HPV16 Down-Regulates the Insulin-Like Growth Factor Binding Protein 2 to Promote Epithelial Invasion in Organotypic Cultures

Cervical cancer is a multi-stage disease caused by human papillomaviruses (HPV) infection of cervical epithelial cells, but the mechanisms regulating disease progression are not clearly defined. Using 3-dimensional organotypic cultures, we demonstrate that HPV16 E6 and E7 proteins alter the secretome of primary human keratinocytes resulting in local epithelial invasion. Mechanistically, absence of the IGF-binding protein 2 (IGFBP2) caused increases in IGFI/II signalling and through crosstalk with KGF/FGFR2b/AKT, cell invasion. Repression of IGFBP2 is mediated by histone deacetylation at the IGFBP2 promoter and was reversed by treatment with histone deacetylase (HDAC) inhibitors. Our in vitro findings were confirmed in 50 invasive cancers and 79 cervical intra-epithelial neoplastic lesions caused by HPV16 infection, where IGFBP2 levels were reduced with increasing disease severity. In summary, the loss of IGFBP2 is associated with progression of premalignant disease, and sensitises cells to pro-invasive IGF signalling, and together with stromal derived factors promotes epithelial invasion.

Compositional data-driven alternatives to single geochemical component maps

Conventional practice in Regional Geochemistry includes as a final step of any geochemical campaign the generation of a series of maps, to show the spatial distribution of each of the components considered. Such maps, though necessary, do not comply with the compositional, relative nature of the data, which unfortunately make any conclusion based on them sensitive
to spurious correlation problems. This is one of the reasons why these maps are never interpreted isolated. This contribution aims at gathering a series of statistical methods to produce individual maps of multiplicative combinations of components (logcontrasts), much in the flavor of equilibrium constants, which are designed on purpose to capture certain aspects of the data.
We distinguish between supervised and unsupervised methods, where the first require an external, non-compositional variable (besides the compositional geochemical information) available in an analogous training set. This external variable can be a quantity (soil density, collocated magnetics, collocated ratio of Th/U spectral gamma counts, proportion of clay particle fraction, etc) or a category (rock type, land use type, etc). In the supervised methods, a regression-like model between the external variable and the geochemical composition is derived in the training set, and then this model is mapped on the whole region. This case is illustrated with the Tellus dataset, covering Northern Ireland at a density of 1 soil sample per 2 square km, where we map the presence of blanket peat and the underlying geology. The unsupervised methods considered include principal components and principal balances
(Pawlowsky-Glahn et al., CoDaWork2013), i.e. logcontrasts of the data that are devised to capture very large variability or else be quasi-constant. Using the Tellus dataset again, it is found that geological features are highlighted by the quasi-constant ratios Hf/Nb and their ratio against SiO2; Rb/K2O and Zr/Na2O and the balance between these two groups of two variables; the balance of Al2O3 and TiO2 vs. MgO; or the balance of Cr, Ni and Co vs. V and Fe2O3. The largest variability appears to be related to the presence/absence of peat.

The association between refractive cutoffs for spectacle provision and visual improvement among school-aged children in South Africa.

