On the ordeal of quinolone preparation via cyclisation of aryl-enamines; synthesis and structure of ethyl 6-methyl-7-iodo-4-(3-iodo-4-methylphenoxy)-quinoline-3-carboxylate

Recent studies directed to the design of compounds targeting the bc(1) protein complex of Plasmodium falciparum, the parasite responsible for most lethal cases of malaria, identified quinolones (4-oxo-quinolines) with low nanomolar inhibitory activity against both the enzyme and infected erythrocytes. The 4-oxo-quinoline 3-ester chemotype emerged as a possible source of potent bc(1) inhibitors, prompting us to expand the library of available analogs for SAR studies and subsequent lead optimization. We now report the synthesis and structural characterization of unexpected ethyl 6-methyl-7-iodo-4-(3-iodo-4-methylphenoxy)quinoline-3-carboxylate, a 4-aryloxy-quinoline 3-ester formed during attempted preparation of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate (4-oxo-quinoline 3-ester). We propose that the 4-aryloxy-quinoline 3-ester derives from 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate (4-hydroxy-quinoline 3-ester), the enol form of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate. Formation of the 4-aryloxy-quinoline 3-ester confirms the impact of quinolone/hydroxyquinoline tautomerism, both on the efficiency of synthetic routes to quinolones and on pharmacologic profiles. Tautomers exhibit different cLogP values and interact differently with the enzyme active site. A structural investigation of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate and 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate, using matrix isolation coupled to FTIR spectroscopy and theoretical calculations, revealed that the lowest energy conformers of 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate, lower in energy than their most stable 4-oxo-quinoline tautomer by about 27 kJ mol(-1), are solely present in the matrix, while the most stable 4-oxo-quinoline tautomer is solely present in the crystalline phase.Fundacao para a Ciencia e Tecnologia (FCT - Portugal) [UID/Multi/04326/2013]; QREN-COMPETE-UE; CCMAR; FCT [SFRH/BD/81821/2011, RECI/BBB-BQB/0230/2012, UI0313/QUI/2013, UID/FIS/04564/2016]; FEDER/COMPETE-UE; [PTDC/QEQ-QFI/3284/2014 - POCI-01-0145-FEDER-016617]info:eu-repo/semantics/publishedVersio

Sensitive areas under radium/uranium mine drainage - the Picoto mine case study, central Portugal

A zona mineira de Picoto está localizada próximo de Vilar Seco (Viseu, Centro de Portugal). Ocorre numa área de declive suave, altitude variando entre 360-380 m, incluída na bacia do rio Cagavaio, com drenagem dominante NE-SW. A mineralização ocorre em veios de quartzo, que intersectam o granito Varisco, porfiróide de duas micas. Os filões de quartzo preenchem falhas N37°-45°E e N50°-70°E, localmente brechificadas. Estes filões contêm meta-torbernite e uranófano, e alguns minerais portadores de U, como clorite e hidróxidos de Fe e Mn. A exploração ocorreu em duas fases, entre 1917 e 1953. Após cessada a exploração, permaneceram as escombreiras resultantes da exploração e a área nunca foi reabilitada. Neste momento, está ocupada por culturas locais, principalmente vinhas e produtos agrícolas. Vinte amostras de águas superficiais e subterrâneas foram colhidas entre 2008 e 2009. Em geral, as águas apresentam valores de pH entre 4.7 a 6.3 e são pouco mineralizadas (CE = 44-190 μS/cm; TDS = 49-137 mg/L). Contudo, algumas águas estão contaminadas em NO2, Fe, Mn, Cu, As e U, e não devem ser utilizadas para consumo humano nem em atividades agrícolas. A contaminação da água está associada principalmente à antiga mina de rádio/urânio e atividades humanas desenvolvidas.The Picoto mine area is located at Vilar Seco village (Viseu, central Portugal), in a soft slope area with altitudes ranging from 360 to 380 m, included in the Cagavaio river catchment, with a dominant NE-SW drainage. The mineralization occurs mainly in quartz veins, which intersect a Variscan porphyritic two-mica granite. The quartz veins fill N37°-45°E and N50°-70°E faults, locally brecciated. The quartz veins contain meta-torbernite and uranophane, and some U-bearing minerals, such as chlorite and Fe- and Mn-hydroxides. The exploitation was carried out in two stages, between 1917 and 1953. Since closure, the area contains mine rejected materials and has never been restored. Therefore, a local cultivated area, mainly for vines and domestic consumption agricultural products, is now deployed. A total of twenty surface and groundwater samples were collected between 2008 and 2009. In general, the waters yield pH values ranging from 4,4 to 6,3 and are poorly mineralized (EC=44-190 µS/cm; TDS= 49-137 mg/L). However, some waters are contaminated with NO₂, Fe, Mn, Cu, As and U and must not be used neither for human consumption nor in agricultural activities. The water contamination is mainly associated with the old radium/uranium mine and subsequent human activities developed in the area.Este trabalho teve suporte financeiro através do ICT e do projeto UID/GEO/04035/2013.info:eu-repo/semantics/publishedVersio

