21 research outputs found

    Cell-penetrating peptides as transporters for morpholino oligomers: effects of amino acid composition on intracellular delivery and cytotoxicity

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    Arginine-rich cell-penetrating peptides (CPPs) are promising transporters for intracellular delivery of antisense morpholino oligomers (PMO). Here, we determined the effect of L-arginine, D-arginine and non-α amino acids on cellular uptake, splice-correction activity, cellular toxicity and serum binding for 24 CPP−PMOs. Insertion of 6-aminohexanoic acid (X) or ÎČ-alanine (B) residues into oligoarginine R8 decreased the cellular uptake but increased the splice-correction activity of the resulting compound, with a greater increase for the sequences containing more X residues. Cellular toxicity was not observed for any of the conjugates up to 10 ΌM. Up to 60 ΌM, only the conjugates with â©Ÿ 5 Xs exhibited time- and concentration-dependent toxicity. Substitution of L-arginine with D-arginine did not increase uptake or splice-correction activity. High concentration of serum significantly decreased the uptake and splice-correction activity of oligoarginine conjugates, but had much less effect on the conjugates containing X or B. In summary, incorporation of X/B into oligoarginine enhanced the antisense activity and serum-binding profile of CPP−PMO. Toxicity of X/B-containing conjugates was affected by the number of Xs, treatment time and concentration. More active, stable and less toxic CPPs can be designed by optimizing the position and number of R, D-R, X and B residues

    Arctic microbial ecosystems and impacts of extreme warming during the International Polar Year

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    As a contribution to the International Polar Year program MERGE (Microbiological and Ecological Responses to Global Environmental change in polar regions), studies were conducted on the terrestrial and aquatic microbial ecosystems of northern Canada (details at: http://www.cen.ulaval.ca/merge/). The habitats included permafrost soils, saline coldwater springs, supraglacial lakes on ice shelves, epishelf lakes in fjords, deep meromictic lakes, and shallow lakes, ponds and streams. Microbiological samples from each habitat were analysed by HPLC pigment assays, light and fluorescence microscopy, and DNA sequencing. The results show a remarkably diverse microflora of viruses, Archaea (including ammonium oxidisers and methanotrophs), Bacteria (including filamentous sulfur-oxidisers in a saline spring and benthic mats of Cyanobacteria in many waterbodies), and protists (including microbial eukaryotes in snowbanks and ciliates in ice-dammed lakes). In summer 2008, we recorded extreme warming at Ward Hunt Island and vicinity, the northern limit of the Canadian high Arctic, with air temperatures up to 20.5 \ub0C. This was accompanied by pronounced changes in microbial habitats: deepening of the permafrost active layer; loss of perennial lake ice and sea ice; loss of ice-dammed freshwater lakes; and 23% loss of total ice shelf area, including complete break-up and loss of the Markham Ice Shelf cryo-ecosystem. These observations underscore the vulnerability of Arctic microbial ecosystems to ongoing climate change.Peer reviewed: YesNRC publication: Ye

    Arctic microbial ecosystems and impacts of extreme warming during the International Polar Year

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    As a contribution to the International Polar Year program MERGE (Microbiological and Ecological Responses to Global Environmental change in polar regions), studies were conducted on the terrestrial and aquatic microbial ecosystems of northern Canada (details at: http://www.cen.ulaval.ca/merge/). The habitats included permafrost soils, saline coldwater springs, supraglacial lakes on ice shelves, epishelf lakes in fjords, deep meromictic lakes, and shallow lakes, ponds and streams. Microbiological samples from each habitat were analysed by HPLC pigment assays, light and fluorescence microscopy, and DNA sequencing. The results show a remarkably diverse microflora of viruses, Archaea (including ammonium oxidisers and methanotrophs), Bacteria (including filamentous sulfur-oxidisers in a saline spring and benthic mats of Cyanobacteria in many waterbodies), and protists (including microbial eukaryotes in snowbanks and ciliates in ice-dammed lakes). In summer 2008, we recorded extreme warming at Ward Hunt Island and vicinity, the northern limit of the Canadian high Arctic, with air temperatures up to 20.5 \ub0C. This was accompanied by pronounced changes in microbial habitats: deepening of the permafrost active layer; loss of perennial lake ice and sea ice; loss of ice-dammed freshwater lakes; and 23% loss of total ice shelf area, including complete break-up and loss of the Markham Ice Shelf cryo-ecosystem. These observations underscore the vulnerability of Arctic microbial ecosystems to ongoing climate change.Peer reviewed: YesNRC publication: Ye

