| 11. |
- Gao, Xueshan, et al.
(författare)
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Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload
- 2010
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Ingår i: Free Radical Biology & Medicine. - : Elsevier Science B.V., Amsterdam.. - 0891-5849 .- 1873-4596. ; 49:3, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- In patients with hemochromatosis, cardiac dysfunction may appear years after they have reached a state of iron overload. We hypothesized that cumulative iron-catalyzed oxidant damage to mitochondrial DNA (mtDNA) might explain the cardiomyopathy of chronic iron overload. Mice were given repetitive injections of iron dextran for a total of 4 weeks after which the iron-loaded mice had elevated cardiac iron, modest cardiac hypertrophy, and cardiac dysfunction. OCR amplification of near-full-length (similar to 16 kb) mtDNA revealed greater than50% loss of full-length product, whereas amounts of a OCR product of a nuclear gene (13 kb region of beta globin) were unaffected. Quantitative rtPCR analyses revealed 60-70% loss of mRNA for proteins encoded by mtDNA with no change in mRNA abundance for nuclear-encoded respiratory subunits. These changes coincided with proportionate reductions in complex I and IV activities and decreased respiration of isolated cardiac mitochondria. We conclude that chronic iron overload leads to cumulative iron-mediated damage to mtDNA and impaired synthesis of mitochondrial respiratory chain subunits. The resulting respiratory dysfunction may explain the slow development of cardiomyopathy in chronic iron overload and similar accumulation of damage to mtDNA may also explain the mitochondrial dysfunction observed in slowly progressing diseases such as neurodegenerative disorders.
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| 12. |
- Hanberger, Håkan, et al.
(författare)
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Increased mortality associated with meticillin-resistant Staphylococcus aureus (MRSA) infection in the Intensive Care Unit: results from the EPIC II study
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier. - 0924-8579 .- 1872-7913. ; 38:4, s. 331-335
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Tidskriftsartikel (refereegranskat)abstract
- Controversy continues regarding whether the presence of meticillin resistance increases mortality risk in Staphylococcus aureus infections. In this study, we assessed the role of meticillin resistance in survival of patients with S. aureus infection included in the EPIC II point-prevalence study of infection in critically ill patients performed on 8 May 2007. Demographic, physiological, bacteriological and therapeutic data were collected for 13 796 adult patients in 1265 participating Intensive Care Units (ICUs) from 75 countries on the study day. ICU and hospital outcomes were recorded. Characteristics of patients with meticillin-sensitive S. aureus (MSSA) and meticillin-resistant S. aureus (MRSA) infections were compared. Co-morbidities, age, Simplified Acute Physiology Score (SAPS) II, site of infection, geographical region and MRSA/MSSA were entered into a multivariate model, and adjusted odds ratios (ORs) [95% confidence interval (CI)] for ICU and hospital mortality rates were calculated. On the study day, 7087 (51%) of the 13 796 patients were classified as infected. There were 494 patients with MRSA infections and 505 patients with MSSA infections. There were no significant differences between the two groups in use of mechanical ventilation or haemofiltration/haemodialysis. Cancer and chronic renal failure were more prevalent in MRSA than in MSSA patients. ICU mortality rates were 29.1% and 20.5%, respectively (P andlt; 0.01) and corresponding hospital mortality rates were 36.4% and 27.0% (P andlt; 0.01). Multivariate analysis of hospital mortality for MRSA infection showed an adjusted OR of 1.46 (95% CI 1.03-2.06) (P = 0.03). In ICU patients, MRSA infection is therefore independently associated with an almost 50% higher likelihood of hospital death compared with MSSA infection.
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| 13. |
- Marshall, John
(författare)
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3-PG simulations of young ponderosa pine plantations under varied management intensity: Why do they grow so differently?
