Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine

It has previously been reported that 1,N6-ethenoadenine (ɛA), deaminated adenine (hypoxanthine, Hx), and 7,8-dihydro-8-oxoguanine (8-oxoG), but not 3,N4-ethenocytosine (ɛC), are released from DNA in vitro by the DNA repair enzyme alkylpurine-DNA-N-glycosylase (APNG). To assess the potential contribution of APNG to the repair of each of these mutagenic lesions in vivo, we have used cell-free extracts of tissues from APNG-null mutant mice and wild-type controls. The ability of these extracts to cleave defined oligomers containing a single modified base was determined. The results showed that both testes and liver cells of these knockout mice completely lacked activity toward oligonucleotides containing ɛA and Hx, but retained wild-type levels of activity for ɛC and 8-oxoG. These findings indicate that (i) the previously identified ɛA-DNA glycosylase and Hx-DNA glycosylase activities are functions of APNG; (ii) the two structurally closely related mutagenic adducts ɛA and ɛC are repaired by separate gene products; and (iii) APNG does not contribute detectably to the repair of 8-oxoG.

A 55-kDa protein isolated from human cells shows DNA glycosylase activity toward 3,N4-ethenocytosine and the G/T mismatch

Etheno adducts in DNA arise from multiple endogenous and exogenous sources. Of these adducts we have reported that, 1,N6-ethenoadenine (ɛA) and 3,N4-ethenocytosine (ɛC) are removed from DNA by two separate DNA glycosylases. We later confirmed these results by using a gene knockout mouse lacking alkylpurine-DNA-N-glycosylase, which excises ɛA. The present work is directed toward identifying and purifying the human glycosylase activity releasing ɛC. HeLa cells were subjected to multiple steps of column chromatography, including two ɛC-DNA affinity columns, which resulted in >1,000-fold purification. Isolation and renaturation of the protein from SDS/polyacrylamide gel showed that the ɛC activity resides in a 55-kDa polypeptide. This apparent molecular mass is approximately the same as reported for the human G/T mismatch thymine-DNA glycosylase. This latter activity copurified to the final column step and was present in the isolated protein band having ɛC-DNA glycosylase activity. In addition, oligonucleotides containing ɛC⋅G or G/T(U), could compete for ɛC protein binding, further indicating that the ɛC-DNA glycosylase is specific for both types of substrates in recognition. The same substrate specificity for ɛC also was observed in a recombinant G/T mismatch DNA glycosylase from the thermophilic bacterium, Methanobacterium thermoautotrophicum THF.

Structure and physical properties of [µ-Tris(1,4-bis(tetrazol-1-yl)butane-N4,N4‘')iron(II)] Bis(hexafluorophosphate), a new Fe(II) spin-crossover compound with a three-dimensional threefold interlocked crystal lattice

[μ-Tris(1,4-bis(tetrazol-1-yl)butane-N4,N4‘)iron(II)] bis(hexafluorophosphate), [Fe(btzb)3](PF6)2, crystallizes in a three-dimensional 3-fold interlocked structure featuring a sharp two-step spin-crossover behavior. The spin conversion takes place between 164 and 182 K showing a discontinuity at about T1/2 = 174 K and a hysteresis of about 4 K between T1/2 and the low-spin state. The spin transition has been independently followed by magnetic susceptibility measurements, 57Fe-Mössbauer spectroscopy, and variable temperature far and midrange FTIR spectroscopy. The title compound crystallizes in the trigonal space group P30¯(No. 147) with a unit cell content of one formula unit plus a small amount of disordered solvent. The lattice parameters were determined by X-ray diffraction at several temperatures between 100 and 300 K. Complete crystal structures were resolved for 9 of these temperatures between 100 (only low spin, LS) and 300 K (only high spin, HS), Z = 1 [Fe(btzb)3](PF  6)2:  300 K (HS), a = 11.258(6) Å, c = 8.948(6) Å, V = 982.2(10) Å3; 100 K (LS), a = 10.989(3) Å, c = 8.702(2) Å, V = 910.1(4) Å3. The molecular structure consists of octahedral coordinated iron(II) centers bridged by six N4,N4‘ coordinating bis(tetrazole) ligands to form three 3-dimensional networks. Each of these three networks is symmetry related and interpenetrates each other within a unit cell to form the interlocked structure. The Fe−N bond lengths change between 1.993(1) Å at 100 K in the LS state and 2.193(2) Å at 300 K in the HS state. The nearest Fe separation is along the c-axis and identical with the lattice parameter c.

catena-[μ-tris(1,2-bis(tetrazol-1-yl)ethane-N4,N4')iron(II)] bis(tetrafluoroborate): Synthesis, structure, spectroscopic and magnetic characterisation of a chain-type coordination polymer spin-crossover compound.

