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| 4. |
- Poyatos, R., et al.
(författare)
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Global transpiration data from sap flow measurements: the SAPFLUXNET database
- 2021
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:6, s. 2607-2649
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Tidskriftsartikel (refereegranskat)abstract
- Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land-atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets, while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes. SAPFLUXNET version 0.1.5 is freely available from the Zenodo repository (https://doi.org/10.5281/zenodo.3971689; Poyatos et al., 2020a). The "sapfluxnetr" R package - designed to access, visualize, and process SAPFLUXNET data - is available from CRAN.
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| 6. |
- Byun, Jinyoung, et al.
(författare)
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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
- 2022
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Ingår i: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
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Tidskriftsartikel (refereegranskat)abstract
- To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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| 7. |
- Bruxvoort, K. J., et al.
(författare)
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The Impact of Introducing Malaria Rapid Diagnostic Tests on Fever Case Management: A Synthesis of Ten Studies from the ACT Consortium
- 2017
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Ingår i: Am J Trop Med Hyg. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 97:4, s. 1170-1179
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Tidskriftsartikel (refereegranskat)abstract
- Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.
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| 8. |
- Hopkins, H., et al.
(författare)
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Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings
- 2017
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia. Analysis of nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study). Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda. Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings. Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole. Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription. This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined.
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| 9. |
- Welsh, Joshua A., et al.
(författare)
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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
- 2024
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Ingår i: Journal of Extracellular Vesicles. - : John Wiley and Sons Inc. - 2001-3078. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Baker, Naomi L., et al.
(författare)
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Molecular consequences of dominant Bethlem myopathy collagen VI mutations
- 2007
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 62:4, s. 390-405
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dominant mutations in the three collagen VI genes cause Bethlem myopathy, a disorder characterized by proximal muscle weakness and commonly contractures of the fingers, wrists, and ankles. Although more than 20 different dominant mutations have been identified in Bethlem myopathy patients, the biosynthetic consequences of only a subset of these have been studied, and in many cases, the pathogenic mechanisms remain unknown. Methods: We have screened fourteen Bethlem myopathy patients for collagen VI mutations and performed detailed analyses of collagen VI biosynthesis and intracellular and extracellular assembly. Results: Collagen VI abnormalities were identified in eight patients. One patient produced around half the normal amount of alpha 1(VI) messenger RNA and reduced amounts of collagen VI protein. Two patients had a previously reported mutation causing skipping of COL6A1 exon 14, and three patients had novel mutations leading to in-frame deletions toward the N-terminal end of the triple-helical domain. These mutations have different and complex effects on collagen VI intracellular and extracellular assembly. Two patients had single amino acid substitutions in the A-domains of COL6A2 and COL6A3. Collagen VI intracellular and extracellular assembly was normal in one of these patients. Interpretation: The key to dissecting the pathogenic mechanisms of collagen VI mutations lies in detailed analysis of collagen VI biosynthesis and assembly. The majority of mutations result in secretion and deposition of structurally abnormal collagen VI. However, one A-domain mutation had no detectable effect on assembly, suggesting that it acts by compromising collagen VI interactions in the extracellular matrix of muscle.
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| 11. |
- Hoencamp, Claire, et al.
(författare)
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3D genomics across the tree of life reveals condensin II as a determinant of architecture type
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 372:6545, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.
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| 13. |
- Moslehi, S., et al.
