Novel endogenous peptide agonists of cannabinoid receptors

Hemopressin (Hp), a 9-residue alpha-hemoglobin-derived peptide, was previously reported to function as a CB(1) cannabinoid receptor antagonist (1). In this study, we report that mass spectrometry (MS) data from peptidomics analyses of mouse brain extracts identified N-terminally extended forms of Hp containing either three (RVD-Hp alpha) or two (VD-Hp alpha) additional amino acids, as well as a beta-hemoglobinderived peptide with sequence similarity to that of hemopressin (VD-Hp beta). Characterization of the alpha-hemoglobin-derived peptides using binding and functional assays shows that in contrast to Hp, which functions as a CB(1) cannabinoid receptor antagonist, both RVD-Hp alpha and VD-Hp alpha function as agonists. Studies examining the increase in the phosphorylation of ERK1/2 levels or release of intracellular Ca(2+) indicate that these peptides activate a signal transduction pathway distinct from that activated by the endo-cannabinoid, 2-arachidonoylglycerol, or the classic CB(1) agonist, Hu-210. This finding suggests an additional mode of regulation of endogenous cannabinoid receptor activity. Taken together, these results suggest that the CB(1) receptor is involved in the integration of signals from both lipid-and peptide-derived signaling molecules.-Gomes, I., Grushko, J. S., Golebiewska, U., Hoogendoorn, S., Gupta, A., Heimann, A. S., Ferro, E. S., Scarlata, S., Fricker, L. D., Devi, L. A. Novel endogenous peptide agonists of cannabinoid receptors. FASEB J. 23, 3020-3029 (2009). www.fasebj.org

Functional Expression of Chemoreceptors with the Help of a Guanine Nucleotide Exchange Factor

Odorant receptors and other chemoreceptors are usually poorly expressed in the plasma membrane of heterologous cells. A key point of regulation in G protein-mediated signaling is the interconversion between the active GTP-bound and inactive GDP-bound states of the G alpha subunit, which regulatory proteins, such as guanine nucleotide exchange factors (GEFs), can control. GEFs stimulate formation of the GTP-bound state of G alpha and therefore are considered to work as positive regulators of G protein-coupled receptor signaling. Ric-8B, a GEF that is specifically expressed in olfactory sensory neurons, promotes functional expression of odorant receptors in HEK293T cells because it amplifies the initially low receptor signaling through G alpha olf. This same strategy could be used to functionally express other types of chemoreceptors.

Insuring cleaner oceans: the economics of oil pollution prevention

The current system of controlling oil spills involves a complex relationship of international, federal and state law, which has not proven to be very effective. The multiple layers of regulation often leave shipowners unsure of the laws facing them. Furthemore, nations have had difficulty enforcing these legal requirements. This thesis deals with the role marine insurance can play within the existing system of legislation to provide a strong preventative influence that is simple and cost-effective to enforce. In principle, insurance has two ways of enforcing higher safety standards and limiting the risk of an accident occurring. The first is through the use of insurance premiums that are based on the level of care taken by the insured. This means that a person engaging in riskier behavior faces a higher insurance premium, because their actions increase the probability of an accident occurring. The second method, available to the insurer, is collectively known as cancellation provisions or underwriting clauses. These are clauses written into an insurance contract that invalidates the agreement when certain conditions are not met by the insured The problem has been that obtaining information about the behavior of an insured party requires monitoring and that incurs a cost to the insurer. The application of these principles proves to be a more complicated matter. The modern marine insurance industry is a complicated system of multiple contracts, through different insurers, that covers the many facets of oil transportation. Their business practices have resulted in policy packages that cross the neat bounds of individual, specific insurance coverage. This paper shows that insurance can improve safety standards in three general areas -crew training, hull and equipment construction and maintenance, and routing schemes and exclusionary zones. With crew, hull and equipment, underwriting clauses can be used to ensure that minimum standards are met by the insured. Premiums can then be structured to reflect the additional care taken by the insured above and beyond these minimum standards. Routing schemes are traffic flow systems applied to congested waterways, such as the entrance to New York harbor. Using natural obstacles or manmade dividers, ships are separated into two lanes of opposing traffic, similar to a road. Exclusionary zones are marine areas designated off limits to tanker traffic either because of a sensitive ecosystem or because local knowledge is required of the region to ensure safe navigation. Underwriting clauses can be used to nullify an insurance contract when a tanker is not in compliance with established exclusionary zones or routing schemes.

Social welfare analysis in a simple financial economy with risk regulation

In the last years, regulating agencies of rnany countries in the world, following recommendations of the Basel Committee, have compelled financiaI institutions to maintain minimum capital requirements to cover market risk. This paper investigates the consequences of such kind of regulation to social welfare and soundness of financiaI institutions through an equilibrium model. We show that the optimum level of regulation for each financiaI institution (the level that maximizes its utility) depends on its appetite for risk and some of them can perform better in a regulated economy. In addition, another important result asserts that under certain market conditions the financiaI fragility of an institution can be greater in a regulated econolny than in an unregulated one

Regulation and wage adjustment patterns : non parametric evidence from longitudinal data

This paper gives a first step toward a methodology to quantify the influences of regulation on short-run earnings dynamics. It also provides evidence on the patterns of wage adjustment adopted during the recent high inflationary experience in Brazil.The large variety of official wage indexation rules adopted in Brazil during the recent years combined with the availability of monthly surveys on labor markets makes the Brazilian case a good laboratory to test how regulation affects earnings dynamics. In particular, the combination of large sample sizes with the possibility of following the same worker through short periods of time allows to estimate the cross-sectional distribution of longitudinal statistics based on observed earnings (e.g., monthly and annual rates of change).The empirical strategy adopted here is to compare the distributions of longitudinal statistics extracted from actual earnings data with simulations generated from minimum adjustment requirements imposed by the Brazilian Wage Law. The analysis provides statistics on how binding were wage regulation schemes. The visual analysis of the distribution of wage adjustments proves useful to highlight stylized facts that may guide future empirical work.

