Local order around rare earth ions during the devitrification of oxyfluoride glasses

Erbium L-3-edge extended x-ray absorption fine structure (EXAFS) measurements were performed on rare earth doped fluorosilicate and fluoroborate glasses and glass ceramics. The well known nucleating effects of erbium ions for the crystallization of cubic lead fluoride (based on x-ray diffraction measurements) and the fact that the rare earth ions are present in the crystalline phase (as indicated by Er3+ emission spectra) seem in contradiction with the present EXAFS analysis, which indicates a lack of medium range structural ordering around the Er3+ ions and suggests that the lead fluoride crystallization does not occur in the nearest neighbor distance of the rare earth ion. Molecular dynamics simulations of the devitrification process of a lead fluoride glass doped with Er3+ ions were performed, and results indicate that Er3+ ions lower the devitrification temperature of PbF2, in good agreement with the experimental results. The genuine role of Er3+ ions in the devitrification process of PbF2 has been investigated. Although Er3+ ions could indeed act as seeds for crystallization, as experiments suggest, molecular dynamics simulation results corroborate the experimental EXAFS observation that the devitrification does not occur at its nearest neighbor distance. (c) 2008 American Institute of Physics.

Theoretical studies on the stability of N-methylformamide in both liquid and gas phases

Ab initio (restricted Hartree-Fock and DFT) and molecular mechanics calculations at MM2 level were performed for N-methylformamide (NMF) molecule and for three dimers in order to investigate the relative stability of the cis and trans conformers. The ab initio calculations show that no intramolecular interaction is relevant for the stability of the conformers explored. The trans conformer is the most stable. The MM calculations revealed that a double H-bonded cyclic cis-cis dimer is the most stable among the studied dimers, followed by a 'linear' H-bonded trans-trans dimer. This 'linear' dimer, however, is prevalent in the liquid phase. (c) 2006 Elsevier B.V. All rights reserved.

Toxicidade de fármacos nitrofurânicos

During the structural designing of new drugs, it is possible predict the influence of specific chemical groups on pharmacological activity. Among these, the nitro group has potential antiparasitic activity, being present in many antimicrobial drugs, such as metronidazole, nitrofurazone, furazolidone, oxamniquine and chloramphenicol. Also, the introduction of the nitro group into a molecule can modify the physicochemical and electronic properties of the substance. Besides antimicrobial drugs, this group is also found in other drug classes, such as antiulcer, anti-inflamatory and anxiolytic. However, the use of the nitro group in drug design has encountered restrictions, due to the associated toxicity. This article is a review of the toxicity of nitrofuran compounds, as well the possible mechanisms involved and the strategy of latentiation by molecular modification to decrease their toxicity.

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.

Possible mechanism by which zinc protects the testicular function of rats exposed to cigarette smoke

Background: The aim of this study was to evaluate the changes in testicular function of rats due to cigarette smoke exposure and the possible mechanism by which zinc protects against these alterations. Methods: MaleWistar rats (60 days old) were randomly divided into 3 groups: control (G1, n = 10); exposed to cigarette smoke (G2, n = 10; 20 cigarettes/day/9 weeks) and exposed to cigarette smoke and supplemented with zinc (G3, n = 8; 20 cigarettes/day/9 weeks; 20 mg/kg zinc chloride daily for 9 weeks, by gavage). After the treatment period, the animals were euthanized, and materials were collected for analyses. Results: G2 rats showed a reduction in body mass; impaired sperm concentration, motility, morphology and vitality; and increased malonaldehyde and thiol group levels and superoxide dismutase activity as compared to G1. Zinc prevented the reduction of sperm concentration and the excessive increase of lipid peroxidation and induced an increase in plasma testosterone levels, wet weight of testis and thiol group concentration. Conclusions: Exposure to cigarette smoke led to harmful effects on testicular function at least partially due to the exacerbation of oxidative stress. Supplementary zinc had an important modulator/protector effect on certain parameters. The mechanism of zinc protection can be through an increase of SH concentration. Thus, zinc supplementation may be a promising addition to conventional treatments for male infertility related to smoking. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.

