DP-2, a heterodimeric partner of E2F: identification and characterization of DP-2 proteins expressed in vivo.

E2F is a heterodimeric transcription factor that regulates the expression of genes at the G1/S boundary and is composed of two related but distinct families of proteins, E2F and DP. E2F/DP heterodimers form complexes with the retinoblastoma (Rb) protein, the Rb-related proteins p107 and p130, and cyclins/cdks in a cell cycle-dependent fashion in vivo. E2F is encoded by at least five closely related genes, E2F-1 through -5. Here we report studies of DP-2, the second member of the DP family of genes. Our results indicate that (i) DP-2 encodes at least five distinct mRNAs, (ii) a site of alternative splicing occurs within the 5' untranslated region of DP-2 mRNA, (iii) at least three DP-2-related proteins (of 55, 48, and 43 kDa) are expressed in vivo, (iv) each of these proteins is phosphorylated, and (v) one DP-2 protein (43 kDa) carries a truncated amino terminus. Our data also strongly suggest that the 55-kDa DP-2-related protein is a novel DP-2 isoform that results from alternative splicing. Thus, we conclude that DP-2 encodes a set of structurally, and perhaps functionally, distinct proteins in vivo.

Preliminary results on the chemical composition of outdoor airborne particles at urban schools and possible implications for the air quality in classrooms

Vehicle emissions are a significant source of fine particles (Dp < 2.5 µm) in an urban environment. These fine particles have been shown to have detrimental health effects, with children thought to be more susceptible. Vehicle emissions are mainly carbonaceous in nature, and carbonaceous aerosols can be defined as either elemental carbon (EC) or organic carbon (OC). EC is a soot-like material emitted from primary sources while OC fraction is a complex mixture of hundreds of organic compounds from either primary or secondary sources (Cao et al., 2006). Therefore the ratio of OC/EC can aid in the identification of source. The purpose of this paper is to use the concentration of OC and EC in fine particles to determine the levels of vehicle emissions in schools. It is expected that this will improve the understanding of the potential exposure of children in a school environment to vehicle emissions.

A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis

Background Several lines of evidence suggests that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but a complete mapping the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors which may be involved in one subtype may not be in others. We investigated the possibility that this network could be mapped using microarray technologies and modern bioinformatics methods on a dataset from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls, Methodology/Principal Findings We have used two different analytical methodologies: a differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that seem to be statistically overrepresented in genes which are either differentially expressed (or differentially co-expressed) in cases and controls (e.g. V$KROX_Q6, p-value < 3.31E-6; V$CREBP1_Q2, p-value < 9.93E-6, V$YY1_02, p-value < 1.65E-5). Conclusions/significance: Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. Analysing the published literature we have found that these transcription factors are involved in the early T-lymphocyte specification and commitment as well as in oligodendrocytes dedifferentiation and development. The most significant transcription factors motifs were for the Early Growth response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families.

Chemical and source characterisation of size-segregated urban air particulate matter

