Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes

The degeneration of dopaminergic neurons in the substantia nigra has been linked to the formation of the endogenous neurotoxin 5-S-cysteinyl-dopamine. Sulforaphane (SFN), an isothiocyanate derived from the corresponding precursor glucosinolate found in cruciferous vegetables has been observed to exert a range of biological activities in various cell populations. In this study, we show that SFN protects primary cortical neurons against 5-S-cysteinyl-dopamine induced neuronal injury. Pre-treatment of cortical neurons with SFN (0.01-1 microM) resulted in protection against 5-S-cysteinyl-dopamine-induced neurotoxicity, which peaked at 100 nM. This protection was observed to be mediated by the ability of SFN to modulate the extracellular signal-regulated kinase 1 and 2 and the activation of Kelch-like ECH-associated protein 1/NF-E2-related factor-2 leading to the increased expression and activity of glutathione-S-transferase (M1, M3 and M5), glutathione reductase, thioredoxin reductase and NAD(P)H oxidoreductase 1. These data suggest that SFN stimulates the NF-E2-related factor-2 pathway of antioxidant gene expression in neurons and may protect against neuronal injury relevant to the aetiology of Parkinson's disease.

Causal relationship between obesity and vitamin D status: bi-directional mendelian randomization analysis of multiple cohorts

BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

Serum carbon and nitrogen stable isotopes as potential biomarkers of dietary intake and their relation with incident type 2 diabetes: the EPIC-Norfolk study

Background: Stable-isotope ratios of carbon (13C/12C, expressed as δ13C) and nitrogen (15N/14N, or δ15N) have been proposed as potential nutritional biomarkers to distinguish between meat, fish, and plant-based foods. Objective: The objective was to investigate dietary correlates of δ13C and δ15N and examine the association of these biomarkers with incident type 2 diabetes in a prospective study. Design: Serum δ13C and δ15N (‰) were measured by using isotope ratio mass spectrometry in a case-cohort study (n = 476 diabetes cases; n = 718 subcohort) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk population-based cohort. We examined dietary (food-frequency questionnaire) correlates of δ13C and δ15N in the subcohort. HRs and 95% CIs were estimated by using Prentice-weighted Cox regression. Results: Mean (±SD) δ13C and δ15N were −22.8 ± 0.4‰ and 10.2 ± 0.4‰, respectively, and δ13C (r = 0.22) and δ15N (r = 0.20) were positively correlated (P < 0.001) with fish protein intake. Animal protein was not correlated with δ13C but was significantly correlated with δ15N (dairy protein: r = 0.11; meat protein: r = 0.09; terrestrial animal protein: r = 0.12, P ≤ 0.013). δ13C was inversely associated with diabetes in adjusted analyses (HR per tertile: 0.74; 95% CI: 0.65, 0.83; P-trend < 0.001], whereas δ15N was positively associated (HR: 1.23; 95% CI: 1.09, 1.38; P-trend = 0.001). Conclusions: The isotope ratios δ13C and δ15N may both serve as potential biomarkers of fish protein intake, whereas only δ15N may reflect broader animal-source protein intake in a European population. The inverse association of δ13C but a positive association of δ15N with incident diabetes should be interpreted in the light of knowledge of dietary intake and may assist in identifying dietary components that are associated with health risks and benefits.

Midday auroral breakup events and related energy and momentum transfer from the magnetosheath

Combined observations by meridian-scanning photometers, all-sky auroral TV camera and the EISCAT radar permitted a detailed analysis of the temporal and spatial development of the midday auroral breakup phenomenon and the related ionospheric ion flow pattern within the 71°–75° invariant latitude radar field of view. The radar data revealed dominating northward and westward ion drifts, of magnitudes close to the corresponding velocities of the discrete, transient auroral forms, during the two different events reported here, characterized by IMF |BY/BZ| < 1 and > 2, respectively (IMF BZ between −8 and −3 nT and BY > 0). The spatial scales of the discrete optical events were ∼50 km in latitude by ∼500 km in longitude, and their lifetimes were less than 10 min. Electric potential enhancements with peak values in the 30–50 kV range are inferred along the discrete arc in the IMF |BY/BZ| < 1 case from the optical data and across the latitudinal extent of the radar field of view in the |BY/BZ| > 2 case. Joule heat dissipation rates in the maximum phase of the discrete structures of ∼ 100 ergs cm−2 s−1 (0.1 W m−2) are estimated from the photometer intensities and the ion drift data. These observations combined with the additional characteristics of the events, documented here and in several recent studies (i.e., their quasi-periodic nature, their motion pattern relative to the persistent cusp or cleft auroral arc, the strong relationship with the interplanetary magnetic field and the associated ion drift/E field events and ground magnetic signatures), are considered to be strong evidence in favour of a transient, intermittent reconnection process at the dayside magnetopause and associated energy and momentum transfer to the ionosphere in the polar cusp and cleft regions. The filamentary spatial structure and the spectral characteristics of the optical signature indicate associated localized ˜1-kV potential drops between the magnetopause and the ionosphere during the most intense auroral events. The duration of the events compares well with the predicted characteristic times of momentum transfer to the ionosphere associated with the flux transfer event-related current tubes. It is suggested that, after this 2–10 min interval, the sheath particles can no longer reach the ionosphere down the open flux tube, due to the subsequent super-Alfvénic flow along the magnetopause, conductivities are lower and much less momentum is extracted from the solar wind by the ionosphere. The recurrence time (3–15 min) and the local time distribution (∼0900–1500 MLT) of the dayside auroral breakup events, combined with the above information, indicate the important roles of transient magnetopause reconnection and the polar cusp and cleft regions in the transfer of momentum and energy between the solar wind and the magnetosphere.

