Analysis of agonist and antagonist effects on thyroid hormone receptor conformation by hydrogen/deuterium exchange

Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) with agonists are available, comparable structures without ligand (apo-TR) or with antagonists are not. It remains important to understand apo-LBD conformation and the way that it rearranges with ligands to develop better TR pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on TR LBDs with or without agonist (T 3) or antagonist (NH3). Both ligands reduce deuterium incorporation into LBD amide hydrogens, implying tighter overall folding of the domain. As predicted, mass spectroscopic analysis of individual proteolytic peptides after hydrogen/ deuterium exchange reveals that ligand increases the degree of solvent protection of regions close to the buried ligand-binding pocket. However, there is also extensive ligand protection of other regions, including the dimer surface at H10-H11, providing evidence for allosteric communication between the ligand-binding pocket and distant interaction surfaces. Surprisingly, Cterminal activation helix H12, which is known to alter position with ligand, remains relatively protected from solvent in all conditions suggesting that it is packed against the LBD irrespective of the presence or type of ligand. T 3, but not NH3, increases accessibility of the upper part of H3-H5 to solvent, and we propose that TR H12 interacts with this region in apo-TR and that this interaction is blocked by T 3 but not NH3.Wepresent data from site-directed mutagenesis experiments and molecular dynamics simulations that lend support to this structural model of apo-TR and its ligand-dependent conformational changes. (Molecular Endocrinology 25: 15-31, 2011). Copyright © 2011 by The Endocrine Society.

Perinatal exposure to parasiticide ivermectin: Long-term effects on reproductive parameters of adult male rats

Ivermectin is one of the most widely used antiparasitic drugs globally. The aim of this study was to evaluate the chronic effects of perinatal exposure to ivermectin on male reproductive parameters in rats. Pregnant rats were treated daily by oral gavage with 0.4 or 1.6 mg kg -1 of ivermectin or vehicle, from gestational day 6 until post-natal day 10. In the adulthood stage, there were significant reductions in the relative testicular weight of rats exposed to the low dose and in relative prostate weight of male rats exposed to the high dose of ivermectin. Furthermore, the animals exposed to the low dose also presented an increased seminal vesicle weight compared to controls. However, neither of the ivermectin doses interfered in daily sperm production, sperm number in testis, or sexual behavior of exposed males. In conclusion, perinatal exposure to ivermectin neither altered the male reproductive system development markedly, nor produced any adverse effects on the parameters evaluated. © 2011 Taylor & Francis.

A study on human error in the interaction with the computer systems

The term human factor is used by professionals of various fields meant for understanding the behavior of human beings at work. The human being, while developing a cooperative activity with a computer system, is subject to cause an undesirable situation in his/her task. This paper starts from the principle that human errors may be considered as a cause or factor contributing to a series of accidents and incidents in many diversified fields in which human beings interact with automated systems. We propose a simulator of performance in error with potentiality to assist the Human Computer Interaction (HCI) project manager in the construction of the critical systems. © 2011 Springer-Verlag.

Cinnamic acid is partially involved in propolis immunomodulatory action on human monocytes

Propolis is a beehive product used in traditional medicine due to its biological properties. It shows a complex chemical composition including phenolics, such as cinnamic acid (Ci). The mechanisms of action of propolis have been the subject of research recently; however, the involvement of Ci on propolis activity was not investigated on immune cells. Ci effects were evaluated on human monocytes, assessing the expression of Toll-like receptors (TLRs), HLA-DR, and CD80. Cytokine production (TNF-α and IL-10) and the fungicidal activity of monocytes were evaluated as well. Data showed that Ci downregulated TLR-2, HLA-DR, and CD80 and upregulated TLR-4 expression by human monocytes. High concentrations of Ci inhibited both TNF-α and IL-10 production, whereas the same concentrations induced a higher fungicidal activity against Candida albicans. TNF-α and IL-10 production was decreased by blocking TLR-4, while the fungicidal activity of monocytes was not affected by blocking TLRs. These results suggest that Ci modulated antigen receptors, cytokine production, and the fungicidal activity of human monocytes depending on concentration, and TLR-4 may be involved in its mechanism of action. Ci seemed to be partially involved in propolis activities. © 2013 Bruno José Conti et al.

Polymorphisms in the MTRN1A gene and their effects on the productive and reproductive traits in buffaloes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Light-curing Time and Aging Effects on the Nanomechanical Properties of Methacrylate- and Silorane-based Restorations

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

Concentrations of and application protocols for hydrogen peroxide bleaching gels: Effects on pulp cell viability and whitening efficacy

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

Low-level laser therapy for osteonecrotic lesions: effects on osteoblasts treated with zoledronic acid

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

Assessing Bacillus subtilis biosurfactant effects on the biodegradation of petroleum products

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cymbopogon martinii essential oil and geraniol at noncytotoxic concentrations exerted immunomodulatory/anti-inflammatory effects in human monocytes

ObjectivesIn traditional medicine, plants have formed the basis of sophisticated systems that have been in existence for thousands of years and still provide mankind with new remedies. Cymbopogon martinii, known as palmarosa, has been used in aromatherapy as a skin tonic due to its antimicrobial properties. It has also used in Ayurvedic medicine for skin problems and to relieve nerve pain. The immunomodulatory action of C.martinii essential oil (EO) and geraniol was evaluated regarding the production of pro- and anti-inflammatory cytokines (tumour necrosis factor (TNF)- and IL-10, respectively) by human monocytes in vitro.MethodsMonocyte cultures were incubated with EO or geraniol. After 18h, cytotoxicity assays were performed using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and cytokine production was determined by ELISA.Key findingsThe variables showed no cytotoxic effects on monocytes. TNF- production was not affected by C.martinii and geraniol, and only the concentration of 5g/ml of C.martinii stimulated its production. On the other hand, all concentrations of C.martinii and geraniol increased IL-10 production by human monocytes.ConclusionsData showed that noncytotoxic concentrations of EO and geraniol exerted an anti-inflammatory action by increasing IL-10 production; moreover, geraniol seemed to be probably responsible for EO immunomodulatory activity in our assay condition.