Recent epidemiological studies have shown a consistent association of the mass concentration of urban air thoracic (PM10) and fine (PM2.5) particles with mortality and morbidity among cardiorespiratory patients. However, the chemical characteristics of different particulate size ranges and the biological mechanisms responsible for these adverse health effects are not well known. The principal aims of this thesis were to validate a high volume cascade impactor (HVCI) for the collection of particulate matter for physicochemical and toxicological studies, and to make an in-depth chemical and source characterisation of samples collected during different pollution situations. The particulate samples were collected with the HVCI, virtual impactors and a Berner low pressure impactor in six European cities: Helsinki, Duisburg, Prague, Amsterdam, Barcelona and Athens. The samples were analysed for particle mass, common ions, total and water-soluble elements as well as elemental and organic carbon. Laboratory calibration and field comparisons indicated that the HVCI can provide a unique large capacity, high efficiency sampling of size-segregated aerosol particles. The cutoff sizes of the recommended HVCI configuration were 2.4, 0.9 and 0.2 μm. The HVCI mass concentrations were in a good agreement with the reference methods, but the chemical composition of especially the fine particulate samples showed some differences. This implies that the chemical characterization of the exposure variable in toxicological studies needs to be done from the same HVCI samples as used in cell and animal studies. The data from parallel, low volume reference samplers provide valuable additional information for chemical mass closure and source assessment. The major components of PM2.5 in the virtual impactor samples were carbonaceous compounds, secondary inorganic ions and sea salt, whereas those of coarse particles (PM2.5-10) were soil-derived compounds, carbonaceous compounds, sea salt and nitrate. The major and minor components together accounted for 77-106% and 77-96% of the gravimetrically-measured masses of fine and coarse particles, respectively. Relatively large differences between sampling campaigns were observed in the organic carbon content of the PM2.5 samples as well as the mineral composition of the PM2.5-10 samples. A source assessment based on chemical tracers suggested clear differences in the dominant sources (e.g. traffic, residential heating with solid fuels, metal industry plants, regional or long-range transport) between the sampling campaigns. In summary, the field campaigns exhibited different profiles with regard to particulate sources, size distribution and chemical composition, thus, providing a highly useful setup for toxicological studies on the size-segregated HVCI samples.

Characterisation and source identification of pollution episodes caused by long-range transported aerosols

Aerosol particles can cause detrimental environmental and health effects. The particles and their precursor gases are emitted from various anthropogenic and natural sources. It is important to know the origin and properties of aerosols to efficiently reduce their harmful effects. The diameter of aerosol particles (Dp) varies between ~0.001 and ~100 μm. Fine particles (PM2.5: Dp < 2.5 μm) are especially interesting because they are the most harmful and can be transported over long distances. The aim of this thesis is to study the impact on air quality by pollution episodes of long-range transported aerosols affecting the composition of the boundary-layer atmosphere in remote and relatively unpolluted regions of the world. The sources and physicochemical properties of aerosols were investigated in detail, based on various measurements (1) in southern Finland during selected long-range transport (LRT) pollution episodes and unpolluted periods and (2) over the Atlantic Ocean between Europe and Antarctica during a voyage. Furthermore, the frequency of LRT pollution episodes of fine particles in southern Finland was investigated over a period of 8 years, using long-term air quality monitoring data. In southern Finland, the annual mean PM2.5 mass concentrations were low but LRT caused high peaks of daily mean concentrations every year. At an urban background site in Helsinki, the updated WHO guideline value (24-h PM2.5 mean 25 μg/m3) was exceeded during 1-7 LRT episodes each year during 1999-2006. The daily mean concentrations varied between 25 and 49 μg/m3 during the episodes, which was 3-6 times higher than the mean concentration in the long term. The in-depth studies of selected LRT episodes in southern Finland revealed that biomass burning in agricultural fields and wildfires, occurring mainly in Eastern Europe, deteriorated air quality on a continental scale. The strongest LRT episodes of fine particles resulted from open biomass-burning fires but the emissions from other anthropogenic sources in Eastern Europe also caused significant LRT episodes. Particle mass and number concentrations increased strongly in the accumulation mode (Dp ~ 0.09-1 μm) during the LRT episodes. However, the concentrations of smaller particles (Dp < 0.09 μm) remained low or even decreased due to the uptake of vapours and molecular clusters by LRT particles. The chemical analysis of individual particles showed that the proportions of several anthropogenic particle types increased (e.g. tar balls, metal oxides/hydroxides, spherical silicate fly ash particles and various calcium-rich particles) in southern Finland during an LRT episode, when aerosols originated from the polluted regions of Eastern Europe and some open biomass-burning smoke was also brought in by LRT. During unpolluted periods when air masses arrived from the north, the proportions of marine aerosols increased. In unpolluted rural regions of southern Finland, both accumulation mode particles and small-sized (Dp ~ 1-3 μm) coarse mode particles originated mostly from LRT. However, the composition of particles was totally different in these size fractions. In both size fractions, strong internal mixing of chemical components was typical for LRT particles. Thus, the aging of particles has significant impacts on their chemical, hygroscopic and optical properties, which can largely alter the environmental and health effects of LRT aerosols. Over the Atlantic Ocean, the individual particle composition of small-sized (Dp ~ 1-3 μm) coarse mode particles was affected by continental aerosol plumes to distances of at least 100-1000 km from the coast (e.g. pollutants from industrialized Europe, desert dust from the Sahara and biomass-burning aerosols near the Gulf of Guinea). The rate of chloride depletion from sea-salt particles was high near the coasts of Europe and Africa when air masses arrived from polluted continental regions. Thus, the LRT of continental aerosols had significant impacts on the composition of the marine boundary-layer atmosphere and seawater. In conclusion, integration of the results obtained using different measurement techniques captured the large spatial and temporal variability of aerosols as observed at terrestrial and marine sites, and assisted in establishing the causal link between land-bound emissions, LRT and air quality.

