Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people

The polymorphisms of endothelial nitric oxide synthase (eNOS) are associated with reduced eNOS activity. Aerobic exercise training (AEX) may influence resting nitric oxide (NO) production, oxidative stress and blood pressure. The purpose of this study was to investigate the effect of AEX on the relationship among blood pressure, eNOS gene polymorphism and oxidative stress in pre-hypertensive older people. 118 pre-hypertensive subjects (59 +/- A 6 years) had blood samples collected after a 12 h overnight fast for assessing plasma NO metabolites (NOx) assays, thiobarbituric acid reactive substances (T-BARS) and superoxide dismutase activity (ecSOD). eNOS polymorphism (T-786C and G-894T) was done by standard PCR methods. All people were divided according to the genotype results (G1: TT/GG, G2: TT/GT + TT, G3: TC + CC/GG, G4: TC + CC/GT + TT). All parameters were measured before and after 6 months of AEX (70% of VO(2 max)). At baseline, no difference was found in systolic and diastolic blood pressure, ecSOD and T-BARS activity. Plasma NOx levels were significantly different between G1 (19 +/- A 1 mu M) and G4 (14.2 +/- A 0.6 mu M) and between G2 (20.1 +/- A 1.7 mu M) and G4 (14.2 +/- A 0.6 mu M). Therefore, reduced NOx concentration in G4 group occurred only when the polymorphisms were associated, suggesting that these results are more related to genetic factors than NO-scavenging effect. After AEX, the G4 increased NOx values (17.2 +/- A 1.2 mu M) and decreased blood pressure. G1, G3 and G4 decreased T-BARS levels. These results suggest the AEX can modulate the NOx concentration, eNOS activity and the relationship among eNOS gene polymorphism, oxidative stress and blood pressure especially in C (T-786C) and T (G-894T) allele carriers.

Conformational Polymorphism in Racemic Crystals of the Diuretic Drug Chlortalidone

Chlortalidone (HIGROTON) is a diuretic drug widely used in antihypertensive therapy. Thus far, only two solid-state polymorphs of chlortalidone have been reported. We elucidated the structure of chlortalidone form I and a new polymorph. This new phase, namely, chlortalidone form III, was also entirely characterized. It was possible to conclude that it is a conformer with a different orientation of the chlorobenzenesulfonamide moiety. Compared to form I, it has a rotation of about 90 degrees on the axis of the C-C bond bridging the substituted phenyl and isoindolinyl rings. This conformational feature is related to the crystal packing patterns of the chlortalidone forms. Furthermore, certain intermolecular hydrogen bonds are present in both polymorphs, giving rise to ribbons with chlortalidone enantiomers alternately placed into them. The chlortalidone form I and form III crystallize in the triclinic space group P (1) over bar as racemic mixtures. Additional conformational details also differentiate the chlortalidone conformers. Slight twists on the isoindolinyl and sulfamyl groups exist. Considering all structural relationships, the fingerprint plots derived from the Hirshfeld surfaces exhibited the characteristics of the chlortalidone form I and form III crystal structures.

eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity

Statins have pleiotropic effects, including endothelial nitric oxide synthase (eNOS) upregulation and increased nitric oxide formation, which can be modulated by a genetic polymorphism in the promoter region of the eNOS gene (T-786C). Here, we report our investigation of whether this polymorphism modulates the effects of atorvastatin on the fluidity of erythrocyte membranes. We genotyped 200 healthy subjects (males, 18-60 years of age) and then randomly selected 15 of these with the TT genotype and 15 with the CC genotype to receive placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell membrane fluidity was evaluated by electron paramagnetic resonance (EPR) and spin-labeling method. The EPR spectra were registered on a VARIAN-E4 spectrometer. Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol were determined in the erythrocytes. Atorvastatin reduced membrane fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P > 0.05). While no significant differences were found in plasma membrane cholesterol concentrations, higher TBA-RS concentrations were found in the CC subjects than in the TT subjects (P < 0.05). These findings suggest that a short treatment with atorvastatin is disadvantageous to subjects with the CC genotype for the T-786C polymorphism compared to those with TT genotype, at least in terms of the hemorheological properties of erythrocytes.

Inferring Contagion in Regulatory Networks

Several gene regulatory network models containing concepts of directionality at the edges have been proposed. However, only a few reports have an interpretable definition of directionality. Here, differently from the standard causality concept defined by Pearl, we introduce the concept of contagion in order to infer directionality at the edges, i.e., asymmetries in gene expression dependences of regulatory networks. Moreover, we present a bootstrap algorithm in order to test the contagion concept. This technique was applied in simulated data and, also, in an actual large sample of biological data. Literature review has confirmed some genes identified by contagion as actually belonging to the TP53 pathway.