OBJECTIVES: To evaluate different refractive cutoffs for spectacle provision with regards to their impact on visual improvement and spectacle compliance. DESIGN: Prospective study of visual improvement and spectacle compliance. PARTICIPANTS: South African school children aged 6-19 years receiving free spectacles in a programme supported by Helen Keller International. METHODS: Refractive error, age, gender, urban versus rural residence, presenting and best-corrected vision were recorded for participants. Spectacle wear was observed directly at an unannounced follow-up examination 4-11 months after initial provision of spectacles. The association between five proposed refractive cutoff protocols and visual improvement and spectacle compliance were examined in separate multivariate models. MAIN OUTCOMES: Refractive cutoffs for spectacle distribution which would effectively identify children with improved vision, and those more likely to comply with spectacle wear. RESULTS: Among 8520 children screened, 810 (9.5%) received spectacles, of whom 636 (79%) were aged 10-14 years, 530 (65%) were girls, 324 (40%) had vision improvement > or = 3 lines, and 483 (60%) were examined 6.4+/-1.5 (range 4.6 to 10.9) months after spectacle dispensing. Among examined children, 149 (31%) were wearing or carrying their glasses. Children meeting cutoffs < or = -0.75 D of myopia, > or = +1.00 D of hyperopia and > or = +0.75 D of astigmatism had significantly greater improvement in vision than children failing to meet these criteria, when adjusting for age, gender and urban versus rural residence. None of the proposed refractive protocols discriminated between children wearing and not wearing spectacles. Presenting vision and improvement in vision were unassociated with subsequent spectacle wear, but girls (p < or = 0.0006 for all models) were more likely to be wearing glasses than were boys. CONCLUSIONS: To the best of our knowledge, this is the first suggested refractive cutoff for glasses dispensing validated with respect to key programme outcomes. The lack of association between spectacle retention and either refractive error or vision may have been due to the relatively modest degree of refractive error in this African population.

Cartografia geoquímica da ilha de Santiago com uma densidade de amostragem média/baixa

A ilha de Santiago é a maior do arquipélago de Cabo Verde, apresenta uma área de 991 km2, com um comprimento e largura máximos de 54,9 km e 29 km, respectivamente, e 1392 m de maior altitude. As condições climáticas e a erosão são alguns dos problemas naturais do arquipélago de Cabo Verde. Além disso, a intervenção humana no ambiente superficial revela-se muitas vezes inadequada e com forte impacto. A construção em solos com aptidão agrícola ou florestal, as actividades industriais, a deposição de materiais sólidos ou líquidos de forma inadequada, as práticas agrícolas incorrectas e intensivas, o uso abusivo de pesticidas e fertilizantes, a rega com água contaminada, a sobreexploração de aquíferos que levam muitas vezes à salinização, etc. têm enorme impacto em termos de contaminação de solos, águas superficiais e subterrâneas nas áreas envolventes. Por conseguinte, o conhecimento da variabilidade geoquímica natural é fundamental para a resolução de questões de índole económica, ambiental e de ordenamento do território, médica, e jurídica. A necessidade de construir uma base de dados de geoquímica georeferenciada que caracterize o ambiente superficial da ilha de Santiago foi a principal motivação para a realização deste estudo. Realizou-se um levantamento geoquímico de 337 amostras de sedimentos de corrente e 249 amostras de solos na ilha de Santiago, tendo sido seguidas as recomendações do Projecto Internacional IGCP 259 não só na fase de amostragem, mas também nas fases seguintes de preparação, análise, tratamento dos dados e elaboração de mapas. Determinaram-se os teores, na fracção < 2 mm, para 36 elementos – 9 elementos maiores (Al, Ca, Fe, K, Mg, Mn, Na, P, Ti) e 27 elementos vestigiais (Ag, As, Au, B, Ba, Bi, Cd, Co, Cr, Cu, Ga, Hg, La, Mo, Ni, Pb, S, Sb, Sc, Se, Sr, Th, Tl, U, V, W, Zn). Efectuou-se ainda a análise textural e estudou-se a composição mineralógica de cerca de 25% das amostras. Analisaram-se, também, 103 amostras de rochas, colhidas nas várias formações da ilha de Santiago, tendo sido determinados os teores de K2O, Na2O, Fe2O3(T), MnO, Sc, Cr, Co, Zn, Ga, As, Br, Rb, Zr, Sb, Cs, Ba, Hf, Ta, W, Th e U e REE, a fim de se fazer uma comparação com os teores destes elementos encontrados nos solos e sedimentos de corrente, averiguando se a sua variação é ou não essencialmente condicionada pela geoquímica da rocha-mãe. Os padrões geoquímicos obtidos através dos mapas de distribuição espacial foram correlacionados com a natureza da rocha mãe, o tipo de solo, e ainda com algumas fontes de contaminação. A interpretação dos resultados foi realizada não só pela observação dos mapas geoquímicos, mas também após análise estatística dos conjuntos de dados obtidos, e apoiada em informação diversa disponível. A utilização da Análise de Componentes Principais permitiu distinguir associações entre elementos químicos, quer de origem geogénica quer antropogénica. Foram ainda elaborados mapas de distribuição espacial de vários índices multielementares de importância ambiental, como o Índice de Acidificação Al/(Ca+Mg+K), Índice de Combi, Índice de Avaliação de Risco Ambiental e Índices de Enriquecimento/Contaminação para vários grupos de elementos considerados como “primary pollutant metals”.