Effect of High Pressure on the Electrical Conductivity of TlInX2 (X = Se, Te) Layered Semiconductors

The dc electrical conductivity of TlInX2 (X = Se, Te) single crystals, parallel and perpendicular to the (001) c-axis is studied under high quasi-hydrostatic pressure up to 7.0 GPa, at room temperature. Conductivity measurements parallel to the c-axis are carried out at high pressures and down to liquid nitrogen temperatures. These materials show continuous metallization under pressure. Both compounds have almost the same pressure coefficient of the electrical activation energy parallel to the c-axis, d(ΔE∥)/dP = −2.9 × 10−10 eV/Pa, which results from the narrowing of the band gap under pressure. The results are discussed in the light of the band structure of these compounds.

A note on tetrablock contractions

A commuting triple of operators (A, B, P) on a Hilbert space H is called a tetrablock contraction if the closure of the set E = {(a(11),a(22),detA) : A = GRAPHICS] with parallel to A parallel to <1} is a spectral set. In this paper, we construct a functional model and produce a set of complete unitary invariants for a pure tetrablock contraction. In this construction, the fundamental operators, which are the unique solutions of the operator equations A - B* P = DPX1DP and B - A* P = DPX2DP where X-1, X-2 is an element of B(D-P) play a pivotal role. As a result of the functional model, we show that every pure tetrablock isometry (A, B, P) on an abstract Hilbert space H is unitarily equivalent to the tetrablock contraction (MG1*+G2z, MG2*+G1z, M-z) on H-DP*(2). (D), where G(1) and G(2) are the fundamental operators of (A*, B*, P*). We prove a Beurling Lax Halmos type theorem for a triple of operators (MF1*+F2z, MF2*+F1z, M-z), where epsilon is a Hilbert space and F-1, F-2 is an element of B(epsilon). We also deal with a natural example of tetrablock contraction on a functions space to find out its fundamental operators.

Efetividade da aplicação semestral de verniz fluoretado no controle da cárie dentária em pré-escolares: resultados após 12 meses de acompanhamento

