85 research outputs found

    The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy

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    The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.Portuguese Foundation for Science and Technology (FCT), the strategic funding of UID/BIO/04469/2013-CEB and UID/EQU/00511/2013-LEPABE units. This study was also supported by FCT and the European Community fund FEDER, through Program COMPETE, under the scope of the Projects “DNA mimics” PIC/IC/82815/2007, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), “BioHealth—Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027 and NORTE-07-0124-FEDER-000025—RL2_ Environment and Health, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. The authors also acknowledge the grant of Susana P. Lopes (SFRH/BPD/95616/2013) and of the COST-Action TD1004: Theragnostics for imaging and therapy

    A Novel Enediynyl Peptide Inhibitor of Furin That Blocks Processing of proPDGF-A, B and proVEGF-C

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    BACKGROUND: Furin represents a crucial member of secretory mammalian subtilase, the Proprotein Convertase (PC) or Proprotein Convertase Subtilisin/Kexin (PCSK) superfamily. It has been linked to cancer, tumorgenesis, viral and bacterial pathogenesis. As a result it is considered a major target for intervention of these diseases. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we report, for the first time, the synthesis and biological evaluation of a newly designed potent furin inhibitor that contains a highly reactive beta-turn inducing and radical generating "enediynyl amino acid" (Eda) moiety. "Eda" was inserted between P1 and P1' residues of hfurin(98-112) peptide, derived from the primary cleavage site of furin's own prodomain. The resulting hexadecapeptide derivative inhibited furin in vitro with IC(50) approximately 40 nM when measured against the fluorogenic substrate Boc-RVRR-MCA. It also inhibited furin-mediated cleavage of a fluorogenic peptide derived from hSARS-CoV spike protein with IC(50) approximately 193 nM. Additionally it also blocked furin-processing of growth factors proPDGF-A, B and VEGF-C that are linked to tumor genesis and cancer. Circular dichroism study showed that this inhibitor displayed a predominantly beta-turn structure while western blots confirmed its ability to protect furin protein from self degradation. CONCLUSION/SIGNIFICANCE: These findings imply its potential as a therapeutic agent for intervention of cancer and other furin-associated diseases

    Assessing the potential responses of 10 important fisheries species to a changing climate with machine learning and observational data across the province of Québec

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    Models are needed to predict changes in game fish abundances with respect to climatic factors undergoing change, but such models are often limited by data availability and the capacity of statistical methods to fit challenging ecological datasets. We use current methods in machine learning to describe the responses of 10 fish species to climatic factors across Québec. We assembled a new province-wide, synthetic dataset of fish catches spanning almost 50 years and 6000 sites. Extreme Gradient Boosting (XGBoost) models revealed that climatic factors are more important predictors of trends in game fish catches than nuisance factors (sampling gear, time), lending support to collating other heterogeneous datasets for analyses. Mean annual temperature and precipitation were the most important drivers of species catches. Fish thermal preference guilds predicted primarily species responses to temperature, suggesting that warmer and wetter climates may not favour the same species. Despite the challenging nature of these datasets, XGBoost models provided excellent fit, predictive capacity, and interpretability, thereby illustrating that large, heterogeneous datasets can be used to inform freshwater fisheries management in a changing climate

    Widespread variation in salt tolerance within freshwater zooplankton species reduces the predictability of community-level salt tolerance

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    The salinization of freshwaters is a global threat to aquatic biodiversity. We quantified variation in chloride (Cl-) tolerance of 19 freshwater zooplankton species in four countries to answer three questions: (1) How much variation in Cl- tolerance is present among populations? (2) What factors predict intraspecific variation in Cl- tolerance? (3) Must we account for intraspecific variation to accurately predict community Cl- tolerance? We conducted field mesocosm experiments at 16 sites and compiled acute LC(50)s from published laboratory studies. We found high variation in LC(50)s for Cl- tolerance in multiple species, which, in the experiment, was only explained by zooplankton community composition. Variation in species-LC50 was high enough that at 45% of lakes, community response was not predictable based on species tolerances measured at other sites. This suggests that water quality guidelines should be based on multiple populations and communities to account for large intraspecific variation in Cl- tolerance.Peer reviewe