- 2014
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 313, s. 69-82
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Tidskriftsartikel (refereegranskat)abstract
- Models can be powerful tools for estimating forest productivity and guiding forest management, but their credibility and complexity are often at issue for forest managers. We parameterized a process-based forest growth model, 3-PG (Physiological Principles Predicting Growth), to simulate growth of ponderosa pine (Pinus ponderosa) plantations in Northern California. We used data collected from the "Garden of Eden" study, which was established in the 1980s to determine the effect of silvicultural treatments on plantation growth. We picked three sites representing a gradient of water availability and site productivity to run 3-PG. We modified the original linear canopy closure function to a power curve to capture observed stand dynamics in situ. We also added new functions to estimate the leaf area index and transpiration of the trees' understory competitors. These new functions restricted shrub growth with light intensity and assumed a fix ratio of shrub/tree transpiration per leaf area index. A delta C-13 submodel, which estimated the ratio of stable carbon isotopes (delta C-13) in plant tissue, played a key role in assigning values to gas-exchange parameters in the model. The resulting parameter values were similar to those fitted using sap flux. We replaced the original age modifier with tree-height based functions to reflect the decreased forest productivity as trees grew taller; tree height drove the change of maximum canopy conductance and its responsiveness to water vapor pressure deficit in the new functions. Some key parameters differed among sites, including quantum yield, maximum canopy conductance, and leaf allocation. The model successfully simulated the tree growth responses to fertilization and vegetation control at all three sites. The temporal variation of simulated shrub leaf area index was similar to the observed variation in shrub cover. These results help us to understand forest-growth responses to fertilizer and vegetation control, identify key tree and site parameters, and provide tuned model parameterizations that can predict the results of management alternatives in a changing climate. (C) 2013 Elsevier B.V. All rights reserved.
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| 14. |
- Marshall, John
(författare)
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Constraining 3-PG with a new delta C-13 submodel: a test using the delta C-13 of tree rings
- 2014
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Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 37, s. 82-100
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Tidskriftsartikel (refereegranskat)abstract
- A semi-mechanistic forest growth model, 3-PG (Physiological Principles Predicting Growth), was extended to calculate C-13 in tree rings. The C-13 estimates were based on the model's existing description of carbon assimilation and canopy conductance. The model was tested in two approximate to 80-year-old natural stands of Abies grandis (grand fir) in northern Idaho. We used as many independent measurements as possible to parameterize the model. Measured parameters included quantum yield, specific leaf area, soil water content and litterfall rate. Predictions were compared with measurements of transpiration by sap flux, stem biomass, tree diameter growth, leaf area index and C-13. Sensitivity analysis showed that the model's predictions of C-13 were sensitive to key parameters controlling carbon assimilation and canopy conductance, which would have allowed it to fail had the model been parameterized or programmed incorrectly. Instead, the simulated C-13 of tree rings was no different from measurements (P>0.05). The C-13 submodel provides a convenient means of constraining parameter space and avoiding model artefacts. This C-13 test may be applied to any forest growth model that includes realistic simulations of carbon assimilation and transpiration.
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| 15. |
- Marshall, John
(författare)
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Environmental and physiological determinants of carbon isotope discrimination in terrestrial plants
- 2013
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 200, s. 950-965
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Forskningsöversikt (refereegranskat)abstract
- Stable carbon isotope ratios (delta C-13) of terrestrial plants are employed across a diverse range of applications in environmental and plant sciences; however, the kind of information that is desired from the delta C-13 signal often differs. At the extremes, it ranges between purely environmental and purely biological. Here, we review environmental drivers of variation in carbon isotope discrimination (Delta) in terrestrial plants, and the biological processes that can either damp or amplify the response. For C-3 plants, where Delta is primarily controlled by the ratio of intercellular to ambient CO2 concentrations (c(i)/c(a)), coordination between stomatal conductance and photosynthesis and leaf area adjustment tends to constrain the potential environmentally driven range of Delta. For C-4 plants, variation in bundle-sheath leakiness to CO2 can either damp or amplify the effects of c(i)/c(a) on Delta. For plants with crassulacean acid metabolism (CAM), Delta varies over a relatively large range as a function of the proportion of daytime to night-time CO2 fixation. This range can be substantially broadened by environmental effects on Delta when carbon uptake takes place primarily during the day. The effective use of Delta across its full range of applications will require a holistic view of the interplay between environmental control and physiological modulation of the environmental signal.
