Feedback on hypothalamic TRH transcription is dependent on thyroid hormone receptor N terminus.

The beta thyroid hormone receptor (TRbeta), but not TRalpha1, plays a specific role in mediating T(3)-dependent repression of hypothalamic TRH transcription. To investigate the structural basis of isoform specificity, we compared the transcriptional regulation and DNA binding obtained with chimeric and N-terminally deleted TRs. Using in vivo transfection assays to follow hypothalamic TRH transcription in the mouse brain, we found that TRbeta1 and chimeras with the TRbeta1 N terminus did not affect either transcriptional activation or repression from the rat TRH promoter, whereas N-terminally deleted TRbeta1 impaired T(3)-dependent repression. TRalpha1 or chimeras with the TRalpha1 N terminus reduced T(3)-independent transcriptional activation and blocked T(3)-dependent repression of transcription. Full deletion of the TRalpha1 N terminus restored ligand-independent activation of transcription. No TR isoform specificity was seen after transcription from a positive thyroid hormone response element. Gel mobility assays showed that all TRs tested bound specifically to the main negative thyroid hormone response element in the TRH promoter (site 4). Addition of neither steroid receptor coactivator 1 nor nuclear extracts from the hypothalamic paraventricular nuclei revealed any TR isoform specificity in binding to site 4. Thus N-terminal sequences specify TR T(3)-dependent repression of TRH transcription but not DNA recognition, emphasizing as yet unknown neuron-specific contributions to protein-promoter interactions in vivo.

Localized, diffuse, and aggregative-adhering Escherichia coli from infants with acute diarrhea and matched-controls

Of 126 infants under 2 years, enrolled in a study on the etiology of acute diarrhea in Recife, Brazil, we selected 37 from whom no recognized enteropathogens, except classic enteropathogenic Escherichia coli, were identified. For comparison, we also examined 37 matched-control infants without diarrhea seen at the same hospital setting. This paper had the purpose to determine the prevalence of localized, diffuse, and aggregative-adhering E. coli strains in both groups. Three to five fecal E. coli colonies, of each case and control, were tested individually for adherence to HeLa cells by using the one step 3-h incubation assay. Strains of E. coli showing localized adherence were found significantly more often in patients (37.8%) than in controls (13.5%), p < 0.02, and they were pratically confined to EPEC serovars 055:H-, 0111:H2, and 119:H6. In contrast, E. coli isolates exhibiting the diffuse or aggregative patterns of adherence were restricted to non-EPEC serogroups and were more frequently encountred among controls.

Nicotine-induced release of vasopressin in the conscious rat: role of opioid peptides and hemodynamic effects.

Nicotine has been shown to stimulate the release of vasopressin and to cause significant hemodynamic changes. The mechanisms leading to enhanced vasopressin secretion and the vascular consequences of the high plasma vasopressin levels during nicotine infusion have not yet been determined. Therefore, the purposes of the present study were 1) to examine in normal conscious rats the role of opioid peptides in the nicotine-induced increase in plasma vasopressin levels and 2) to assess the role of vasopressin in the hemodynamic effects of nicotine (20 micrograms/min for 15 min) using a specific V1 antagonist of the vascular actions of vasopressin. Plasma vasopressin levels were significantly increased in the nicotine-treated animals (39.5 +/- 10 vs. 3.7 +/- 0.6 pg/ml in the controls, P less than .01). Pretreatment with naloxone, an antagonist of opioids at their receptors, did not reduce the vasopressin levels (47.7 +/- 9 pg/ml). Nicotine also increased mean blood pressure (122.5 +/- 2.5 to 145.2 +/- 3.3 mm Hg, P less than .01) and decreased heart rate (461 +/- 6 to 386 +/- 14.5 beats/min, P less than .05). Administration of the vasopressin V1 antagonist before the nicotine infusion did not affect the systemic hemodynamics or the regional blood flow distribution, as assessed by radiolabeled microspheres. Thus, these results suggest that the nicotine-induced secretion of vasopressin is not mediated by opioid receptors and that the high plasma vasopressin levels do not exert any significant hemodynamic effect on cardiac output or blood flow distribution.

