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- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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- Woodcroft, Ben J., et al.
(author)
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Genome-centric view of carbon processing in thawing permafrost
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 560:7716, s. 49-
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Journal article (peer-reviewed)abstract
- As global temperatures rise, large amounts of carbon sequestered in permafrost are becoming available for microbial degradation. Accurate prediction of carbon gas emissions from thawing permafrost is limited by our understanding of these microbial communities. Here we use metagenomic sequencing of 214 samples from a permafrost thaw gradient to recover 1,529 metagenome-assembled genomes, including many from phyla with poor genomic representation. These genomes reflect the diversity of this complex ecosystem, with genus-level representatives for more than sixty per cent of the community. Meta-omic analysis revealed key populations involved in the degradation of organic matter, including bacteria whose genomes encode a previously undescribed fungal pathway for xylose degradation. Microbial and geochemical data highlight lineages that correlate with the production of greenhouse gases and indicate novel syntrophic relationships. Our findings link changing biogeochemistry to specific microbial lineages involved in carbon processing, and provide key information for predicting the effects of climate change on permafrost systems.
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- Emerson, Joanne B., et al.
(author)
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Host-linked soil viral ecology along a permafrost thaw gradient
- 2018
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In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 3:8, s. 870-880
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Journal article (peer-reviewed)abstract
- Climate change threatens to release abundant carbon that is sequestered at high latitudes, but the constraints on microbial metabolisms that mediate the release of methane and carbon dioxide are poorly understood(1-7). The role of viruses, which are known to affect microbial dynamics, metabolism and biogeochemistry in the oceans(8-10), remains largely unexplored in soil. Here, we aimed to investigate how viruses influence microbial ecology and carbon metabolism in peatland soils along a permafrost thaw gradient in Sweden. We recovered 1,907 viral populations (genomes and large genome fragments) from 197 bulk soil and size-fractionated metagenomes, 58% of which were detected in metatranscriptomes and presumed to be active. In silico predictions linked 35% of the viruses to microbial host populations, highlighting likely viral predators of key carbon-cycling microorganisms, including methanogens and methanotrophs. Lineage-specific virus/host ratios varied, suggesting that viral infection dynamics may differentially impact microbial responses to a changing climate. Virus-encoded glycoside hydrolases, including an endomannanase with confirmed functional activity, indicated that viruses influence complex carbon degradation and that viral abundances were significant predictors of methane dynamics. These findings suggest that viruses may impact ecosystem function in climate-critical, terrestrial habitats and identify multiple potential viral contributions to soil carbon cycling.
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- Kramer, Daniel Boyd, et al.
(author)
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Top 40 questions in coupled human and natural systems (CHANS) research
- 2017
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In: Ecology and Society. - 1708-3087. ; 22:2
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Journal article (peer-reviewed)abstract
- Understanding and managing coupled human and natural systems (CHANS) is a central challenge of the 21st century, but more focus is needed to pursue the most important questions within this vast field given limited research capacity and funding. We present 40 important questions for CHANS research, identified through a two-part crowdsourcing exercise within the CHANS community. We solicited members of the International Network of Research on Coupled Human and Natural Systems (CHANS-Net) to submit up to three questions that they considered transformative, receiving 540 questions from 207 respondents. After editing for clarity and consistency, we asked the network’s members to each evaluate a random subset of 20 questions in importance on a scale from 1 (least important) to 7 (extremely important). Questions on land use and agriculture topped the list, with a median importance ranking of 5.7, followed by questions of scale, climate change and energy, sustainability and development, adaptation and resilience, in addition to seven other categories. We identified 40 questions with a median importance of 6.0 or above, which we highlight as the current view of researchers active in the field as research questions to pursue in order to maximize impact on understanding and managing coupled human and natural systems for achieving sustainable development goals and addressing emerging global challenges.
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- Linder, Adam, et al.
(author)
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Short-term organ dysfunction is associated with long-term (10-Yr) mortality of septic shock
- 2016
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In: Critical Care Medicine. - 0090-3493. ; 44:8, s. 728-736
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Journal article (peer-reviewed)abstract
- Objectives: As mortality of septic shock decreases, new therapies focus on improving short-term organ dysfunction. However, it is not known whether short-term organ dysfunction is associated with long-term mortality of septic shock. Design: Retrospective single-center. Setting: Mixed medical-surgical ICU. Patients: One thousand three hundred and thirty-one patients with septic shock were included from 2000-2004. To remove the bias of 28-day nonsurvivors' obvious association with long-term mortality, we determined the associations of days alive and free of ventilation, vasopressors and renal replacement therapy in 28-day and 1-year survivors with 1-, 5- and 10-year mortality in unadjusted analyses and analyses adjusted for age, gender, Acute Physiology and Chronic Health Evaluation II and presence of chronic comorbidities. Interventions: None. Measurements and Main Results: Days alive and free of ventilation, vasopressors, and renal replacement therapy were highly significantly associated with 1-, 5-, and 10-year mortality (p <0.0001). In 28-day survivors, using Bonferroni-corrected multiple logistic regression, days alive and free of ventilation (p <0.0001, p = 0.0002, and p = 0.001), vasopressors (p <0.0001, p <0.0001, and p = 0.0004), and renal replacement therapy (p = 0.0008, p = 0.0008, and p = 0.0002) were associated with increased 1-, 5-, and 10-year mortality, respectively. In 1-year survivors, none of the acute organ support and dysfunction measures were associated with 5- and 10-year mortality. Conclusions: Days alive and free of ventilation, vasopressors, and renal replacement therapy in septic shock in 28-day survivors was associated with 1-, 5-, and 10-year mortality. These associations are nullified in 1-year survivors in whom none of the acute organ support measures were associated with 5- and 10-year mortality. This suggests that therapies that decrease short-term organ dysfunction could also improve long-term outcomes of 28-day survivors of septic shock.
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- Singleton, Caitlin M., et al.
(author)
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Methanotrophy across a natural permafrost thaw environment
- 2018
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In: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 12:10, s. 2544-2558
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Journal article (peer-reviewed)abstract
- The fate of carbon sequestered in permafrost is a key concern for future global warming as this large carbon stock is rapidly becoming a net methane source due to widespread thaw. Methane release from permafrost is moderated by methanotrophs, which oxidise 20-60% of this methane before emission to the atmosphere. Despite the importance of methanotrophs to carbon cycling, these microorganisms are under-characterised and have not been studied across a natural permafrost thaw gradient. Here, we examine methanotroph communities from the active layer of a permafrost thaw gradient in Stordalen Mire (Abisko, Sweden) spanning three years, analysing 188 metagenomes and 24 metatranscriptomes paired with in situ biogeochemical data. Methanotroph community composition and activity varied significantly as thaw progressed from intact permafrost palsa, to partially thawed bog and fully thawed fen. Thirteen methanotroph population genomes were recovered, including two novel genomes belonging to the uncultivated upland soil cluster alpha (USCa) group and a novel potentially methanotrophic Hyphomicrobiaceae. Combined analysis of porewater delta C-13-CH 4 isotopes and methanotroph abundances showed methane oxidation was greatest below the oxic-anoxic interface in the bog. These results detail the direct effect of thaw on autochthonous methanotroph communities, and their consequent changes in population structure, activity and methane moderation potential.
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