O presente estudo teve como objetivos avaliar se a aplicação de verniz fluoretado com periodicidade semestral em crianças pré-escolares reduz o número de crianças com lesões de cárie em dentina na dentição decídua, diminui a incidência de lesões de cárie em esmalte e dentina, está inversamente associado à ocorrência de dor e abscesso dentário e produz quaisquer efeitos adversos. A população de estudo consistiu de 200 crianças na faixa etária de 12 a 48 meses, recrutadas em uma unidade de saúde pública da cidade do Rio de Janeiro, as quais foram alocadas aleatoriamente nos grupos teste (verniz fluoretado Duraphat) e controle (verniz placebo). Para o registro da incidência de cárie, as crianças foram examinadas na linha de base e a cada seis meses, durante um ano, por dois odontopediatras previamente treinados e calibrados (Kappa=0,85). A ocorrência de dor, abscesso e efeitos adversos foi verificada a partir de entrevistas com os responsáveis. Os participantes, os seus responsáveis, os operadores e os examinadores desconheciam a qual grupo cada criança pertencia. No final do período de acompanhamento, 71 crianças do grupo teste e 77 do grupo controle foram avaliadas. Constatou-se que, nos grupos teste e controle, o número de crianças com novas lesões de cárie em dentina foi igual a 13 e 20 (teste Qui-quadrado, p=0,34) e que a média do incremento de cárie considerando apenas lesões em dentina (c3eos) foi de 1,1(dp=3,4) e de 1,4(dp=2,8), respectivamente (teste de Mann-Whitney, p=0,29). Uma criança apresentou dor de dente e abscesso dentário e outras duas crianças apresentaram apenas dor de dente. Todas pertenciam ao grupo teste. Com relação aos efeitos adversos, encontrou-se que uma criança pertencente ao grupo controle relatou ardência na cavidade bucal após a aplicação do placebo e que o responsável por um participante do grupo teste sentiu-se incomodado com a coloração amarelada dos dentes da criança após a aplicação do verniz fluoretado. Concluiu-se que a aplicação de verniz fluoretado com periodicidade semestral em crianças pré-escolares é segura e parece contribuir para o controle da progressão de cárie. Contudo, é necessário um período de acompanhamento mais longo para se obter evidência conclusiva a respeito da efetividade dessa intervenção. Não houve associação entre a ocorrência de dor e abscesso dentário e o uso profissional do verniz fluoretado.

Prevalência das injúrias orofaciais e uso de protetores bucais em uma população de atletas que praticam futebol e jiu-jitsu

Este estudo epidemiológico teve por objetivo investigar a prevalência de injúria orofacial em dois grupos de atletas. O primeiro grupo foi de atletas integrantes do Fluminense Futebol Clube, em Xerém, e o segundo de atletas praticantes do jiu-jitsu em diferentes academias ou que participaram do Campeonato Brasileiro em 2011, no Rio de Janeiro. Um examinador calibrado, auxiliado por um assistente, preencheu os questionários com todos os atletas, seguido do exame clínico de todos. Grupo I: 260 atletas do Fluminense Futebol Clube com idade média de 14,08 (DP 2,71) anos de idade, todos do gênero masculino. Grupo II: 315 atletas de diversas academias de jiu-jitsu com idade média de 26,86 (DP 8,99), dentre esses indivíduos, apenas 10 eram do gênero feminino. A prevalência de injúrias orofaciais encontrada para o Grupo I foi de 47% (n=122; IC 95% 40,94% a 52,99%) e no Grupo II de 74,6% (n=235; IC 95% 69,52% a 79,09%). Considerando-se a prevalência de trauma apenas no elemento dentário, a prevalência diminuiu de 147 injúrias para 57 traumas dentais no futebol e de 289 injúrias para 93 traumas dentais no jiu-jitsu. Foi observada uma menor prevalência de injúria orofacial nos goleiros quando comparados aos outros jogadores de futebol. A maior parte das injúrias ocorreu durante o período do treino (n=42; IC 95% 26,59% a 43,22%) e apenas 4 desses atletas usavam protetor bucal. Por outro lado, no jiu-jitsu, a prevalência de injúria variou de acordo com a cor da faixa do uniforme do atleta. Os atletas da faixa preta exibiram mais injúrias (n=83). Atletas que treinavam de 7 a 15 horas por semana, sofreram mais injúria (n=109). A maioria das injúrias ocorreu durante o treino. Somente 28,57% dos atletas (IC 95% 23,86% a 33,79%) usavam protetor bucal. Nos dois esportes, a maioria dos atletas sofreu apenas uma injúria, sendo o tipo mais frequente em tecido mole. O dente mais atingido foi o incisivo central superior. Estes dados ressaltam a importância de incentivar o uso de protetores bucais em esportes de contato como o futebol e o jiu-jitsu, onde o seu uso não é obrigatório, apesar da prevalência de injúria orofacial ser alta.