O processo de licenciamento de empreendimentos de infraestrutura no Brasil: estudo de caso da intervenção ambiental no setor elétrico

A adoção da modelagem institucional de governança do processo de avaliação ambiental norte-americano, centrada na figura da agência líder, deverá demandar a edição de uma lei formal, prevendo o referido arranjo jurídico-institucional, na forma de uma moldura (framework) adaptável às necessidades especificas e peculiaridades de cada setor da Administração. Dessa forma, a referida lei formal funcionaria como uma norma geral, e como tal poderia ser complementada pela legislação infralegal, que viria a estabelecer as disposições especificas para dar efetividade ao instituo da agência líder nos setores em que seja desejável e oportuna a implantação do mesmo, a critério da Administração. Destarte, a atuação do Poder Legislativo estaria restrita à introdução ao sistema jurídico doméstico do instituto estrangeiro, estabelecendo apenas seus contornos básicos, cabendo à Administração a avaliação da oportunidade e conveniência da escolha dos setores específicos, do estabelecimento dos contornos normativos e do momento da efetiva regulamentação concreta do instituto.

HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions

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

Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation

Previous studies have indicated the importance of angiotensin II (ANG II) in skeletal muscle angiogenesis. The present study explored the effect of regulation of the renin gene on angiogenesis induced by electrical stimulation with the use of physiological, pharmacological, and genetic manipulations of the renin-angiotensin system (RAS). Transfer of the entire chromosome 13, containing the physiologically regulated renin gene, from the normotensive inbred Brown Norway (BN) rat into the background of an inbred substrain of the Dahl salt-sensitive (SS/Mcwi) rat restored renin levels and the angiogenic response after electrical stimulation. This restored response was significantly attenuated when SS-13BN/Mcwi consomic rats were treated with lisinopril or high-salt diet. The role of ANG II on this effect was confirmed by the complete restoration of skeletal muscle angiogenesis in SS/Mcwi rats infused with subpressor doses of ANG II. Congenic strains derived from the SS-13BN/Mcwi consomic were used to further verify the role of the renin gene in this response. Microvessel density was markedly increased after stimulation in congenic strains that contained the renin gene from the BN rat (congenic lines A and D). This angiogenic response was suppressed in control strains that carried regions of the BN genome just above (congenic line C) or just below (congenic line B) the renin gene. The present study emphasizes the importance of maintaining normal renin regulation as well as ANG II levels during the angiogenesis process with a combination of physiological, genetic, and pharmacological manipulation of the RAS.

Biophysical Characterization of Interactions Involving Importin-α during Nuclear Import

Proteins containing the classical nuclear localization sequences (NLSs) are imported into the nucleus by the importin-α/β heterodimer. Importin-α contains the NLS binding site, whereas importin-β mediates the translocation through the nuclear pore. We characterized the interactions involving importin-α during nuclear import using a combination of biophysical techniques (biosensor, crystallography, sedimentation equilibrium, electrophoresis, and circular dichroism). Importin-α is shown to exist in a monomeric autoinhibited state (association with NLSs undetectable by biosensor). Association with importin-β (stoichiometry, 1:1; K D = 1.1 × 10 -8 M) increases the affinity for NLSs; the importin-α/β complex binds representative monopartite NLS (simian virus 40 large T-antigen) and bipartite NLS (nucleoplasmin) with affinities (K D = 3.5 × 10 -8 M and 4.8 × 10 -8 M, respectively) comparable with those of a truncated importin-α lacking the autoinhibitory domain (T-antigen NLS, K D = 1.7 × 10 -8 M; nucleoplasmin NLS, K D = 1.4 × 10 -8 M). The autoinhibitory domain (as a separate peptide) binds the truncated importin-α, and the crystal structure of the complex resembles the structure of full-length importin-α. Our results support the model of regulation of nuclear import mediated by the intrasteric autoregulatory sequence of importin-α and provide a quantitative description of the binding and regulatory steps during nuclear import.

Control of amylase production and growth characteristics of Aspergillus ochraceus

The growth and the extracellular amylase production by Aspergillus ochraceus were studied in a stationary culture medium. Maximum growth rate of this fungus was found after 5 days of incubation at 30° C, but maximum amylase production was obtained after 2 days. The highest amylase production were attained with lactose, maltose, xylose and starch as carbon sources. The extracellular amylase production and mycelial growth were influenced by the concentration of starch. Other carbohydrates supported growth but did not induce amylase synthesis and glucose repressed it, indicating catabolite repression in this microorganism. The presence of both mechanisms of induction and repression suggests that at least these multiple forms of regulation are present in A. ochraceus. Of the nitrogen sources tested, casaminoacids, ammonium nitrate and sodium nitrate stimulated the highest yield of amylase. Optimal amylase production was obtained at pH 5.0, but enzyme activity was found only in the 4.0-6.0 pH range. These results were probably due to the inhibitory effect of NH 4 +-N in the culture medium.

SMEs in the environmental goods and services market: identifying areas of opportunity, policies and instruments: case studies: Argentina, Chile, Colombia and Mexico

Includes bibliography

Trade in services in Latin America and the Caribbean: an analysis of recent trends

Includes bibliography

Regulating the private provision of drinking water and sanitation services

Includes bibliography

The natural gas industry and its regulation in Latin America

Includes bibliography

Avaliação dos impactos econômicos do potencial de desenvolvimento da mitilicultura no município de Ubatuba-SP

Pós-graduação em Aquicultura - FCAV