(författare)
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Fractal Electronics for Stimulating and Sensing Neural Networks : Enhanced Electrical, Optical, and Cell Interaction Properties
- 2024
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Ingår i: The Fractal Geometry of the Brain. - 2190-5223 .- 2190-5215. - 9783031476068 - 9783031476051 ; 36, s. 849-875
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Bokkapitel (refereegranskat)abstract
- Imagine a world in which damaged parts of the body – an arm, an eye, and ultimately a region of the brain – can be replaced by artificial implants capable of restoring or even enhancing human performance. The associated improvements in the quality of human life would revolutionize the medical world and produce sweeping changes across society. In this chapter, we discuss several approaches to the fabrication of fractal electronics designed to interface with neural networks. We consider two fundamental functions – stimulating electrical signals in the neural networks and sensing the location of the signals as they pass through the network. Using experiments and simulations, we discuss the favorable electrical performances that arise from adopting fractal rather than traditional Euclidean architectures. We also demonstrate how the fractal architecture induces favorable physical interactions with the cells they interact with, including the ability to direct the growth of neurons and glia to specific regions of the neural–electronic interface.
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| 14. |
- Rifai, Sami W., et al.
(författare)
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ENSO Drives interannual variation of forest woody growth across the tropics
- 2018
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2970 .- 0962-8436. ; 373:1760
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Tidskriftsartikel (refereegranskat)abstract
- Meteorological extreme events such as El Niño events are expected to affect tropical forest net primary production (NPP) and woody growth, but there has been no large-scale empirical validation of this expectation. We collected a large high-temporal resolution dataset (for 1-13 years depending upon location) of more than 172 000 stem growth measurements using dendrometer bands from across 14 regions spanning Amazonia, Africa and Borneo in order to test how much month-to-month variation in stand-level woody growth of adult tree stems (NPPstem) can be explained by seasonal variation and interannual meteorological anomalies. A key finding is that woody growth responds differently to meteorological variation between tropical forests with a dry season (where monthly rainfall is less than 100 mm), and aseasonal wet forests lacking a consistent dry season. In seasonal tropical forests, a high degree of variation in woody growth can be predicted from seasonal variation in temperature, vapour pressure deficit, in addition to anomalies of soil water deficit and shortwave radiation. The variation of aseasonal wet forest woody growth is best predicted by the anomalies of vapour pressure deficit, water deficit and shortwave radiation. In total, we predict the total live woody production of the global tropical forest biome to be 2.16 Pg C yr-1, with an interannual range 1.96-2.26 Pg C yr-1 between 1996-2016, and with the sharpest declines during the strong El Niño events of 1997/8 and 2015/6. There is high geographical variation in hotspots of El Niño-associated impacts, with weak impacts in Africa, and strongly negative impacts in parts of Southeast Asia and extensive regions across central and eastern Amazonia. Overall, there is high correlation (r = -0.75) between the annual anomaly of tropical forest woody growth and the annual mean of the El Niño 3.4 index, driven mainly by strong correlations with anomalies of soil water deficit, vapour pressure deficit and shortwave radiation.This article is part of the discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.
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| 15. |
- Rowland, L, et al.
(författare)
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Death from drought in tropical forests is triggered by hydraulics not carbon starvation.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 528:7580, s. 119-122
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Tidskriftsartikel (refereegranskat)abstract
- Drought threatens tropical rainforests over seasonal to decadal timescales, but the drivers of tree mortality following drought remain poorly understood. It has been suggested that reduced availability of non-structural carbohydrates (NSC) critically increases mortality risk through insufficient carbon supply to metabolism ('carbon starvation'). However, little is known about how NSC stores are affected by drought, especially over the long term, and whether they are more important than hydraulic processes in determining drought-induced mortality. Using data from the world's longest-running experimental drought study in tropical rainforest (in the Brazilian Amazon), we test whether carbon starvation or deterioration of the water-conducting pathways from soil to leaf trigger tree mortality. Biomass loss from mortality in the experimentally droughted forest increased substantially after >10 years of reduced soil moisture availability. The mortality signal was dominated by the death of large trees, which were at a much greater risk of hydraulic deterioration than smaller trees. However, we find no evidence that the droughted trees suffered carbon starvation, as their NSC concentrations were similar to those of non-droughted trees, and growth rates did not decline in either living or dying trees. Our results indicate that hydraulics, rather than carbon starvation, triggers tree death from drought in tropical rainforest.