Jovens em risco: projectos de vida e motivação para a frequência do ensino profissional

Dissertação de mest., Psicologia da Educação (Necessidades Educativas Especiais), Faculdade de Ciências Humanas e Sociais, Univ. do Algarve, 2011

Produção científica em revistas internacionais pelos autores da acta médica portuguesa

As revistas científicas locais e regionais têm sido amplamente criticadas por alguns autores. Além disso, dificilmente são indexadas nas bases de dados internacionais, o que reduz a visibilidade dos seus artigos. Objectivo: Analisar a produção científica internacional dos autores que publicaram na Acta Médica Portuguesa no ano de 2008. Métodos: Construi-se uma base de dados com todos os autores que publicaram durante o ano de 2008 na Acta Médica Portuguesa. Em Julho de 2009 recolheu-se do Science Citation Index a produção de todos estes autores publicada nos cinco anos anteriores (2003-2007). Analisaram-se as revistas em que publicaram, o Factor de Impacto destas revistas, as referencias destes artigos, e as citações recebidas. Resultados: Os 78 artigos publicados pela Acta Médica Portuguesa em 2008 foram escritos por 259 autores diferentes. Destes autores, 94 (36,3%) escreveram 420 artigos entre 2003-2007, indexados no Science Citation Index. Estes artigos apareceram em 249 revistas diferentes, com um Factor de Impacto médio de 2,973 (DP = 2,92). A revista com maior Factor de Impacto foi The Lancet (FI2008 = 28,409) com dois artigos publicados. Destes autores, 87 tinham recebido alguma citação aos seus artigos, com um total de 5001 citações. Das 14035 referências destes 420 artigos, apenas 10 eram a algum trabalho publicado na Acta Médica Portuguesa. Conclusão: Os autores que publicam na Acta Médica Portuguesa têm uma boa quantidade de publicações internacionais, em revistas com um considerável Factor de Impacto e recebem um razoável número de citações. Pelo contrário, estes autores quando publicam em revistas internacionais citam extremamente pouco os artigos da Acta Médica Portuguesa.

Visual processing of concentric sine-wave gratings in adolescents and adults

The aim of this study was to compare the contrast visual processing of concentric sinusoidal gratings stimuli between adolescents and adults. The study included 20 volunteers divided into two groups: 10 adolescents aged 13-19 years (M=16.5, SD=1.65) and 10 adults aged 20-26 years (M=21.8, SD=2.04). In order to measure the contrast sensitivity at spatial frequencies of 0.6, 2.5, 5 and 20 degrees of visual angle (cpd), it was used the psychophysical method of two alternative forced choice (2AFC). A One Way ANOVA performance showed a significant difference in the comparison between groups: F [(4, 237)=3.74, p<.05]. The post-hoc Tukey HSD showed a significant difference between the frequencies of 0.6 (p <.05) and 20 cpd (p<.05). Thus, the results showed that the visual perception behaves differently with regard to the sensory mechanisms that render the contrast towards adolescents and adults. These results are useful to better characterize and comprehend human vision development.

Relação entre personalidade, vulnerabilidade ao stress e burnout nos elementos da polícia de segurança pública

Os polícias são profissionais expostos a diversos fatores de stress, podendo este ser percecionado de diferentes formas consoante a personalidade de cada pessoa. Tentámos conhecer a vulnerabilidade ao stress e a relação com a personalidade em elementos da Polícia de Segurança Pública, verificando também se o stress e as perturbações da personalidade estão correlacionados. A amostra utilizada neste estudo foi constituída por 119 indivíduos adultos, 13 do sexo feminino com uma média de idades de 26 anos (DP=1.53) e 106 do sexo masculino com uma média de idades de 25.31 anos (DP=2.14). Como medidas foram utilizadas, para as Perturbações da Personalidade, o Inventário Clínico Multiaxial de Millon - MCMI (Millon, 1969), para a vulnerabilidade ao stress, o 23 Q.V.S (Vaz Serra, 2000) e para a Síndrome de Burnout (exaustão, cinismo e eficácia profissional) o M.B.I-G.S. (Scaufeli; Leiter; Maslach; Jackson, 1996 ; Nunes, 2003). Os resultados confirmam as relações esperadas, designadamente entre o narcisimo e a exaustão emocional e entre o perfecionismo e o burnout. Os resultados são discutidos de acordo com a literatura.

