MPO Inhibitors Selected by Virtual Screening

The hemeprotein myeloperoxidase (MPO) participates in innate immune defense through its ability to generate potent microbicidal oxidants. However, these oxidants are also key mediators of the tissue damage associated with many inflammatory diseases. Thus, there is considerable interest in developing therapeutically useful MPO inhibitors. Here, we used structure-based drug design (SBDD) and ligand-based drug design (LBDD) to select for potentially new and selective MPO inhibitors. A pharmacophore model was developed based on the crystal structure of human MPO in complex with salicylhydroxamic acid (SHA), a known inhibitor of the enzyme. The pharmacophore model was used to screen the ZINC database for potential ligands, which were further filtered on the basis of their physical-chemical properties and docking score. The filtered compounds were visually inspected, and nine were purchased for experimental studies. Surprisingly, almost all of the selected compounds belonged to the aromatic hydrazide class, which had been previously described as MPO inhibitors. The compounds selected by virtual screening were shown to inhibit the chlorinating activity of MPO; the top four compounds displayed IC(50) values ranging from 1.0 to 2.8 mM. MPO inactivation by the most effective compound was shown to be irreversible. Overall, our results show that SBDD and LBDD may be useful for the rational development of new MPO inhibitors.

Ability of Ru complexes for ROMP tuned through a combination of phosphines and amines

Polynorbonerne with high molecular weight was obtained via ring opening metathesis polymerization using catalysts derived from [RuCl(2)(PPh(2)Bz)(2) L] (1 for L = PPh(2) Bz; 2 for L = piperidine) type of complexes when in the presence of ethyl diazoacetate in CHCl(3). The polymer precipitated within a few minutes at 50 degrees C when using 1 with ca. 50% yield ([NBE]/[Ru] = 5000). Regarding 2, for either 30 min at 25 C or 5 min at 50 degrees C, more than 90% of yields are obtained; and at 50 C for 30 min a quantitative yield is obtained. The yield and PDI values are sensitive to the [NBE]/[Ru] ratio. The reaction of 1 with either isonicotinamide or nicotinamide produces six-coordinated complexes of [RuCl(2)(PPh(2)Bz)(2)(L)(2)] type, which are almost inactive and produce only small amounts of polymers at 50 C for 30 min. Thus, we Concluded that the novel complexes show very distinct reactivities for ROMP of NBE. This has been rationalized on account of a combination of synergistic effects of the phosphine-amine ancillary ligands. (C) 2009 Elsevier B.V. All rights reserved.

Variations in the sensitivity of different primers for detecting Wolbachia in Anastrepha (diptera: tephritidae)

Wolbachia are endosymbiont bacteria of the family Rickettsiacea that are widespread in invertebrates and occur between 20% and 60% of Neotropical insects. These bacteria are responsible for reproductive phenomena such as cytoplasmic incompatibility, male killing, feminization and parthenogenesis. Supergroups A and B of Wolbachia are common in insects and can be identified using primers for 16S rDNA, ftsZ and wsp; these primers vary in their ability to detect Wolbachia. The ftsZ primer was the first primer used to detect Wolbachia in Anastrepha fruit flies. The primers for 16S rDNA, ftsZ and wsp and the corresponding PCR conditions have been optimized to study the distribution of Wolbachia and their effect on the biology of Anastrepha in Brazil. In this work, we examined the ability of these primers to detect Wolbachia in Anastrepha populations from three regions in the State of São Paulo, southeastern Brazil. All of the samples were positive for Wolbachia supergroup A when screened with primers for 16S A rDNA and wsp A; the wsp B primer also gave a positive result, indicating cross-reactivity. The ftsZ primer showed a poor ability to detect Wolbachia in Anastrepha and generated false negatives in 44.9% of the samples. These findings indicate that reliable PCR detection of Wolbachia requires the use of primers for 16S rDNA and wsp to avoid cross-reactions and false negatives, and that the ftsZ primer needs to be redesigned to improve its selectivity.

Sex ratio and morphological characteristics of rufous gnateaters, Conopophaga lineata (Aves, Passeriformes) in Atlantic forest fragments

Unequal sex ratios lead to the loss of genetic variability, decreasing the viability of populations in the long term. Anthropogenic activities often disturb the natural habitats and can cause alterations in sex ratio and morphological characteristics of several species. Forest fragmentation is a major conservation concern, so that understanding its effects in natural populations is essential. In this study, we evaluated the sex ratio and the morphological characteristics of Rufous Gnateaters (Conopophaga lineata (Wied, 1831)) in small and large forest fragments in Minas Gerais, Brazil. Birds (n = 89) were sexed by plumage characteristics and molecular markers. The molecular analysis showed that plumage is not a totally reliable method for sexing Rufous Gnateaters. We observed that sex ratio did not differ between large and small forest fragments, but birds in small fragments had larger wings and tarsus. Wing and tarsus changes may affect the movement ability of individuals within and among forest fragments. In conclusion, Rufous Gnateaters have been able to survive in both small and large Atlantic rain forest fragments without altering their sex ratio, but morphological changes can be prejudicial to their long term survival.