GRASSIUS: A Platform for Comparative Regulatory Genomics across the Grasses

Transcription factors (TFs) are major players in gene regulatory networks and interactions between TFs and their target genes furnish spatiotemporal patterns of gene expression. Establishing the architecture of regulatory networks requires gathering information on TFs, their targets in the genome, and the corresponding binding sites. We have developed GRASSIUS (Grass Regulatory Information Services) as a knowledge-based Web resource that integrates information on TFs and gene promoters across the grasses. In its initial implementation, GRASSIUS consists of two separate, yet linked, databases. GrassTFDB holds information on TFs from maize (Zea mays), sorghum (Sorghum bicolor), sugarcane (Saccharum spp.), and rice (Oryza sativa). TFs are classified into families and phylogenetic relationships begin to uncover orthologous relationships among the participating species. This database also provides a centralized clearinghouse for TF synonyms in the grasses. GrassTFDB is linked to the grass TFome collection, which provides clones in recombination-based vectors corresponding to full-length open reading frames for a growing number of grass TFs. GrassPROMDB contains promoter and cis-regulatory element information for those grass species and genes for which enough data are available. The integration of GrassTFDB and GrassPROMDB will be accomplished through GrassRegNet as a first step in representing the architecture of grass regulatory networks. GRASSIUS can be accessed from www.grassius.org.

Human regulatory protein Ki-1/57 has characteristics of an intrinsically unstructured protein

The human protein Ki-1/57 was first identified through the cross reactivity of the anti-CD30 monoclonal antibody Ki-1; in Hodgkin lymphoma cells. The expression of Ki-1/57 in diverse cancer cells and its phosphorylation in peripheral blood leukocytes after mitogenic activation suggested its possible role in cell signaling. Ki-1/57 interacts with several other regulatory proteins involved in cellular signaling, transcriptional regulation and RNA metabolism, suggesting it may have pleiotropic functions. In a previous spectroscopic analysis, we observed a low content of secondary structure for Ki-1/57 constructs. Here, Circular dichroism experiments, in vitro RNA binding analysis, and limited proteolysis assays of recombinant Ki-1/57(122-413) and proteolysis assays of endogenous full length protein from human HEK293 cells suggested that Ki-1/57 has characteristics of an intrinsically unstructured protein. Small-angle X-ray scattering (SAXS) experiments were performed with the C-terminal fragment Ki-1/57(122-413). These results indicated an elongated shape and a partially unstructured conformation of the molecule in solution, confirming the characteristics of an intrinsically unstructured protein. Experimental curves together with ab initio modeling approaches revealed an extended and flexible molecule in solution. An elongated shape was also observed by analytical gel filtration. Furthermore, sedimentation velocity analysis suggested that Ki-1/57 is a highly asymmetric protein. These findings may explain the functional plasticity of Ki-1/57, as suggested by the wide array of proteins with which it is capable of interacting in yeast two-hybrid interaction assays.

Supervision as control system : the design of supervision as a regulatory instrument in the social services sector in Sweden

In this article, the prevailing official view of supervision as a regulatory instrument is examined as it applies to the social services sector in Sweden. The study is based on a comparison of the views expressed on the design of supervision as a regulatory instrument by two government commissions, the Supervision Commission and the Commission on Supervision within the Social Services (UTIS), and on the positions taken by the Government regarding the definitions of the concept of supervision proposed by these commissions. The view of supervision as a regulatory instrument expressed in these policy documents is analysed with the help of a theoretical framework describing the components, their functions and the governance characteristics of control systems. In the framework separate interrelated characteristics of the components are identified and summarized into two models of control systems. The analysis shows that supervision in the Swedish social services sector can be described in terms of both a disciplinary and non-disciplinary system. By its system theoretical basis and the identification of interrelated characteristics the study contributes to a broadened understanding of the construction and functions of supervision as a regulatory instrument and of how supervision within the Swedish social sector is meant to be designed.

Brazil's regulatory framework: predictability or uncertainty?

