| 1. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Chami, Nathalie, et al.
(författare)
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Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 8-21
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
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| 5. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 6. |
- Currier, Russell W, et al.
(författare)
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The evolution of infectious agents in relation to sex in animals and humans: brief discussions of some individual organisms.
- 2011
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1230, s. 74-107, s. 74-107
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Forskningsöversikt (refereegranskat)abstract
- The following series of concise summaries addresses the evolution of infectious agents in relation to sex in animals and humans from the perspective of three specific questions: (1) what have we learned about the likely origin and phylogeny, up to the establishment of the infectious agent in the genital econiche, including the relative frequency of its sexual transmission; (2) what further research is needed to provide additional knowledge on some of these evolutionary aspects; and (3) what evolutionary considerations might aid in providing novel approaches to the more practical clinical and public health issues facing us currently and in the future?
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| 7. |
- Dastani, Zari, et al.
(författare)
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Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- 2012
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607-
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Tidskriftsartikel (refereegranskat)abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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| 8. |
- Deyhle, Richard T, et al.
(författare)
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Maintenance of near normal bone mass and architecture in lethally irradiated female mice following adoptive transfer with as few as 750 purified hematopoietic stem cells
- 2019
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Ingår i: Radiation Research. - 0033-7587. ; 5, s. 413-427
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Tidskriftsartikel (refereegranskat)abstract
- Total-body irradiation (TBI) followed by transfer of bone marrow cells from donors is routinely performed in immunology research and can be used to manipulate differentiation and/or function of bone cells. However, exposure to high-dose radiation can result in irreversible osteopenia, and transfer of heterogeneous cell populations can complicate interpretation of results. The goal of this research was to establish an approach for reconstituting bone marrow using small numbers of purified donor-derived hematopoietic stem cells (HSCs) without negatively affecting bone metabolism. Gamma-irradiated (9 Gy) WBB6F1 mice were engrafted with bone marrow cells (5 × 106 cells) or purified HSCs (3,000 cells) obtained from GFP transgenic mice. In vivo analysis and in vitro differentiation assays performed two months later established that both methods were effective in reconstituting the hematopoietic compartment with donor-derived cells. We confirmed these findings by engrafting C57Bl/6 (B6) mice with bone marrow cells or purified HSCs from CD45.1 B6 congenic mice. We next performed adoptive transfer of purified HSCs (750 cells) into WBB6F1 and radiosensitive KitW/W-v mice and evaluated the skeleton two months later. Minimal differences were observed between controls and WBB6F1-engrafted mice that received fractionated doses of 2 × 5 Gy. Kitw/wv mice lost weight and became osteopenic after 2 × 5 Gy irradiations but these abnormalities were negligible after 5 Gy irradiation. Importantly, adoptive transfer of wild-type cells into Kitw/wv mice restored normal Kit expression in bone marrow. Together, these findings provide strong evidence for efficient engraftment with purified HSCs after lethal TBI with minimal collateral damage to bone. This approach will be useful for investigating mechanisms by which hematopoietic lineage cells regulate bone metabolism.
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| 9. |
- Eicher, John D., et al.
(författare)
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Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 40-55
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Tidskriftsartikel (refereegranskat)abstract
- Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common(ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV(PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
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| 10. |
- Fuertes, Elaine, et al.
(författare)
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Leisure-time vigorous physical activity is associated with better lung function : the prospective ECRHS study
- 2018
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 73:4, s. 376-384
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort. Methods: FEV1 and FVC were measured in 3912 participants at 27-57 years and 39-67 years (mean time between examinations= 11.1 years). Physical activity frequency and duration were assessed using questionnaires and used to identify active individuals (physical activity >= 2 times and >= 1 hour per week) at each examination. Adjusted mixed linear regression models assessed associations of regular physical activity with FEV1 and FVC. Results: Physical activity frequency and duration increased over the study period. In adjusted models, active individuals at the first examination had higher FEV1 (43.6 mL (95% CI 12.0 to 75.1)) and FVC (53.9 mL (95% CI 17.8 to 89.9)) at both examinations than their non-active counterparts. These associations appeared restricted to current smokers. In the whole population, FEV1 and FVC were higher among those who changed from inactive to active during the follow-up (38.0 mL (95% CI 15.8 to 60.3) and 54.2 mL (95% CI 25.1 to 83.3), respectively) and who were consistently active, compared with those consistently non-active. No associations were found for lung function decline. Conclusion: Leisure-time vigorous physical activity was associated with higher FEV1 and FVC over a 10-year period among current smokers, but not with FEV1 and FVC decline.
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| 11. |
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| 12. |
- Horgan, Briony, et al.
(författare)
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Mineralogy, Morphology, and Emplacement History of the Maaz Formation on the Jezero Crater Floor From Orbital and Rover Observations
- 2023
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Ingår i: Journal of Geophysical Research: Planets. - 2169-9097. ; 128:8
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Tidskriftsartikel (refereegranskat)abstract
- The first samples collected by the Perseverance rover on the Mars 2020 mission were from the Maaz formation, a lava plain that covers most of the floor of Jezero crater. Laboratory analysis of these samples back on Earth would provide important constraints on the petrologic history, aqueous processes, and timing of key events in Jezero crater. However, interpreting these samples requires a detailed understanding of the emplacement and modification history of the Maaz formation. Here we synthesize rover and orbital remote sensing data to link outcrop-scale interpretations to the broader history of the crater, including Mastcam-Z mosaics and multispectral images, SuperCam chemistry and reflectance point spectra, Radar Imager for Mars' subsurface eXperiment ground penetrating radar, and orbital hyperspectral reflectance and high-resolution images. We show that the Maaz formation is composed of a series of distinct members corresponding to basaltic to basaltic-andesite lava flows. The members exhibit variable spectral signatures dominated by high-Ca pyroxene, Fe-bearing feldspar, and hematite, which can be tied directly to igneous grains and altered matrix in abrasion patches. Spectral variations correlate with morphological variations, from recessive layers that produce a regolith lag in lower Maaz, to weathered polygonally fractured paleosurfaces and crater-retaining massive blocky hummocks in upper Maaz. The Maaz members were likely separated by one or more extended periods of time, and were subjected to variable erosion, burial, exhumation, weathering, and tectonic modification. The two unique samples from the Maaz formation are representative of this diversity, and together will provide an important geochronological framework for the history of Jezero crater.
