Radiocarbon geochronology of the sediments of the São Paulo Bight (southern Brazilian upper margin)

The aim of this work was to generate an inventory of the data on radiocarbon datings obtained from sediments of the São Paulo Bight (southern Brazilian upper margin) and to analyze the data in terms of Late Quaternary sedimentary processes and sedimentation rates. A total of 238 radiocarbon datings from materials collected using differents ampling procedures was considered for this work. The sedimentation rates varied from less than 2 to 68 cm.kyr-1. The highest sedimentation rate values were found in a low-energy (ría type) coastal system as well as in the upwelling zones of Santa Catarina and Cabo Frio. The lowest rates were found on the outer shelf and upper slopes. Our results confirm the strong dependency of the shelf currents, with an emphasis to the terrigenous input from the Río de La Plata outflow which is transported via the Brazilian Coastal Current, as well as of the coupled Brazil Current - Intermediate Western Boundary Current (BC-IWBC) dynamics on the sedimentary processes. At least three indicators ofthe paleo sea level were found at 12200 yr BP (conventional radiocarbon age) (103 meters below sea level - mbsl),8300-8800 cal yr BP (13 mbsl) and 7700-8100 cal yr BP (6 mbsl).O objetivo deste trabalho foi a geração de um inventário dos dados de datação de radiocarbono obtidos de sedimentos do Embaiamento de São Paulo (Margem Continental Superior do Sul do Brasil) e analisar os dados em termos de processos sedimentares quaternários e taxas de sedimentação. Um total de238 datações ao radiocarbono de materiais coletados com autilização de procedimentos amostrais diferentes foi considerado neste trabalho. As taxas de sedimentação variaram de menor que 2 a 68 cm.kyr-1. As taxas de sedimentação mais altas foram encontradas em um sistema costeiro de baixa energia (tipo ría), bem como nas zonas de ressurgência de Santa Catarina e Cabo Frio. As taxas mais baixas foram encontradas na plataforma externa e talude superior. Nossos resultados confirmam a forte dependência do sistema de correntes de plataforma, com ênfase no aporte terrígeno oriundo do Rio daPrata, transportado através da Corrente Costeira do Brasil, e da dinâmica da Corrente do Brasil - Corrente de Contorno Intermediária (CB-CCI) nos processos sedimentares. Pelo menostrês indicadores de paleo-níveis marinhos foram encontrados a 12200 anos AP (idade radiocarbônica convencional) (103 metros abaixo do nível do mar atual - manm), 8300-8800 cal anos AP (13 manm) e 7700-8100 cal anos BP (6 manm).Fundação de Amparo à Pesquisado Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Measurements of CFTR-Mediated Cl- Secretion in Human Rectal Biopsies Constitute a Robust Biomarker for Cystic Fibrosis Diagnosis and Prognosis

BACKGROUND: Cystic Fibrosis (CF) is caused by ∼1,900 mutations in the CF transmembrane conductance regulator (CFTR) gene encoding for a cAMP-regulated chloride (Cl(-)) channel expressed in several epithelia. Clinical features are dominated by respiratory symptoms, but there is variable organ involvement thus causing diagnostic dilemmas, especially for non-classic cases. METHODOLOGY/PRINCIPAL FINDINGS: To further establish measurement of CFTR function as a sensitive and robust biomarker for diagnosis and prognosis of CF, we herein assessed cholinergic and cAMP-CFTR-mediated Cl(-) secretion in 524 freshly excised rectal biopsies from 118 individuals, including patients with confirmed CF clinical diagnosis (n=51), individuals with clinical CF suspicion (n=49) and age-matched non-CF controls (n=18). Conclusive measurements were obtained for 96% of cases. Patients with "Classic CF", presenting earlier onset of symptoms, pancreatic insufficiency, severe lung disease and low Shwachman-Kulczycki scores were found to lack CFTR-mediated Cl(-) secretion (<5%). Individuals with milder CF disease presented residual CFTR-mediated Cl(-) secretion (10-57%) and non-CF controls show CFTR-mediated Cl(-) secretion ≥ 30-35% and data evidenced good correlations with various clinical parameters. Finally, comparison of these values with those in "CF suspicion" individuals allowed to confirm CF in 16/49 individuals (33%) and exclude it in 28/49 (57%). Statistical discriminant analyses showed that colonic measurements of CFTR-mediated Cl(-) secretion are the best discriminator among Classic/Non-Classic CF and non-CF groups. CONCLUSIONS/SIGNIFICANCE: Determination of CFTR-mediated Cl(-) secretion in rectal biopsies is demonstrated here to be a sensitive, reproducible and robust predictive biomarker for the diagnosis and prognosis of CF. The method also has very high potential for (pre-)clinical trials of CFTR-modulator therapies.This work was supported by grants TargetScreen2 (EU/FP6/LSH/2005/037365), PIC/IC/83103/2007; PTDC/MAT/118335/2010; PEstOE/BIA/UI4046/2011 (to BioFIG) and PEstOE/MAT/UI0006/2011 (to CEAUL) from FCT (Portugal); and FAPESP (SPRF, Brazil), CNPq (40.8924/2006/3, Brazil) and Mukoviszidose e.V. S02/10 (Germany). MS and IU are recipients of SFRH/BD/35936/2007 and SFRH/BD/69180/2010 PhD fellowships (FCT, Portugal), respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Subacute and chronic hypersensitivity pneumonitis: Histopathological patterns and survival