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| 16. |
- Marshall, John, et al.
(författare)
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Mineral nutrition and elevated [CO2] interact to modify delta C-13, an index of gas exchange, in Norway spruce
- 2013
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Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 33, s. 1132-1144
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Tidskriftsartikel (refereegranskat)abstract
- The effects of the past century's increase in atmospheric CO2 concentration ([CO2]) have been recorded in the stable carbon isotope composition (delta C-13) of the annual growth rings of trees. The isotope record frequently shows increases in photosynthetic CO2 uptake relative to stomatal conductance, which estimates the CO2 concentration gradient across the stomata (c(a) - c(i)). This variable, which is one control over the net photosynthetic rate, has been suggested as a homeostatic gas-exchange set point that is easy to estimate from delta C-13 and [CO2]. However, in high-latitude conifer forests, the literature is mixed; some studies show increases in (c(a) - c(i)) and others show homeostasis. Here we present leaf and tree-ring delta C-13 data from a controlled experiment that tested factorial combinations of elevated [CO2] (365 and 700 proportional to mol mol(-1)) and fertilization on mature Norway spruce (Picea abies (L.) Karst.) trees in northern Sweden. We found first that the leaf carbon pool was contaminated by the current photosynthate in the older leaf cohorts. This is the reverse of the common observation that older photosynthate reserves can be used to produce new tissue; here the older tissue contains recent photosynthate. We found that the tree-ring data lack such contamination and in any case they better integrate over the canopy and the growing season than do leaves. In the second and third years of treatment, elevated [CO2] alone increased (c(a) - c(i)) by 38%; when combined with fertilization, it increased (c(a) - c(i)) by 60%. The results of this study support the idea that annual rings provide a clearer isotopic signal than do foliage age-classes. The tree-ring data show that inferred (c(a) - c(i)) depends not only on [CO2], but also on mineral-nutrient status. The differences in (c(a) - c(i)) are sufficiently large to account for the treatment-induced increase in wood-volume production in these stands.
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| 17. |
- Marshall, John, et al.
(författare)
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Reconstructing Disturbances and Their Biogeochemical Consequences over Multiple Timescales
- 2014
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Ingår i: Bioscience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 64, s. 105-116
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Tidskriftsartikel (refereegranskat)abstract
- Ongoing changes in disturbance regimes are predicted to cause acute changes in ecosystem structure and function in the coming decades, but many aspects of these predictions are uncertain. A key challenge is to improve the predictability of postdisturbance biogeochemical trajectories at the ecosystem level. Ecosystem ecologists and paleoecologists have generated complementary data sets about disturbance (type, severity, frequency) and ecosystem response (net primary productivity, nutrient cycling) spanning decadal to millennial timescales. Here, we take the first steps toward a full integration of these data sets by reviewing how disturbances are reconstructed using dendrochronological and sedimentary archives and by summarizing the conceptual frameworks for carbon, nitrogen, and hydrologic responses to disturbances. Key research priorities include further development of paleoecological techniques that reconstruct both disturbances and terrestrial ecosystem dynamics. In addition, mechanistic detail from disturbance experiments, long-term observations, and chronosequences can help increase the understanding of ecosystem resilience.
