| 1. |
- Abbasi, R., et al.
(författare)
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Solar energetic particle spectrum on 2006 December 13 determined by IceTop
- 2008
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 689:1, s. L65-L68
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Tidskriftsartikel (refereegranskat)abstract
- On 2006 December 13 the IceTop air shower array at the South Pole detected a major solar particle event. By numerically simulating the response of the IceTop tanks, which are thick Cerenkov detectors with multiple thresholds deployed at high altitude with no geomagnetic cutoff, we determined the particle energy spectrum in the energy range 0.6-7.6 GeV. This is the first such spectral measurement using a single instrument with a well-defined viewing direction. We compare the IceTop spectrum and its time evolution with previously published results and outline plans for improved resolution of future solar particle spectra.
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| 2. |
- Hathazi, D., et al.
(författare)
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Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency
- 2020
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Ingår i: Embo Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 39:23
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Tidskriftsartikel (refereegranskat)abstract
- Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only similar to 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease.
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| 3. |
- Austin, John, et al.
(författare)
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Chemistry-climate model simulations of spring Antarctic ozone
- 2010
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115, s. D00M11-
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Tidskriftsartikel (refereegranskat)abstract
- Coupled chemistry-climate model simulations covering the recent past and continuing throughout the 21st century have been completed with a range of different models. Common forcings are used for the halogen amounts and greenhouse gas concentrations, as expected under the Montreal Protocol (with amendments) and Intergovernmental Panel on Climate Change A1b Scenario. The simulations of the Antarctic ozone hole are compared using commonly used diagnostics: the minimum ozone, the maximum area of ozone below 220 DU, and the ozone mass deficit below 220 DU. Despite the fact that the processes responsible for ozone depletion are reasonably well understood, a wide range of results is obtained. Comparisons with observations indicate that one of the reasons for the model underprediction in ozone hole area is the tendency for models to underpredict, by up to 35%, the area of low temperatures responsible for polar stratospheric cloud formation. Models also typically have species gradients that are too weak at the edge of the polar vortex, suggesting that there is too much mixing of air across the vortex edge. Other models show a high bias in total column ozone which restricts the size of the ozone hole (defined by a 220 DU threshold). The results of those models which agree best with observations are examined in more detail. For several models the ozone hole does not disappear this century but a small ozone hole of up to three million square kilometers continues to occur in most springs even after 2070.
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| 4. |
- Menger, K. E., et al.
(författare)
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Two type I topoisomerases maintain DNA topology in human mitochondria
- 2022
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 50:19, s. 11154-11174
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Tidskriftsartikel (refereegranskat)abstract
- Genetic processes require the activity of multiple topoisomerases, essential enzymes that remove topological tension and intermolecular linkages in DNA. We have investigated the subcellular localisation and activity of the six human topoisomerases with a view to understanding the topological maintenance of human mitochondrial DNA. Our results indicate that mitochondria contain two topoisomerases, TOP1MT and TOP3A. Using molecular, genomic and biochemical methods we find that both proteins contribute to mtDNA replication, in addition to the decatenation role of TOP3A, and that TOP1MT is stimulated by mtSSB. Loss of TOP3A or TOP1MT also dysregulates mitochondrial gene expression, and both proteins promote transcription elongation in vitro. We find no evidence for TOP2 localisation to mitochondria, and TOP2B knockout does not affect mtDNA maintenance or expression. Our results suggest a division of labour between TOP3A and TOP1MT in mtDNA topology control that is required for the proper maintenance and expression of human mtDNA.
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| 5. |
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| 6. |
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| 7. |
- Horvath, Rita, et al.
(författare)
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Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.
- 2009
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 132:Pt 11, s. 3165-74
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Tidskriftsartikel (refereegranskat)abstract
- Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.
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| 8. |
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| 9. |
- Peter, Bradley, et al.