Este Trabalho Discute as Perspectivas da Regulação Econômica no Brasil. para Tanto, Primeiramente Apresenta-Se a Evolução Histórica da Regulação no País, Discutindo as Principais Questões Relacionadas Às Agências Reguladoras Federais. em Segundo Lugar, os Marcos Regulatórios de Cinco Diferentes Setores (Telecomunicações, Eletricidade, Saneamento Básico, Petróleo e Gás Natural) são Analisados. em Terceiro Lugar, a Questão do Financiamento de Investimentos em Infra-Estrutura é Tratada, Enfatizando o Papel das Parcerias Público-Privadas (Ppps). uma Seção Final Cont~Em um Possível Agenda para a Regulação no Brasil

Essays on regulatory risk issues

Most studies around that try to verify the existence of regulatory risk look mainly at developed countries. Looking at regulatory risk in emerging market regulated sectors is no less important to improving and increasing investment in those markets. This thesis comprises three papers comprising regulatory risk issues. In the first Paper I check whether CAPM betas capture information on regulatory risk by using a two-step procedure. In the first step I run Kalman Filter estimates and then use these estimated betas as inputs in a Random-Effect panel data model. I find evidence of regulatory risk in electricity, telecommunications and all regulated sectors in Brazil. I find further evidence that regulatory changes in the country either do not reduce or even increase the betas of the regulated sectors, going in the opposite direction to the buffering hypothesis as proposed by Peltzman (1976). In the second Paper I check whether CAPM alphas say something about regulatory risk. I investigate a methodology similar to those used by some regulatory agencies around the world like the Brazilian Electricity Regulatory Agency (ANEEL) that incorporates a specific component of regulatory risk in setting tariffs for regulated sectors. I find using SUR estimates negative and significant alphas for all regulated sectors especially the electricity and telecommunications sectors. This runs in the face of theory that predicts alphas that are not statistically different from zero. I suspect that the significant alphas are related to misspecifications in the traditional CAPM that fail to capture true regulatory risk factors. On of the reasons is that CAPM does not consider factors that are proven to have significant effects on asset pricing, such as Fama and French size (ME) and price-to-book value (ME/BE). In the third Paper, I use two additional factors as controls in the estimation of alphas, and the results are similar. Nevertheless, I find evidence that the negative alphas may be the result of the regulated sectors premiums associated with the three Fama and French factors, particularly the market risk premium. When taken together, ME and ME/BE regulated sectors diminish the statistical significance of market factors premiums, especially for the electricity sector. This show how important is the inclusion of these factors, which unfortunately is scarce in emerging markets like Brazil.

Is enterprise value affected by political nominations for a regulatory agency's presidency?

Economists have argued that regulation is the appropriate approach to maintain output in its economically efficient level in a natural monopoly, and that can be achieved by submitting these companies to regulatory agencies’ decisions. The autonomous agencies are, however, not free in an absolute sense, and it is important to ask what the priorities of the new administration are. One answer is that it is designed to give leeway and powers of discretion to unbiased professionals with expertise in their field. In practice, however, professional experts might often be politically motivated. The objective of this study is to investigate whether political nominations to the presidency of regulatory agencies, rather than technical appointments, affect the level of regulatory risk. In order to achieve this purpose, an event study was performed, where the regulatory risk in a political nomination will be compared to a technical nomination, in terms of abnormal return.

Share bidding auctions, sliding scale royalty rates and the new brazilian regulatory framework for the pre-salt areas

O governo brasileiro recentemente aprovou uma legislação instituindo um novo marco regulatório para as reservas petrolíferas do pré-sal. Segundo as novas regras, estas áreas deverão ser licitadas mediante um leilão de partilha de lucro. Motivado por esta mudança, apresentamos um modelo de leilão de partilha sob afiliação, demonstrando a existência de um equilíbrio monótono em estratégias puras e caracterizando a solução. Alem disso, provamos que este mecanismo gera receita esperada maior ou igual a um leilão de primeiro preço usual. Em seguida, introduzimos no modelo uma função representando taxas de royalties que dependem do valor do objeto. Este instrumento permite uma elevação na receita esperada de ambos os modelos, fazendo com que a diferença entre eles encolha. Finalmente, analisando o novo marco regulatório sob o ponto de vista dos resultados obtidos, concluímos que o antigo modelo de concessão utilizado pelo governo brasileiro é mais adequado e lucrativo.

Regulatory reform in the brazilian railway sector and concession valuation: a preliminary assessment

Trabalho apresentado na 4th Conference on the Regulation of Infrastructures

Regulatory reform in the brazilian railway sector and its potential effects

Trabalho apresentado no Law and Society Annual Conference, 2015