Análisis multi-región input-output (MRIO) de emisiones de gases efecto invernadero (GEI) incorporado en el comercio. Un modelo birregional aplicado a Cataluña y el resto de España

El siguiente trabajo realiza un análisis regional y sectorial para el estudio de la emisiones de gases efecto invernadero (GEI) incorporadas en el comercio entre las regiones de Cataluña y el resto de España para el año 2001, estimando así el Balance Neto en GEI incorporado. El objetivo es el desarrollo de un metodología que nos permita realizar esta estimación de forma rigurosa, con la intención de efectuar un análisis comparativo de ambas estructuras productivas territoriales, en cuanto a la intensidad de emisión y el impacto de la demanda final de las regiones consideradas. Para este propósito se utiliza el marco metodológico del análisis input-output, en particular se aplica dos tipologías de modelos: el modelo básico o single-región y el multi-región, lo que nos permite la comparabilidad entre ambos, demostrando como el modelo MRIO (multi-región input-output) es el método más apropiado para dicho propósito, permitiendo, entre otras ventajas, analizar los vínculos interregionales e intersectoriales de las regiones consideradas. La incorporación de la técnica de la integración vertical o subsistemas, nos permite un enfoque alternativo para el Balance Neto resultante, no tenemos constancia de que este enfoque haya sido utilizado con anterioridad en los análisis MRIO aplicados al estudio de los impactos medioambientales incorporados en el comercio. Tampoco la tenemos sobre la aplicación de los MRIO de forma general para estos impactos a nivel interregional de la economía española. El principal resultado obtenido nos indica que aún teniendo Cataluña un importante superávit comercial con el resto de España, hemos comprobado la existencia de un importante déficit para la primera en cuanto a la polución incorporada en este comercio.

IRF4 regulates IL-17A promoter activity and controls RORγt-dependent Th17 colitis in vivo.

Background: The transcription factor IRF4 is involved in several T-cell-dependent chronic inflammatory diseases. To elucidate the mechanisms for pathological cytokine production in colitis, we addressed the role of the IRF transcription factors in human inflammatory bowel disease (IBD) and experimental colitis.Methods: IRF levels and cytokine production in IBD patients were studied as well as the effects of IRF4 deficiency in experimental colitis.Results: In contrast to IRF1, IRF5, and IRF8, IRF4 expression in IBD was augmented in the presence of active inflammation. Furthermore, IRF4 levels significantly correlated with IL-6 and IL-17 mRNA expression and to a lesser extent with IL-22 mRNA expression in IBD. To further explore the role of IRF4 under in vivo conditions, we studied IRF4-deficient and wildtype mice in experimental colitis. In contrast to DSS colitis, IRF4 deficiency was protective in T-cell-dependent transfer colitis associated with reduced ROR alpha/gamma t levels and impaired IL-6, IL-17a, and IL-22 production, suggesting that IRF4 acts as a master regulator of mucosal Th17 cell differentiation. Subsequent mechanistic studies using database analysis, chromatin immunoprecipitation, and electrophoretic mobility shift assays identified a novel IRF4 binding site in the IL-17 gene promoter. Overexpression of IRF4 using retroviral infection induced IL-17 production and IL-17 together with IL-6 induced ROR gamma t expression.Conclusions: IRF4 can directly bind to the IL-17 promotor and induces mucosal ROR gamma t levels and IL-17 gene expression thereby controlling Th17-dependent colitis. Targeting of this molecular mechanism may lead to novel therapeutic approaches in human IBD.

Use of levosimendan as rescue therapy in children with low cardiac output syndrome.

Objective: Aim of post operative treatments after cardiac surgery is to avoid low cardiac output syndrome (LCOS). Levosimendan, a new inotrope agent, has been demonstrated in adult patient to be an effective treatment for this purpose when classical therapy is not effective. It shows a positive effect on cardiac output, with fewer adverse effects and lower mortality than with dopamine. There is very few data on its benefit in the paediatric population. The aim of this study is to evaluate the effect of levosimendan in cardiac children with LCOS.Methods: Retrospective analysis of 25 children hospitalised in our PICU after cardiac surgery that demonstrated LCOS not responding to classical catecholamine therapy and who received levosimendan as rescue. LCOS parameters like urine output, mixed venous oxygen saturation (SvO2), arterio-venous differences in CO2 (AVCO2) and plasmatic lactate were compared before therapy and at 12, 24, 48 and 72 hours after the beginning of the levosimendan infusion. We also analyzed the effect on the utilisation of amines (amine score), adverse events and mortality.Results: After the beginning of levosimendan infusion, urine output (3.1 vs 5.3ml/kg/h, p=0.003) and SVO2 (56 vs 64mmHg, p=0.001) increase significantly during first 72 hours and at the same time plasmatic lactate (2.6 vs 1.4 mmole/l, p<0.001), AVCO2 (11 vs 8 mmHg, p=0.002) and amine score (63 vs 39, p=0.007) decrease significantly. No side effects were noted during administration of levosimendan. In this group of patients, mortality was 0%.Conclusion: Levosimendan is an effective treatment in children after congenital heart surgery. Our study, with a greater sample of patient than other studies, confirms the improvement of cardiac output already shown in other paediatric studies.

