A link between FXYD3 (Mat-8)-mediated Na,K-ATPase regulation and differentiation of Caco-2 intestinal epithelial cells.

FXYD3 (Mat-8) proteins are regulators of Na,K-ATPase. In normal tissue, FXYD3 is mainly expressed in stomach and colon, but it is also overexpressed in cancer cells, suggesting a role in tumorogenesis. We show that FXYD3 silencing has no effect on cell proliferation but promotes cell apoptosis and prevents cell differentiation of human colon adenocarcinoma cells (Caco-2), which is reflected by a reduction in alkaline phosphatase and villin expression, a change in several other differentiation markers, and a decrease in transepithelial resistance. Inhibition of cell differentiation in FXYD3-deficient cells is accompanied by an increase in the apparent Na+ and K+ affinities of Na,K-ATPase, reflecting the absence of Na,K-pump regulation by FXYD3. In addition, we observe a decrease in the maximal Na,K-ATPase activity due to a decrease in its turnover number, which correlates with a change in Na,K-ATPase isozyme expression that is characteristic of cancer cells. Overall, our results suggest an important role of FXYD3 in cell differentiation of Caco-2 cells. One possibility is that FXYD3 silencing prevents proper regulation of Na,K-ATPase, which leads to perturbation of cellular Na+ and K+ homeostasis and changes in the expression of Na,K-ATPase isozymes, whose functional properties are incompatible with Caco-2 cell differentiation.

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Plants naturally produce the lipid-derived polyester cutin, which is found in the plant cuticle that is deposited at the outermost extracellular matrix of the epidermis covering nearly all aboveground tissues. Being at the interface between the cell and the external environment, cutin and the cuticle play important roles in the protection of plants from several stresses. A number of enzymes involved in the synthesis of cutin monomers have recently been identified, including several P450s and one acyl-CoA synthetase, thus representing the first steps toward the understanding of polyester formation and, potentially, polyester engineering to improve the tolerance of plants to stresses, such as drought, and for industrial applications. However, numerous processes underlying cutin synthesis, such as a controlled polymerization, still remain elusive. Suberin is a second polyester found in the extracellular matrix, most often synthesized in root tissues and during secondary growth. Similar to cutin, the function of suberin is to seal off the respective tissue to inhibit water loss and contribute to resistance to pathogen attack. Being the main constituent of cork, suberin is a plant polyester that has already been industrially exploited. Genetic engineering may be worth exploring in order to change the polyester properties for either different applications or to increase cork production in other species. Polyhydroxyalkanoates (PHAs) are attractive polyesters of 3-hydroxyacids because of their properties as bioplastics and elastomers. Although PHAs are naturally found in a wide variety of bacteria, biotechnology has aimed at producing these polymers in plants as a source of cheap and renewable biodegradable plastics. Synthesis of PHA containing various monomers has been demonstrated in the cytosol, plastids, and peroxisomes of plants. Several biochemical pathways have been modified in order to achieve this, including the isoprenoid pathway, the fatty acid biosynthetic pathway, and the fatty acid β-oxidation pathway. PHA synthesis has been demonstrated in a number of plants, including monocots and dicots, and up to 40% PHA per gram dry weight has been demonstrated in Arabidopsis thaliana. Despite some successes, production of PHA in crop plants remains a challenging project. PHA synthesis at high level in vegetative tissues, such as leaves, is associated with chlorosis and reduced growth. The challenge for the future is to succeed in synthesis of PHA copolymers with a narrow range of monomer compositions, at levels that do not compromise plant productivity. This goal will undoubtedly require a deeper understanding of plant biochemical pathways and how carbon fluxes through these pathways can be manipulated, areas where plant "omics" can bring very valuable contributions.

Anorectal malformations and pregnancy-related disorders: a registry-based case-control study in 17 European regions.