Two new species of Loricariidae (Teleostei: Siluriformes) from main channels of the upper and middle Amazon Basin, with discussion of deep water specialization in loricariids

Hemiancistrus pankimpuju, new species, and Panaque bathyphilus, new species, are described from the main channel of the upper (Maranon) and middle (Solimoes)Amazon River, respectively. Both species are diagnosed by having a nearly white body, long filamentous extensions of both simple caudal-fin rays, small eyes, absence of an iris operculum and unique combinations of morphometrics. The coloration and morphology of these species, unique within Loricariidae, are hypothesized to be apomorphies associated with life in the dark, turbid depths of the Amazon mainstem. Extreme elongation of the caudal filaments in these and a variety of other main channel catfishes is hypothesized to have a mechanosensory function associated with predator detection.

A role for regulatory T cells in renal acute kidney injury

Ischemia reperfusion injury (IRI) is a potential contributor for the development of chronic allograft nephropathy. T cells are important mediators of injury, even in the absence of alloantigens. We performed a depletion of TCD4(+)CTLA4(+)Foxp3(+) cells with anti-CD25(PC61), a treatment with anti-GITR (DTA-1) and rat-IgG, followed by 45 min of ischemia and 24/72 h of reperfusion, and then analyzed blood urea, kidney histopathology and gene expression in kidneys by QReal Time PCR. After 24 h of reperfusion, depletion of TCD4(+)CTLA4(+)Foxp3(+) cells reached 30.3%(spleen) and 67.8%(lymph nodes). 72 h after reperfusion depletion reached 43.1%(spleen) and 90.22%(lymph nodes) and depleted animals presented with significantly poorer renal function, while DTA-1 (anti-GITR)-treated ones showed a significant protection, all compared to serum urea from control group (IgG: 150.10 +/- 50.04; PC61: 187.23 +/- 31.38; DTA-1: 64.53 +/- 25.65, mg/dL, p<0.05). These data were corroborated by histopathology. We observed an increase of HO-1 expression in animals treated with DTA-1 at 72 h of reperfusion with significant differences. Thus, our results suggest that PC61 (anti-CD25) mAb treatment is deleterious, while DTA-1 (anti-GITR) mAb treatment presents a protective role in the renal IRI, indicating that some regulatory populations of T cells might have a role in IRI. (C) 2009 Elsevier B.V. All rights reserved.

Limited global diversity of the Plasmodium vivax merozoite surface protein 4 gene

Merozoite surface proteins (MSPs) of the malaria parasites are major candidates for vaccine development targeting asexual blood stages. However, the diverse antigenic repertoire of these antigens that induce strain-specific protective immunity in human is a major challenge for vaccine design and often determines the efficacy of a vaccine. Here we further assessed the genetic diversity of Plasmodium vivax MSP4 (PvMSP4) protein using 195 parasite samples collected mostly from Thailand, Indonesia and Brazil. Overall, PvMSP4 is highly conserved with only eight amino acid substitutions. The majority of the haplotype diversity was restricted to the two short tetrapeptide repeat arrays in exon 1 and 2, respectively. Selection and neutrality tests indicated that exon 1 and the entire coding region of PvMSP4 were under purifying selection. Despite the limited nucleotide polymorphism of PvMSP4, significant genetic differentiation among the three major parasite populations was detected. Moreover, microgeographical heterogeneity was also evident in the parasite populations from different endemic areas of Thailand. (C) 2009 Elsevier B.V. All rights reserved.