    Towards sustainable agricultural landscapes: Lessons from an interdisciplinary research-based framework applied to the Saint Lawrence floodplain

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    Abstract Floodplains are unique environments that provide a dynamic link between terrestrial and aquatic systems. Intensification of human activity – particularly agriculture and urbanisation – has resulted in the degradation of floodplains worldwide. Restoration and sustainable management of floodplains requires holistic assessment and compromise between stakeholders to successfully balance environmental, economic, and social benefits. Yet, understanding these complex systems sufficiently to provide evidence-based recommendations is a challenge. We present the lessons learned from establishing an interdisciplinary research-based framework on the agricultural floodplain of Lake Saint Pierre, Québec, Canada, whose mandate was to a) understand and define key environmental, agricultural, and socioeconomic attributes of the landscape, b) quantify the trade-offs and synergies between these attributes across different agricultural practices, regions, and land uses, and c) explore novel agri-environmental management practices to assess their role in sustainable floodplain management. Within this manuscript, we explore the benefits that such an approach offers in evaluating sustainable floodplain land use. We found that an interdisciplinary research-based approach demonstrated important benefits such as knowledge transfer, more efficient use of resources (e.g., personnel, funding), and a flexible yet robust research framework. A framework of individual research projects connected to broader interdisciplinary themes allowed a more holistic synthesis of the floodplain systems and assessment of agri-environmental practices. By implicitly considering spatial and social scales, we conceptualised not just how redistribution of the land use types can meet sustainable management objectives, but also explored how compromises within existing uses can optimise socio-economic, agricultural and environmental dimensions and move towards a sustainable multifunctional landscape

    Prioritizing taxa for genetic reference database development to advance inland water conservation

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    Biodiversity loss has accelerated over the past century and freshwater species overall are among those experiencing greatest declines. Genetic resources have the potential to help evaluate the full magnitude of this loss and represent a key tool to effectively allocate conservation resources and monitor the success of restoration efforts. The full power of genetic resources will be realized when the daunting task of referencing all DNA sequences of freshwater organisms is complete. Here, we quantified the availability and distribution of barcode and genome data for freshwater macroscopic organisms in Canada, a country rich in inland water resources and thus particularly vulnerable to aquatic species losses. Impressively, most inland water species (86 %) were represented by barcodes recorded in the BOLD Systems database, while very few had full genomes available (<4 %) in the NCBI database. We identified barcode data deficiencies in northern regions and for taxa assessed as most at risk or without sufficient information for conservation status classification. As expected, the speciose insect group had a lower-than-average number of records per species and a high proportion of data deficient species without adequate barcode coverage. This study highlights where future sequencing resources should be prioritized within initiatives such as the Canada BioGenome Project and BIOSCAN Canada and provides a workflow that could be applied internationally to inform conservation management plans and to mitigate biodiversity loss

    Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

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    14 p.Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

    FreshLanDiv: A Global Database of Freshwater Biodiversity Across Different Land Uses

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    Motivation: Freshwater ecosystems have been heavily impacted by land-use changes, but data syntheses on these impacts are still limited. Here, we compiled a global database encompassing 241 studies with species abundance data (from multiple biological groups and geographic locations) across sites with different land-use categories. This compilation will be useful for addressing questions regarding land-use change and its impact on freshwater biodiversity. Main Types of Variables Contained: The database includes metadata of each study, sites location, sample methods, sample time, land-use category and abundance of each taxon. Spatial Location and Grain: The database contains data from across the globe, with 85% of the sites having well-defined geographical coordinates. Major Taxa and Level of Measurement: The database covers all major freshwater biological groups including algae, macrophytes, zooplankton, macroinvertebrates, fish and amphibians
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