OBJECTIVE: To identify pregnancy-related risk factors for different manifestations of congenital anorectal malformations (ARMs). DESIGN: A population-based case-control study. SETTING: Seventeen EUROCAT (European Surveillance of Congenital Anomalies) registries, 1980-2008. POPULATION: The study population consisted of 1417 cases with ARM, including 648 cases of isolated ARM, 601 cases of ARM with additional congenital anomalies, and 168 cases of ARM-VACTERL (vertebral, anal, cardiac, tracheo-esophageal, renal, and limb defects), along with 13 371 controls with recognised syndromes or chromosomal abnormalities. METHODS: Multiple logistic regression analyses were used to calculate adjusted odds ratios (ORs) for potential risk factors for ARM, such as fertility treatment, multiple pregnancy, primiparity, maternal illnesses during pregnancy, and pregnancy-related complications. MAIN OUTCOME MEASURES: Adjusted ORs for pregnancy-related risk factors for ARM. RESULTS: The ARM cases were more likely to be firstborn than the controls (OR 1.6, 95% CI 1.4-1.8). Fertility treatment and being one of twins or triplets seemed to increase the risk of ARM in cases with additional congenital anomalies or VACTERL (ORs ranging from 1.6 to 2.5). Maternal fever during pregnancy and pre-eclampsia were only associated with ARM when additional congenital anomalies were present (OR 3.9, 95% CI 1.3-11.6; OR 3.4, 95% CI 1.6-7.1, respectively), whereas maternal epilepsy during pregnancy resulted in a five-fold elevated risk of all manifestations of ARM (OR 5.1, 95% CI 1.7-15.6). CONCLUSIONS: This large European study identified maternal epilepsy, fertility treatment, multiple pregnancy, primiparity, pre-eclampsia, and maternal fever during pregnancy as potential risk factors primarily for complex manifestations of ARM with additional congenital anomalies and VACTERL.

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Bacteria adapt and become quite rapidly selected to xenobiotic compounds introduced into the environment, mainly via the usage of the compound as carbon, energy or nitrogen source. Important examples include chlorobenzenes, the herbicide 2,4-dichlorophenoxyacetic acid, chloroalkanes, lindane, atrazine and nitroaromatic compounds. At the genomic level, such bacteria show evidence for genetic rearrangements mediated by transposable elements or general recombination, the result being most often an expansion of existing catabolic properties with additional gene modules from outside sources. DNA from outside sources appears to have been trapped and mobilized via conjugative plasmids and genomic islands. Genomic evidence further shows that most bacterial genomes contain considerable numbers of insertion elements, integrases, prophages and/or plasmids, which in general can contribute to their adaptation capacities.

Burnout levels among Portuguese family doctors: a nationwide survey

AIM: To characterise the prevalence of burnout syndrome in a sample of family doctors (FDs) working in the Portuguese National Health System. DESIGN: Cross-sectional survey. SETTING: Primary healthcare centres from the 18 continental districts and two archipelagos of Portugal. METHOD: The Portuguese version of the Maslach Burnout Inventory-Human Services Survey was sent to 40 randomly selected healthcare centres and distributed to the FDs employed. Socio-demographic and work-related data were also collected. Participants were classified as having high, average or low levels of emotional exhaustion (EE), depersonalisation (DP) and personal accomplishment (PA) dimensions of burnout. RESULTS: 371 questionnaires were sent, of which 153 (83 women, age range 29-64 years; response rate 41%) returned. One-quarter (25.3%, 95% CI 18.6% to 33.1%) of FDs scored high for EE, 16.2% (10.7% to 23.2%) for DP and 16.7% (11.1% to 23.6%) for lack of PA. On multivariate analysis, being married, of older age, having many years of practice or working in a personalised healthcare unit tended to be associated with increased burnout components. Men tended to present higher EE and DP but lower lack of PA than women. Finally, the prevalence (95% CI) of burnout ranged between 4.1% (1.5% to 8.6%) and 32.4% (25.0% to 40.6%), depending on the definition used. CONCLUSIONS: High burnout is relatively common among Portuguese FDs. Burnout relief measures should be developed in order to prevent a further increase of burnout syndrome among Portuguese FDs.

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Cette contribution a pour objectif d'analyser le degré d'implémentation des systèmes d'indicateurs dans les établissements scolaires. Elle cherche aussi à savoir si les indicateurs retenus intègrent les préoccupations et les acquis de la recherche, et singulièrement de la recherche en économie de l'éducation, en matière de déterminants de la performance scolaire. Autrement dit, si les directions d'établissements utilisent des systèmes d'indicateurs, ces systèmes permettent-ils de suivre des variables dont la littérature a démontré ou tend à montrer l'influence sur la performance scolaire ? Autrement dit encore, y a-t-il une capitalisation des variables potentiellement explicatives de la performance scolaire dans les indicateurs utilisés pour le pilotage des établissements scolaires ?

Brief communication: Report on the impact of the 27 February 2010 earthquake (Chile, Mw 8.8) on rockfalls in the Las Cuevas valley, Argentina

Numerous rockfalls were detected in the Las Cuevas valley, Argentina, after the 27 February 2010 earthquake in Chile. Live rockfalls were observed during aftershocks of 11 March 2010. Many rockfall source areas coincide with known thrust fault and some areas presented a rockfall activity even after the tremors. Some rockfalls crossed the National Road 7 but no damages to houses or vehicles were reported. This study illustrates how the 27 February 2010 earthquake impacted on unstable slopes in a valley far from the earthquakes epicentre. It is an interesting addition to previous studies on landslides caused by earthquakes because of the high magnitude of the event and of its aftershocks.