60 research outputs found

    Reverse engineering synthetic antiviral amyloids

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    Human amyloids have been shown to interact with viruses and interfere with viral replication. Based on this observation, we employed a synthetic biology approach in which we engineered virus-specific amyloids against influenza A and Zika proteins. Each amyloid shares a homologous aggregation-prone fragment with a specific viral target protein. For influenza we demonstrate that a designer amyloid against PB2 accumulates in influenza A-infected tissue in vivo. Moreover, this amyloid acts specifically against influenza A and its common PB2 polymorphisms, but not influenza B, which lacks the homologous fragment. Our model amyloid demonstrates that the sequence specificity of amyloid interactions has the capacity to tune amyloid-virus interactions while allowing for the flexibility to maintain activity on evolutionary diverging variants. Some human amyloid proteins have been shown to interact with viral proteins, suggesting that they may have potential as therapeutic agents. Here the authors design synthetic amyloids specific for influenza A and Zika virus proteins, respectively, and show that they can inhibit viral replication

    De novo design of a biologically active amyloid

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    Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic amyloid peptide, based on an amyloidogenic fragment of vascular endothelial growth factor receptor 2 (VEGFR2), a protein that is not associated to amyloidosis. Vascin recapitulates key biophysical and biochemical characteristics of natural amyloids, penetrates cells, and seeds the aggregation of VEGFR2 through direct interaction. We found that amyloid toxicity is observed only in cells that both express VEGFR2 and are dependent on VEGFR2 activity for survival. Thus, amyloid toxicity here appears to be both protein-specific and conditional—determined by VEGFR2 loss of function in a biological context in which target protein function is essential.This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Framework Programme, ERC grant agreement 647458 (MANGO) to J.S. The Switch Laboratory was supported by grants from VIB, Industrial Research Funds of KU Leuven (IOF), the Funds for Scientific Research Flanders (FWO), the Flanders Institute for Science and Technology (IWT), and the Federal Office for Scientific Affairs of Belgium (Belspo), IUAP P7/16. G.V.V., F.D.S., and F.C. were supported by postdoctoral fellowships of FWO. G.V.V. was also supported by KU Leuven competitive funding (PF/10/014). L.Y. is funded by a Wellcome Trust Institutional Strategic Support Fund (ISSF) (grant 015615/Z/14/Z). The Synapt high-definition mass spectroscopy mass spectrometer was purchased with funds from the Biotechnology and Biological Sciences Research Council through its Research Equipment Initiative scheme (BB/E012558/1). The Linköping University laboratories were supported by The Göran Gustafsson Foundation, The Swedish Research Council, and The Swedish Alzheimer Foundation. P.C. was supported by FWO, Methusalem funding by the Flemish government, and an AXA Research grant. M.K. is supported by a Marie Skłodowska-Curie Individual Fellowship under the European Union’s Horizon 2020 Framework Programme (grant H2020-MSCA-IF-2014-ST). C.V. was supported by the KU Leuven Stem Cell Programme. F.R. and J.S. are inventors on patent applications WO2007/071789 and WO2012/123419 submitted by VIB vzw, Belgium, that covers the use of targeted protein aggregation for therapeutic or biotechnological applications

    Pervasive gaps in Amazonian ecological research

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    Pervasive gaps in Amazonian ecological research

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    Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

    Predação de sementes de andiroba [Carapa guianensis Aubl. e Carapa procera DC. (Meliaceae)] por insetos na Amazônias

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    Os objetivos deste trabalho foram identificar os insetos associados à predação de sementes de Carapa guianensis e Carapa procera e avaliar o potencial de dano nas sementes por insetos e a ocorrência de estratificação vertical na predação de sementes de andiroba. O estudo foi realiado em plantios de C. guianensis e C. procera na Reserva Florestal Ducke, Manaus, Estado do Amazonas, Brasil. As coletas foram realizadas semanalmente no chão da floresta e mensalmente em três diferentes alturas (terços) da copa das árvores. Para avaliar o efeito da predação na germinação, 30 sementes não predadas e 30 sementes predadas coletadas mensalmente do chão da floresta foram colocadas para germinar por um período de um mês. Os resultados indicaram que Hypsipyla grandella e H. ferrealis (Lepidoptera, Pyralidae) foram as principais espécies de insetos associadas à predação das sementes de C. procera e C. guianensis, resultando em taxas de predação média de 39% a 61,96%, respectivamente. Observou-se estratificação vertical na predação dos frutos e sementes na copa das árvores de ambas as espécies de Carapa. A predação das sementes de C. procera e C. guianensis por Hypsipyla spp. reduziu o processo de germinação. Este estudo produziu informações sobre a associação entre C. procera e C. guianensis e as espécies de Hypsipyla

    Priorities to inform research on marine plastic pollution in Southeast Asia

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    This is the final version. Available from Elsevier via the DOI in this record. Southeast Asia is considered to have some of the highest levels of marine plastic pollution in the world. It is therefore vitally important to increase our understanding of the impacts and risks of plastic pollution to marine ecosystems and the essential services they provide to support the development of mitigation measures in the region. An interdisciplinary, international network of experts (Australia, Indonesia, Ireland, Malaysia, the Philippines, Singapore, Thailand, the United Kingdom, and Vietnam) set a research agenda for marine plastic pollution in the region, synthesizing current knowledge and highlighting areas for further research in Southeast Asia. Using an inductive method, 21 research questions emerged under five non-predefined key themes, grouping them according to which: (1) characterise marine plastic pollution in Southeast Asia; (2) explore its movement and fate across the region; (3) describe the biological and chemical modifications marine plastic pollution undergoes; (4) detail its environmental, social, and economic impacts; and, finally, (5) target regional policies and possible solutions. Questions relating to these research priority areas highlight the importance of better understanding the fate of marine plastic pollution, its degradation, and the impacts and risks it can generate across communities and different ecosystem services. Knowledge of these aspects will help support actions which currently suffer from transboundary problems, lack of responsibility, and inaction to tackle the issue from its point source in the region. Being profoundly affected by marine plastic pollution, Southeast Asian countries provide an opportunity to test the effectiveness of innovative and socially inclusive changes in marine plastic governance, as well as both high and low-tech solutions, which can offer insights and actionable models to the rest of the world.Natural Environment Research CouncilNational Research Foundation, Prime Minister’s Office (Singapore

    What Performance Analysts Need to Know About Research Trends in Association Football (2012–2016): A Systematic Review

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    Evolving patterns of match analysis research need to be systematically reviewed regularly since this area of work is burgeoning rapidly and studies can offer new insights to performance analysts if theoretically and coherently organized
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