A identidade moral e a integridade são preditoras da motivação moral?

Com o objetivo de analisar os componentes que induzem o comportamento moral, apoiámo-nos nas teorias psicológicas que admitem a importância do papel das emoções e da identidade na motivação para a ação moral, contrariamente ao que era defendido pelas teorias construtivistas, que apenas referiam a cognição como motor do funcionamento moral. Deste modo elegemos a identidade moral e a integridade como variáveis que podem estar associadas à motivação moral. Participaram 91 adultos emergentes, com idades compreendidas entre os 18 e os 25 anos (M = 20,63; Dp = 2,33), 14 do género masculino e 77 do género feminino. Para avaliar a motivação moral, a identidade moral e a integridade utilizámos respetivamente a PMAM, EIM e EI. Os objetivos foram verificar se existem diferenças individuais na consciência moral e nas emoções atribuídas a atos de transgressão, se a intensidade das emoções auto-atribuídas varia em função da consciência moral, e se a identidade moral e a integridade estão associadas à motivação moral. Os resultados mostram que existem diferenças individuais tanto na consciência moral como na atribuição de emoções. Os sujeitos avaliaram as transgressões de cuidado, não cuidar de parente e infidelidade, com emoções mais negativas e com maior utilização de consciência moral de transgressão, do que as transgressões anti-sociais, fraude e mentira. Verificámos também que a intensidade emocional varia em função da consciência moral. As categorias de Transgressão Identitária e Transgressão estão associadas com emoções mais negativas e as de Transgressão Relativizada e Não Transgressão estão relacionadas com emoções menos negativas. Foi ainda encontrada associação entre a identidade moral e integridade com a motivação moral, mas apenas para as transgressões anti-sociais.

Inhibition of E2F abrogates the development of cardiac myocyte hypertrophy

Growth of the post- natal mammalian heart occurs primarily by cardiac myocyte hypertrophy. Previously, we and others have shown that a partial re- activation of the cell cycle machinery occurs in myocytes undergoing hypertrophy such that cells progress through the G(1)/ S transition. In this study, we have examined the regulation of the E2F family of transcription factors that are crucial for the G(1)/ S phase transition during normal cardiac development and the development of myocyte hypertrophy in the rat. Thus, mRNA and protein levels of E2F- 1, 3, and 4 and DP- 1 and DP- 2 were down- regulated during development to undetectable levels in adult myocytes. Interestingly, E2F- 5 protein levels were substantially up- regulated during development. In contrast, an induction of E2F- 1, 3, and 4 and the DP- 1 protein was observed during the development of myocyte hypertrophy in neonatal myocytes treated with serum or phenylephrine, whereas the protein levels of E2F- 5 were decreased with serum stimulation. E2F activity, as measured by a cyclin E promoter luciferase assay and E2F- DNA binding activity, increased significantly during the development of hypertrophy with serum and phenylephrine compared with non- stimulated cells. Inhibiting E2F activity with a specific peptide that blocks E2F- DP heterodimerization prevented the induction of hypertrophic markers ( atrial natriuretic factor and brain natriuretic peptide) in response to serum and phenylephrine, reduced the increase in myocyte size, and inhibited protein synthesis in stimulated cells. Thus, we have shown that the inhibition of E2F function prevents the development of hypertrophy. Targeting E2F function might be a useful approach for treating diseases that cause pathophysiological hypertrophic growth.