Pro-inflammatory gene expression and neurotoxic effects of activated microglia are attenuated by absence of CCAAT/enhancer binding protein beta

Background. Microglia and astrocytes respond to homeostatic disturbances with profound changes of gene expression. This response, known as glial activation or neuroinflammation, can be detrimental to the surrounding tissue. The transcription factor CCAAT/enhancer binding protein ß (C/EBPß) is an important regulator of gene expression in inflammation but little is known about its involvement in glial activation. To explore the functional role of C/EBPß in glial activation we have analyzed pro-inflammatory gene expression and neurotoxicity in murine wild type and C/EBPß-null glial cultures. Methods. Due to fertility and mortality problems associated with the C/EBPß-null genotype we developed a protocol to prepare mixed glial cultures from cerebral cortex of a single mouse embryo with high yield. Wild-type and C/EBPß-null glial cultures were compared in terms of total cell density by Hoechst-33258 staining; microglial content by CD11b immunocytochemistry; astroglial content by GFAP western blot; gene expression by quantitative real-time PCR, western blot, immunocytochemistry and Griess reaction; and microglial neurotoxicity by estimating MAP2 content in neuronal/microglial cocultures. C/EBPß DNA binding activity was evaluated by electrophoretic mobility shift assay and quantitative chromatin immunoprecipitation. Results. C/EBPß mRNA and protein levels, as well as DNA binding, were increased in glial cultures by treatment with lipopolysaccharide (LPS) or LPS + interferon ¿ (IFN¿). Quantitative chromatin immunoprecipitation showed binding of C/EBPß to pro-inflammatory gene promoters in glial activation in a stimulus- and gene-dependent manner. In agreement with these results, LPS and LPS+IFN¿ induced different transcriptional patterns between pro-inflammatory cytokines and NO synthase-2 genes. Furthermore, the expressions of IL-1ß and NO synthase-2, and consequent NO production, were reduced in the absence of C/EBPß. In addition, neurotoxicity elicited by LPS+IFN¿-treated microglia co-cultured with neurons was completely abolished by the absence of C/EBPß in microglia.

Effects of long-term estrogen replacement therapy in postmenopausal women with coronary risk factors

Objective: Hormone replacement therapy (HRT) with estrogen alone or in concert with progesterone may exert beneficial effects on coronary endothelium-dependent vasomotion in postmenopausal women without traditional coronary risk factors. We aimed to evaluate the effect of HRT on coronary vasomotor function in postmenopausal women with traditional coronary risk factors such as hypertension, hypercholesterolemia and smoking as compared to those without HRT. Methods: Combining N-13 ammonia with PET, myocardial blood flow (MBF) was measured in ml/g/min at rest, during cold pressor test (CPT, reflecting predominantly endothelium-dependent vasomotion)and during pharmacologic vasodilation (representing predominantly endothelium-independent vasomotion) in 48 postmenopausal women with various coronary risk factors during a mean follow up (FU) of 20_9 months. postmenopausal women wer grouped according to HRT: group 1 with HRT (n_18), group 2 without HRT (n_18) and group 3 with HRT at baseline but not at FU (n_12). Results: during FU, HRT did not significantly affect lipid profile and plasma glucose levels. At baseline resting MBF was similar between groups (Table).After the FU, in group 2 and 3 the endothelium-related increase in MBF from rest to CPT (_ MBF) was significantly less than at baseline (*p_0.05) (Table). Conversely, in group 1 _MBF to CPT at FU was not significantly different from the baseline study. The group comparison of CPT-induced _MBF in group 2 and group 3 after the FU period was significantly different from group 1 (p_0.006 by ANOVA). Finally, in all three groups, hyperemic MBFs during pharmacologic vasodilation did not differ significantly between baseline and FU (Table). Conclusion: In postmenopausal women with coronary risk factors, HRT may counterbalance the adverse effects of traditional coronary risk factors on endothelium-dependent coronary vasomotion. Consequently, in addition to standard management of coronary risk factors, HRT may exert beneficial effects on the coronary endothelium that may delay the progression of coronary artery disease in postmenopausal women.

