31 research outputs found

    Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

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    White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined

    Fluoro-Aryl Substituted &#945;,&#946;2,3-Peptides in the Development of Foldameric Antiparallel &#946;-Sheets: A Conformational Study

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    \u3b1,\u3b22,3 -Disteroisomeric foldamers of general formula Boc(S-Ala-\u3b2-2R,3R-Fpg)n OMe or Boc(S-Ala-\u3b2-2S,3S-Fpg)n OMe were prepared from both enantiomers of syn H-2-(2-F-Phe)-h-PheGly-OH (named \u3b2-Fpg) and S-alanine. Our peptides show two appealing features for biomedical applications: the presence of fluorine, attractive for non-covalent interactions, and aryl groups, crucial for \u3c0-stacking. A conformational study was performed, using IR, NMR and computational studies of diastereoisomeric tetra- and hexapeptides containing the \u3b22,3-amino acid in the R,R- and S,S-stereochemistry, respectively. We found that the stability of peptide conformation is dependent on the stereochemistry of the \u3b2-amino acid. Combining S-Ala with \u3b2-2R,3R-Fpg, a stable extended \u3b2-strand conformation was obtained. Furthermore, \u3b2-2R,3R-Fpg containing hexapeptide self-assembles to form antiparallel \u3b2-sheet structure stabilized by intermolecular H-bonds and \u3c0,\u3c0-interactions. These features make peptides containing the \u3b22,3-fluoro amino acid very appealing for the development of bioactive proteolytically stable foldameric \u3b2-sheets as modulators of protein-protein interaction (PPI)

    Data for wetlandscapes and their changes around the world

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    Geography and associated hydrological, hydroclimate and land-use conditions and their changes determine the states and dynamics of wetlands and their ecosystem services. The influences of these controls are not limited to just the local scale of each individual wetland but extend over larger landscape areas that integrate multiple wetlands and their total hydrological catchment – the wetlandscape. However, the data and knowledge of conditions and changes over entire wetlandscapes are still scarce, limiting the capacity to accurately understand and manage critical wetland ecosystems and their services under global change. We present a new Wetlandscape Change Information Database (WetCID), consisting of geographic, hydrological, hydroclimate and land-use information and data for 27 wetlandscapes around the world. This combines survey-based local information with geographic shapefiles and gridded datasets of large-scale hydroclimate and land-use conditions and their changes over whole wetlandscapes. Temporally, WetCID contains 30-year time series of data for mean monthly precipitation and temperature and annual land-use conditions. The survey-based site information includes local knowledge on the wetlands, hydrology, hydroclimate and land uses within each wetlandscape and on the availability and accessibility of associated local data. This novel database (available through PANGAEA https://doi.org/10.1594/PANGAEA.907398; Ghajarnia et al., 2019) can support site assessments; cross-regional comparisons; and scenario analyses of the roles and impacts of land use, hydroclimatic and wetland conditions, and changes in whole-wetlandscape functions and ecosystem services

    Priorities and interactions of Sustainable Development Goals (SDGs) with focus on wetlands

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    Wetlands are often vital physical and social components of a country's natural capital, as well as providers of ecosystem services to local and national communities. We performed a network analysis to prioritize Sustainable Development Goal (SDG) targets for sustainable development in iconic wetlands and wetlandscapes around the world. The analysis was based on the information and perceptions on 45 wetlandscapes worldwide by 49 wetland researchers of the GlobalWetland Ecohydrological Network (GWEN). We identified three 2030 Agenda targets of high priority across the wetlandscapes needed to achieve sustainable development: Target 6.3-'Improve water quality'; 2.4-'Sustainable food production'; and 12.2-'Sustainable management of resources'. Moreover, we found specific feedback mechanisms and synergies between SDG targets in the context of wetlands. The most consistent reinforcing interactions were the influence of Target 12.2 on 8.4-'Efficient resource consumption'; and that of Target 6.3 on 12.2. The wetlandscapes could be differentiated in four bundles of distinctive priority SDG-targets: 'Basic human needs', 'Sustainable tourism', 'Environmental impact in urban wetlands', and 'Improving and conserving environment'. In general, we find that the SDG groups, targets, and interactions stress that maintaining good water quality and a 'wise use' of wetlandscapes are vital to attaining sustainable development within these sensitive ecosystems. © 2019 by the authors

    Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

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    Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P &lt;0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

    Future Climate Change Renders Unsuitable Conditions for Paramo Ecosystems in Colombia