Efeitos da angiotensina-I e isquemia na recuperação funcional em corações isolados

FUNDAMENTO: A ressuscitação de parada cardíaca pode apresentar disfunção miocárdica determinada pelo tempo da isquemia, e a inibição da enzima conversora de angiotensina (ECA) pode reduzir a disfunção cardíaca durante a reperfusão. OBJETIVO: Investigar os efeitos da angiotensina-I e diferentes períodos de isquemia na recuperação funcional em corações de ratos isolados. MÉTODOS: Os corações isolados de ratos Wistar (n = 45; 250-300 g) foram submetidos a diferentes períodos de isquemia global (20, 25 ou 30 min) e reperfundidos (30 min) com o tampão Krebs-Henseleit, ou com a adição de 400 nmol/L de angiotensina-I, ou com 400 nmol/L de angiotensina-I + 100 µmol/L de captopril durante o período de reperfusão. RESULTADOS: A derivada positiva máxima de pressão (+dP/dt max) e o produto frequência-pressão foram reduzidos nos corações expostos à isquemia de 25 min (~ 73%) e à isquemia de 30 min (~ 80%) vs. isquemia de 20 min. A pressão diastólica final do ventrículo esquerdo (PDFVE) e a pressão de perfusão (PP) foram aumentadas nos corações expostos à isquemia de 25 min (5,5 e 1,08 vezes, respectivamente) e à isquemia de 30 min (6 e 1,10 vezes, respectivamente) vs. isquemia de 20 min. A angiotensina-I ocasionou uma diminuição no +dP/dt max e no produto frequência-pressão (~ 85-94%) em todos os períodos de isquemia e um aumento na PDFVE e na PP (6,9 e 1,25 vezes, respectivamente) apenas na isquemia de 20 min. O captopril foi capaz de reverter parcial ou completamente os efeitos da angiotensina-I na recuperação funcional nas isquemias de 20 e 25 min CONCLUSÃO: Os dados sugerem que a angiotensina-II participa direta ou indiretamente no dano pós-isquêmico e que a capacidade de um inibidor da ECA atenuar esse dano depende do tempo de isquemia.

Emprego de regras de associação para extração de padrões mercadológicos de touros Nelore com avaliação genética

Objetivou-se com este trabalho utilizar regras de associação para identificar forças de mercado que regem a comercialização de touros com avaliação genética pelo programa Nelore Brasil. Essas regras permitem evidenciar padrões implícitos nas transações de grandes bases de dados, indicando causas e efeitos determinantes da oferta e comercialização de touros. Na análise foram considerados 19.736 registros de touros comercializados, 17 fazendas e 15 atributos referentes às diferenças esperadas nas progênies dos reprodutores, local e época da venda. Utilizou-se um sistema com interface gráfica usuário-dirigido que permite geração e seleção interativa de regras de associação. Análise de Pareto foi aplicada para as três medidas objetivas (suporte, confiança e lift) que acompanham cada uma das regras de associação, para validação das mesmas. Foram geradas 2.667 regras de associação, 164 consideradas úteis pelo usuário e 107 válidas para lift ≥ 1,0505. As fazendas participantes do programa Nelore Brasil apresentam especializações na oferta de touros, segundo características para habilidade materna, ganho de peso, fertilidade, precocidade sexual, longevidade, rendimento e terminação de carcaça. Os perfis genéticos dos touros são diferentes para as variedades padrão e mocho. Algumas regiões brasileiras são nichos de mercado para touros sem registro genealógico. A análise de evolução de mercado sugere que o mérito genético total, índice oficial do programa Nelore Brasil, tornou-se um importante índice para comercialização dos touros. Com o uso das regras de associação, foi possível descobrir forças do mercado e identificar combinações de atributos genéticos, geográficos e temporais que determinam a comercialização de touros no programa Nelore Brasil.

Screening of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase enzyme inhibitors

The inhibitory activity of crude extracts of Meliaceae and Rutaceae plants on glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) enzyme from Trypanosoma cruzi was evaluated at 100 μg/mL. Forty-six extracts were tested and fifteen of them showed significant inhibitory activity (IA % > 50). The majority of the assayed extracts of Meliaceae plants (Cedrela fissilis, Cipadessa fruticosa and Trichilia ramalhoi) showed high ability to inhibit the enzymatic activity. The fractionation of the hexane extract from branches of C. fruticosa led to the isolation of three flavonoids: flavone, 7-methoxyflavone and 3',4',5',5,7-pentamethoxyflavone. The two last compounds showed high ability to inhibit the gGAPDH activity. Therefore, the assayed Meliaceae species could be considered as a promising source of lead compounds against Chagas' disease.

