the ScTPS1 gene with S. lepidophylla SlTPS1 restored growth on fermentable sugars and the synthesis of trehalose at high levels. Moreover, the SlTPS1 gene introduced into the tps1Δ mutant was able to complement both deficiencies: sensitivity to sublethal heat treatment at 39°C and induced thermotolerance at 50°C. The osmosensitive phenotype of the yeast tps1Δ mutant grown in NaCl and sorbitol was also restored by the SlTPS1 gene. Thus, SlTPS1 protein is a functional plant homolog capable of sustaining trehalose biosynthesis and could play a major role in stress tolerance in S. lepidophylla.

Overexpression of a Novel Arabidopsis Gene Related to Putative Zinc-Transporter Genes from Animals Can Lead to Enhanced Zinc Resistance and Accumulation

We describe the isolation of an Arabidopsis gene that is closely related to the animal ZnT genes (Zn transporter). The protein encoded by the ZAT (Zn transporter of Arabidopsis thaliana) gene has 398 amino acid residues and is predicted to have six membrane-spanning domains. To obtain evidence for the postulated function of the Arabidopsis gene, transgenic plants with the ZAT coding sequence under control of the cauliflower mosaic virus 35S promoter were analyzed. Plants obtained with ZAT in the sense orientation exhibited enhanced Zn resistance and strongly increased Zn content in the roots under high Zn exposure. Antisense mRNA-producing plants were viable, with a wild-type level of Zn resistance and content, like plants expressing a truncated coding sequence lacking the C-terminal cytoplasmic domain of the protein. The availability of ZAT can lead to a better understanding of the mechanism of Zn homeostasis and resistance in plants.

Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF

Most endocrine hormones are produced in tissues and organs with permeable microvessels that may provide an excess of hormones to be transported by the blood circulation to the distal target organ. Here, we investigate whether leptin, an endocrine hormone, induces the formation of vascular fenestrations and permeability, and we characterize its angiogenic property in the presence of other angiogenic factors. We provide evidence that leptin-induced new blood vessels are fenestrated. Under physiological conditions, capillary fenestrations are found in the leptin-producing adipose tissue in lean mice. In contrast, no vascular fenestrations were detected in the adipose tissue of leptin-deficient ob/ob mice. Thus, leptin plays a critical role in the maintenance and regulation of vascular fenestrations in the adipose tissue. Leptin induces a rapid vascular permeability response when administrated intradermally. Further, leptin synergistically stimulates angiogenesis with fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF), the two most potent and commonly expressed angiogenic factors. These findings demonstrate that leptin has another new function—the increase of vascular permeability.

The operator algebra approach to quantum groups

A relatively simple definition of a locally compact quantum group in the C*-algebra setting will be explained as it was recently obtained by the authors. At the same time, we put this definition in the historical and mathematical context of locally compact groups, compact quantum groups, Kac algebras, multiplicative unitaries, and duality theory.