Estudo dos depósitos lutíticos da orla ocidental: matérias-primas minerais

Neste trabalho foram efectuados estudos de natureza químico – mineralógica e tecnológica em quatro depósitos sedimentares: Vale Grande, Aguada de Cima, Anadia e Monsarros. Estes estudo permitiram o estabelecimento da coluna tipológica em cada um dos depósitos. No jazigo de Aguada evidencia-se a existência de dois níveis argilosos: a unidade “Barro Negro” de natureza ilito-quartzo-caulinítica (argilas especiais) e a unidade “Argilas de Boialvo” com composição quartzo – ilite – caulinite (argilas comuns). Nos jazigos de Anadia e Monsarros o enchimento argiloso é constituído por argilas compatíveis com as da unidade “Argilas de Boialvo” do jazigo de Aguada, não existindo evidências de deposição de argilas de natureza da unidade “Barro Negro”. Em complemento, foram realizados estudos químicos (elementos menores e Terras Raras) nos diferentes depósitos lutíticos para inferir a importância dos minerais acessórios e argilosos na sua distribuição, de modo a poder determinar-se a sua proveniência. Neste trabalho foi também realizado um estudo de pormenor, de natureza mineralógica (DRX) e química (maiores, menores e Terras Raras), das possíveis rochas-fonte. Perante os resultados obtidos através do estudo mineralógico, químico (elementos maiores, menores e Terras Raras) e, ainda, dos estudos isotópicos Rb-Sr e Sm-Nd, pode inferir-se que o Complexo Xisto-Grauváquico foi a formação geológica que mais material forneceu para a formação dos sedimentos argilosos que ocorrem nas áreas de Vale Grande, Aguada, Anadia e Monsarros. Por último, apresenta-se uma definição para o conceito de argila especial cerâmica, utilizado na gama alta da indústria cerâmica, tendo em consideração o padrão químico, mineralógico e tecnológico.

Metodologia de avaliação da sustentabilidade económica de edifícios com base no ciclo de vida

O Comité Técnico CEN/TC 350 “Sustainability of construction works” elaborou um conjunto de normas que propõem um sistema de avaliação do contributo da construção para o desenvolvimento sustentável, nomeadamente através da avaliação dos seus desempenhos ambiental, social e económico, baseado numa abordagem de ciclo de vida. Os sistemas de avaliação da sustentabilidade de edifícios têm um papel importante em todas as fases do ciclo de vida (anterior à utilização, utilização e fim de vida) de um edifício que se pretenda sustentável, pois agilizam a integração entre os aspetos ambientais, sociais e económicos com outros critérios de decisão. Esta dissertação tem como objetivo apresentar uma metodologia inovadora de avaliação sistemática do desempenho económico de edifícios dentro do conceito sustentabilidade, com base na análise do ciclo de vida, conforme estabelecido na EN 16627:2015, que descreve o processo de tomada de decisão e documentação da avaliação do desempenho económico de edifícios dentro do conceito da avaliação da sustentabilidade, com base na análise de ciclo de vida (ACV). A metodologia, intitulada “Methodology of Assessment of Economic Performance - Residential Buildings – MAEP-RB”, permite a avaliação do desempenho e da sustentabilidade económica de edifícios na fase anterior à utilização do ciclo de vida. A metodologia segue o princípio de modularidade, onde os aspetos e impactes que influenciam o desempenho económico do edifício durante as fases do seu ciclo de vida, são atribuídos aos indicadores de cada módulo do ciclo de vida em que eles ocorrem dentro da respectiva etapa. Faz parte integrante desta metodologia uma base de dados contendo um modelo de custos na construção baseado na subdivisão do edifício em sistemas, subsistemas, elementos, componentes e subcomponentes, em que este último se encontra ao nível dos recursos. Os resultados da avaliação do desempenho económico e da sustentabilidade económica são desagregados em vários níveis, ou seja, ao nível da fase anterior à utilização do ciclo de vida do edifício, de cada etapa, de cada módulo e de cada indicador económico. A MAEP-RB avalia simultaneamente o desempenho económico e a sustentabilidade económica de edifícios sendo o resultado do desempenho económico expresso em unidade monetária e o da sustentabilidade comunicado por um Índice de Sustentabilidade Económica (A+, A, B, C, D, E).