Artigos científicos como recurso didático no ensino superior de Química

Chemistry teachers increasingly use research articles in their undergraduate courses. This trend arises from current pedagogical emphasis on active learning and scientific process. In this paper, we describe some educational experiences on the use of research articles in chemistry higher education. Additionally, we present our own conclusions on the use of such methodology applied to a scientific communication course offered to undergraduate chemistry students at the University of São Paulo, Brazil.

Formação docente no ensino superior de Química: contribuições dos programas de aperfeiçoamento de ensino

The literature on the challenges of teacher education in undergraduate chemistry teaching is limited. In the present study, the application of didactic proposals elaborated by two authors of this paper, graduate students and teaching assistants of the teaching improvement program at University of São Paulo, was investigated in terms of their contribution to the teaching assistants' education and undergraduate students' receptivity toward them. Such proposals were based on the jigsaw cooperative learning strategy and applied in two undergraduate courses. The results indicate students' good receptivity and suggest their importance to teaching assistants' education.

The ability of the BANA test to detect different levels of P. gingivalis, T. denticola and T. forsythia

The aim of this study was to evaluate the ability of the BANA Test to detect different levels of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia or their combinations in subgingival samples at the initial diagnosis and after periodontal therapy. Periodontal sites with probing depths between 5-7 mm and clinical attachment level between 5-10 mm, from 53 subjects with chronic periodontitis, were sampled in four periods: initial diagnosis (T0), immediately (T1), 45 (T2) and 60 days (T3) after scaling and root planing. BANA Test and Checkerboard DNA-DNA hybridization identified red complex species in the subgingival biofilm. In all experimental periods, the highest frequencies of score 2 (Checkerboard DNA-DNA hybridization) for P. gingivalis, T. denticola and T. forsythia were observed when strong enzymatic activity (BANA) was present (p < 0.01). The best agreement was observed at initial diagnosis. The BANA Test sensitivity was 95.54% (T0), 65.18% (T1), 65.22% (T2) and 50.26% (T3). The specificity values were 12.24% (T0), 57.38% (T1), 46.27% (T2) and 53.48% (T3). The BANA Test is more effective for the detection of red complex pathogens when the bacterial levels are high, i.e. in the initial diagnosis of chronic periodontitis.

Working at night and work ability among nursing personnel: when precarious employment makes the diVerence

Purpose To test the association between night work and work ability, and verify whether the type of contractual employment has any inXuence over this association. Methods Permanent workers (N = 642) and workers with precarious jobs (temporary contract or outsourced; N = 552) were interviewed and Wlled out questionnaires concerning work hours and work ability index. They were classiWed into: never worked at night, ex-night workers, currently working up to Wve nights, and currently working at least six nights/2-week span. Results After adjusting for socio-demography and work variables, current night work was signiWcantly associated with inadequate WAI (vs. day work with no experience in night work) only for precarious workers (OR 2.00, CI 1.01- 3.95 and OR 1.85, CI 1.09-3.13 for those working up to Wve nights and those working at least six nights in 2 weeks, respectively). Conclusions Unequal opportunities at work and little experience in night work among precarious workers may explain their higher susceptibility to night work

Prediction of good glass formers in the Al-Ni-La and Al-Ni-Gd systems using topological instability and electronegativity

A new criterion has been recently proposed combining the topological instability (lambda criterion) and the average electronegativity difference (Delta e) among the elements of an alloy to predict and select new glass-forming compositions. In the present work, this criterion (lambda.Delta e) is applied to the Al-Ni-La and Al-Ni-Gd ternary systems and its predictability is validated using literature data for both systems and additionally, using own experimental data for the Al-La-Ni system. The compositions with a high lambda.Delta e value found in each ternary system exhibit a very good correlation with the glass-forming ability of different alloys as indicated by their supercooled liquid regions (Delta T(x)) and their critical casting thicknesses. In the case of the Al-La-Ni system, the alloy with the largest lambda.Delta e value, La(56)Al(26.5)Ni(17.5), exhibits the highest glass-forming ability verified for this system. Therefore, the combined lambda.Delta e criterion is a simple and efficient tool to select new glass-forming compositions in Al-Ni-RE systems. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3563099]

Fully Connected PLL Networks: How Filter Determines the Number of Nodes

Synchronization plays an important role in telecommunication systems, integrated circuits, and automation systems. Formerly, the masterslave synchronization strategy was used in the great majority of cases due to its reliability and simplicity. Recently, with the wireless networks development, and with the increase of the operation frequency of integrated circuits, the decentralized clock distribution strategies are gaining importance. Consequently, fully connected clock distribution systems with nodes composed of phase-locked loops (PLLs) appear as a convenient engineering solution. In this work, the stability of the synchronous state of these networks is studied in two relevant situations: when the node filters are first-order lag-lead low-pass or when the node filters are second-order low-pass. For first-order filters, the synchronous state of the network shows to be stable for any number of nodes. For second-order filter, there is a superior limit for the number of nodes, depending on the PLL parameters. Copyright (C) 2009 Atila Madureira Bueno et al.