La ONU y la construcción de la paz en Haití y Guatemala

En los años noventa del siglo XX, un conjunto de circunstancias en el panorama internacional abrieron paso a un nuevo perfil intervencionista de la ONU en la resolución de conflictos armados materializado en marcos de actuación significativamente más amplios y en la extensión a nuevos escenarios de intervención. Estas circunstancias estaban vinculadas fundamentalmente a un nuevo orden internacional salido de la guerra fría que, por una nueva primacía de la democracia y de los derechos humanos frente al principio absoluto de la no injerencia en los asuntos internos de los Estados, favoreció los mecanismos multilaterales de seguridad y de promoción de la paz. Sin embargo, la proliferación de nuevas intervenciones en este ámbito, lideradas por las Naciones Unidas y centradas ya no estrictamente en la contención de la violencia, sino en la transformación y resolución de sus causas, no se mostró siempre eficaz conduciendo frecuentemente a la reemergencia de situaciones de violencia. El presente trabajo de investigación tiene como finalidad comprobar que estas nuevas intervenciones para la resolución de conflictos armados intraestatales estuvieron inspiradas en un concepto muy propio de los estudios para la paz ofrecido por uno de sus padres fundadores (Johan Galtung) – la paz positiva – y que su impacto y grado de eficacia fueron tan más elevados cuanto el acercamiento a esta nueva propuesta de paz afectó no solamente su narrativa legitimadora, sino también a sus prácticas en el terreno. Quiere igualmente confirmar que dificultades encontradas en el terreno en la puesta en práctica de una paz positiva tienen que ver también con características endémicas de la ONU que, con frecuencia, obstaculizan proyectos de construcción de paz de trazos más locales y sostenibles. Como metodología, optamos por realizar un análisis comparativo de dos intervenciones para la paz lideradas por las Naciones Unidas en dos países – Guatemala y Haití – en donde la ONU asumió, en un primer momento, el rol de mediadora entre las partes respectivas para, posteriormente, implementar la paz salida de cada uno de los procesos de negociación por vía de la instauración de misiones de paz. Para llevar a cabo dicha investigación, aparte del uso de fuentes secundarias disponibles, fueron realizadas entrevistas en el terreno a actores locales e internacionales en los países en cuestión. Además, fue usado un conjunto de índices e indicadores que intentaron añadir un componente de carácter más cualitativo al análisis. Más allá de observar los procesos de paz en Guatemala y Haití a través de lentes internacionales, se buscaron referentes locales para evaluar el impacto de la intervención de la ONU en cada escenario. Verificamos que en Guatemala la propuesta de una paz sostenible facilitada por la mediación de la ONU y la consecuente instauración de la MINUGUA, aunque con sus debilidades propias, fue extensiblemente más eficaz que la alcanzada en Haití, sostenida por un proceso de mediación frágil y por una sucesión de misiones de paz no exitosas, fracaso evidenciado por el regreso a la violencia diez años después. Los resultados de esta investigación plantean que, por haber cumplido más fielmente con los principios de la propuesta de la paz positiva en la resolución de la guerra civil en Guatemala, facilitando un amplio diálogo nacional, integrador y local sobre las causas del conflicto, la ONU permitió generar semillas de paz más sostenibles. Por el contrario, en Haití, las Naciones Unidas, con su estructura rígida y extremamente dependiente de sus Estados miembros, encontraron serias dificultades en atraer a las partes a una solución pacífica sostenible en el tiempo. Más que un interviniente secundario en los procesos en los que actúa, la ONU tiene a su disposición mecanismos y recursos que condicionan con significativa influencia los resultados de paz alcanzados, fenómeno que sugiere la necesidad de una reflexión crítica sobre su intervención en pro de la paz, sus fortalezas y debilidades, de forma que se potencie un desempeño más eficaz de la Organización en la búsqueda de modelos de paz más fecundos y duraderos a largo plazo.

Stationarity and regularity of infinite collections of sets. Applications to infinitely constrained optimization

This article continues the investigation of stationarity and regularity properties of infinite collections of sets in a Banach space started in Kruger and López (J. Optim. Theory Appl. 154(2), 2012), and is mainly focused on the application of the stationarity criteria to infinitely constrained optimization problems. We consider several settings of optimization problems which involve (explicitly or implicitly) infinite collections of sets and deduce for them necessary conditions characterizing stationarity in terms of dual space elements—normals and/or subdifferentials.

The Gaia-ESO Survey: processing FLAMES-UVES spectra

The Gaia-ESO Survey is a large public spectroscopic survey that aims to derive radial velocities and fundamental parameters of about 105 Milky Way stars in the field and in clusters. Observations are carried out with the multi-object optical spectrograph FLAMES, using simultaneously the medium-resolution (R ~ 20 000) GIRAFFE spectrograph and the high-resolution (R ~ 47 000) UVES spectrograph. In this paper we describe the methods and the software used for the data reduction, the derivation of the radial velocities, and the quality control of the FLAMES-UVES spectra. Data reduction has been performed using a workflow specifically developed for this project. This workflow runs the ESO public pipeline optimizing the data reduction for the Gaia-ESO Survey, automatically performs sky subtraction, barycentric correction and normalisation, and calculates radial velocities and a first guess of the rotational velocities. The quality control is performed using the output parameters from the ESO pipeline, by a visual inspection of the spectra and by the analysis of the signal-to-noise ratio of the spectra. Using the observations of the first 18 months, specifically targets observed multiple times at different epochs, stars observed with both GIRAFFE and UVES, and observations of radial velocity standards, we estimated the precision and the accuracy of the radial velocities. The statistical error on the radial velocities is σ ~ 0.4 km s-1 and is mainly due to uncertainties in the zero point of the wavelength calibration. However, we found a systematic bias with respect to the GIRAFFE spectra (~0.9 km s-1) and to the radial velocities of the standard stars (~0.5 km s-1) retrieved from the literature. This bias will be corrected in the future data releases, when a common zero point for all the set-ups and instruments used for the survey is be established.