In analogy to a common synthesis of 1-substituted 5-H tetrazoles (Tetrahedron Lett. 36 (1995)1759; Beloruss. Gos. Univ., Minsk, USSR. Khim. Geterotsikl. Soedin. 11 (1985) 1521; Beloruss. Gos. Univ., Minsk, USSR. Khim. Geterotsikl. Soedin. 1 (1991) 66; BGU, Belarus. Vestsi Akad. Navuk Belarusi, Ser. Khim. Navuk 1 (1992) 73), the new bidentate ligand 1,2-bis(tetrazol-1-yl)ethane [endi] was synthesized and characterized by X-ray diffraction, NMR, IR and UV–Vis spectroscopy. By using iron(II) tetrafluoroborate hexahydrate the complexation with this ligand yields a 1-dimensional linear coordination polymer similar to the recently published chain compound (Inorg. Chem. 39 (2000) 1891) exhibiting a thermally induced spin-crossover phenomenon. Similar to the 1,2-bis(tetrazol-1-yl)propane-bridged compound, our 1,2-bis(tetrazol-1-yl)ethane-bridged compound shows a gradual spin transition, but the spin-crossover temperature T1/2≈140 K is found to be 10 K above the other T1/2. The T1/2 was determined by temperature-dependent 57Fe-Mössbauer, far FT-IR and UV–Vis spectroscopy as well as by temperature-dependent magnetic susceptibility measurements. Single crystals of the complex were grown in situ from a solution of the ligand and iron(II) tetrafluoroborate. The X-ray structure determinations of both the high spin as well as the low spin state of the compound revealed a solid state structure, which is comparable to that of catena-[Fe(1,2-bis(tetrazole-1-yl)propane)3](ClO4)2 (Inorg. Chem. 39 (2000) 1891; 2nd TMR-TOSS Meeting, 4th Spin Crossover Family Meeting, Lufthansa Training Center, Seeheim/Germany, April 30–May 2, 1999). Both the 1,2-bis(tetrazol-1-yl)propane-bridged and our compound do not show a thermal hysteresis effect (J. Am. Chem. Soc. 115 (1993) 9810; Inorg. Chim. Acta 37 (1979) 169; Chem. Phys. Lett. 93 (1982) 567). The synthesis of the complex described in the experimental section yielded a fine powdered product being poorly soluble in most common solvents. The single crystal measurements were done with crystals obtained by various diffusion methods. Most of them yielded either thin needles or small hexagonal prism crystals depending on the specific conditions.

De territorios y fronteras… el devenir de una literatura territorial. En: LaRivada V.3 Nº4

En este artículo nos proponemos desplegar el itinerario y las constelaciones que orientaron nuestras investigaciones de los últimos años sobre el territorio literario y cultural misionero. Las dimensiones y segmentaciones que se ponen en funcionamiento en las operaciones de lectura en las que estamos comprometidos nosotros mismos, las hemos pensado como un territorio identitario(s) con fronteras móviles, como un lugar de la cultura en tanto zonas de transacción, negociación y pasajes perpetuos. Pensamos que resultaría pertinente argumentar sobre la situación cultural compleja, desde la interculturalidad y no desde una mirada homogeneizadora y monológica; esto nos brindará la oportunidad de reflexionar acerca de los desplazamientos, despliegues y repliegues de los proyectos creadores y de la dinámica de la vida cotidiana en relación con el desglose de un espacio geográfico-cultural.

Transition metal complexes of some N4-phenylsemicarbazones: crystal structures and spectral studies

The work embodied in this thesis was carried out by the author in the Department of Applied Chemistry, CUSAT, Kochi, during the period 2009-2012. The thesis is an introduction to our attempts to evaluate the coordination behavior of some compounds of our interest. The biological activities of semicarbazones and their metal complexes have been an active area of research during the past years because of their significant role in naturally occurring biological systems. Tridentate NNO and ONO semicarbazone systems formed from heterocyclic and aromatic carbonyl compounds and their transition metal complexes are wellauthenticated compounds in this field and their synthesis, crystal structures and spectral studies are well desirable. Hence, we decided to develop a research program aimed at the syntheses, crystal structures and spectral studies of new N4- phenylsemicarbazones derived from 2-formylpyridine and 3-ethoxysalicylaldehyde and their transition metal complexes and new transition metal complexes of 2- benzoylpyridine-N4-phenylsemicarbazone. In addition to various physicochemical methods of analysis, single crystal X-ray diffraction studies were also used for the characterization of the complexes.