Horton's Disease. 40 Clinical Cases

Apresentamos uma casuística de 40 casos de Doença de Horton observados no Serviço de Medicina 2 e na Consulta de Doenças Autoimunes do Hospital de Santo António dos Capuchos, entre 1984 e 2002. Pretendemos comentar e destacar os aspectos práticos, clínicos, de diagnóstico e de terapêutica, relacionados com o adequado controle da doença, através da análise comparativa da literatura com os nossos dados

In vitro determination of extracellular proteins from xylella fastidiosa

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The phytopathogen Xylella fastidiosa causes economic losses in important agricultural crops. Xylem vessel occlusion caused by biofilm formation is the major mechanism underlying the pathogenicity of distinct strains of X. fastidiosa. Here, we provide a detailed in vitro characterization of the extracellular proteins of X. fastidiosa. Based on the results, we performed a comparison with a strain J1a12, which cannot induce citrus variegated chlorosis symptoms when inoculated into citrus plants. We then extend this approach to analyze the extracellular proteins of X. fastidiosa in media supplemented with calcium. We verified increases in extracellular proteins concomitant with the days of growth and, consequently, biofilm development (330 days). Outer membrane vesicles carrying toxins were identified beginning at 10 days of growth in the 9a5c strain. In addition, a decrease in extracellular proteins in media supplemented with calcium was observed in both strains. Using mass spectrometry, 71 different proteins were identified during 30 days of X. fastidiosa biofilm development, including proteases, quorum-sensing proteins, biofilm formation proteins, hypothetical proteins, phage-related proteins, chaperones, toxins, antitoxins, and extracellular vesicle membrane components.The phytopathogen Xylella fastidiosa causes economic losses in important agricultural crops. Xylem vessel occlusion caused by biofilm formation is the major mechanism underlying the pathogenicity of distinct strains of X. fastidiosa. Here, we provide a de7Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2001/07533-7, 2012/51580-4]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Computational Biology Program)CAPESFAPESP [2011/50268-4]CAPES (Computational Biology Program)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

The Use of Polypropylene and High-Density Polyethylene on Cork Plastic Composites for Large Scale 3D Printing

