 Simulation of glacial-interglacial atmospheric CO2 variations using a comprehensive Earth system model of intermediate complexity; ; et al Conference (2010, May 04) The mechanisms of strong glacial-interglacial variations in the atmospheric CO2 concentration and the role of CO2 in driving glacial cycles still remain debatable. Here using the model of intermediate ... [more ▼] The mechanisms of strong glacial-interglacial variations in the atmospheric CO2 concentration and the role of CO2 in driving glacial cycles still remain debatable. Here using the model of intermediate complexity CLIMBER-2 which includes all major components of the Earth system – atmosphere, ocean, land surface, ice sheets, terrestrial biota and weathering, aeolian dust and marine biogeochemistry – we performed simulation of the last glacial cycle using variations in the Earth’s orbital parameters as the only prescribed climatic forcing. The model simulates rather realistically temporal and spatial dynamics of the Northern Hemisphere glaciation and temporal dynamics of the atmospheric CO2 concentration. During the glacial inception, the model is able to simulate a decrease in the atmospheric CO2, despite of release of terrestrial biosphere carbon. The drop in CO2 concentration during the first part of the glacial cycle is between 20 and 40 ppmv. It is related primarily to the physical mechanisms – increase of the ocean solubility and relative volume and the age of the Antarctic bottom water masses. The latter is related to increased sea ice formation in the Southern Ocean and lowering of the surface salinity in the northern North Atlantic. During the second part of the glacial cycle, the atmospheric CO2 concentration decreases towards the level of 200 ppmv. A part of this drop is due an increase of biological productivity in the Southern Ocean which is directly related in the CLIMBER-2 model to increase of aeolian dust supply into the Southern Hemisphere via the iron fertilization mechanism. Significant part of the decreasing CO2 trend is also explained by increased weathering on land, especially on the exposed tropical shelves. A decrease in shallow water carbonate sedimentation and shift of CaCO3 sedimentation towards the deep ocean also plays important role in CO2 decrease. With the onset of the glacial termination, initial rise in the atmospheric CO2 concentration is explained by a weakening of the Atlantic thermohaline circulation due to increased freshwater input into the northern North Atlantic. The model is able to simulate the return of CO2 concentration to its interglacial value after termination of the glacial cycle but simulated CO2 concentration still lags considerably behind the ice core reconstructions. [less ▲] Detailed reference viewed: 42 (1 ULg) Holocene carbon cycle dynamics; ; et al in Geophysical Research Letters (2010), 37 We are investigating the late Holocene rise in CO2 by performing four experiments with the climate-carbon-cycle model CLIMBER2-LPJ. Apart from the deep sea sediments, important carbon cycle processes ... [more ▼] We are investigating the late Holocene rise in CO2 by performing four experiments with the climate-carbon-cycle model CLIMBER2-LPJ. Apart from the deep sea sediments, important carbon cycle processes considered are carbon uptake or release by the vegetation, carbon uptake by peatlands, and CO2 release due to shallow water sedimentation of CaCO3. Ice core data of atmospheric CO2 between 8 ka BP and preindustrial climate can only be reproduced if CO2 outgassing due to shallow water sedimentation of CaCO3 is considered. In this case the model displays an increase of nearly 20 ppmv CO2 between 8 ka BP and present day. Model configurations that do not contain this forcing show a slight decrease in atmospheric CO2. We can therefore explain the late Holocene rise in CO2 by invoking natural forcing factors only, and anthropogenic forcing is not required to understand preindustrial CO2 dynamics. [less ▲] Detailed reference viewed: 6 (1 ULg) Atmospheric Lifetime of Fossil Fuel Carbon Dioxide; ; et al in Annual Review of Earth & Planetary Sciences (2009), 37 CO2 released from combustion of fossil fuels equilibrates among the various carbon reservoirs of the atmosphere, the ocean, and the terrestrial biosphere on timescales of a few centuries. However, a ... [more ▼] CO2 released from combustion of fossil fuels equilibrates among the various carbon reservoirs of the atmosphere, the ocean, and the terrestrial biosphere on timescales of a few centuries. However, a sizeable fraction of the CO2 remains in the atmosphere, awaiting a return to the solid earth by much slower weathering processes and deposition of CaCO3. Common measures of the atmospheric lifetime of CO2, including the e-folding time scale, disregard the long tail. Its neglect in the calculation of global warming potentials leads many to underestimate the longevity of anthropogenic global warming. Here, we review the past literature on the atmospheric lifetime of fossil fuel CO2 and its impact on climate, and we present initial results from a model intercomparison project on this topic. The models agree that 20–35% of the CO2 remains in the atmosphere after equilibration with the ocean (2–20 centuries). Neutralization by CaCO3 draws the airborne fraction down further on timescales of 3 to 7 kyr. [less ▲] Detailed reference viewed: 207 (13 ULg)Engineering a camelid antibody fragment that binds to the active site of human lysozyme and inhibits its conversion into amyloid fibrils; ; et al in Biochemistry (2008), 47 single-domain fragment, cAb-HuL22, of a camelid heavy-chain antibody specific for the active site of human lysozyme has been generated, and its effects on the properties of the I56T and D67H amyloidogenic ... [more ▼] single-domain fragment, cAb-HuL22, of a camelid heavy-chain antibody specific for the active site of human lysozyme has been generated, and its effects on the properties of the I56T and D67H amyloidogenic variants of human lysozyme, which are associated with a form of systemic amyloidosis, have been investigated by a wide range of biophysical techniques. Pulse-labeling hydrogen-deuterium