Repply to: Brito, A.C., Brotas, V., Caetano, M., Coutinho, T.P., Bordalo, A.A., Icely, J., Neto, J.M., Serôdio, J., Moita, T. (2012) "Defining phytoplankton class boundaries in Portuguese transitional waters: an evaluation of the ecological quality status according to the Water Framework Directive" [Ecological Indicators 19, 5-14]

We write to comment on the recently published paper “Defining phytoplankton class boundaries in Portuguese transitional waters: an evaluation of the ecological quality status according to the Water Framework Directive” (Brito et al., 2012). This paper presents an integrated methodology to analyse the ecological quality status of several Portuguese transitional waters, using phytoplanktonrelated metrics. One of the systems analysed, the Guadiana estuary in southern Portugal, is considered the most problematic estuary, with its upstream water bodies classified as Poor in terms of ecological status. We strongly disagree with this conclusion and we would like to raise awareness to some methodological constraints that, in our opinion, are the basis of such deceptive conclusions and should therefore not be neglected when using phytoplankton to assess the ecological status of natural waters.

Grazing impact of microzooplankton upon phytoplankton

Alterations of freshwater flow regimes and increasing eutrophication can lead to alterations in phytoplankton biomass, composition, and growth in estuaries and adjacent coastal waters. Since phytoplankton is the first trophic level of most aquatic foodwebs, these changes can be propagated to other biological compartments, eventually impacting water quality and ecosystem services. However, phytoplankton responses to environmental changes in abiotic variables (e.g., light, nutrients) are additionally controlled by mortality or removal processes (e.g., grazing, horizontal advection and viral lysis). Grazing exerted by microzooplankton, usually dominated by phagotrophic protists, is considered the most relevant phytoplankton mortality factor in most aquatic systems (see Calbet, Landry 2004). In fact, grazing impact of microzooplankton can prevent phytoplankton accumulation in marine systems despite an overall increase in phytoplankton replication rate. By consequence, microzooplankton grazing may minimize problems associated to increased eutrophication and, ultimately, prevent the occurrence of harmful phytoplankton blooms. Thus, microzooplankton grazing on phytoplankton constitutes a key biological process required to understand and predict relationships between hydrological and biological processes in aquatic ecosystems and to use ecosystem properties to improve water quality and enhance ecosystem services, general principles of the Ecohydrology Concept (Zalewski 2000).

Effects of nutrient and light enrichment on phytoplankton growth

Alterations of freshwater flow regimes and increasing eutrophication lead to alterations in light availability and nutrient loading into adjacent estuaries and coastal areas. Phytoplankton community respond to these changes in many ways. Harmful phytoplankton blooms, for instance, may be a consequence of changes in nutrient supply, as well as the replacement of some phytoplankton species (like diatoms, that contribute for the development of large fish and shellfish populations) by ohers (like cyanobacteria, that may be toxic and represent an undesirable food source for higher trophic levels). Nutrient and light enrichment experiments allow us to understand and predict the effects of eutrophication on the growth of phytoplankton. This is a fundamental tool in water management issues, since it enables the prediction of changes in the phytoplankton community that may be harmful to the whole ecosystem, and the design of mitigation strategies (Zalewski 2000).

