Enantiomeric conformation controls rate and yield of photoinduced electron transfer in DNA sensitized by Ru(II) Dipyridophenazine complexes

Photosensitized oxidation of guanine is an important route to DNA damage. Ruthenium polypyridyls are very useful photosensitizers as their reactivity and DNA-binding properties are readily tunable. Here we show a strong difference in the reactivity of the two enantiomers of [Ru(TAP)2(dppz)]2+, by using time-resolved visible and IR spectroscopy. This reveals that the photosensitized one-electron oxidation of guanine in three oligonucleotide sequences proceeds with similar rates and yields for bound delta-[Ru(TAP)2(dppz)]2+, whereas those for the lambda enantiomer are very sensitive to base sequence. It is proposed that these differences are due to preferences of each enantiomer for different binding sites in the duplex.

Molecular conformation of the racemic indan derivative (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxamide

This paper presents the structural characterization of the indan derivative (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxamide, which was unambiguously determined by X-ray diffraction (XRD) to be a racemate (R/S: 50/50) crystallizing in an achiral crystal structure (P2(1)/c, a = 9.3180(1) , b = 7.9070(2) , c = 19.7550(4) , beta = 103.250(1)A degrees, V = 1416.75(5) (3) and Z = 4). The diastereomers are related by the inversion symmetry and linked by H bond forming a dimer. The crystal packing is stabilized by hydrogen bonds, including the classical one responsible for the formation of centrosymmetric dimers, and non-classical ones involving C-H center dot center dot center dot O and C-H center dot center dot center dot pi-aryl interactions. The intra and intermolecular geometry of the title compound is compared to the (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxylic acid one, which also present an achiral crystal structure from racemates (R/S: 50/50). The two indan derivatives crystallize in a very similar unit cell.

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 (NH(3)). 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, C-terminal 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 NH(3), 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 NH(3.) We present 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)

Experimental and theoretical investigation of molecular structure and conformation of the 4-isopropylthioxanthone

In this study, the molecular structure and conformational analyses of the 4-isopropylthioxanthone (4-ITX) are reported according to experimental and theoretical results. The compound crystallizes in the centrosymmetric P (1) over bar space group with only one molecule in the asymmetric unit, presenting the most stable conformation, in which the three fused-rings adopt a planar geometry, and the isopropyl group assumes a torsional angle with less sterical hindrance. The structural and conformational analyses were performed using theoretical calculations such as Hartree-Fock (HF), DFT method in combination with 6-311G(d,p) and 6-31++G(d,p) and the results were compared with infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The supramolecular assembly of 4-ITX is kept by non-classical C-H center dot center dot center dot O hydrogen bonds and weak interactions such as pi-pi stacking. 4-ITX was also studied by (1)H and (13)C NMR spectroscopy. UV-Vis absorption spectroscopic properties of the 4-ITX showed the long-wavelength maximum shifts towards high energy when the solvent polarity increases. (C) 2011 Elsevier B.V. All rights reserved.

Studies towards the identification of putative bioactive conformation of potent vasodilator arylidene N-acylhydrazone derivatives

In this report we disclose the synthesis, vasodilatory activity, and identification of bioactive conformation of new N-acylhydrazone and N-methyl-N-acylhydrazone derivatives, structurally designed by bioisosteric replacements of previously described cardioactive compounds LASSBio-294 and its N-methyl derivative LASSBio-785. Some of these novel derivatives presented improved vasorelaxant properties, being new cardiovascular drug candidates. (C) 2009 Elsevier Masson SAS. All rights reserved.