Background: in hypersensitivity pneumonitis (HP), survival can be predicted on the basis of the severity of fibrosis in surgical lung biopsy, but few data are available on the influence of clinical, functional, tomographic and histologic findings on prognosis. Objectives: To describe the impact on survival. of clinical data, histological patterns, and HRCT findings in subacute/chronic HP.Methods: A retrospective analysis of 103 patients diagnosed with HP submitted to surgical lung biopsy. Chronic HP was characterized by HRCT findings indicative of fibrosis (n = 76).Results: the most relevant exposures were to molds and birds. Lung biopsies revealed typical HP with granulomas in 46 patients, bronchiolocentric interstitial pneumonia in 27, and nonspecific interstitial pneumonia (NSIP) in 16. By univariate analysis, several findings were predictors of mortality: older age, mate sex, velcro crackles, higher FEV(1)/FVC ratio, lower oxygen saturation during exercise, and absence of mosaic pattern/air trapping and presence of fibrosis on HRCT. By multivariate analysis, remained significant: age (p = 0.007), oxygen saturation during exercise (p = 0.003), and mosaic pattern/air trapping on HRCT (p = 0.004). Patients with NSIP had a greater survival than did those with typical histology and those with bronchiolocentric pneumonia (p = 0.033).Conclusions: A wide range of histological features are found in FIR Typical findings are seen in 45% of cases, Other common patterns are NSIP and centriacinar lesions. Survival is better in patients with NSIP and worse in those with older age, desaturation during exercise, and absence of mosaic pattern/air trapping on HRCT. (c) 2009 Etsevier Ltd. All rights reserved.Universidade Federal de São Paulo, Div Resp Dis, Dept Med, Escola Paulista Med, BR-04023062 São Paulo, BrazilHosp Servidor Publ Estadual, Div Resp Dis, Dept Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Div Resp Dis, Dept Med, Escola Paulista Med, BR-04023062 São Paulo, BrazilWeb of Scienc

Mid-lower bathyal benthic foraminifera of the Campos Basin, southeastern Brazilian margin: biotopes and controlling ecological factors

Abstrac

Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study

<p>Abstract</p> <p>Background</p> <p>Structure-based drug design (SBDD) can provide valuable guidance to drug discovery programs. Robust construct design and expression, protein purification and characterization, protein crystallization, and high-resolution diffraction are all needed for rapid, iterative inhibitor design. We describe here robust methods to support SBDD on an oral anti-cytokine drug target, human MAPKAP kinase 2 (MK2). Our goal was to obtain useful diffraction data with a large number of chemically diverse lead compounds. Although MK2 structures and structural methods have been reported previously, reproducibility was low and improved methods were needed.</p> <p>Results</p> <p>Our construct design strategy had four tactics: <it>N</it>- and <it>C</it>-terminal variations; entropy-reducing surface mutations; activation loop deletions; and pseudoactivation mutations. Generic, high-throughput methods for cloning and expression were coupled with automated liquid dispensing for the rapid testing of crystallization conditions with minimal sample requirements. Initial results led to development of a novel, customized robotic crystallization screen that yielded MK2/inhibitor complex crystals under many conditions in seven crystal forms. In all, 44 MK2 constructs were generated, ~500 crystals were tested for diffraction, and ~30 structures were determined, delivering high-impact structural data to support our MK2 drug design effort.</p> <p>Conclusion</p> <p>Key lessons included setting reasonable criteria for construct performance and prioritization, a willingness to design and use customized crystallization screens, and, crucially, initiation of high-throughput construct exploration very early in the drug discovery process.</p

