| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 3. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 4. |
- Heskel, Mary A., et al.
(författare)
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Convergence in the temperature response of leaf respiration across biomes and plant functional types
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:14, s. 3832-3837
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Tidskriftsartikel (refereegranskat)abstract
- Plant respiration constitutes a massive carbon flux to the atmosphere, and a major control on the evolution of the global carbon cycle. It therefore has the potential to modulate levels of climate change due to the human burning of fossil fuels. Neither current physiological nor terrestrial biosphere models adequately describe its short-term temperature response, and even minor differences in the shape of the response curve can significantly impact estimates of ecosystem carbon release and/or storage. Given this, it is critical to establish whether there are predictable patterns in the shape of the respiration-temperature response curve, and thus in the intrinsic temperature sensitivity of respiration across the globe. Analyzing measurements in a comprehensive database for 231 species spanning 7 biomes, we demonstrate that temperature-dependent increases in leaf respiration do not follow a commonly used exponential function. Instead, we find a decelerating function as leaves warm, reflecting a declining sensitivity to higher temperatures that is remarkably uniform across all biomes and plant functional types. Such convergence in the temperature sensitivity of leaf respiration suggests that there are universally applicable controls on the temperature response of plant energy metabolism, such that a single new function can predict the temperature dependence of leaf respiration for global vegetation. This simple function enables straightforward description of plant respiration in the land-surface components of coupled earth system models. Our cross-biome analyses shows significant implications for such fluxes in cold climates, generally projecting lower values compared with previous estimates.
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| 5. |
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| 6. |
- Roche, Jessica, et al.
(författare)
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Coordinated nitrogen and carbon remobilization for nitrate assimilation in leaf, sheath and root and associated cytokinin signals during early regrowth of Lolium perenne
- 2017
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Ingår i: Annals of Botany. - : Oxford University Press. - 0305-7364 .- 1095-8290. ; 119:8, s. 1353-1364
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims The efficiency of N assimilation in response to defoliation is a critical component of plant regrowth and forage production. The aim of this research was to test the effect of the internal C/N balance on NO3- assimilation and to estimate the associated cytokinin signals following defoliation of perennial ryegrass (Lolium perenne L. 'Grasslands Nui') plants. Methods Plants, manipulated to have contrasting internal N content and contrasting availability of water soluble carbohydrates (WSCs), were obtained by exposure to either continuous light or short days (8: 16 h light-dark), and watered with modified N-free Hoagland medium containing either high (5 mM) or low (50 mu M) NO3- as sole N source. Half of the plants were defoliated and the root, sheath and leaf tissue were harvested at 8, 24 and 168 h after cutting. The spatiotemporal changes in WSCs, synthesis of amino acids and associated cytokinin content were recorded after cutting. Key Results Leaf regrowth following defoliation involved changes in the low-and high-molecular weight WSCs. The extent of the changes and the partitioning of the WSC following defoliation were dependant on the initial WSC levels and the C and N availability. Cytokinin levels varied in the sheath and root as early as 8 h following defoliation and preceded an overall increase in amino acids at 24 h. Subsequently, negative feedback brought the amino acid response back towards pre-defoliation levels within 168 h after cutting, a response that was under control of the C/N ratio. Conclusions WSC remobilization in the leaf is coordinated with N availability to the root, potentially via a systemic cytokinin signal, leading to efficient N assimilation in the leaf and the sheath tissues and to early leaf regrowth following defoliation.
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| 7. |
- Searle, Stephanie Y, et al.
(författare)
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Leaf respiration and alternative oxidase in field-grown alpine grasses respond to natural changes in temperature and light
- 2011
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 189:4, s. 1027-1039
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Tidskriftsartikel (refereegranskat)abstract
- • We report the first investigation of changes in electron partitioning via the alternative respiratory pathway (AP) and alternative oxidase (AOX) protein abundance in field-grown plants and their role in seasonal acclimation of respiration. • We sampled two alpine grasses native to New Zealand, Chionochloa rubra and Chionochloa pallens, from field sites of different altitudes, over 1 yr and also intensively over a 2-wk period. • In both species, respiration acclimated to seasonal changes in temperature through changes in basal capacity (R₁₀) but not temperature sensitivity (E₀). In C. pallens, acclimation of respiration may be associated with a higher AOX : cytochrome c oxidase (COX) protein abundance ratio. Oxygen isotope discrimination (D), which reflects relative changes in AP electron partitioning, correlated positively with daily integrated photosynthetically active radiation (PAR) in both species over seasonal timescales. Respiratory parameters, the AOX : COX protein ratio and D were stable over a 2-wk period, during which significant temperature changes were experienced in the field. • We conclude that respiration in Chionochloa spp. acclimates strongly to seasonal, but not to short-term, temperature variation. Alternative oxidase appears to be involved in the plant response to both seasonal changes in temperature and daily changes in light, highlighting the complexity of the function of AOX in the field.
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