Effects of differential taxation on factor accumulation and growth

In this paper we try to analyze the role of fiscal policy in fostering a higher participation of the different production factors in the human capital production sector in the long-run. Introducing a tax on physical capital and differentiating both a tax on raw labor wage and a tax on skills or human capital we also attempt to present a way to influence inequality as measured by the skill premium, thus trying to relate the increase in human capital with the decrease in income inequality. We will do that in the context of a non-scale growth model.The model here is capable to alter the shares of private factors devoted to each of the two production sectors, final output and human capital, and affect inequality in a different way according to the different tax changes. The simulation results derived in the paper show how a human capital (skills) tax cut, which could be interpreted as a reduction in progressivity, ends up increasing both the shares of labor and physical capital devoted to the production of knowledge and decreasing inequality. Moreover, a raw labor wage tax decrease, which could also be interpreted as an increase in the progressivity of the system, increases the share of labor devoted to the production of final output and increases inequality. Finally, a physical capital tax decrease reduces the share of physical capital devoted to the production of knowledge and allows for a lower inequality value. Nevertheless, none of the various types of taxes ends up changing the share of human capital in the knowledge production, which will deserve our future attention

Long-term Outcome and Late Side Effects in Endometrial Cancer Patients Treated with Surgery and Postoperative Radiation Therapy.

BACKGROUND: We retrospectively reviewed the long-term outcome and late side effects of endometrial cancer (EC) patients treated with different techniques of postoperative radiotherapy (PORT). METHODS: Between 1999 and 2012, 237 patients with EC were treated with PORT. Two-dimensional external beam radiotherapy (2D-EBRT) was used in 69 patients (30 %), three-dimensional EBRT (3D-EBRT) in 51 (21 %), and intensity-modulated RT (IMRT) with helical Tomotherapy in 47 (20 %). All patients received a vaginal brachytherapy (VB) boost. Seventy patients (29 %) received VB alone. RESULTS: After a median of 68 months (range, 6-154) of follow-up, overall survival was 75 % [95 % confidence interval (CI), 69-81], disease-free survival was 72 % (95% CI, 66-78), cancer-specific survival was 85 % (95 % CI, 80-89), and locoregional control was 86 % (95 % CI, 81-91). The 5-year estimates of grade 3 or more toxicity and second cancer rates were 0 and 7 % (95 % CI, 1-13) for VB alone, 6 % (95 % CI, 1-11) and 0 % for IMRT + VB, 9 % (95 % CI, 1-17) and 5 % (95 % CI, 1-9) for 3D-EBRT + VB, and 22 % (95 % CI, 12-32) and 12 % (95 % CI, 4-20) for 2D-EBRT + VB (P = 0.002 and P = 0.01), respectively. CONCLUSIONS: Pelvic EBRT should be tailored to patients with high-risk EC because the severe late toxicity observed might outweigh the benefits. When EBRT is prescribed for EC, IMRT should be considered, because it was associated with a significant reduction of severe late side effects.

The effects of tax deductibility on the mix of property taxes and use charges: an empirical analysis of the spanish case

This paper tests some hypothesis about the determinants of the local tax structure. In particular, we focus on the effects that the property tax deductibility in the national income tax has on the relative use of the property tax and user charges. We deal with the incentive effects that local governments face regarding the different sources of revenue by means of a model in which the local tax structure and the level of public expenditure arise as a result of the maximizing behaviour of local politicians subject to the economic effects of the tax system. We attempt to test the hypothesis developed with data corresponding to a set of Spanish municipalities during the period 1987-9l. We find that tax deductibility provides incentives to raise revenues from the property tax but does not introduce a biass against user charges or in favor of overall spending growth

Soil fertility, organic carbon and fractions of the organic matter at different distances from eucalyptus stumps

Knowledge on variations in vertical, horizontal and temporal characteristics of the soil chemical properties under eucalyptus stumps left in the soil is of fundamental importance for the management of subsequent crops. The objective of this work was to evaluate the effect of eucalyptus stumps (ES) left after cutting on the spatial variability of chemical characteristics in a dystrophic Yellow Argisol in the eastern coastal plain region of Brazil. For this purpose, ES left for 31 and 54 months were selected in two experimental areas with similar characteristics, to assess the decomposition effects of the stumps on soil chemical attributes. Soil samples were collected directly around these ES, and at distances of 30, 60, 90, 120 and 150 cm away from them, in the layers 0-10, 10-20 and 20-40 cm along the row of ES, which is in-between the rows of eucalyptus trees of a new plantation, grown at a spacing of 3 x 3 m. The soil was sampled in five replications in plots of 900 m² each and the samples analyzed for pH, available P and K (Mehlich-1), exchangeable Al, Ca and Mg, total organic carbon (TOC) and C content in humic substances (HS) and in the free light fraction. The pH values and P, K, Ca2+, Mg2+ and Al3+ contents varied between the soil layers with increasing distance from the 31 and 54-monthold stumps. The highest pH, P, K, Ca2+ and Mg2+ values and the lowest Al3+ content were found in the surface soil layer. The TOC of the various fractions of soil organic matter decreased with increasing distance from the 31 and 54-month-old ES in the 0-10 and 10-20 cm layers, indicating that the root (and stump) cycling and rhizodeposition contribute to maintain soil organic matter. The C contents of the free light fraction, of the HS and TOC fractions were higher in the topsoil layer under the ES left for 31 months due to the higher clay levels of this layer, than in those found under the 54-month-old stumps. However, highest C levels of the different fractions of soil organic matter in the topsoil layer reflect the deposition and maintenance of forest residues on the soil surface, mainly after forest harvest.