A comparison of input-output models: ghosh reduces to leontief (but "closing" ghosh makes it more plausible)

Ghosh's model is discussed in this paper under two alternative scenarios. In an open version we compare it with Leontief's model and prove that they reduce to each other under some specific productive conditions. We then move onto reconsidering Ghosh's model alleged implausibility and we do so reformulating the model to incorporate a closure rule. The closure solves, to some extent, the implausibility problem very clearly put out by Oosterhaven for then value-added is correctly computed and responsive to allocation changes resulting from supply shocks.

Dynamics of phonological-phonetic encoding in word production: Evidence from diverging ERPs between stroke patients and controls.

While the dynamics of lexical-semantic and lexical-phonological encoding in word production have been investigated in several event-related potential (ERP) studies, the estimated time course of phonological-phonetic encoding is the result of rather indirect evidence. We investigated the dynamics of phonological-phonetic encoding combining ERP analyses covering the entire encoding process in picture naming and word reading tasks by comparing ERP modulations in eight brain-damaged speakers presenting impaired phonological-phonetic encoding relative to 16 healthy controls. ERPs diverged between groups in terms of local waveform amplitude and global topography at ∼400ms after stimulus onset in the picture naming task and at ∼320-350ms in word reading and sustained until 100ms before articulation onset. These divergences appeared in later time windows than those found in patients with underlying lexical-semantic and lexical-phonological impairment in previous studies, providing evidence that phonological-phonetic encoding is engaged around 400ms in picture naming and around 330ms in word reading.

FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1.

The mechanisms of blood vessel maturation into distinct parts of the blood vasculature such as arteries, veins, and capillaries have been the subject of intense investigation over recent years. In contrast, our knowledge of lymphatic vessel maturation is still fragmentary. In this study, we provide a molecular and morphological characterization of the major steps in the maturation of the primary lymphatic capillary plexus into collecting lymphatic vessels during development and show that forkhead transcription factor Foxc2 controls this process. We further identify transcription factor NFATc1 as a novel regulator of lymphatic development and describe a previously unsuspected link between NFATc1 and Foxc2 in the regulation of lymphatic maturation. We also provide a genome-wide map of FOXC2-binding sites in lymphatic endothelial cells, identify a novel consensus FOXC2 sequence, and show that NFATc1 physically interacts with FOXC2-binding enhancers. As damage to collecting vessels is a major cause of lymphatic dysfunction in humans, our results suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention.

Understanding the low-temperature limitations to forest growth through calibration of a forest dynamics model with tree-ring data

The sensitivity of altitudinal and latitudinal tree-line ecotones to climate change, particularly that of temperature, has received much attention. To improve our understanding of the factors affecting tree-line position, we used the spatially explicit dynamic forest model TreeMig. Although well-suited because of its landscape dynamics functions, TreeMig features a parabolic temperature growth response curve, which has recently been questioned. and the species parameters are not specifically calibrated for cold temperatures. Our main goals were to improve the theoretical basis of the temperature growth response curve in the model and develop a method for deriving that curve's parameters from tree-ring data. We replaced the parabola with an asymptotic curve, calibrated for the main species at the subalpine (Swiss Alps: Pinus cembra, Larix decidua, Picea abies) and boreal (Fennoscandia: Pinus sylvestris, Betula pubescens, P. abies) tree-lines. After fitting new parameters, the growth curve matched observed tree-ring widths better. For the subalpine species, the minimum degree-day sum allowing, growth (kDDMin) was lowered by around 100 degree-days; in the case of Larix, the maximum potential ring-width was increased to 5.19 mm. At the boreal tree-line, the kDDMin for P. sylvestris was lowered by 210 degree-days and its maximum ring-width increased to 2.943 mm; for Betula (new in the model) kDDMin was set to 325 degree-days and the maximum ring-width to 2.51 mm; the values from the only boreal sample site for Picea were similar to the subalpine ones, so the same parameters were used. However, adjusting the growth response alone did not improve the model's output concerning species' distributions and their relative importance at tree-line. Minimum winter temperature (MinWiT, mean of the coldest winter month), which controls seedling establishment in TreeMig, proved more important for determining distribution. Picea, P. sylvestris and Betula did not previously have minimum winter temperature limits, so these values were set to the 95th percentile of each species' coldest MinWiT site (respectively -7, -11, -13). In a case study for the Alps, the original and newly calibrated versions of TreeMig were compared with biomass data from the National Forest Inventor), (NFI). Both models gave similar, reasonably realistic results. In conclusion, this method of deriving temperature responses from tree-rings works well. However, regeneration and its underlying factors seem more important for controlling species' distributions than previously thought. More research on regeneration ecology, especially at the upper limit of forests. is needed to improve predictions of tree-line responses to climate change further.

Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

Revisiting the size-R&D productivity relation: introducing the mediating role of decision-making style on the scale and quality of innovative output

We develop a mediation model in which firm size is proposed to affect the scale and quality of innovative output through the adoption of different decision styles during the R&D process. The aim of this study is to understand how the internal changes that firms undergo as they evolve from small to larger organizations affect R&D productivity. In so doing, we illuminate the underlying theoretical mechanism affecting two different dimensions of R&D productivity, namely the scale and quality of innovative output which have not received much attention in previous literature. Using longitudinal data of Spanish manufacturing firms we explore the validity of this mediation model. Our results show that as firms evolve in size, they increasingly emphasize analytical decision making, and consequently, large-sized firms aim for higher-quality innovations while small firms aim for a larger scale of innovative output.

Variation in novel exons (RACEfrags) of the MECP2 gene in Rett syndrome patients and controls.

The study of transcription using genomic tiling arrays has lead to the identification of numerous additional exons. One example is the MECP2 gene on the X chromosome; using 5'RACE and RT-PCR in human tissues and cell lines, we have found more than 70 novel exons (RACEfrags) connecting to at least one annotated exon.. We sequenced all MECP2-connected exons and flanking sequences in 3 groups: 46 patients with the Rett syndrome and without mutations in the currently annotated exons of the MECP2 and CDKL5 genes; 32 patients with the Rett syndrome and identified mutations in the MECP2 gene; 100 control individuals from the same geoethnic group. Approximately 13 kb were sequenced per sample, (2.4 Mb of DNA resequencing). A total of 75 individuals had novel rare variants (mostly private variants) but no statistically significant difference was found among the 3 groups. These results suggest that variants in the newly discovered exons may not contribute to Rett syndrome. Interestingly however, there are about twice more variants in the novel exons than in the flanking sequences (44 vs. 21 for approximately 1.3 Mb sequenced for each class of sequences, p=0.0025). Thus the evolutionary forces that shape these novel exons may be different than those of neighboring sequences.

Structural decomposition analysis and input-output subsystems: An application to Spanish CO2 emissions

Analysis of gas emissions by the input-output subsystem approach provides detailed insight into pollution generation in an economy. Structural decomposition analysis, on the other hand, identifies the factors behind the changes in key variables over time. Extending the input-output subsystem model to account for the changes in these variables reveals the channels by which environmental burdens are caused and transmitted throughout the production system. In this paper we propose a decomposition of the changes in the components of CO2 emissions captured by an input-output subsystems representation. The empirical application is for the Spanish service sector, and the economic and environmental data are for years 1990 and 2000. Our results show that services increased their CO2 emissions mainly because of a rise in emissions generated by non-services to cover the final demand for services. In all service activities, the decomposed effects show an increase in CO2 emissions due to a decrease in emission coefficients (i.e., emissions per unit of output) compensated by an increase in emissions caused both by the input-output coefficients and the rise in demand for services. Finally, large asymmetries exist not only in the quantitative changes in the CO2 emissions of the various services but also in the decomposed effects of these changes. Keywords: structural decomposition analysis, input-output subsystems, CO2 emissions, service sector.

Water Reallocation in the Input-Output Model

Water reallocation between economic agents has been –and continues to be- the subject of a considerable amount of research. This paper proposes a method for evaluating how water is reallocated within the economy in response to changes in final demand and changes in the technical water needs of activities and consumers. The empirical application, which is for the Catalan economy, shows important asymmetries in the effects that exogenous inflows and changes in water technical requirements cause on water reallocation. In the process of water distribution, exogenous inflows mostly benefit agriculture and damage private consumers. On the other hand, increases in technical water requirements have negative effects on agriculture and positive effects on the other production activities. The results of the study suggest that agriculture is an important activity not only in terms of water distribution but also in terms of water reallocation due to changes in final demand and technical water needs. Keywords: Water reallocation, water distribution, exogenous shock, technical water needs.