Effects of high-dose creatine supplementation on kidney and liver responses in sedentary and exercised rats

This study evaluated the effects of high-dose of short-term creatine supplementation (5g.kg(-1). day(-1) to 1 week) and long-term creatine supplementation (1g.kg(-1). day(-1) to 4-8 weeks) on kidney and liver structure and function of sedentary and exercised Wistar rats ( Exercise sessions consisted of swimming at 80% of maximal work load supported during 5 days per week with daily sessions of 60 minutes throughout the duration of the supplementation). Seventy-two animals ( 245 +/- 5g) were divided into four groups (n = 18): control diet Sedentary ( SED), Creatine diet Sedentary (CRE), control diet Exercised (EXE), and Creatine diet Exercised (EXECRE). Histological and blood biochemical studies were performed after one, four, and eight weeks of creatine supplementation and exercise ( n = 6). No differences were found when comparing SED, EXE and EXECRE groups for kidney and liver structure and function at one, four and eight weeks. However, the CRE group showed higher levels of creatinine (1.1 +/- 0.2 vs. 0.4 +/- 0.1 mg.dl(-1); p < 0.05), and urea ( 37 +/- 3 vs. 19 +/- 1 mg. dl(-1); p < 0.05) when compared with all others groups at four and eight weeks. At eight weeks, the CRE group presented increased levels of ALT (41 +/- 7 vs. 23 +/- 7 U.L(-1); p < 0.05), AST (89 +/- 6 vs. 62 +/- 5 U. L(-1); p < 0.05), GGT (8.0 +/- 0.9 vs. 3.9 +/- 1.0 U. L(-1); p < 0.05), and AP (125 +/- 10 vs. 69 +/- 9 U. L(-1); p < 0.05) also when compared with all others groups. Moreover, the CRE group demonstrated some structural alterations indicating renal and hepatic damage at four and eight weeks, respectively. These results suggest that long-term creatine supplementation (up to 4-8 weeks) may adversely affect kidney and liver structure and function of sedentary but not of exercised rats.

Noticiários de horário nobre em Portugal: duração e valor-notícia

Dado o papel que a informação, designadamente os jornais televisivos de horário nobre, têm nos canais televisivos generalistas e as estratégias de captação de audiências cada vez mais competitivas, vários modelos têm sido adoptados com implicações ao nível da estrutura, alinhamento e conteúdos. Considerando diversos estudos que utilizam uma metodologia de comparação de jornais televisivos de horário nobre em vários países, e partindo da ideia de que os jornais televisivos portugueses são em média demasiado longos, esta abordagem considera como eixo central de análise a sua duração. Pretende-se estudar a relação entre a duração do jornal televisivo e o seu modelo, ao nível da estrutura, alinhamento e conteúdos. Neste estudo adopta-se a perspectiva metodológica desenvolvida no projecto internacional “News definitions across cultures”, sendo a análise das notícias centrada, sobretudo, nos valores notícia (valência, desviância e significância). Dos resultados obtidos é possível concluir que há diferenças, quer quanto ao conteúdo, quer quanto à estrutura das notícias em função da duração dos jornais televisivos. Já ao nível do alinhamento do noticiário não foram encontradas diferenças significativas.

Interacción entre poblaciones de Triatoma infestans y Triatoma sordida

Para conocer si se producía algún tipo de interacción entre poblaciones de Triatoma infestans y Triatoma sordida que convivían en una unidad experimental y explotaban el mismo recurso alimentario (ave) se las estudió desde setiembre/1988 a abril/1989. La composición etaria inicial para cada especie fue: 27 N1, 7 N2, 11 N3, 3 N4, 8 N5, 4 machos y 10 hembras. La dinámica de población, el estado nutricional, la predación y la conducta gregaria, utilizados como parámetros de comparación, fueron estimados mediante censos mensuales. Triatoma infestans logró mayor éxito colonizador que T. sordida dado los valores alcanzados en: fecundidad (146 huevos/hembra), longevidad (157,8 días) y mortalidad (39,4%), en comparación a los obtenidos por T. sordida: 118 huevos/hembra, 81,1 días y 54,0% respectivamente. La población de T. infestans tuvo un crecimiento de tipo exponencial, con una alta tasa de renovación ninfal, en contraposición, la población de T. sordida se extinguió tempranamente. En general, el peso promedio de los ejemplares de T. infestans se mantuvo en valores próximos al inicial, mientras que en T. sordida se redujo. Los grupos gregarios se conformaron mayoritariamente en el sector inferior de la pared 1 (próximo al hospedador), observándose mayor nivel de contagio en T. infestans. A partir de los resultados obtenidos se formula la hipótesis de la superioridad competitiva en T. infestans.

Six sigma methodologies: implementation and impacts on Portuguese small and medium companies (SMES)

Artigo elaborador no âmbito dos trabalhos decorrentes à dissertação de Mestrado do Aluno David Leite, no Mestrado em Gestão Integrada Qualidade, Ambiente e Segurança, ESTGF-IPP, Oreintados pelos Professores Luís Fonseca (ISEP-IPP) e Vanda Lima (ESTGF-IPP).