(författare)
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Defective mitochondrial protease LonP1 can cause classical mitochondrial disease
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1743-1753
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Tidskriftsartikel (refereegranskat)abstract
- LonP1 is a mitochondrial matrix protease whose selective substrate specificity is essential for maintaining mitochondrial homeostasis. Recessively inherited, pathogenic defects in LonP1 have been previously reported to underlie cerebral, ocular, dental, auricular and skeletal anomalies (CODAS) syndrome, a complex multisystemic and developmental disorder. Intriguingly, although classical mitochondrial disease presentations are well-known to exhibit marked clinical heterogeneity, the skeletal and dental features associated with CODAS syndrome are pathognomonic. We have applied whole exome sequencing to a patient with congenital lactic acidosis, muscle weakness, profound deficiencies in mitochondrial oxidative phosphorylation associated with loss of mtDNA copy number and MRI abnormalities consistent with Leigh syndrome, identifying biallelic variants in the LONP1 (NM_004793.3) gene; c.1693T > C predicting p.(Tyr565His) and c.2197G > A predicting p.(Glu733Lys); no evidence of the classical skeletal or dental defects observed in CODAS syndrome patients were noted in our patient. In vitro experiments confirmed the p.(Tyr565His) LonP1 mutant alone could not bind or degrade a substrate, consistent with the predicted function of Tyr565, whilst a second missense [p.(Glu733Lys)] variant had minimal effect. Mixtures of p.(Tyr565His) mutant and wild-type LonP1 retained partial protease activity but this was severely depleted when the p.(Tyr565His) mutant was mixed with the p.(Glu733Lys) mutant, data consistent with the compound heterozygosity detected in our patient. In summary, we conclude that pathogenic LONP1 variants can lead to a classical mitochondrial disease presentations associated with severe biochemical defects in oxidative phosphorylation in clinically relevant tissues.
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| 10. |
- Raap, A. K., et al.
(författare)
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Non-Random mtDNA Segregation Patterns Indicate a Metastable Heteroplasmic Segregation Unit in m.3243A>G Cybrid Cells
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12, s. e52080-
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Tidskriftsartikel (refereegranskat)abstract
- Many pathogenic mitochondrial DNA mutations are heteroplasmic, with a mixture of mutated and wild-type mtDNA present within individual cells. The severity and extent of the clinical phenotype is largely due to the distribution of mutated molecules between cells in different tissues, but mechanisms underpinning segregation are not fully understood. To facilitate mtDNA segregation studies we developed assays that measure m.3243A>G point mutation loads directly in hundreds of individual cells to determine the mechanisms of segregation over time. In the first study of this size, we observed a number of discrete shifts in cellular heteroplasmy between periods of stable heteroplasmy. The observed patterns could not be parsimoniously explained by random mitotic drift of individual mtDNAs. Instead, a genetically metastable, heteroplasmic mtDNA segregation unit provides the likely explanation, where stable heteroplasmy is maintained through the faithful replication of segregating units with a fixed wild-type/m.3243A>G mutant ratio, and shifts occur through the temporary disruption and re-organization of the segregation units. While the nature of the physical equivalent of the segregation unit remains uncertain, the factors regulating its organization are of major importance for the pathogenesis of mtDNA diseases.
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| 11. |
- Watt, Sebastian F. L., et al.
(författare)
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Holocene tephrochronology of the Hualaihue region (Andean southern volcanic zone, similar to 42 degrees S), southern Chile
- 2011
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Ingår i: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 246, s. 324-343
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Tidskriftsartikel (refereegranskat)abstract
- Late Glacial and Holocene soils and sediments in southern Chile contain an important record of explosive volcanic activity since the end of the last glaciation, and have considerable potential for the development of a regional tephrostratigraphical framework. This paper reports the discovery of several new tephra deposits from the Hualaihue region (similar to 42 degrees S) of southern Chile. Eruption sizes, constrained from field observations, and ages, constrained by 25 new radiocarbon dates, show that the volcanoes of the Hualaihue peninsula have had relatively few explosive, tephra-generating eruptions during the Holocene. An eruption of Apagado deposited similar to 1 km(3) of bedded basaltic scoria at similar to 2.6 calibrated (cal) ka BP, and Hornopiren produced a similar, but volumetrically-smaller unit at similar to 5.7 cal ka BR Activity at Yate over the same time period has been predominantly characterised by lava production, although small explosive eruptions, the products of which span a range of compositions, have also occurred, including one at similar to 0.9 cal ka BR The northern part of the regional tephra sequence is dominated by andesitic pumice fall deposits derived from Calbuco volcano. These include deposits from several eruptions during a 3500-year-long period at the start of the Holocene, as well as two large explosive eruptions in the past 2000 years. A distinctive rhyolitic tephra layer that is interbedded with the locally derived tephra sequence is the Cha1 unit, from Chaiten volcano, 108 km south of Hornopiren. This rhyolitic pumice deposit, dated at similar to 9.75 cal ka BP, is the largest volumetrically of those described here, with a volume of 3.5 km(3). This new tephrostratigraphy covers a region whose volcanic history was previously very little known, and contributes to a regional record of large explosive eruptions that now spans a 500 km-long segment of the southern Andean arc, between Calbuco and Hudson volcanoes.