Diphtheria toxoid conformation in the context of its nanoencapsulation within liposomal particles sandwiched by chitosan

Chitosan (alpha alpha-(1-4)-amino-2-deoxy-beta beta-D-glucan) is a deacetylated form of chitin, a polysaccharide from crustacean shells. Its unique characteristics, such as positive charge, biodegradability, biocompatibility, nontoxicity, and rigid structure, make this macromolecule ideal for an oral vaccine delivery system. We prepared reverse-phase evaporation vesicles (REVs) sandwiched by chitosan (Chi) and polyvinylic alcohol (PVA). However, in this method, there are still some problems to be circumvented related to protein stabilization. During the inverted micelle phase of protein nanoencapsulation, hydrophobic interfaces are expanded, leading to interfacial adsorption, followed by protein unfolding and aggregation. Here, spectroscopic and immunological techniques were used to ascertain the effects of the Hoffmeister series ions on diphtheria toxoid (Dtxd) stability during the inverted micelle phase. A correlation was established between the salts used in aqueous solutions and the changes in Dtxd solubility and conformation. Dtxd alpha alpha-helical content was quite stable, which led us to conclude that encapsulation occurred without protein aggregation or without exposition of hydrophobic residues. Dtxd aggregation was 98% avoided by the kosmotropic, PO

The interdisciplinary perspective on International Law and International Relations by Anne-Marie Slaughter

Este artigo consiste em uma resenha crítica sobre a reflexão de Anne-Marie Slaughter para uma aproximação interdisciplinar entre Direito Internacional e Relações Internacionais. Slaughter tem sido apontada, internacionalmente, como uma das protagonistas neste debate acadêmico, e sua obra é indicada como uma das mais influentes na academia dos Estados Unidos da América, no século XX. Em tempos de aproximação entre juristas e internacionalistas no Brasil, o artigo procura contribuir com a contextualização da produção da autora, bem como elucidar os momentos de influência das suas atividades em outros centros de discussão e produção. A proposta principal deste artigo é, assim, favorecer um mapeamento histórico e contextualizado da chamada para o debate interdisciplinar entre Direito Internacional e Relações Internacionais, a partir dos trabalhos de um de seus pivôs na academia nos Estados Unidos.

Antimicrobial resistance of Salmonella serotypes isolated from slaughter-age pigs and environmental samples

The aim of this study was to determine the antimicrobial resistance patterns of Salmonella strains isolated from slaughter-age pigs and environmental samples collected at modern swine raising facilities in Brazil. Seventeen isolates of six serotypes of Salmonella enterica subsp. enterica were isolated out of 1,026 collected samples: Salmonella Typhimurium (1), Salmonella Agona (5), Salmonella Sandiego (5), Salmonella Rissen (1), Salmonella Senftenberg (4), and Salmonella Javiana (1). Resistance patterns were determined to extended-spectrum penicillin (ampicillin), broad-spectrum cephalosporins (cefotaxime and ceftriaxone), aminoglycosides (streptomycin, neomycin, gentamicin, amikacin, and tobramycin), narrow-spectrum quinolone (nalidixic acid), broad-spectrum quinolone (ciprofloxacin and norfloxacin), tetracycline, trimethoprim, and chloramphenicol. Antimicrobial resistance patterns varied among serotypes, but isolates from a single serotype consistently showed the same resistance profile. All isolates were resistant to tetracycline, streptomycin, and nalidixic acid. One isolate, Salmonella Rissen, was also resistant to cefotaxime and tobramycin. All serotypes were susceptible to ceftriaxone, norfloxacin, ciprofloxacin, ampicillin, gentamicin, and chloramphenicol. The high resistance to tetracycline and streptomycin may be linked to their common use as therapeutic drugs on the tested farms. No relation was seen between nalidixic acid and fluoroquinolone resistance.

Prevalence of pigs infected by Salmonella typhimurium at slaughter after an enterocolitis outbreak

A cross-sectional study was performed to estimate the prevalence of slaughter pigs infected by Salmonella typhimurium after an enterocolitis outbreak in a commercial pig farm, which was characterised by diarrhoea during the growing phase. Anatomopathological and histopathological findings were suggestive of salmonellosis, which was further confirmed by isolation of S. typhimurium from organs and faeces samples from diseased animals. Ileocolic lymph nodes were aseptically collected from 43 pigs during slaughter procedures. The estimated prevalence of Salmonella-infected pigs was 53.48% [confidence interval (CI): 42.94:64.02%]. This finding demonstrates that the carriage of S. typhimurium at slaughter might be high if pigs originate from a batch previously affected by Salmonella-enterocolitis outbreak at the pre-harvest pork production chain. (c) 2005 Elsevier B.V. All rights reserved.