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| 18. |
- Marshall, John
(författare)
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Vertical and seasonal variation in the δ13C of leaf-respired CO2 in a mixed conifer forest
- 2011
-
Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 31, s. 414-427
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Tidskriftsartikel (refereegranskat)abstract
- The C-isotopic composition (delta C-13) of leaf respiration (delta(LR)) has previously been shown to vary among functional groups, plant organs and times of day. We here investigated vertical and seasonal variation in delta(LR) through deep (similar to 35 m) forest canopies. We measured delta(LR), delta C-13 of leaf bulk organic matter (delta(LB)), specific leaf area, net photosynthesis (A) and dark respiration in shade, middle and sun foliage in four conifer species from May to August. We used Keeling plots to estimate delta(LR); we developed a novel technique for ensuring that the respiratory substrate was not changing over the course of the measurement. Variables delta(LR) and delta(LB) displayed a vertical pattern in Abies grandis, Pseudotsuga menziesii and Thuja plicata, but were independent of canopy position in Larix occidentalis. Vertical gradients in delta(LB) (3.6 parts per thousand) and delta(LR) (2.8 parts per thousand) were similar. The respiratory enrichment (delta(LR)-delta(LB)) was smaller in expanding (3 parts per thousand) than mature (4-8 parts per thousand) foliage. There was a linear relationship between the respiratory enrichment and A. Our data support the hypothesis that delta(LR) values are related to patterns of C allocation among metabolic pathways. We demonstrated that considerable variation in delta(LR) occurs vertically through the canopy (3 parts per thousand gradient) and seasonally (3-7 parts per thousand). Understanding sources of variation in respiratory signals is fundamental to comprehending C dynamics and for global model applications.
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| 19. |
- Marshall, Misty R, et al.
(författare)
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Functional roles of a C-terminal signaling complex of CaV1 channels and A-kinase anchoring protein 15 in brain neurons
- 2011
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:14
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of CaV1.2 channels in cardiac myocytes by the β-adrenergic pathway requires a signaling complex in which the proteolytically processed distal C-terminal domain acts as an autoinhibitor of channel activity and mediates up-regulation by the β-adrenergic receptor and PKA bound to A-kinase anchoring protein 15 (AKAP15). We examined the significance of this distal C-terminal signaling complex for CaV1.2 and CaV1.3 channels in neurons. AKAP15 co-immunoprecipitates with CaV1.2 and CaV1.3 channels. AKAP15 has overlapping localization with CaV1.2 and CaV1.3 channels in cell bodies and proximal dendrites and is closely co-localized with CaV1.2 channels in punctate clusters. The neuronal AKAP MAP2B, which also interacts with CaV1.2 and CaV1.3 channels, has complementary localization to AKAP15, suggesting different functional roles in calcium channel regulation. Studies with mice that lack the distal C-terminal domain of CaV1.2 channels (CaV1.2ΔDCT) reveal that AKAP15 interacts with neuronal CaV1.2 channels via their C terminus in vivo and is co-localized in punctate clusters of CaV1.2 channels via that interaction. CaV1.2ΔDCT neurons have reduced L-type calcium current, indicating that the distal C-terminal domain is required for normal functional expression in vivo. Deletion of the distal C-terminal domain impairs calcium-dependent signaling from CaV1.2 channels to the nucleus, as shown by reduction in phosphorylation of the cAMP response element-binding protein. Our results define AKAP signaling complexes of CaV1.2 and CaV1.3 channels in brain and reveal three previously unrecognized functional roles for the distal C terminus of neuronal CaV1.2 channels in vivo: increased functional expression, anchoring of AKAP15 and PKA, and initiation of excitation-transcription coupling.
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| 20. |
- McNamara, John M., et al.
(författare)
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Environmental variability can select for optimism or pessimism
- 2011
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 14:1, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- We propose operational definitions of reproductive optimism and pessimism; optimism involves behaving in a way that gives too much weight (in terms of producing surviving offspring) to positive events, pessimism gives too much weight to negative events. Natural selection maximizes the long-term growth of a lineage rather than short-term measures such as numbers of offspring. Consequently, optimism or pessimism can be favoured by natural selection, even though such biases appear irrational from a short-term perspective. We investigate the evolution of optimism in a metapopulation. The circumstances of a patch change over time, independently of other patches. With sufficient dispersal between patches, stochasticity affects members of a lineage largely independently and optimism is favoured. With little dispersal, the temporal fluctuations of a patch affect many members similarly; pessimism is then favoured. Our results establish that the spatial and temporal structure of the environment is crucial in determining the direction of evolved biases. © 2010 Blackwell Publishing Ltd/CNRS.
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