exchange experiments monitored by mass spectrometry reveal that binding of the antibody fragment strongly inhibits the locally cooperative unfolding of the I56T and D67H variants and restores their global cooperativity to that characteristic of the wild-type protein. The antibody fragment was, however, not stable enough under the conditions used to explore its ability to perturb the aggregation behavior of the lysozyme amyloidogenic variants. We therefore engineered a more stable version of cAb-HuL22 by adding a disulfide bridge between the two beta-sheets in the hydrophobic core of the protein. The binding of this engineered antibody fragment to the amyloidogenic variants of lysozyme inhibited their aggregation into fibrils. These findings support the premise that the reduction in global cooperativity caused by the pathogenic mutations in the lysozyme gene is the determining feature underlying their amyloidogenicity. These observations indicate further that molecular targeting of enzyme active sites, and of protein binding sites in general, is an effective strategy for inhibiting or preventing the aberrant self-assembly process that is often a consequence of protein mutation and the origin of pathogenicity. Moreover, this work further demonstrates the unique properties of camelid single-domain antibody fragments as structural probes for studying the mechanism of aggregation and as potential inhibitors of fibril formation. [less ▲] Detailed reference viewed: 83 (21 ULg)Impact of the native-state stability of human lysozyme variants on protein secretion by Pichia pastoris; ; et al in FEBS Journal (2006), 273 We report the secreted expression by Pichia pastoris of two human lysozyme variants F57I and W64R, associated with systemic amyloid disease, and describe their characterization by biophysical methods ... [more ▼] We report the secreted expression by Pichia pastoris of two human lysozyme variants F57I and W64R, associated with systemic amyloid disease, and describe their characterization by biophysical methods. Both variants have a substantially decreased thermostability compared with wild-type human lysozyme, a finding that suggests an explanation for their increased propensity to form fibrillar aggregates and generate disease. The secreted yields of the F57I and W64R variants from P. pastoris are 200- and 30-fold lower, respectively, than that of wild-type human lysozyme. More comprehensive analysis of the secretion levels of 10 lysozyme variants shows that the low yields of these secreted proteins, under controlled conditions, can be directly correlated with a reduction in the thermostability of their native states. Analysis of mRNA levels in this selection of variants suggests that the lower levels of secretion are due to post-transcriptional processes, and that the reduction in secreted protein is a result of degradation of partially folded or misfolded protein via the yeast quality control system. Importantly, our results show that the human disease-associated mutations do not have levels of expression that are out of line with destabilizing mutations at other sites. These findings indicate that a complex interplay between reduced native-state stability, lower secretion levels, and protein aggregation propensity influences the types of mutation that give rise to familial forms of amyloid disease. [less ▲] Detailed reference viewed: 20 (0 ULg)Stability of recombinant 2 S albumin allergens in vitro; Dumoulin, Mireille  ; et alin Biochemical Society Transactions (2002), 30 Two well known 2 S albumins, Ber e 1 from brazil nut and sunflower 2 S albumin 8 (SFA-8), have been expressed in a eukaryotic system and purified. Analysis of recombinant versions of Ber e 1 and SFA-8 ... [more ▼] Two well known 2 S albumins, Ber e 1 from brazil nut and sunflower 2 S albumin 8 (SFA-8), have been expressed in a eukaryotic system and purified. Analysis of recombinant versions of Ber e 1 and SFA-8 revealed them to be significantly more resistant to digestion by pepsin than BSA, and to be stable for up to 30 min in simulated gastric fluid. Unfolding monitored by CD indicated that both proteins were also very resistant to denaturation induced by heat and low pH. These results suggest that, although the ability of 2 S albumins to reach the circulatory system may be a prerequisite for the allergenicity of this group of proteins, stability is just one of a number of characteristics that provoke a selective immune response. [less ▲] Detailed reference viewed: 13 (0 ULg)The Disulphide Mapping, Folding and Characterisation of Recombinant Ber e 1, an Allergenic Protein, and SFA8, Two Sulphur-rich 2 S Plant Albumins; ; et al in Journal of Molecular Biology (2002), 324 We have cloned and expressed genes encoding the allergenic brazil nut 2 S albumin (Ber e 1) and the sunflower albumin 8 (SFA8) in the methylotrophic yeast Pichia pastoris. We show that both proteins were ... [more ▼] We have cloned and expressed genes encoding the allergenic brazil nut 2 S albumin (Ber e 1) and the sunflower albumin 8 (SFA8) in the methylotrophic yeast Pichia pastoris. We show that both proteins were secreted at high levels and that the purified proteins were properly folded. We also showed that Ber e 1 is glycosylated during secretion and that the glycan does not interfere with the folding or immunoreactivity. The disulphide map of the Ber e 1 protein was experimentally established and is in agreement with the conserved disulphide structure of other members of the 2 S albumin family. A model three-dimensional structure of the allergen was generated. During the expression studies and through mutation we have also shown that alteration of the sequences around the Kex2 endoproteolytic processing site in the expressed fusion protein can compromise the secretion by targeting part of the protein for possible degradation. The secreted production of these properly folded sulphurrich plant albumins presents an opportunity to delineate the attributes that make an allergen and to facilitate the diagnosis and therapy of type I allergy. [less ▲] Detailed reference viewed: 16 (2 ULg) |
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