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| 16. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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| 18. |
- Cuthill, Innes C., et al.
(författare)
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The biology of color
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 357:6350
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Forskningsöversikt (refereegranskat)abstract
- Coloration mediates the relationship between an organism and its environment in important ways, including social signaling, antipredator defenses, parasitic exploitation, thermoregulation, and protection from ultraviolet light, microbes, and abrasion. Methodological breakthroughs are accelerating knowledge of the processes underlying both the production of animal coloration and its perception, experiments are advancing understanding of mechanism and function, and measurements of color collected noninvasively and at a global scale are opening windows to evolutionary dynamics more generally. Here we provide a roadmap of these advances and identify hitherto unrecognized challenges for this multi- and interdisciplinary field.
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| 23. |
- Girardin, Cécile A J, et al.
(författare)
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Seasonal trends of Amazonian rainforest phenology, net primary productivity, and carbon allocation
- 2016
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Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 30:5, s. 700-715
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Tidskriftsartikel (refereegranskat)abstract
- The seasonality of solar irradiance and precipitation may regulate seasonal variations in tropical forests carbon cycling. Controversy remains over their importance as drivers of seasonal dynamics of net primary productivity in tropical forests. We use ground data from nine lowland Amazonian forest plots collected over 3 years to quantify the monthly primary productivity (NPP) of leaves, reproductive material, woody material, and fine roots over an annual cycle. We distinguish between forests that do not experience substantial seasonal moisture stress (“humid sites”) and forests that experience a stronger dry season (“dry sites”). We find that forests from both precipitation regimes maximize leaf NPP over the drier season, with a peak in production in August at both humid (mean 0.39 ± 0.03 Mg C ha−1 month−1 in July, n = 4) and dry sites (mean 0.49 ± 0.03 Mg C ha−1 month−1 in September, n = 8). We identify two distinct seasonal carbon allocation patterns (the allocation of NPP to a specific organ such as wood leaves or fine roots divided by total NPP). The forests monitored in the present study show evidence of either (i) constant allocation to roots and a seasonal trade-off between leaf and woody material or (ii) constant allocation to wood and a seasonal trade-off between roots and leaves. Finally, we find strong evidence of synchronized flowering at the end of the dry season in both precipitation regimes. Flower production reaches a maximum of 0.047 ± 0.013 and 0.031 ± 0.004 Mg C ha−1 month−1 in November, in humid and dry sites, respectively. Fruitfall production was staggered throughout the year, probably reflecting the high variation in varying times to development and loss of fruit among species.
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| 24. |
- Harper, Anna B., et al.
(författare)
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Improvement of modeling plant responses to low soil moisture in JULESvn4.9 and evaluation against flux tower measurements
- 2021
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 14:6, s. 3269-3294
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Tidskriftsartikel (refereegranskat)abstract
- Drought is predicted to increase in the future due to climate change, bringing with it myriad impacts on ecosystems. Plants respond to drier soils by reducing stomatal conductance in order to conserve water and avoid hydraulic damage. Despite the importance of plant drought responses for the global carbon cycle and local and regional climate feedbacks, land surface models are unable to capture observed plant responses to soil moisture stress. We assessed the impact of soil moisture stress on simulated gross primary productivity (GPP) and latent energy flux (LE) in the Joint UK Land Environment Simulator (JULES) vn4.9 on seasonal and annual timescales and evaluated 10 different representations of soil moisture stress in the model. For the default configuration, GPP was more realistic in temperate biome sites than in the tropics or high-latitude (cold-region) sites, while LE was best simulated in temperate and high-latitude (cold) sites. Errors that were not due to soil moisture stress, possibly linked to phenology, contributed to model biases for GPP in tropical savanna and deciduous forest sites. We found that three alternative approaches to calculating soil moisture stress produced more realistic results than the default parameterization for most biomes and climates. All of these involved increasing the number of soil layers from 4 to 14 and the soil depth from 3.0 to 10.8 m. In addition, we found improvements when soil matric potential replaced volumetric water content in the stress equation (the "soil14_psi" experiments), when the critical threshold value for inducing soil moisture stress was reduced ("soil14_p0"), and when plants were able to access soil moisture in deeper soil layers ("soil14_dr&z.ast;2"). For LE, the biases were highest in the default configuration in temperate mixed forests, with overestimation occurring during most of the year. At these sites, reducing soil moisture stress (with the new parameterizations mentioned above) increased LE and increased model biases but improved the simulated seasonal cycle and brought the monthly variance closer to the measured variance of LE. Further evaluation of the reason for the high bias in LE at many of the sites would enable improvements in both carbon and energy fluxes with new parameterizations for soil moisture stress. Increasing the soil depth and plant access to deep soil moisture improved many aspects of the simulations, and we recommend these settings in future work using JULES or as a general way to improve land surface carbon and water fluxes in other models. In addition, using soil matric potential presents the opportunity to include plant functional type-specific parameters to further improve modeled fluxes.
