109 research outputs found

    In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts.

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    Here we integrated multiphoton laser scanning microscopy and the registration of second harmonic generation images of collagen fibers to overcome difficulties in tracking stromal cell-matrix interactions for several days in live mice. We show that the matrix-modifying hormone relaxin increased tumor-associated fibroblast (TAF) interaction with collagen fibers by stimulating beta1-integrin activity, which is necessary for fiber remodeling by matrix metalloproteinases

    Measuring the Impacts of Community-based Grasslands Management in Mongolia's Gobi

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    We assessed a donor-funded grassland management project designed to create both conservation and livelihood benefits in the rangelands of Mongolia's Gobi desert. The project ran from 1995 to 2006, and we used remote sensing Normalized Differential Vegetation Index data from 1982 to 2009 to compare project grazing sites to matched control sites before and after the project's implementation. We found that the productivity of project grazing sites was on average within 1% of control sites for the 20 years before the project but generated 11% more biomass on average than the control areas from 2000 to 2009. To better understand the benefits of the improved grasslands to local people, we conducted 280 household interviews, 8 focus group discussions, and 31 key informant interviews across 6 districts. We found a 12% greater median annual income as well as a range of other socioeconomic benefits for project households compared to control households in the same areas. Overall, the project generated measurable benefits to both nature and people. The key factors underlying project achievements that may be replicable by other conservation projects include the community-driven approach of the project, knowledge exchanges within and between communities inside and outside the country, a project-supported local community organizer in each district, and strong community leadership

    Natural climate solutions for the United States

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    © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 4 (2018): eaat1869, doi:10.1126/sciadv.aat1869.Limiting climate warming to <2°C requires increased mitigation efforts, including land stewardship, whose potential in the United States is poorly understood. We quantified the potential of natural climate solutions (NCS)—21 conservation, restoration, and improved land management interventions on natural and agricultural lands—to increase carbon storage and avoid greenhouse gas emissions in the United States. We found a maximum potential of 1.2 (0.9 to 1.6) Pg CO2e year−1, the equivalent of 21% of current net annual emissions of the United States. At current carbon market prices (USD 10 per Mg CO2e), 299 Tg CO2e year−1 could be achieved. NCS would also provide air and water filtration, flood control, soil health, wildlife habitat, and climate resilience benefits.This study was made possible by funding from the Doris Duke Charitable Foundation. C.A.W. and H.G. acknowledge financial support from NASA’s Carbon Monitoring System program (NNH14ZDA001N-CMS) under award NNX14AR39G. S.D.B. acknowledges support from the DOE’s Office of Biological and Environmental Research Program under the award DE-SC0014416. J.W.F. acknowledges financial support from the Florida Coastal Everglades Long-Term Ecological Research program under National Science Foundation grant no. DEB-1237517

    Hundreds of variants clustered in genomic loci and biological pathways affect human height

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    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

    Striking a Balance: Socioeconomic Development and Conservation in Grassland through Community-Based Zoning

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    The goal of preserving nature is often in conflict with economic development and the aspirations of the rural poor. Nowhere is this more striking than in native grasslands, which have been extensively converted until a mere fraction of their original extent remains. This is not surprising; grasslands flourish in places coveted by humans, primed for agriculture, plantations, and settlements that nearly always trump conservation efforts. The Umgano grassland conservation and poverty reduction project in KwaZulu-Natal Province, South Africa uses community-based spatial planning to balance the conversion of its lower-conservation value grasslands to a timber plantation, while conserving higher-value grasslands for heritage purposes and managed livestock grazing. Ten years after project launch, we measured the ecological and socioeconomic impacts of the project using Normalized Differential Vegetation Index remote sensing data and over 500 household interviews, as compared with similar non-conserved areas. Zoned management of the Umgano area had resulted in between 9% and 17% greater average peak production in the grassland areas compared to control sites. There was also a 21% gain in incomes for the roughly one hundred people employed by the forestry efforts, when compared to others in their village. Community-based spatial zoning is an overlooked tool for balancing conservation and development but may require, as we found in Umgano, certain critical factors including strong local leadership, an accountable financial management mechanism to distribute income, outside technical expertise for the zoning design, and community support

    An attainable global vision for conservation and human well-being

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    A hopeful vision of the future is a world in which both people and nature thrive, but there is little evidence to support the feasibility of such a vision. We used a global, spatially explicit, systems modeling approach to explore the possibility of meeting the demands of increased populations and economic growth in 2050 while simultaneously advancing multiple conservation goals. Our results demonstrate that if, instead of “business as usual” practices, the world changes how and where food and energy are produced, this could help to meet projected increases in food (54%) and energy (56%) demand while achieving habitat protection (>50% of natural habitat remains unconverted in most biomes globally; 17% area of each ecoregion protected in each country), reducing atmospheric greenhouse-gas emissions consistent with the Paris Climate Agreement (≤1.6°C warming by 2100), ending overfishing, and reducing water stress and particulate air pollution. Achieving this hopeful vision for people and nature is attainable with existing technology and consumption patterns. However, success will require major shifts in production methods and an ability to overcome substantial economic, social, and political challenges

    Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

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    Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Many Labs 5:Testing pre-data collection peer review as an intervention to increase replicability

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    Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3?9; median total sample = 1,279.5, range = 276?3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (?r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00?.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19?.50)
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