Effects of age at slaughter and sire genotype on fatness, muscularity, and the quality of meat from ram lambs born to Romney ewes

Ram lambs (n = 356) born to Romney ewes and sired by a range of straightbred or crossbred sires were evaluated for carcass composition and, for a subsample (n = 236), some meat quality characteristics over a period of 4 years. Within each year, 2 to 4 sire genotypes, including Romney controls, were evaluated at 2 slaughter ages (5-9 months and 10-11 months). Weight-adjusted carcass length was greater for lambs with some East Friesian or Finn genes, but no differences were found in dressing-out percent. At a constant carcass weight, carcass fatness (fat depths and leg dissectible fat) was lower in lambs with East Friesian, Texel, or Finn genes. Meat yield at a constant weight tended to be greatest in sire groups that were least fat, and M:B ratio in the femur region was highest in lambs with Texel genes and, to a lesser extent, those with Poll Dorset genes. Leg muscularity in the femur region generally paralleled differences in M:B, except in a comparison of East Friesian-cross and Romney lambs where the former had lower muscularity but slightly better M:B. Lambs slaughtered at the older age for each year had longer and leaner carcasses at the same weight, possibly because they had been taken part way through a winter or because of slower growth rates leading up to slaughter. Meat quality characteristics differed little between the genotype groups, but for 2 of 3 years, meat from the semimembranosus muscle of lambs in the older slaughter lot was significantly tougher.

Effects of energy level in finisher diets and slaughter age of on the performance and carcass yield in broiler chickens

Male broilers were used to evaluate the effects of different energy levels in finisher diets and age of slaughter on performance, production pattern and carcass yield. Experimental design was a 2x3 factorial arrangement: energy level (ME) in the finisher diet (3,200 and 3,600 kcal ME/kg) and age of slaughter (42, 49 and 56 days), resulting in six treatments with four replicates. The finisher diet was fed only in the last week of the growing period. Characteristics evaluated were feed consumption (FC), body weight gain (WG), feed conversion (FC), energy intake (EI), caloric conversion (CC), efficiency production index, production pattern, and carcass yield. The results showed better WG and CC for broilers fed 3,200 kcal ME/kg finisher diet. Broilers slaughtered at 42 and 49 days of age had better performance and higher annual production than broilers slaughtered at 56 days of age. Carcass yield was influenced by slaughter age and better breast yield was seen at 49 and 56 days than at 42 days of age. It was concluded that 3,200 kcal ME/kg induced the best overall performance. Poultry houses were efficiently used when broilers were slaughtered at 42 days of age. Meat:bone ratio was improved for broilers slaughtered at 49 and 56 days of age.

Genetic associations of sexual precocity with growth traits and visual scores of conformation, finishing, and muscling in Nelore cattle

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

Genetic associations of conformation, finishing precocity and muscling visual scores with mature weight in Nelore cattle

Were estimate (co)variance and genetic associations between conformation, finishing precocity and muscling visual scores measured at weaning (SCW, SFW and SMW, respectively) and yearling (SCY. SFY and SMY, respectively) with mature weight (MW) in Nelore cows, in order to predict the possible changes that inclusion of visual scores in beef cattle selection indices would bring to female mature weight. The data set contained records of 36,757 females, born between 1993 and 2006, belonging to the Jacarezinho cattle raising farm. (Co)variance components were estimated by bivariate animal models using Bayesian inference method through Gibbs sampling, assuming a linear model for MW and a nonlinear (threshold) model for conformation, finishing precocity and muscling visual scores. The first 10,000 rounds were considered as the burn-in period and discarded. The posterior means of direct heritability distributions were: 0.16 +/- 0.02 (SCW); 0.20 +/- 0.02 (SFW); 0.19 +/- 0.02 (SMW); 0.24 +/- 0.02 (SCY); 0.31 +/- 0.02 (SFY); 0.32 +/- 0.02 (SMY) and 0.46 +/- 0.04 (MW). Estimates of genetic correlations between visual scores and MW were positive and moderate, ranging from 0.27 +/- 0.06 to 0.36 +/- 0.04. Visual scores and MW should respond favorably to direct selection. Mature weight can be used in Nelore breeding programs designed to monitor the cows' size. Selection of animals with higher conformation, finishing precocity and muscling scores, especially at yearling, should promote an increase in cows' mature weight. (c) 2010 Elsevier B.V. All rights reserved.

