3,498 research outputs found

    Differential stability of 2'F-ANA*RNA and ANA*RNA hybrid duplexes: roles of structure, pseudohydrogen bonding, hydration, ion uptake and flexibility

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    14 pags., 7 figs., 3 tabs.Hybrids of RNA with arabinonucleic acids 2′F-ANA and ANA have very similar structures but strikingly different thermal stabilities. We now present a thorough study combining NMR and other biophysical methods together with state-of-the-art theoretical calculations on a fully modified 10-mer hybrid duplex. Comparison between the solution structure of 2′F-ANA•RNA and ANA•RNA hybrids indicates that the increased binding affinity of 2′F-ANA is related to several subtle differences, most importantly a favorable pseudohydrogen bond (2′F-purine H8) which contrasts with unfavorable 2′-OH-nucleobase steric interactions in the case of ANA. While both 2′F-ANA and ANA strands maintained conformations in the southern/eastern sugar pucker range, the 2′F-ANA strand's structure was more compatible with the A-like structure of a hybrid duplex. No dramatic differences are found in terms of relative hydration for the two hybrids, but the ANA•RNA duplex showed lower uptake of counterions than its 2′F-ANA•RNA counterpart. Finally, while the two hybrid duplexes are of similar rigidities, 2′F-ANA single strands may be more suitably preorganized for duplex formation. Thus the dramatically increased stability of 2′F-ANA•RNA and ANA•RNA duplexes is caused by differencesin at least four areas, of which structure and pseudohydrogen bonding are the most important. © The Author(s) 2010. Published by Oxford University Press.Spanish Ministerio de Ciencia e Innovacion (grants CTQ2007-68014-C02-02 to CG and BIO2009-10964 to MO); Fundacion Marcelino Botin (grant to MO); Canadian Institutes for Health Research (grant to M.J.D.); Natural Sciences and Engineering Research Council of Canada (postgraduate scholarship to J.K.W.). Funding for open access charge: Canadian Institutes for Health Research

    David B. Brownlee interviewed by Ana Tostões

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    In February 2018, Ana Tostões interviewed David Brownlee, pioneer researcher on Louis I. Kahn and an historian of modern architecture and professor of the history of art at the University of Pennsylvania, in order to debate Kahn’s realm of ideas and their contemporary significance. David Brownlee was guest curator of the exhibition Louis I. Kahn: In the Realm of Architecture (Museum of Modern Art, New York, 1992), and is co-author of the homonymous book (with David G. De Long, New York, 1991, translated into four other languages) that stands as the first worldwide comprehensive publication on Louis I. Kahn

    William Whitaker interviewed by Ana Tostões

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    In February 2018, Ana Tostões interviewed William Whitaker, curator and collections manager of the Architectural Archives of the University of Pennsylvania School of Design, where the Louis I. Kahn Collection is hosted, in order to debate the importance of documentation for the preservation of Kahn’s legacy. William Whitaker was curatorial consultant of the exhibition Louis Kahn: The Power of Architecture (Vitra Design Museum, 2012) and is the co-author of The Houses of Louis I. Kahn (with George Marcus, 2013), the first comprehensive publication on the architect’s house designs. The management of the Louis I. Kahn Collection has been having a fundamental role, not only in the documentation and interpretation of Kahn’s life and work, but also in the success of the contemporary rehabilitation projects undertaken in his buildings

    Stages for the More Sustainable Farm

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    Currently, agricultural farm units are faced with a double and most times contradictory challenge, in order to be successful: on the one hand the invested capital has to be profitable and the economic performance has to be maximised. On the other hand, given the socio-environmental situation, it is necessary to preserve and to protect the environment and natural resources. Given the potential conflict of the two aims, since the satisfaction of one implies the underperformance of the other (and vice versa), the question then is: which is the solution to choose? We intend, in this work, to formulate a farm plan with the purpose of reconciling the criteria of environmental sustainability with that of economic competitiveness. For this achievement we proceed to the comparative study of sustainability of different groups of farms identified in the study area (first evaluation cycle) through MESMIS (“Marco para la Evaluación de Sistemas de Manejo de Recursos Naturales Mediante Indicadores de Sustentabilidad” - Framework for Evaluation of Natural-Resource Systems Handling through Sustainability Indicators) methodology, that allowed to select the more sustainable group of farms. Based on the found potentialities and weakness on these production systems, we stepped to the planning of a production unit of bovine meat, which obeys simultaneously to economic and environmental objectives, using Multicriteria Decision. We finished the work with the sustainability evaluation between groups of farms identified previously and the planned farms (second evaluation cycle), based, again, in the MESMIS methodology, to confirm (or not) the greatest sustainability of the last ones. Analyses of the results allow us to confirm the greatest relative sustainability of the planned farm, for the diverse traced scenarios.Decision taking, planning, sustainability, Environmental Economics and Policy, Farm Management,