Testing permutation properties through subpermutations

There has been great interest in deciding whether a combinatorial structure satisfies some property, or in estimating the value of some numerical function associated with this combinatorial structure, by considering only a randomly chosen substructure of sufficiently large, but constant size. These problems are called property testing and parameter testing, where a property or parameter is said to be testable if it can be estimated accurately in this way. The algorithmic appeal is evident, as, conditional on sampling, this leads to reliable constant-time randomized estimators. Our paper addresses property testing and parameter testing for permutations in a subpermutation perspective; more precisely, we investigate permutation properties and parameters that can be well approximated based on a randomly chosen subpermutation of much smaller size. In this context, we use a theory of convergence of permutation sequences developed by the present authors [C. Hoppen, Y. Kohayakawa, C.G. Moreira, R.M. Sampaio, Limits of permutation sequences through permutation regularity, Manuscript, 2010, 34pp.] to characterize testable permutation parameters along the lines of the work of Borgs et al. [C. Borgs, J. Chayes, L Lovasz, V.T. Sos, B. Szegedy, K. Vesztergombi, Graph limits and parameter testing, in: STOC`06: Proceedings of the 38th Annual ACM Symposium on Theory of Computing, ACM, New York, 2006, pp. 261-270.] in the case of graphs. Moreover, we obtain a permutation result in the direction of a famous result of Alon and Shapira [N. Alon, A. Shapira, A characterization of the (natural) graph properties testable with one-sided error, SIAM J. Comput. 37 (6) (2008) 1703-1727.] stating that every hereditary graph property is testable. (C) 2011 Elsevier B.V. All rights reserved.

Maximizing measures for endomorphisms of the circle

We study a given fixed continuous function phi : S(1) -> R and an endomorphism f : S(1)-> S(1), whose f-invariant probability measures maximize integral phi d mu. We prove that the set of endomorphisms having a f maximizing invariant measure supported on a periodic orbit is C(0) dense.

Carga de trabalho de enfermagem e infecções relacionadas à assistência à saúde na unidade de terapia intensiva

In recent decades, the search for quality care has been widely discussed by the institutions and health professionals. In this context, it is the nurse coordinator of the process of providing nursing staff, reflecting the commitment to quality of care. In this process, it is the appearance of Infections Related to health care and its potential association with the workload in nursing as a valuable indicator of quality of care. Thus, this research contributes to studies to characterize the demand of nursing work to promote a safe healthcare practice. This study aimed to identify the association of nursing workload with the number of cases of Ventilator-Associated Pneumonia, urinary tract infection and central venous catheter infection in the intensive care unit. This is a quantitative research approach, descriptive, cross-sectional and prospective, held at Unimed Hospital in Natal-RN. The study population consisted of all patients treated in the Intensive Care Unit, Hospital for a period of 90 consecutive days in 2011. The convenience sample was compostapelos patients admitted to the ICU during the period of data collection, a total sample of 286 patients. To perform the data analysis software were used: Statistica 6.0, SPPS (Statistical Package for Social Sciences) version 17.0 (2004) and Excel 2007. In the descriptive analysis, we used Measures of Central Tendency and Measures of Dispersion or Variability and the use of nonparametric tests. Of the 286 patients, 88 were from the ICU and 198 ICU II II. Males predominated in the ICU I (51.1%) and female ICU II (57.6%) patients in the ICU I were aged 61-80 years (39.8%) followed by greater than 80 years (39.8%). In the ICU II, most of the patients were aged 61-80 years (38.9%) and then from 41 to 60 years (24.2%). In relation to the class of TISS inlet predominant class II in the two ICUs (59.1%), followed by Class III also in the two units (34.6%). Most patients (70.6%) out of the ICUs belonging to class II TISS. In the ICU I, the average number of forms of the TISS 28 was 6, has in ICU II this value drops to 3.2 forms. The overall mean was 19.9 TISS points in ICU patients I and ICU II.the 17 points in the average hours required to provide adequate nursing care to patients in the ICU I found that is 10 , 7 hours, and the ICU II 9.2 hours. It was found that the time provided by the nursing staff were higher in ICU II, with an average of 19 hours available for nurses in this sector. In the ICU I, which showed higher need of available hours, it was found that the mean value of 12.7 available hours. It was found that only 2.4% of patients had these units Ventilator-Associated Pneumonia, 1.0% were infected central venous catheter and 1.4% of patients had urinary tract infection. Infection associated with health care occurs, on average, on the tenth day of hospitalization. In the ICU II, this average value extends to the twelfth day with an excess of 2.7 hours of nursing care while in ICU I value decays to the ninth day of hospitalization with a deficiency of 12-hour assistance. It is concluded that patients generally showed a need for classification of semi-intensive care and has been assisted in their need to load. As for his association with the Related Infections Health will assist this analysis could not be performed due to the small number of notifications in this period. It is suggested further study how other factors related to infections me a longer period of analysis

Parametric correlation functions to model the structure of permanent environmental (co)variances in milk yield random regression models