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    Paramo ecosystems are tropical alpine grasslands, located above 3000 m.a.s.l. in the Andean mountain range. Their unique vegetation and soil characteristics, in combination with low temperature and abundant precipitation, create the most advantageous conditions for regulating and storing surface and groundwater. However, increasing temperatures and changing patterns of precipitation due to greenhouse-gas-emission climate change are threatening these fragile environments. In this study, we used regional observations and downscaled data for precipitation and minimum and maximum temperature during the reference period 1960&ndash;1990 and simulations for the future period 2041&ndash;2060 to study the present and future extents of paramo ecosystems in the Chingaza National Park (CNP), nearby Colombia&rsquo;s capital city, Bogot&aacute;. The historical data were used for establishing upper and lower precipitation and temperature boundaries to determine the locations where paramo ecosystems currently thrive. Our results found that increasing mean monthly temperatures and changing precipitation will render 39 to 52% of the current paramo extent in CNP unsuitable for these ecosystems during the dry season, and 13 to 34% during the wet season. The greatest loss of paramo area will occur during the dry season and for the representative concentration pathway (RCP) scenario 8.5, when both temperature and precipitation boundaries are more prone to be exceeded. Although our initial estimates show the future impact on paramos and the water security of Bogot&aacute; due to climate change, complex internal and external interactions in paramo ecosystems make it essential to study other influencing climatic parameters (e.g., soil, topography, wind, etc.) apart from temperature and precipitation

    Simulação de Produção de Sedimentos em uma Bacia Hidrográfica caracterizada pela expansão da cana-de-açúcar/ Sediment Yield Simulation in a Watershed characterized by the expansion of sugarcane

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    Este trabalho apresenta resultados referentes à produção de sedimentos da Bacia Hidrográfica do Ribeirão do Pinhal, inserida no município de Limeira, São Paulo, sob 3 cenários de uso e ocupação do solo, simulados através do modelo hidrológico SWAT. A bacia total foi dividida em 5 sub-bacias de acordo com o uso predominantes. Foram realizados ajustes em parâmetros da base de dados de solos e culturas do SWAT, para adequá-la a realidade brasileira. Foram utilizados dados climatológicos de 8 anos (2007-2014) para esta modelagem. As diferentes produções de sedimento de cada cenário puderam ser notadas em função da mudança do uso em cada um deles. O cenário 2 apresentou a menor produção de sedimentos (7,74Mg.ha-1). O cenário 1 apresentou 8,37Mg.ha-1 e o 3 8,58Mg.ha-1. Quanto aos usos, os que mais geraram sedimentos, em ordem decrescente, foram: Pastagem, Cultura Anual, Citros, Cana-de-açúcar e Vegetação Natural. Quanto as sub-bacias, a número 2 teve a maior produção de sedimentos (~10 Mg.ha-1), enquanto a sub-bacia 5, a menor (5,51Mg.ha-1). O SWAT foi considerado eficiente para simular a produção de sedimentos por cenários e por uso, combinando-se diferentes dados temáticos e tabulares quando realizados os ajustes necessários em sua base de dado nativa

    Simulação de Produção de Sedimentos em uma Bacia Hidrográfica caracterizada pela expansão da cana-de-açúcar/ Sediment Yield Simulation in a Watershed characterized by the expansion of sugarcane

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    Este trabalho apresenta resultados referentes à produção de sedimentos da Bacia Hidrográfica do Ribeirão do Pinhal, inserida no município de Limeira, São Paulo, sob 3 cenários de uso e ocupação do solo, simulados através do modelo hidrológico SWAT. A bacia total foi dividida em 5 sub-bacias de acordo com o uso predominantes. Foram realizados ajustes em parâmetros da base de dados de solos e culturas do SWAT, para adequá-la a realidade brasileira. Foram utilizados dados climatológicos de 8 anos (2007-2014) para esta modelagem. As diferentes produções de sedimento de cada cenário puderam ser notadas em função da mudança do uso em cada um deles. O cenário 2 apresentou a menor produção de sedimentos (7,74Mg.ha-1). O cenário 1 apresentou 8,37Mg.ha-1 e o 3 8,58Mg.ha-1. Quanto aos usos, os que mais geraram sedimentos, em ordem decrescente, foram: Pastagem, Cultura Anual, Citros, Cana-de-açúcar e Vegetação Natural. Quanto as sub-bacias, a número 2 teve a maior produção de sedimentos (~10 Mg.ha-1), enquanto a sub-bacia 5, a menor (5,51Mg.ha-1). O SWAT foi considerado eficiente para simular a produção de sedimentos por cenários e por uso, combinando-se diferentes dados temáticos e tabulares quando realizados os ajustes necessários em sua base de dado nativa
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