Estudo da importância do transporte ferroviário de mercadorias no Eixo Leixões- Salamanca

A evolução dos transportes de mercadorias, em Portugal e na União Europeia, assume uma enorme repercussão na economia global, de modo que a combinação dos vários modos de transporte, com vista à obtenção de ganhos ao nível da eficiência, adquire extrema importância. Os programas europeus de apoio aos transportes, enquadrados na rede transeuropeia de transportes e plataformas logísticas, também contribuem para a otimização do transporte de mercadorias. A importância do transporte ferroviário de mercadorias no eixo Leixões- Salamanca, nomeadamente para as empresas exportadoras e importadoras da região norte e centro, que utilizam meios alternativos ao ferroviário, constitui o principal objetivo desta dissertação. A revisão bibliográfica inclui uma abordagem aos transportes de mercadorias em geral e de forma mais aprofundada aos modos ferroviário e rodoviário na península ibérica, passando pela logística, bem como pela integração de modos: intermodalidade e multimodalidade na rede europeia de transportes e ainda a referência aos portos secos e às plataformas logísticas. Isto permite caraterizar as diferentes empresas operadoras do setor dos transportes de mercadorias e os produtos transacionados, assim como enumerar vantagens e/ou desvantagens do meio de transporte ferroviário face a outros meios, mais concretamente no eixo alvo deste estudo. A metodologia utilizada consiste na análise de informação proveniente de fontes secundárias havendo lugar a uma referência mais detalhada sobre as plataformas logísticas de Leixões e Salamanca, o eixo E-80, o corredor ferroviário nº4 e os programas europeus promotores da eficiência no transporte ferroviário de mercadorias: Marathon, Ferremed e Marco Polo. Para a recolha de informação primária o instrumento adotado foi a entrevista semiestruturada, efetuada a dois representantes da empresa CP-Carga e a um representante da empresa KLog, ambas as empresas ligadas ao setor dos transportes e logística. A análise e tratamento de toda a informação recolhida possibilitam, desde logo, evidenciar as potencialidades do eixo Leixões-Salamanca no que se refere ao transporte ferroviário de mercadorias, delinear recomendações para a sua otimização, bem como efetuar uma análise SWOT. As considerações finais revelam que é imperativo adotar medidas, de forma integrada, para que o seu efeito na potenciação do transporte ferroviário de mercadorias, não só no eixo Leixões-Salamanca, mas também a nível europeu, se afirme como uma verdadeira alternativa a outros modos, particularmente ao domínio rodoviário.

Energy-aware task mapping onto heterogeneous platforms using DVFS and sleep states

Heterogeneous multicore platforms are becoming an interesting alternative for embedded computing systems with limited power supply as they can execute specific tasks in an efficient manner. Nonetheless, one of the main challenges of such platforms consists of optimising the energy consumption in the presence of temporal constraints. This paper addresses the problem of task-to-core allocation onto heterogeneous multicore platforms such that the overall energy consumption of the system is minimised. To this end, we propose a two-phase approach that considers both dynamic and leakage energy consumption: (i) the first phase allocates tasks to the cores such that the dynamic energy consumption is reduced; (ii) the second phase refines the allocation performed in the first phase in order to achieve better sleep states by trading off the dynamic energy consumption with the reduction in leakage energy consumption. This hybrid approach considers core frequency set-points, tasks energy consumption and sleep states of the cores to reduce the energy consumption of the system. Major value has been placed on a realistic power model which increases the practical relevance of the proposed approach. Finally, extensive simulations have been carried out to demonstrate the effectiveness of the proposed algorithm. In the best-case, savings up to 18% of energy are reached over the first fit algorithm, which has shown, in previous works, to perform better than other bin-packing heuristics for the target heterogeneous multicore platform.

Mecanismos de degradação de compostos de relevância biológica por radicais oxidantes

Dissertação para obtenção do Grau de Doutor em Química, especialidade Química Orgânica

Utilization of Quality Tools: does sector and size matter?

This research focuses on the influence of company sector and size on the level of utilization of Basic and Advanced Quality Tools. The paper starts with a literature review and then presents the methodology used for the survey. Based on the responses from 202 managers of Portuguese ISO 9001:2008 Quality Management System certified organizations, statistical tests were performed. Results show, with 95% confidence level, that industry and services have a similar proportion of use of Basic and Advanced Quality Tools. Concerning size, bigger companies show a higher trend to use Advanced Quality Tools than smaller ones. For Basic Quality Tools, there was no statistical significant difference at a 95% confidence level for different company sizes. The three basic Quality tools with higher utilization were Check sheets, Flow charts and Histograms (for Services) or Control Charts/ (for Industry), however 22% of the surveyed organizations reported not using Basic Quality Tools, which highlights a major improvement opportunity for these companies. Additional studies addressing motivations, benefits and barriers for Quality Tools application should be undertaken for further validation and understanding of these results.