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Controlador preditivo generalizado multi-modelo aplicado ao controle de pressão arterial

Postsurgical complication of hypertension may occur in cardiac patients. To decrease the chances of complication it is necessary to reduce elevated blood pressure as soon as possible. Continuous infusion of vasodilator drugs, such as sodium nitroprusside (Nipride), would quickly lower the blood pressure in most patients. However, each patient has a different sensitivity to infusion of Nipride. The parameters and the time delays of the system are initially unknown. Moreover, the parameters of the transfer function associated with a particular patient are time varying. the objective of the study is to develop a procedure for blood pressure control i the presence of uncertainty of parameters and considerable time delays. So, a methodology was developed multi-model, and for each such model a Preditive Controller can be a priori designed. An adaptive mechanism is then needed for deciding which controller should be dominant for a given plant

Método dinâmico aplicado para antenas cilíndricas

Nowadays there has been a major breakthrough in the aerospace area, with regard to rocket launches to research, experiments, telemetry system, remote sensing, radar system (tracking and monitoring), satellite communications system and insertion of satellites in orbit. This work aims at the application of a circular cylindrical microstrip antenna, ring type, and other cylindrical rectangular in structure of a rocket or missile to obtain telemetry data, operating in the range of 2 to 4 GHz, in S-band. Throughout this was developed just the theoretical analysis of the Transverse transmission line method which is a method of rigorous analysis in spectral domain, for use in rockets and missiles. This analyzes the spread in the direction "ρ" , transverse to dielectric interfaces "z" and "φ", for cylindrical coordinates, thus taking the general equations of electromagnetic fields in function of e [1]. It is worth mentioning that in order to obtain results, simulations and analysis of the structure under study was used HFSS program (High Frequency Structural Simulator) that uses the finite element method. With the theory developed computational resources were used to obtain the numerical calculations, using Fortran Power Station, Scilab and Wolfram Mathematica ®. The prototype was built using, as a substrate, the ULTRALAM ® 3850, of Rogers Corporation, and an aluminum plate as a cylindrical structure used to support. The agreement between the measured and simulated results validate the established processes. Conclusions and suggestions are presented for continuing this work

Uso de dados fotogramétricos no refinamento geométrico de contornos de telhados de edifícios extraídos de dados laser

In this paper, a methodology is proposed for the geometric refinement of laser scanning building roof contours using high-resolution aerial images and Markov Random Field (MRF) models. The proposed methodology takes for granted that the 3D description of each building roof reconstructed from the laser scanning data (i.e., a polyhedron) is topologically correct and that it is only necessary to improve its accuracy. Since roof ridges are accurately extracted from laser scanning data, our main objective is to use high-resolution aerial images to improve the accuracy of roof outlines. In order to meet this goal, the available roof contours are first projected onto the image-space. After that, the projected polygons and the straight lines extracted from the image are used to establish an MRF description, which is based on relations ( relative length, proximity, and orientation) between the two sets of straight lines. The energy function associated with the MRF is minimized by using a modified version of the brute force algorithm, resulting in the grouping of straight lines for each roof object. Finally, each grouping of straight lines is topologically reconstructed based on the topology of the corresponding laser scanning polygon projected onto the image-space. The preliminary results showed that the proposed methodology is promising, since most sides of the refined polygons are geometrically better than corresponding projected laser scanning straight lines.

Proposal of an alternative transmission line model for symmetrical and asymmetrical configurations

This article shows a transmission line model for simulation of fast and slow transients, applied to symmetrical or asymmetrical configurations. A transmission line model is developed based on lumped elements representation and state-space techniques. The proposed methodology represents a practical procedure to model three-phase transmission lines directly in time domain, without the explicit or implicit use of inverse transforms. In three-phase representation, analysis modal techniques are applied to decouple the phases in their respective propagation modes, using a correction procedure to set a real and constant matrix for untransposed lines with or without vertical symmetry plane. The proposed methodology takes into account the frequency-dependent parameters of the line and in order to include this effect in the state matrices, a fitting procedure is applied. To verify the accuracy of the proposed state-space model in frequency domain, a simple methodology is described based on line distributed parameters and transfer function associated with input/output signals of the lumped parameters representation. In addition, this article proposes the use of a fast and robust integration procedure to solve the state equations, enabling transient and steady-state simulations. The results obtained by the proposed methodology are compared with several established transmission line models in EMTP, taking into account an asymmetrical three-phase transmission line. The principal contribution of the proposed methodology is to handle a steady fundamental signal mixed with fast and slow transients, including impulsive and oscillatory behavior, by a practical procedure applied directly in time domain for symmetrical or asymmetrical representations. (C) 2011 Elsevier Ltd. All rights reserved.