Molecular epidemiology of Aspergillus collected from cystic fibrosis patients

Background - Aspergillus respiratory infection is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function and allergic disease. Methods - Fifty-three Aspergillus isolates recovered from CF patients were identified to species by Internal Transcribed Spacer Region (ITS), β-tubulin, and calmodulin sequencing. Results - Three species complexes (Terrei, Nigri, and Fumigati) were found. Identification to species level gave a single Aspergillus terreus sensu stricto, one Aspergillus niger sensu stricto and 51 Aspergillus fumigatus sensu stricto isolates. No cryptic species were found. Conclusions - To our knowledge, this is the first prospective study of Aspergillus species in CF using molecular methods. The paucity of non-A. fumigatus and of cryptic species of A. fumigatus suggests a special association of A. fumigatus sensu stricto with CF airways, indicating it likely displays unique characteristics making it suitable for chronic residence in that milieu. These findings could refine an epidemiologic and therapeutic approach geared to this pathogen.

Fate Hazardous elements in soils surrounding a coal-fired power plant complex

Proceedings of the 13th International UFZ-Deltares Conference on Sustainable Use and Management of Soil, Sediment and Water Resources - 9–12 June 2015 • Copenhagen, Denmark

Enhanced expression of 70-kilodalton heat shock protein limits cell division in a sepsis-induced model of acute respiratory distress syndrome.

OBJECTIVE: Fibrotic changes are initiated early in acute respiratory distress syndrome. This may involve overproliferation of alveolar type II cells. In an animal model of acute respiratory distress syndrome, we have shown that the administration of an adenoviral vector overexpressing the 70-kd heat shock protein (AdHSP) limited pathophysiological changes. We hypothesized that this improvement may be modulated, in part, by an early AdHSP-induced attenuation of alveolar type II cell proliferation. DESIGN: Laboratory investigation. SETTING: Hadassah-Hebrew University and University of Pennsylvania animal laboratories. SUBJECTS: Sprague-Dawley Rats (250 g). INTERVENTIONS: Lung injury was induced in male Sprague-Dawley rats via cecal ligation and double puncture. At the time of cecal ligation and double puncture, we injected phosphate-buffered saline, AdHSP, or AdGFP (an adenoviral vector expressing the marker green fluorescent protein) into the trachea. Rats then received subcutaneous bromodeoxyuridine. In separate experiments, A549 cells were incubated with medium, AdHSP, or AdGFP. Some cells were also stimulated with tumor necrosis factor-alpha. After 48 hrs, cytosolic and nuclear proteins from rat lungs or cell cultures were isolated. These were subjected to immunoblotting, immunoprecipitation, electrophoretic mobility shift assay, fluorescent immunohistochemistry, and Northern blot analysis. MEASUREMENTS AND MAIN RESULTS: Alveolar type I cells were lost within 48 hrs of inducing acute respiratory distress syndrome. This was accompanied by alveolar type II cell proliferation. Treatment with AdHSP preserved alveolar type I cells and limited alveolar type II cell proliferation. Heat shock protein 70 prevented overexuberant cell division, in part, by inhibiting hyperphosphorylation of the regulatory retinoblastoma protein. This prevented retinoblastoma protein ubiquitination and degradation and, thus, stabilized the interaction of retinoblastoma protein with E2F1, a key cell division transcription factor. CONCLUSIONS: : Heat shock protein 70-induced attenuation of cell proliferation may be a useful strategy for limiting lung injury when treating acute respiratory distress syndrome if consistent in later time points.