Acknowledgements This work is supported by the Fundação para a Ciência e a Tecnologia (FCT) and Centro2020 through the Project references: UID/Multi/04044/2013 and PAMI - ROTEIRO/0328/2013 (Nº 022158). In addition, the authors acknowledge the funding from the project World of Outstanding Wool and Wood (WOWW), POCI-01-0247-FEDER-017574 from the Portuguese National Innovation Agency. The authors gratefully acknowledge to Amorim Cork Composites for the cork powder. We thank Ana O. Tojeira and Ana R. Fonseca for the support provided in performing the laboratorial tests as Laboratory Managing Engineers.This work focuses on studying the possibility of 3D printing of composite materials composed by cork and a polymer matrix (CPC). Initially the cork was mixed with two types of polymers (HDPE and PP) in different proportions and later processed using extrusion and injection. The composites were tested to study the physical, chemical and mechanical properties. The material was then tested on a large-scale 3D printer to study its feasibility and the ability to produce new products through 3D printing. Attention was focused on the use of pure cork, varying the concentration of cork and coupling agent in thermoplastic matrix composites of PP and HDPE. It was demonstrated that the increase of 5wt.% of coupling agent in the two types of polymers significantly improved the mechanical properties and adhesion between the phases but the increase in cork concentration decreased mechanical properties and crystallinity. The CPCs with PP showed to have better mechanical properties, better aesthetic and internal structural quality, and easier processability than those with HDPE matrix. Nevertheless, the HDPE CPCs showed a high degree of crystallization. Concerning 3D printing, it was demonstrated the possibility of making new products based on natural cork fibers, showing promising results, although additional research is still needed to optimize the process.info:eu-repo/semantics/publishedVersio

Assessment of metal and metalloid contamination in the waters and stream sediments around the abandoned uranium mine area from Mortórios, central Portugal

In the abandoned Mortórios uranium mine area there are quartz veins containing wolframite and sulphides and basic rock dykes with torbernite and autunite cutting a porphyritic granite. The basic rock dykes were exploited and produced about 27 tonnes of U3O8, from 1982 to 1988. There are an open pit lake and nine dumps. Surface water and groundwater are contaminated in U, As, Cd, Cr, Cu, Fe, Mn, Ni and Pb. Stream sediments are contaminated in U, As, Th and W, which are adsorbed by smectite, kaolinite and iron- and aluminium- oxy-hydroxides. The maximum U concentrations are of 1268 ug/L in the open pit lake, 100 g/L in surface water, 103 ug/L in groundwater and 81.5 mg/kg in stream sediments all downstream of the open pit lake and dumps. Further downstream the U concentration in water decreases, due to the high mobility of U (VI), but the U concentration in stream sediments increases. Calcium uranyl carbonate dominates in the open pit lake, but uranyl carbonate complexes dominate in surface water and groundwater. The maximum As concentrations are 56.0 g/L in the open pit lake, 63.4 g/L in the surface water and 66.7 g/L in the groundwater, both downstream of the open pit lake and dumps. The arsenic occurs as As (V). The Mortórios area is compared with two other areas exploited from open pits, all located in the uranium-bearing Beira area of central Portugal. Vale de Abrutiga produced 90 tonnes of U3O8 between 1982 and 1989 and Mondego Sul produced 75 tonnes of U3O8 from 1987 to 1991. The two mines consist of quartz veins containing sulphides, saleeite and meta-saleeite at Vale de Abrutiga and with sulphides, autunite, torbernite, meta-uranocircite and meta-saleeite at Mondego Sul cutting the Schist-graywacke complex. The mine area of Vale de Abrutiga with the highest exploitation of U2O3 has strongly acidic to slight alkaline water, which is the most contaminated. Mortórios with the lowest exploitation presents a higher contamination of slightly acidic to alkaline water than that of acidic to alkaline water from Mondego Sul, but the former has As (V), whereas the latter has As (III), which is toxic. The stream sediments from Mortórios present the lowest contamination, except for Th that has a higher median value than that from Vale de Abrutiga. Stream sediments from Mondego Sul have higher U, Th, Pb and lower Co, Cr, Cu and Zn median values than those of Vale de Abrutiga.We are grateful to J.F.C. Mendes for the determination of organic matter and cation exchange capacity in samples of stream sediments. We thank Robert Ayuso and three anonymous reviewers for their comments. Some financial support was given by the project UID/GEO/04035/2013