ORGANIC RESIDUE AND PHOSPHORUS AS CONDITIONERS OF DEGRADED SOIL AND EFFECTS ON THE INITIAL GROWTH OF Dipteryx alata Vog.

In northwestern Sao Paulo State, it was established, in 1965, the hydroelectric station of Ilha Solteira (CESP) that produced extensive degraded areas, from where it was removed the soil superficial layers. For the re-establishment of the vegetation, in areas like these, it is necessary the addition of chemical inputs and organic material. Associating the presence in the area of macrophytes, to the need of recovery of degraded areas and the availability of seeds from native species of Cerrado, it was intended the development of this work, with the objective of evaluating the addition effects of organic residue and phosphorus on the material of degraded soil and on the initial growth of Dipteryx alata, arboreal species of 'cerrado'. The soil material was collected in area of degraded soil by the construction of Ilha Solteira hydroelectric station. The experiment was conducted in two environmental conditions, greenhouse and plenty of sun. The treatments consisted of four phosphorus doses (0, 100, 200 and 300 mg dm(-3) of P2O5), with or without macrophytes addition, with 16 treatments and 10 repetitions each one. The used macrophytes, collected at Jupia hydroelectric station, in Mato Grosso do Sul state, were dried, sliced, incorporated to the soil material and incubated during 60 days. The seeds of Dipteryx alata, collected around of the area, were sowed in washed sand and after 60 days introduced in the treatments. The plants were appraised monthly for height, stem diameter and leaves chlorophyll. After 210 days, the plants were collected and evaluated for fresh and dry weight of aerial part and radicular system and the soil material was evaluated for fertility and microbial activity by the carbon of liberated CO2. The organic residue, incorporated to the material of soil degraded, positively affects the soil fertility and the soil microbial activity. The applied phosphorus doses influenced the behavior of Ca, SB, H+Al and CTC, when applied in the absence of organic residue, it promoted significant and linear increments for values of potential acidity, and indicated the organic residue importance. The initial growth of the Dipteryx alata was favored by the protected cultivation, for the incorporation of organic residue and for the phosphorus addition to the soil. At the end although the material of degraded soil comes as good perspective for disposal of this residue, studies about the field conditions are necessary.

Congestion Effects on Regional & System Emission and Consumers Allocated Cost

This paper considers the congestion effects on emission and consumers' allocated cost. In order to consider some environmental and operational effects of congestion, an environmental constrained active-reactive optimal power flow (AROPF) considering capability curve is presented. On outage conditions, the total cost of the system will increase. On the other hand in power systems, the operating cost and system emission have conflicted objectives, then it may be concluded that the outage in the system may lead to a total emission decrease. In this paper the famous Aumann-Shapley method is used as a pricing methodology. Two case studies such as 14-bus and US-bus IEEE test systems are conducted. Results demonstrate that, although the line outage in power systems leads to increase the total cost, the amount of emission depending on the place where the outage occurs can be more than, less than or equal to the normal conditions' emission. Also results show that although from power sellers' standpoint the well-known Aumann-Shapley method is a precise pricing method to cover the incurred cost with an acceptable error that can show the real effect of congestion on consumers' cost, from consumers' standpoint it is not a good method for cost allocation, because some consumers will face with an increase in cost and the others will face with a decrease on their cost.

Differential environmental impacts on small and medium size rivers from center of São Paulo State, Brazil, and regional management perspectives

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O

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

Diurnal effects on spearmint oil yields and composition

'Native'spearmint (Mentha spicata L.) is one of the two spearmint species grown commercially in the United States and other countries for essential oil production. The two major constituents of spearmint oil are carvone and limonene. It is not known if the essential oil yield (content) and composition of spearmint oil are affected by diurnal variation, and when it would be the best time for harvesting flowering spearmints within a 24h period. Therefore, the objective of this study was to evaluate the effect of diurnal variation on yield and composition of spearmint 'Native'essential oil for the environmental conditions of Northern Wyoming, at elevation 1170 m above the sea level. The experiment was conducted on a 3-year old well established spearmint plantation. The harvest times were every 2 h within a 24-h period: 7:00 AM, 9:00 AM, 11:00AM, 1:00 PM, 3:00 PM, 5:00 PM, 7:00 PM, 9:00 PM, 11:00 PM, 1:00 AM, 3:00 AM, and 5:00 AM. Essential oil yield varied from 0.96 to 1.47 g of oil per 100 g of dry herbage; the maximum oil yield was obtained at 9:00 AM and the minimum at 7:00 PM. The concentration of carvone in the oil varied from 44.1% (at 1:00 PM) to 66.4% (at 9:00 PM) of the total oil. However, the yield of carvone (a function of oil yield and carvone concentration in the oil) was the highest at 3:00 AM and the lowest at 1:00 PM. The concentration of limonene (10.7-15.8% of the oil) was the highest at 7:00 PM and the lowest at 1:00 PM, whereas the yield of limonene was the highest at 9:00 PM. For best essential oil yields, flowering spearmint should be harvested at around 9:00 AM. However, to obtain oil with high carvone concentration, spearmint should be harvested at 9:00 PM. Harvests at 1:00 PM would result in spearmint oil with low concentrations of both carvone and limonene, and hence, should be avoided. (C) 2014 Elsevier B.V. All rights reserved.