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| 13. |
- Li, Wei, et al.
(författare)
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Soluble Immune Checkpoints Are Dysregulated in COVID-19 and Heavy Alcohol Users With HIV Infection
- 2022
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Ingår i: FRONTIERS IN IMMUNOLOGY. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.
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| 14. |
- Maxwell, Tania L., et al.
(författare)
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Global dataset of soil organic carbon in tidal marshes
- 2023
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM). The MarSOC dataset includes 17,454 data points from 2,329 unique locations, and 29 countries. We generated a general transfer function for the conversion of SOM to SOC. Using this data we estimated a median (± median absolute deviation) value of 79.2 ± 38.1 Mg SOC ha−1 in the top 30 cm and 231 ± 134 Mg SOC ha−1 in the top 1 m of tidal marsh soils globally. This data can serve as a basis for future work, and may contribute to incorporation of tidal marsh ecosystems into climate change mitigation and adaptation strategies and policies.
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| 15. |
- Negre, Nicolas, et al.
(författare)
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A cis-regulatory map of the Drosophila genome
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 471:7339, s. 527-531
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Tidskriftsartikel (refereegranskat)abstract
- Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide(1,2) has successfully identified specific subtypes of regulatory elements(3). In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements(4), chromatin states(5), transcription factor binding sites(6-9), RNA polymerase II regulation(8) and insulator elements(10); however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships.
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| 16. |
- Russell, Melissa A., et al.
(författare)
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Physical activity and asthma : a longitudinal and multi-country study
- 2017
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Ingår i: Journal of Asthma. - Abingdon : Taylor & Francis. - 0277-0903 .- 1532-4303. ; 54:9, s. 938-945
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the impact of physical activity on asthma in middle-aged adults, in one longitudinal analysis, and one multi-centre cross-sectional analysis.Methods: The Respiratory Health in Northern Europe (RHINE) is a population-based postal questionnaire cohort study. Physical activity, height and weight were self-reported in Bergen, Norway, at RHINE II (1999–2001) and all centres at RHINE III (2010–2012). A longitudinal analysis of Bergen data investigated the association of baseline physical activity with follow-up asthma, incident asthma and symptoms, using logistic and zero-inflated Poisson regression (n = 1782). A cross-sectional analysis of all RHINE III centres investigated the association of physical activity with concurrent asthma and symptoms (n = 13,542) using mixed-effects models. Body mass index (BMI) was categorised (<20, 20–24.99, 25–29.99, 30+ kg/m2) and physical activity grouped by amount and frequency of lighter (no sweating/heavy breathing) and vigorous (sweating/heavy breathing) activity.Results: In the Bergen longitudinal analysis, undertaking light activity 3+ times/week at baseline was associated with less follow-up asthma (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.22, 0.89), whilst an effect from undertaking vigorous activity 3+ times/week was not detected (OR 1.22, 95% CI 0.44, 2.76). The associations were attenuated with BMI adjustment. In the all-centre cross-sectional analysis an interaction was found, with the association between physical activity and asthma varying across BMI categories.Conclusion: These findings suggest potential longer-term benefit from lighter physical activity, whilst improvement in asthma outcomes from increasing activity intensity was not evident. Additionally, it appears the benefit from physical activity may differ according to BMI.
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| 17. |
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| 18. |
- Russell, Melissa, et al.
(författare)
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The association of vigorous physical activity with 10-year adult asthma incidence
- 2018
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Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Studies investigating the effect of physical activity on asthma incidence have often been limited to one sex, and given mixed results.Aim: To investigate the association of vigorous physical activity with asthma incidence in middle-aged, predominantly European adults.Methods: Participants from the European Community Respiratory Health Survey with no history of asthma were included (n=2532). The association between baseline vigorous physical active (>1 hour and >2 times per week) and (1) self-report of newly doctor diagnosed asthma and (2) time to first asthma attack, over the following 10 years, was analysed using mixed effects logistic regression and cox regression respectively. To reduce potential reverse causation, incident asthma cases in the 2 years after baseline were excluded. Associations were adjusted for baseline sex, age, smoking, BMI, occupation, heart disease and education.Results: At baseline the mean age was 43 years and 47% were female. There were 44 (1.7%) incident doctor diagnosed asthma cases and 38 (1.5%) new cases of asthma attack reported. There was evidence that being vigorously physically active at baseline was associated with an increased odds of newly doctor diagnosed asthma (odds ratio 1.93, 95% Confidence Interval 1.04, 3.57, p=0.036). There was no association with time to first asthma attack.Conclusion: The health benefits of physical activity are well documented. However, our data do not support the presupposition that vigorous physical activity would reduce asthma incidence. We observed an increased risk of report of doctor diagnosed asthma with vigorous physical activity in this general adult population, as has been observed with athletes.
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| 19. |
- Zuntini, Alexandre R., et al.
(författare)
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Phylogenomics and the rise of the angiosperms
- 2024
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Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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