Biophysical characterization of the recombinant importin-α from neurospora crassa

Neurospora crassa has been widely used as a model organism and contributed to the development of biochemistry and molecular biology by allowing the identification of many metabolic pathways and mechanisms responsible for gene regulation. Nuclear proteins are synthesized in the cytoplasm and need to be translocated to the nucleus to exert their functions which the importin-α receptor has a key role for the classical nuclear import pathway. In an attempt to get structural information of the nuclear transport process in N. crassa, we present herein the cloning, expression, purification and structural studies with N-terminally truncated IMPα from N. crassa (IMPα-Nc). Circular dichroism analysis revealed that the IMPα-Nc obtained is correctly folded and presents a high structural conservation compared to other importins-α. Dynamic light scattering, analytical size-exclusion chromatography experiments and molecular dynamics simulations indicated that the IMPα-Nc unbound to any ligand may present low stability in solution. The IMPα-Nc theoretical model displayed high similarity of its inner concave surface, which binds the cargo proteins containing the nuclear localization sequences, among IMPα from different species. However, the presence of non-conserved amino acids relatively close to the NLS binding region may influence the binding specificity of IMPα-Nc to cargo proteins. Copyright © 2012 Bentham Science Publishers. All Rights Reserved.

Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. © 2013 Moura et al; licensee BioMed Central Ltd.

Androgen deprivation from pre-puberty to peripuberty interferes in proteins expression in pubertal and adult rat epididymis

Few studies have focused on experimental testosterone deprivation in immature animals. Therefore, this study used sexually immature rats aiming to evaluate the testes and epididymis histology and proteins expression in these organs on PND50 and 75, after premature antiandrogen exposure, from PND21 to 44. Although the androgen deprivation from pre-puberty up to peripuberty did not alter the histological organization of the testes and epididymis either at puberty or at adulthood, the treatment impaired the expression of specific proteins in epididymal tissue at puberty and adulthood (androgen receptor, calmodulin, Rab11A). These changes may be related to impaired epididymal function, sperm quality and fertility capacity as observed in a previous study. Further studies are necessary to better investigate the molecular mechanisms involved in the impairment on reproductive competence of male rats after precocious hormonal injury. © 2013 Elsevier Inc.

Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling

The cysteine proteinase inhibitor cystatin C inhibited RANKL-stimulated osteoclast formation in mouse bone marrow macrophage cultures, an effect associated with decreased mRNA expression of Acp5, Calcr, Ctsk, Mmp9, Itgb3, and Atp6i, without effect on proliferation or apoptosis. The effects were concentration dependent with half-maximal inhibition at 0.3 μM. Cystatin C also inhibited osteoclast formation when RANKL-stimulated osteoclasts were cultured on bone, leading to decreased formation of resorption pits. RANKL-stimulated cells retained characteristics of phagocytotic macrophages when cotreated with cystatin C. Three other cysteine proteinase inhibitors, cystatin D, Z-RLVG-CHN2 (IC50 0.1 μM), and E-64 (IC 50 3 μM), also inhibited osteoclast formation in RANKL-stimulated macrophages. In addition, cystatin C, Z-RLVG-CHN2, and E-64 inhibited osteoclastic differentiation of RANKL-stimulated CD14+ human monocytes. The effect by cystatin C on differentiation of bone marrow macrophages was exerted at an early stage after RANKL stimulation and was associated with early (4 h) inhibition of c-Fos expression and decreased protein and nuclear translocation of c-Fos. Subsequently, p52, p65, IκBα, and Nfatc1 mRNA were decreased. Cystatin C was internalized in osteoclast progenitors, a process requiring RANKL stimulation. These data show that cystatin C inhibits osteoclast differentiation and formation by interfering intracellularly with signaling pathways downstream RANK. © FASEB.

Análise conformacional dos petídeos protonectina e protonectina (1-6), isolados e em associação, em mistura TFE-água

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Desenvolvimento e implementação de modelos para simulação de dados SNPs

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Tailoring Thermal Transport Property of Graphene through Oxygen Functionalization

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estudo da Estrutura da Proteína SH do Vírus Sincicial Respiratório Humano: análise funcional da estrutura pentamérica por ferramentas de bioinformática

Pós-graduação em Biofísica Molecular - IBILCE

The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species

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

Estrutura eletrônica de derivados de politieno[3,4-b]-tiofeno-co-benzoditiofeno para aplicação em camadas ativas de células solares orgânicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)