Geochemistry and petrogenesis of the Proterozoic Pater metavolcanic suite, Spragge, Ontario /

The Pater metavolcanic suite (PVS) was extruded as part O'f the basal Pater Formation of the Huronian Supergroup ca. 2.4 Ga. They Ars classified as wi thin-plate tholeiites associated with an immature ri-fting episode, and are inter layered with associated vol cani clastic and metasedimentary units. Post-solidif ication alteration caused redistribution o-f the alkalies, Sr, Rb, Ba, Cu, and SiO^. Ce, Y, Zr, CFezOs (as total Fe), Al^Os, TiOa, and, PaOa are considered to have remained essentially immobile in least altered samples. Petrogenetic modelling indicates the PVS was derived from the partial melting of two geochemical ly similar sources in the sub-continental lithosphere. Fractionation was characterized by an oli vine-plagioclase assemblage and a sub-volcanic plagioclase-clinopyroxene assemblage. A comparative study indicates that enrichment of the postulated Huronian source cannot be reconciled by Archean contamination. Enrichment is thought to have been caused by hydrous veined metasomatic heterogeneities in the sub-continental lithosphere, generated by an Archean subduct ion event before 2.68 Ga.

An investigation of geological and geochemical characteristics of late-Quaternay sediments in the Georgian Bay Region, Southern Ontario

Core samples of postglacial sediments and sediment surface samples from Shepherd Lake on the Bruce Peninsula, Harts Lake on the Canadian Shield, and two cores from Georgian Bay (core P-l in the western deep part and core P-7 in the eastern shallow part) have been analyzed for pH, grain size distribution, water content, bulk density, loss on ignition at 4500C and 11000 C, major oxides (Si02 ,A1203,!FeO,MgO,CaO, Na20,K20,Ti02 ,MnO and P205) and trace elements (Ba,Zr,Sr,y,S, Zn,Cu,Ni,Ce and Rb). The sediment in Georgian Bay are generally fine grained (fine silt to very fine silty clay) and the grain size decreases from the Canadian Shield (core p-7) towards the Bruce Peninsula (core P-l) along the assumed direction of sediment transport. This trend coincides with a decrease in sorting coefficient and an increase in roundness. Other physical characteristics, such as water content, bulk density and loss on ignition are positively correlated with the composition of sediments and their compaction, as well as with the energy of the depositional environment. Analyses of sediment surface samples from Shepherd Lake and Harts Lake indicate the influence of bedrock and surficial deposits in the watershed on pH condition that is also influenced by the organic matter content and probably I ! I man's activities. Organic matter content increases significantly in the surface sediment in these small lakes as a result of either natural eutrophication or anthropogenic organic loading. The extremely high organic matter content in Shepherd Lake sediment indicates rapid natural eutrophication in this closed basin and high biological productivity during postglacial time, probably due to high nutrient levels and shallow depth. The chemical composition of the Canadian Shield bedrock is positively correlated with the chemical characteristics of predominantly inorganic lake sediments that were derived from the Shield rocks by glacial abrasion and by postglacial weathering and erosion of both bedrock and surficial deposits. High correlation coefficients were found between organic matter in lake sediments and major oxides (Si02,AI203,.~FeO, MgO,CaO,K20 and MnO) , as well as some trace elements (Ba,Y, S,Zn,Cu,Ni and Rb). The chemical composition of sediments in Harts Lake and core P-7 in Georgian Bay on the Canadian Shield differs from the chemistry of sediments in Shepherd Lake and core P-l in Georgian Bay on the Bruce Peninsula. The difference between cores P-l and P-7 is indicated by values of Si02 , AI203 ,:LFeo,Mgo,CaO,Ba,Zr,Sr,y and S, and also by the organic matter content. This study indicates that the processes of sediment transport, depositional environment, weathering of the rocks and surficial deposits in the watershed, as well as chemical composition of source rocks all affect the chemical characteristics of lake sediments. The stratigraphic changes and variations in lake sediment chemistry with regard to major oxides, trace elements, and organic matter content are probably related to the history of glacial and postglacial lake stages of the Georgian Bay Region and, therefore, the geochemical data can make a useful contribution to a better understanding of the Late-Quaternary history of the Great Lakes.