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| 12. |
- Fisher, Rebecca E., et al.
(författare)
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Measurement of the C-13 isotopic signature of methane emissions from northern European wetlands
- 2017
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:3, s. 605-623
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Tidskriftsartikel (refereegranskat)abstract
- Isotopic data provide powerful constraints on regional and global methane emissions and their source profiles. However, inverse modeling of spatially resolved methane flux is currently constrained by a lack of information on the variability of source isotopic signatures. In this study, isotopic signatures of emissions in the Fennoscandian Arctic have been determined in chambers over wetland, in the air 0.3 to 3m above the wetland surface and by aircraft sampling from 100m above wetlands up to the stratosphere. Overall, the methane flux to atmosphere has a coherent delta C-13 isotopic signature of -71 +/- 1%, measured in situ on the ground in wetlands. This is in close agreement with delta C-13 isotopic signatures of local and regional methane increments measured by aircraft campaigns flying through air masses containing elevated methane mole fractions. In contrast, results from wetlands in Canadian boreal forest farther south gave isotopic signatures of -67 +/- 1%. Wetland emissions dominate the local methane source measured over the European Arctic in summer. Chamber measurements demonstrate a highly variable methane flux and isotopic signature, but the results from air sampling within wetland areas show that emissions mix rapidly immediately above the wetland surface and methane emissions reaching the wider atmosphere do indeed have strongly coherent C isotope signatures. The study suggests that for boreal wetlands (>60 degrees N) global and regional modeling can use an isotopic signature of -71 parts per thousand to apportion sources more accurately, but there is much need for further measurements over other wetlands regions to verify this.
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| 13. |
- Ford, Alex T., et al.
(författare)
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The Role of Behavioral Ecotoxicology in Environmental Protection
- 2021
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 55:9, s. 5620-5628
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Tidskriftsartikel (refereegranskat)abstract
- For decades, we have known that chemicals affect human and wildlife behavior. Moreover, due to recent technological and computational advances, scientists are now increasingly aware that a wide variety of contaminants and other environmental stressors adversely affect organismal behavior and subsequent ecological outcomes in terrestrial and aquatic ecosystems. There is also a groundswell of concern that regulatory ecotoxicology does not adequately consider behavior, primarily due to a lack of standardized toxicity methods. This has, in turn, led to the exclusion of many behavioral ecotoxicology studies from chemical risk assessments. To improve understanding of the challenges and opportunities for behavioral ecotoxicology within regulatory toxicology/risk assessment, a unique workshop with international representatives from the fields of behavioral ecology, ecotoxicology, regulatory (eco)toxicology, neurotoxicology, test standardization, and risk assessment resulted in the formation of consensus perspectives and recommendations, which promise to serve as a roadmap to advance interfaces among the basic and translational sciences, and regulatory practices.
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| 14. |
- Nuntiyakul, W., et al.
