26 research outputs found

    Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

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    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

    Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

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    Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

    Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

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    Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

    Data from: Incorporating interspecific competition into species-distribution mapping by upward scaling of small-scale model projections to the landscape

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    There are a number of overarching questions and debate in the scientific community concerning the importance of biotic interactions in species distribution models at large spatial scales. In this paper, we present a framework for revising the potential distribution of tree species native to the Western Ecoregion of Nova Scotia, Canada, by integrating the long-term effects of interspecific competition into an existing abiotic-factor-based definition of potential species distribution (PSD). The PSD model is developed by combining spatially explicit data of individualistic species’ response to normalized incident photosynthetically active radiation, soil water content, and growing degree days. A revised PSD model adds biomass output simulated over a 100-year timeframe with a robust forest gap model and scaled up to the landscape using a forestland classification technique. To demonstrate the method, we applied the calculation to the natural range of 16 target tree species as found in 1,240 provincial forest-inventory plots. The revised PSD model, with the long-term effects of interspecific competition accounted for, predicted that eastern hemlock (Tsuga canadensis), American beech (Fagus grandifolia), white birch (Betula papyrifera), red oak (Quercus rubra), sugar maple (Acer saccharum), and trembling aspen (Populus tremuloides) would experience a significant decline in their original distribution compared with balsam fir (Abies balsamea), black spruce (Picea mariana), red spruce (Picea rubens), red maple (Acer rubrum L.), and yellow birch (Betula alleghaniensis). True model accuracy improved from 64.2% with original PSD evaluations to 81.7% with revised PSD. Kappa statistics slightly increased from 0.26 (fair) to 0.41 (moderate) for original and revised PSDs, respectively

    Incorporating interspecific competition into species-distribution mapping by upward scaling of small-scale model projections to the landscape.

    No full text
    There are a number of overarching questions and debate in the scientific community concerning the importance of biotic interactions in species distribution models at large spatial scales. In this paper, we present a framework for revising the potential distribution of tree species native to the Western Ecoregion of Nova Scotia, Canada, by integrating the long-term effects of interspecific competition into an existing abiotic-factor-based definition of potential species distribution (PSD). The PSD model is developed by combining spatially explicit data of individualistic species' response to normalized incident photosynthetically active radiation, soil water content, and growing degree days. A revised PSD model adds biomass output simulated over a 100-year timeframe with a robust forest gap model and scaled up to the landscape using a forestland classification technique. To demonstrate the method, we applied the calculation to the natural range of 16 target tree species as found in 1,240 provincial forest-inventory plots. The revised PSD model, with the long-term effects of interspecific competition accounted for, predicted that eastern hemlock (Tsuga canadensis), American beech (Fagus grandifolia), white birch (Betula papyrifera), red oak (Quercus rubra), sugar maple (Acer saccharum), and trembling aspen (Populus tremuloides) would experience a significant decline in their original distribution compared with balsam fir (Abies balsamea), black spruce (Picea mariana), red spruce (Picea rubens), red maple (Acer rubrum L.), and yellow birch (Betula alleghaniensis). True model accuracy improved from 64.2% with original PSD evaluations to 81.7% with revised PSD. Kappa statistics slightly increased from 0.26 (fair) to 0.41 (moderate) for original and revised PSDs, respectively

    Wood Mechanical Properties and Discoloured Heartwood Proportion in Sugar Maple and Yellow Birch Grown in New Brunswick

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    Rising interest in using wood in non-residential multi-story building structures opens up new opportunities for utilising low-grade hardwoods. The primary objective of this study was to evaluate the geographic variation in modulus of elasticity (MOE) and modulus of rupture (MOR) of sugar maple and yellow birch wood in relation to stand and tree characteristics for two regions in New Brunswick, Canada. Mixed effects statistical models were developed to test the effects of stand, tree, and wood sample variables. A second objective was to examine geographic variation in heartwood discolouration in relation to stand and tree characteristics. Between-tree differences (trees nested within sites) accounted for 44% and 35% of the total variation in yellow birch (MOE and MOR, respectively) and for 69% and 60% of total variation in sugar maple. The fixed effects explained only a very small part for the variation in MOE and MOR in the sugar maple data (10% for MOE and 5% for MOR). For sugar maple, mechanical properties (MOE and MOR) at 50% of the radius were considerably lower than those close to the bark, but this radial variation was not noteworthy for yellow birch. Discoloured heartwood proportion had no significant effect on wood mechanical properties.Validerad; 2016; Nivå 2; 20150827 (aliwan)</p

    Deriving wood quality properties through their links with tree and stand attributes

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    One of the important Canadian Wood Fibre Centre’s mandates is to develop methods to facilitate the flow of information on the wood quality and quantity along the chain of forest values. Among its research projects, one entitled Enhanced Forest Inventory aims to produce tools to map the wood attributes in terms of physico-mechanical properties by using prediction models based on the attributes of the forest tree and stand. The main inputs of these models come from non-destructive measurements on standing trees (acoustic probe, resistograph, terrestrial lidar) and from spatial data (aerial lidar). Among the obtained results, the correlations are significant between acoustic velocity, drill resistance, tree and stand attributes. These results open the prospect of using the data of non destructive measurements such as acoustic probe and resistograph as complementary input with tree and stand attributes (dbh, crown, and competition index) for prescribing the intensity of thinning to a desired level of wood density.Godkänd; 2012; 20121026 (aliwan

    Spatial distribution of modeled PSD surfaces (original vs. revised) for balsam fir, black spruce, eastern larch, and red pine.

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    <p>Original PSD represents species' potential distribution in responses to photosynthetically active radiation (PAR), soil water content (SWC), and growing degree days (GDD); revised PSD (right) indicates distribution in response to PAR, SWC, GDD, and species competitive ability simulated with JABOWA-III forest gap model. Dark blue colors represent least favorable growing conditions and potential absence of species (legend), whereas brown and yellow represent the most favorable conditions and probable presence of the species; green represents intermediate growing conditions and associated species presence.</p

    Results of an accuracy assessment between revised PSD (Eq (11)) values and plot observations.

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    <p>Class limits for the assessment scale are based on Monserud and Leemans [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171487#pone.0171487.ref028" target="_blank">28</a>], namely <0.20 (poor), 0.20–0.40 (fair), 0.40–0.50 (moderate), 0.50–0.70 (good), 0.70–0.80 (very good), and >0.80 (excellent).</p
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