    Diterpenoids from the Brown Alga <i>Rugulopteryx okamurae</i> and Their Anti-Inflammatory Activity

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    Brown algae of the Family Dictyotaceae produce an array of structurally diverse terpenoids, whose biomedical potential in the anti-inflammatory area has been scarcely explored. Herein, the chemical study of the alga Rugulopteryx okamurae has led to the isolation of ten new diterpenoids: rugukadiol A (1), rugukamurals A–C (2–4), and ruguloptones A–F (6–10). The structures of the new compounds were established by spectroscopic means. Compound 1 exhibits an unprecedented diterpenoid skeleton featuring a bridged tricyclic undecane system. Compounds 2–10 belong to the secospatane class of diterpenoids and differ by the oxygenated functions that they contain. In anti-inflammatory assays, the new diterpenoid 1 and the secospatanes 5 and 10 significantly inhibited the production of the inflammatory mediator NO in LPS-stimulated microglial cells Bv.2 and macrophage cells RAW 264.7. Moreover, compounds 1 and 5 were found to strongly inhibit the expression of Nos2 and the pro-inflammatory cytokine Il1b in both immune cell lines

    ACWWS Talk Di Tings: with Ana Menendez

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    This is an interview with Cuban-American writer, Ana Menéndez, author of In Cuba I Was A German Shepherd, Loving Che, The Last War and Adios Happy Homeland! This video is in 2 parts

    Inhibition of protein tyrosine phosphatase 1B improves IGF-I receptor signaling and protects against inflammation-induced gliosis in the retina

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    [Purpose]: Insulin-like growth factor-I receptor (IGF-IR) signaling mediates retinal growth and survival and its failure may contribute to aggravate diabetic retinopathy (DR). Protein tyrosine phosphatase 1B (PTP1B) negatively modulates IGF-IR signaling, but its involvement in inflammation during DR remains unknown. We investigated whether PTP1B participates in the cross-talk between proinflammatory signaling pathways and IGF-IR–mediated signaling in the retina. [Methods]: 661W photoreceptors or mouse retinal explants were treated with TNFa, IL6, and IL1b. Insulin-like growth factor-I receptor signaling cascade was evaluated in the absence or presence of PTP1B. db/db mice were used to test a PTP1B inhibitor in retinal gliosis. [Results]: 661W retinal cells and retinal explants responded to IGF-I by inducing IGF-IR tyrosine (13-fold) and Akt phosphorylations (7- and 3-fold for serine 473 and threonine 308, respectively). Cytokines triggered early activation of stress kinases (c-jun [NH2] terminal kinase [JNK] and p38 MAPK), resulting in insulin receptor substrate 1 (IRS1) serine 307 phosphorylation that precedes its degradation. Pretreatment of 661W cells or retinal explants with cytokines upregulated PTP1B protein levels (1.45- and 4.5-fold, respectively), induced IRS1 degradation and decreased IGF-I–mediated IGF-IR/Akt phosphorylation. Silencing or deficiency in PTP1B ameliorated the negative effects of cytokines on IGF-IR signaling. Cytokines increased glial fibrillary acidic protein (GFAP) expression in retinal explants by 4.5- fold, this response being reduced by 2-fold with a PTP1B inhibitor. Protein tyrosine phosphatase 1B protein levels increased by 3-fold in retinas from db/db mice and its inhibition reduced gliosis. [Conclusions]: Targeting PTP1B might be useful for modulating IGF-I effects in retinal cells during DR.Supported by grants from Spanish Ministry of Economy and Competitivity (SAF2012-33283; Madrid, Spain), Comunidad de Madrid S2010/BMD-2423 (Madrid, Spain), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBEDEM, Instituto Carlos III, Madrid, Spain), and European Union (EUROCONDOR; FP7 HEALTH.2011.2.4.3.1.; Barcelona, Spain).Peer Reviewe

    Tagging of Biomedical Articles on CiteULike: A Comparison of User, Author and Professional Indexing

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    This paper examines the context of online indexing from the viewpoint of three different groups: users, authors, and professional indexers. User tags, author keywords and descriptors were collected from academic journal articles, which were both indexed in Pubmed and tagged on CiteULike, and analysed. Descriptive statistics, informetric measures, and thesaural term comparison shows that there are important differences in the use of keywords between the three groups in addition to similarities which can be used to enhance support for search and browse. While tags and author keywords were found that matched descriptors exactly, other terms which did not match but provided important expansion to the indexing lexicon were found. These additional terms could be used to enhance support for searching and browsing in article databases as well as to provide invaluable data for entry vocabulary and emergent terminology for regular updates to indexing systems. Additionally, the study suggests that tags support organisation by association to task, projects and subject while making important connections to traditional systems which classify into subject categories
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