(författare)
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Direct Determination of a Bare Neutron Counter Yield Function
- 2020
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 125:4
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Tidskriftsartikel (refereegranskat)abstract
- Ground-based neutron counters are a standard tool for detecting atmospheric showers from GeV range primary cosmic rays of either solar or galactic origin. Bare neutron counters, a type of lead-free neutron monitor, function much like standard neutron monitors but have different yield functions primarily because they are more sensitive to neutrons of lower energy. When operated together with standard monitors, the different yield functions allow estimates to be made of the energy spectrum of galactic or solar particles. In 2010 a new array of 12 bare neutron detectors was installed at the South Pole to operate together with the neutron monitor there. Prior to installation, two of the detectors were operated on a ship that traveled from Sweden to Antarctica and back from November 2009 to April 2010. The purpose of this latitude survey was to use Earth's magnetic field as a spectrometer, blocking cosmic rays below the local cutoff rigidity (momentum per unit charge), from which we determined the response function versus rigidity of these bare counters. By comparing that measured response function to direct measurements of the cosmic ray spectrum taken by the PAMELA spacecraft, we were able to make a direct determination of the yield function for these detectors.
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| 15. |
- Nuntiyakul, W., et al.
(författare)
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Direct Determination of a Bare Neutron Counter Yield Function
- 2022
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Ingår i: 37th International Cosmic Ray Conference, ICRC2021. - Trieste, Italy : Proceedings of Science.
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Konferensbidrag (refereegranskat)abstract
- Ground based neutron counters are a standard tool for detecting atmospheric showers from GeV-range primary cosmic rays of either solar or galactic origin. Bare neutron counters, a type of lead-free neutron monitor, function much like standard neutron monitors but have different yield functions primarily because they are more sensitive to neutrons of lower energy. When operated together with standard monitors the different yield functions allow estimates to be made of the energy spectrum of galactic or solar particles. In 2010 a new array of twelve bare neutron detectors was installed at the South Pole to operate together with the neutron monitor there. Prior to installation, two of the detectors were operated on a ship that traveled from Sweden to Antarctica and back from November 2009 to April 2010. The purpose of this latitude survey was to use Earth's magnetic field as a spectrometer, blocking cosmic rays below the local cutoff rigidity (momentum per unit charge), from which we determined the response function vs. rigidity of these bare counters. By comparing that measured response function to direct measurements of the cosmic ray spectrum taken by the PAMELA spacecraft, we were able to make a direct determination of the yield function for these detectors.
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| 16. |
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| 17. |
- Pluta, J, et al.
(författare)
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Identification of 22 susceptibility loci associated with testicular germ cell tumors
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 4487-
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Tidskriftsartikel (refereegranskat)abstract
- Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.
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| 18. |
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| 19. |
- Young, P. J., et al.
(författare)
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The CO2 inhibition of terrestrial isoprene emission significantly affects future ozone projections
- 2009
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Ingår i: Atmospheric Chemistry and Physics. - 1680-7324. ; 9:8, s. 2793-2803
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Tidskriftsartikel (refereegranskat)abstract
- Simulations of future tropospheric composition often include substantial increases in biogenic isoprene emissions arising from the Arrhenius-like leaf emission response and warmer surface temperatures, and from enhanced vegetation productivity in response to temperature and atmospheric CO2 concentration. However, a number of recent laboratory and field data have suggested a direct inhibition of leaf isoprene production by increasing atmospheric CO2 concentration, notwithstanding isoprene being produced from precursor molecules that include some of the primary products of carbon assimilation. The cellular mechanism that underlies the decoupling of leaf photosynthesis and isoprene production still awaits a full explanation but accounting for this observation in a dynamic vegetation model that contains a semi-mechanistic treatment of isoprene emissions has been shown to change future global isoprene emission estimates notably. Here we use these estimates in conjunction with a chemistry-climate model to compare the effects of isoprene simulations without and with a direct CO2-inhibition on late 21st century O-3 and OH levels. The impact on surface O-3 was significant. Including the CO2-inhibition of isoprene resulted in opposing responses in polluted (O-3 decreases of up to 10 ppbv) vs. less polluted (O-3 increases of up to 10 ppbv) source regions, due to isoprene nitrate and peroxy acetyl nitrate (PAN) chemistry. OH concentration increased with relatively lower future isoprene emissions, decreasing methane lifetime by similar to 7 months (6.6%). Our simulations underline the large uncertainties in future chemistry and climate studies due to biogenic emission patterns and emphasize the problems of using globally averaged climate metrics (such as global radiative forcing) to quantify the atmospheric impact of reactive, heterogeneously distributed substances.
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