    Particulate emissions from commercial shipping: chemical, physical, and optical properties

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    , 39% OM, and 15% BC and differs from inventories that used 81%, 14%, and 5% and 31%, 63%, and 6% SO 4 2À , OM, and BC, respectively. SO 4 2À and OM mass were found to be dependent on fuel sulfur content as were SSA, hygroscopicity, and CCN concentrations. BC mass was dependent on engine type and combustion efficiency. A plume evolution study conducted on one vessel showed conservation of particle light absorption, decrease in CN > 5 nm, increase in particle hygroscopicity, and an increase in average particle size with distance from emission. These results suggest emission of small nucleation mode particles that subsequently coagulate/condense onto larger BC and OM. This work contributes to an improved understanding of the impacts of ship emissions on climate and air quality and will also assist in determining potential effects of altering fuel standards

    Working paper analysing the economic implications of the proposed 30% target for areal protection in the draft post-2020 Global Biodiversity Framewor

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    58 pages, 5 figures, 3 tables- The World Economic Forum now ranks biodiversity loss as a top-five risk to the global economy, and the draft post-2020 Global Biodiversity Framework proposes an expansion of conservation areas to 30% of the earth’s surface by 2030 (hereafter the “30% target”), using protected areas (PAs) and other effective area-based conservation measures (OECMs). - Two immediate concerns are how much a 30% target might cost and whether it will cause economic losses to the agriculture, forestry and fisheries sectors. - Conservation areas also generate economic benefits (e.g. revenue from nature tourism and ecosystem services), making PAs/Nature an economic sector in their own right. - If some economic sectors benefit but others experience a loss, high-level policy makers need to know the net impact on the wider economy, as well as on individual sectors. [...]A. Waldron, K. Nakamura, J. Sze, T. Vilela, A. Escobedo, P. Negret Torres, R. Button, K. Swinnerton, A. Toledo, P. Madgwick, N. Mukherjee were supported by National Geographic and the Resources Legacy Fund. V. Christensen was supported by NSERC Discovery Grant RGPIN-2019-04901. M. Coll and J. Steenbeek were supported by EU Horizon 2020 research and innovation programme under grant agreement No 817578 (TRIATLAS). D. Leclere was supported by TradeHub UKRI CGRF project. R. Heneghan was supported by Spanish Ministry of Science, Innovation and Universities, Acciones de Programacion Conjunta Internacional (PCIN-2017-115). M. di Marco was supported by MIUR Rita Levi Montalcini programme. A. Fernandez-Llamazares was supported by Academy of Finland (grant nr. 311176). S. Fujimori and T. Hawegawa were supported by The Environment Research and Technology Development Fund (2-2002) of the Environmental Restoration and Conservation Agency of Japan and the Sumitomo Foundation. V. Heikinheimo was supported by Kone Foundation, Social Media for Conservation project. K. Scherrer was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 682602. U. Rashid Sumaila acknowledges the OceanCanada Partnership, which funded by the Social Sciences and Humanities Research Council of Canada (SSHRC). T. Toivonen was supported by Osk. Huttunen Foundation & Clare Hall college, Cambridge. W. Wu was supported by The Environment Research and Technology Development Fund (2-2002) of the Environmental Restoration and Conservation Agency of Japan. Z. Yuchen was supported by a Ministry of Education of Singapore Research Scholarship Block (RSB) Research FellowshipPeer reviewe

    Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

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    It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations
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