The ITRAX core scanner, a useful tool to distinguish anthropic vs. climatic influences in lagoon of Aveiro (N Portugal)

The main goal of this work is to distinguish anthropic and climatic influences in sediments from the lagoon of Aveiro (Portugal). This study is based on a core (240-cm long) collected in Murtosa Channel. Optical and X-radiographic images and high-resolution elemental profiles were acquired with ITRAX micro-X-ray fluorescence (XRF) core scanner. Samples collected at each ≈3 cm along the core were analysed for grain size and total organic carbon. Furthermore, the fine fraction of selected layers was subjected to geochemical analysis by ICP-MS, after total acid digestion of the sediments, and mineralogical analysis, by XRD techniques. A radiocarbon age was determined by AMS, using molluscs shells collected at a depth of 90 cm. Sediments along the core are composed by fine and medium sand, with several mud layers. Sediments composing the first 100-cm may have been deposited after 1950, as it is indicated by the radiocarbon data, the increasing trend of Zn/Al, Pb/Al and Cu/Al and total concentrations of Zn, Pb, Cu, V, Cr, As and Ni in this interval that therefore might be linked with industrial activities of Chemical Complex of Estarreja. The progressive increase of Si/Al, Cl/Al, Rb/Al, K/Al and Br/Al and reduced Al concentrations, from the base to the top of this core, are interpreted as being related to higher marine influence and greater differences in tidal currents with longer exposition to air of the sediments with the consequent formation of brines favouring minerals precipitation in the area (e.g. anhydrite). These results seem to be a consequence of several works developed over time like: i) dredging to improve the navigation access to the harbour, located in the external sector of the lagoon; ii) the control of the course of some rivers influencing the supply of sediments. The tendency of sea level rise may have also emphasized the gradual increase of marine influence in this area. Fine-grained sections, related to an increase in Al, phyllosilicates, organic matter, pyrite and siderite contents would be attributed to phases of greater supply of fine-sediments during heavy rainfall events by the nearby Antuã river and other streams during negative phases of North Atlantic Oscillation. Higher deposition of organic matter enhanced diagenetic changes with pyrite and siderite formation. In the bottom of the core another record of pollution was unveiled to mining activities at the beginning of 20th century.FCT de Portugal - C/CTE/UI4035/2011CNPq - 401803/2010-

Stellar Astrophysics and Exoplanet Science with the Maunakea Spectroscopic Explorer (MSE)

The Maunakea Spectroscopic Explorer (MSE) is a planned 11.25-m aperture facility with a 1.5 square degree field of view that will be fully dedicated to multi-object spectroscopy. A rebirth of the 3.6m Canada-France-Hawaii Telescope on Maunakea, MSE will use 4332 fibers operating at three different resolving powers (R ~ 2500, 6000, 40000) across a wavelength range of 0.36-1.8mum, with dynamical fiber positioning that allows fibers to match the exposure times of individual objects. MSE will enable spectroscopic surveys with unprecedented scale and sensitivity by collecting millions of spectra per year down to limiting magnitudes of g ~ 20-24 mag, with a nominal velocity precision of ~100 m/s in high-resolution mode. This white paper describes science cases for stellar astrophysics and exoplanet science using MSE, including the discovery and atmospheric characterization of exoplanets and substellar objects, stellar physics with star clusters, asteroseismology of solar-like oscillators and opacity-driven pulsators, studies of stellar rotation, activity, and multiplicity, as well as the chemical characterization of AGB and extremely metal-poor stars.Comment: 31 pages, 11 figures; To appear as a chapter for the Detailed Science Case of the Maunakea Spectroscopic Explore