The effects of electron-hole separation on the photoconductivity of individual metal oxide nanowires

The responses of individual ZnO nanowires to UV light demonstrate that the persistent photoconductivity (PPC) state is directly related to the electron¿hole separation near the surface. Our results demonstrate that the electrical transport in these nanomaterials is influenced by the surface in two different ways. On the one hand, the effective mobility and the density of free carriers are determined by recombination mechanisms assisted by the oxidizing molecules in air. This phenomenon can also be blocked by surface passivation. On the other hand, the surface built-in potential separates the photogenerated electron¿hole pairs and accumulates holes at the surface. After illumination, the charge separation makes the electron¿hole recombination difficult and originates PPC. This effect is quickly reverted after increasing either the probing current (self-heating by Joule dissipation) or the oxygen content in air (favouring the surface recombination mechanisms). The model for PPC in individual nanowires presented here illustrates the intrinsic potential of metal oxide nanowires to develop optoelectronic devices or optochemical sensors with better and new performances.

Coverage effects on the magnetism of Fe/MgO(001) ultrathin films

Different aspects of the structure-magnetism and morphology-magnetism correlation in the ultrathin limit are studied in epitaxial Fe films grown on MgO(001). In the initial stages of growth the presence of substrate steps, intrinsically higher than an Fe atomic layer, prevent the connection between Fe islands and hence the formation of large volume magnetic regions. This is proposed as an explanation to the superparamagnetic nature of ultrathin Fe films grown on MgO in addition to the usually considered islanded, or Vollmer-Weber, growth. Using this model, we explain the observed transition from superparamagnetism to ferromagnetism for Fe coverages above 3 monolayers (ML). However, even though ferromagnetism and magnetocrystalline anisotropy are observed for 4 ML, complete coverage of the MgO substrate by the Fe ultrathin films only occurs around 6 ML as determined by polar Kerr spectra and simulations that consider different coverage situations. In annealed 3.5 ML Fe films, shape or configurational anisotropy dominates the intrinsic magnetocrystalline anisotropy, due to an annealing induced continuous to islanded morphological transition. A small interface anisotropy in thicker films is observed, probably due to dislocations observed at the Fe¿MgO(001) interface.

Size effects in the magneto-optical response of Co nanoparticles

A study of the magneto-optical (MO) spectral response of Co nanoparticles embedded in MgO as a function of their size and concentration in the spectral range from 1.4 to 4.3 eV is presented. The nanoparticle layers were obtained by sputtering at different deposition temperatures. Transmission electron microscopy measurements show that the nanoparticles have a complex structure which consists of a crystalline core having a hexagonal close-packed structure and an amorphous crust. Using an effective-medium approximation we have obtained the MO constants of the Co nanoparticles. These MO constants are different from those of continuous Co layers and depend on the size of the crystalline core. We associate these changes with the size effect of the intraband contribution to the MO constants, related to a reduction of the relaxation time of the electrons into the nanoparticles.

Relation for the nonequilibrium population of the interface states: effects on the bias dependence of the ideality factors

By an analysis of the exchange of carriers through a semiconductor junction, a general relationship for the nonequilibrium population of the interface states in Schottky barrier diodes has been derived. Based on this relationship, an analytical expression for the ideality factor valid in the whole range of applied bias has been given. This quantity exhibits two different behaviours depending on the value of the applied bias with respect to a critical voltage. This voltage, which depends on the properties of the interfacial layer, constitutes a new parameter to complete the characterization of these junctions. A simple interpretation of the different behaviours of the ideality factor has been given in terms of the nonequilibrium charging properties of interface states, which in turn explains why apparently different approaches have given rise to similar results. Finally, the relevance of our results has been considered on the determination of the density of interface states from nonideal current-voltage characteristics and in the evaluation of the effects of the interfacial layer thickness in metal-insulator-semiconductor tunnelling diodes.