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| 25. |
- James, M. O., et al.
(författare)
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Properties and regional expression of a CYP3A-like protein in channel catfish intestine
- 2005
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X. ; 72:4, s. 361-371
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Tidskriftsartikel (refereegranskat)abstract
- Biotransformation in the intestine may influence the bioavailability and toxicity of ingested xenobiotics. The objective of this study was to examine the expression and catalytic properties of a constitutive cytochrome P450 (CYP) 3A-like protein along the intestine of channel catfish, Ictalurus punctatus. Fish were maintained on commercial chow or nutritionally complete semi-purified diets. Polyclonal antibodies generated against rainbow trout CYP3A proteins reacted strongly with catfish washed intestinal microsomes on Western blots showing a major protein band with MW of 59 kDa. In catfish maintained on a standard chow diet, the expression of this protein was higher in the proximal segment (0.101 &PLUSMN; 0.031 units/mg protein, mean &PLUSMN; S.D., n = 4) than in the distal part (0.032 &PLUSMN; 0.023 units/mg protein). Microsomal testosterone 6β-hydroxylation activity was monitored as the catalytic indicator of CYP3A, and was higher in proximal than distal catfish intestine (263 &PLUSMN; 80.3 and 88.6 &PLUSMN; 15.6 pmol/min/mg protein for proximal and distal, respectively, mean S.D., n = 4). CYP3A protein levels and testosterone 6β-hydroxylation activities were lower in microsomes from the proximal segment of intestine from catfish maintained on a semi-purified diet, compared with commercial chow, but again the proximal intestine had higher CYP3A and 6β-hydroxylase activities than distal intestine. Testosterone 6β-hydroxylase activities in all samples correlated with the CYP3A protein levels, r(2) = 0.8. Testosterone 6β-hydroxylation was inhibited by specific CYP3A inhibitors, ketoconazole (IC50 = 0.02 μ M) and erythromycin (IC50 = 41 μ M), as well as general CYP inhibitors, metyrapone (IC50 = 2.8 μ M) and SKF-525A (IC50 = 25 μ M). There was evidence for the involvement of CYP3A in the mono-oxygenation of benzo(a)pyrene and of (-)-benzo(a)pyrene-7,8-dihydrodiol in intestinal microsomes from catfish maintained on the semi-purified diet. Mono-oxygenation of both substrates was increased in a concentration-dependent manner by in vitro addition of a-naphthoflavone. Benzo(a)pyrene hydroxylase activities were higher in proximal than in distal intestine; 3.72 &PLUSMN; 0.77 pmol/min/mg protein, mean &PLUSMN; S.D., n = 5 and 1.45 &PLUSMN; 0.42 in these respective segments. The results of this study strongly suggest that CYP3A is important in the first pass metabolism of dietary xenobiotics in untreated fish. © 2005 Elsevier B.V. All rights reserved.
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