Características de carcaça e parâmetros de qualidade de carne de bovinos jovens alimentados com grãos úmidos de milho ou sorgo

Objetivou-se, com este estudo, verificar as diferenças nas características da carcaça, assim como nos parâmetros qualitativos da carne de novilhos jovens alimentados com dietas contendo silagem de grão úmido de milho ou sorgo. Foram utilizados dois tratamentos experimentais, nos quais a dieta total possuía como ingrediente energético principal a silagem de grão úmido de milho (TMU) ou a silagem de grão úmido de sorgo (TSU). Trinta e seis novilhos inteiros F1 Red Angus ´ Nelore com 8 meses de idade e peso médio inicial de 240 kg foram alimentados durante 172 dias e abatidos em seguida. O experimento foi conduzido em um delineamento inteiramente casualizado. Houve similaridade para o ganho de peso diário, ganho de peso total e peso final de abate. Não foi verificada diferença para o rendimento de carcaça, assim como para os rendimentos de dianteiro, traseiro e ponta de agulha. Os tratamentos TMU e TSU não afetaram os escores para cor, conformação e acabamento de gordura da carcaça. Marmorização, área de olho-de-lombo, espessura de gordura subcutânea e gordura perirenal, assim como as avaliações químicas da carne (proteína bruta e lipídios totais), também não diferiram entre os tratamentos. As dietas experimentais não afetaram a maciez da carne, assim como as perdas físicas no processo de cozimento (gotejamento e evaporação). Concluiu-se que a substituição integral da silagem de grão úmido de milho pela silagem de grão úmido de sorgo não alterou as características qualitativas e quantitativas da carcaça de bovinos jovens em confinamento.

Características de carcaça de caprinos de cinco grupos raciais criados em confinamento

Este trabalho foi realizado com o objetivo de avaliar a influência do grupo racial e da condição sexual nas características da carcaça de caprinos jovens criados em confinamento. Foram utilizados 91 animais, 52 machos e 39 fêmeas, pertencentes a cinco grupos raciais: Alpino, ½Boer + ½Alpino, ½Anglo Nubiano + ½Alpino, ¾Boer + ¼Alpino, e ½Anglo Nubiano + ¼Boer + ¼Alpino. Foi tomado o peso ao jejum, no dia do abate, após 24 horas de jejum de sólidos. Foram tomadas medidas biométricas e de carcaça, objetiva e subjetivamente. O grupo racial influenciou a altura de cernelha, o comprimento interno e externo da carcaça e o comprimento de perna, que foram maiores nos animais Alpinos, bem como a largura do peito, o escore corporal, os índices de compacidade da carcaça e da perna e a cobertura de gordura da carcaça, que foram melhores nos animais com grau de sangue Boer. Animais machos tiveram maior altura de cernelha, medidas da estérnebra com ultrassom, comprimento interno da carcaça, comprimento de perna, profundidade dos tecidos na altura da 3ª e 4ª estérnebras tomadas na carcaça. Nas demais características corporais avaliadas, não foram encontradas diferenças entre grupos raciais e sexo dos animais. O cruzamento do grupo Boer com Alpino reduz o comprimento das carcaças e aumenta a cobertura de gordura e a quantidade de tecidos depositados, mas não influencia o desempenho do animal.