Nitrogen incorporation effects in Fe(001) thin films

Nitrogen incorporates into Fe thin films during reactively sputtered TiN capping layer deposition. The influence that this nitrogen incorporation has both on the structure and magnetic properties is discussed for a series of Fe~001! thin films grown at different temperatures. A higher nitrogen content is accompanied by distortion in the Fe lattice and by reduction in the Fe magnetization saturation as well as in the effective anisotropy constant, K. The reduction of K brings as a consequence lowering in the coercive field with respect to equivalent Fe films with no nitrogen present.

Response of irrigated wheat cultivars to different nitrogen rates and sources

High wheat yields require good N fertilization management. The objective of this study was to evaluate the effects of different N applications at sowing using Entec (N source with nitrification inhibitor) and urea (traditional N source) at covering, on four wheat cultivars. The experiment was conducted in a randomized block design in a factorial scheme, with four replications, at the Experimental Station of the Faculdade de Engenharia de Ilha Solteira - UNESP, on a dystrophic, epi-eutrophic alic Red Latosol with loamy texture, formerly under savannah vegetation. Four N rates (0, 60, 120, and 180 kg ha-1) were tested, applied at sowing in the case of Entec and top-dressed 40 days after plant emergence in the case of urea, and the four wheat cultivars E 21, E 22, E 42, and IAC 370. The yield of the wheat cultivars E 21 and E 42 was highest. Plant height and lodging index of cultivar E 22 were greatest, with consequently lowest grain yield. There was no significant difference between Entec (applied at sowing) and urea (top-dressed) in terms of grain yield and yield components. Nevertheless, urea resulted in a higher N leaf content, and Entec in a larger number of undeveloped spikelets. High nitrogen rates influenced the hectoliter mass negatively, affecting wheat grain quality. Grain yield increased under N rates of up to 82 kg ha-1 N, through Entec applied at sowing or top-dressed urea.

Simultaneous multielement extraction with the Mehlich-1 solution for Southern Brazilian soils determined by ICP-OES and the effects on the nutrients recommendations to crops

The amounts of macro (P, K, Ca and Mg) and micronutrients (Cu and Zn) extracted with the Mehlich-1 (M1) solution, by the 1.0 mol L-1 KCl (KCl) and with the 0.1 mol L-1 HCl (HCl) for representative soil types of the Rio Grande do Sul state (Brazil) were compared with those extracted with the Mehlich-1 solution determined with the inductively coupled plasma optical emission spectroscopy (ICP). The amounts of nutrients extracted by the different methods showed high correlation coefficients. On average, the Mehlich-1 solution extracted similar amounts of P, determined with colorimetric and ICP methods, and, K determined with emission and ICP. The amounts of Ca and Mg extracted with the Mehlich-1 solution, determined by ICP, were similar to those extracted with the KCl solution determined by the atomic absorption spectrophotometry. The amounts of Cu and Zn extracted with the Mehlich-1 solution, determined by the ICP, were higher than those extracted with the 0.1 mol L-1 HCl determined by the atomic absorption spectrophotometry. The results indicate that the Mehlich-1 solution and ICP can be used for simultaneous multielement extraction and determination for Southern Brazilian soils. However, a conversion factor for values interpretation is needed. The use of the conversion factor to determine the K availability index in soils is adequate and does not affect the K recommendations for crops in southern Brazilian soils.

Effects of differential taxation on factor accumulation and growth

In this paper we try to analyze the role of fiscal policy in fostering a higher participation of the different production factors in the human capital production sector in the long-run. Introducing a tax on physical capital and differentiating both a tax on raw labor wage and a tax on skills or human capital we also attempt to present a way to influence inequality as measured by the skill premium, thus trying to relate the increase in human capital with the decrease in income inequality. We will do that in the context of a non-scale growth model.The model here is capable to alter the shares of private factors devoted to each of the two production sectors, final output and human capital, and affect inequality in a different way according to the different tax changes. The simulation results derived in the paper show how a human capital (skills) tax cut, which could be interpreted as a reduction in progressivity, ends up increasing both the shares of labor and physical capital devoted to the production of knowledge and decreasing inequality. Moreover, a raw labor wage tax decrease, which could also be interpreted as an increase in the progressivity of the system, increases the share of labor devoted to the production of final output and increases inequality. Finally, a physical capital tax decrease reduces the share of physical capital devoted to the production of knowledge and allows for a lower inequality value. Nevertheless, none of the various types of taxes ends up changing the share of human capital in the knowledge production, which will deserve our future attention