Sensitivity of the Eocene climate to CO₂ and orbital variability

The early Eocene, from about 56 Ma, with high atmospheric CO2 levels, offers an analogue for the response of the Earth’s climate system to anthropogenic fossil fuel burning. In this study, we present an ensemble of 50 Earth system model runs with an early Eocene palaeogeography and variation in the forcing values of atmospheric CO2 and the Earth’s orbital parameters. Relationships between simple summary metrics of model outputs and the forcing parameters are identified by linear modelling, providing estimates of the relative magnitudes of the effects of atmospheric CO2 and each of the orbital parameters on important climatic features, including tropical–polar temperature difference, ocean–land temperature contrast, Asian, African and South (S.) American monsoon rains, and climate sensitivity. Our results indicate that although CO2 exerts a dominant control on most of the climatic features examined in this study, the orbital parameters also strongly influence important components of the ocean–atmosphere system in a greenhouse Earth. In our ensemble, atmospheric CO2 spans the range 280–3000 ppm, and this variation accounts for over 90 % of the effects on mean air temperature, southern winter high-latitude ocean– land temperature contrast and northern winter tropical–polar temperature difference. However, the variation of precession accounts for over 80 % of the influence of the forcing parameters on the Asian and African monsoon rainfall, and obliquity variation accounts for over 65 % of the effects on winter ocean–land temperature contrast in high northern latitudes and northern summer tropical–polar temperature difference. Our results indicate a bimodal climate sensitivity, with values of 4.36 and 2.54 ◦C, dependent on low or high states of atmospheric CO2 concentration, respectively, with a threshold at approximately 1000 ppm in this model, and due to a saturated vegetation–albedo feedback. Our method gives a quantitative ranking of the influence of each of the forcing parameters on key climatic model outputs, with additional spatial information from singular value decomposition providing insights into likely physical mechanisms. The results demonstrate the importance of orbital variation as an agent of change in climates of the past, and we demonstrate that emulators derived from our modelling output can be used as rapid and efficient surrogates of the full complexity model to provide estimates of climate conditions from any set of forcing parameters

Human rhinovirus infection up-regulates MMP-9 production in airway epithelial cells via NF-{kappa}B

Human rhinovirus (HRV) infections up-regulate proinflammatory mediators and growth factors that are associated with exacerbations of inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Matrix metalloproteinase (MMP)-9 was shown to be increased in the airways of patients with asthma and COPD. We sought to determine whether HRV infection modulated the expression of MMP-9 and its highest-affinity inhibitor, the tissue inhibitor of metalloproteinase (TIMP)-1, and we explored the mechanism by which this modulation occurs. In vitro studies, using RT-PCR, ELISA, zymography, and a fluorescent activity assay, demonstrated that MMP-9 mRNA, protein, and activity were increased upon infection with HRV, whereas TIMP-1 mRNA and protein remained unchanged. These results were verified in vivo, using nasal lavage samples obtained from subjects with confirmed rhinovirus infections. Human rhinovirus infections were shown to up-regulate NF-kappaB, and NF-kappaB has also been reported to play a role in the expression of MMP-9. We therefore investigated the role of NF-kappaB in HRV-induced MMP-9 expression. Using two inhibitors of IkappaBalpha kinase beta, we observed a concentration-dependent decrease in HRV-induced MMP-9 expression. The role of NF-kappaB in HRV-induced MMP-9 expression was further confirmed using MMP-9 promoter luciferase constructs, which demonstrated that an NF-kappaB site at -620/-607 base pairs was necessary for HRV-induced MMP-9 expression. Electrophoretic mobility shift assays and supershift assays confirmed the nuclear translocation and binding of p50/p65 NF-kappaB subunits to an MMP-9-specific NF-kappaB oligonucleotide. This increase in MMP-9 may be a mechanism by which rhinovirus infections contribute to airway inflammation and, potentially, to airway remodeling

Coupled climate–carbon cycle simulation of the Last Glacial Maximum atmospheric CO2 decrease using a large ensemble of modern plausible parameter sets

During the Last Glacial Maximum (LGM), atmospheric CO2 was around 90 ppmv lower than during the pre-industrial period. The reasons for this decrease are most often elucidated through factorial experiments testing the impact of individual mechanisms. Due to uncertainty in our understanding of the real system, however, the different models used to conduct the experiments inevitably take on different parameter values and different structures. In this paper, the objective is therefore to take an uncertainty-based approach to investigating the LGM CO2 drop by simulating it with a large ensemble of parameter sets, designed to allow for a wide range of large-scale feedback response strengths. Our aim is not to definitely explain the causes of the CO2 drop but rather explore the range of possible responses. We find that the LGM CO2 decrease tends to predominantly be associated with decreasing sea surface temperatures (SSTs), increasing sea ice area, a weakening of the Atlantic Meridional Overturning Circulation (AMOC), a strengthening of the Antarctic Bottom Water (AABW) cell in the Atlantic Ocean, a decreasing ocean biological productivity, an increasing CaCO3 weathering flux and an increasing deep-sea CaCO3 burial flux. The majority of our simulations also predict an increase in terrestrial carbon, coupled with a decrease in ocean and increase in lithospheric carbon. We attribute the increase in terrestrial carbon to a slower soil respiration rate, as well as the preservation rather than destruction of carbon by the LGM ice sheets. An initial comparison of these dominant changes with observations and paleoproxies other than carbon isotope and oxygen data (not evaluated directly in this study) suggests broad agreement. However, we advise more detailed comparisons in the future, and also note that, conceptually at least, our results can only be reconciled with carbon isotope and oxygen data if additional processes not included in our model are brought into play

Modeling the ecology and evolution of biodiversity: Biogeographical cradles, museums, and graves

Individual processes shaping geographical patterns of biodiversity are increasingly understood, but their complex interactions on broad spatial and temporal scales remain beyond the reach of analytical models and traditional experiments. To meet this challenge, we built a spatially explicit, mechanistic simulation model implementing adaptation, range shifts, fragmentation, speciation, dispersal, competition, and extinction, driven by modeled climates of the past 800,000 years in South America. Experimental topographic smoothing confirmed the impact of climate heterogeneity on diversification. The simulations identified regions and episodes of speciation (cradles), persistence (museums), and extinction (graves). Although the simulations had no target pattern and were not parameterized with empirical data, emerging richness maps closely resembled contemporary maps for major taxa, confirming powerful roles for evolution and diversification driven by topography and climate

Human rhinovirus infection of epithelial cells modulates airway smooth muscle migration

Rationale: Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell mass with a greater proximity of the airway smooth muscle cells (ASMC) to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMC. Methods: ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer. Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8 and CXCL10 were also examined. Results: Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pre-treatment of ASMC with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8 and CXCL10 were used at levels found in epithelial supernatants they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration and treatment of supernatant from HRV-infected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. Conclusion: These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis, and thus may contribute to the pathogenesis of airway remodeling in asthmatic patients

Environmental and health impacts of atmospheric CO₂ removal by enhanced rock weathering depend on nations’ energy mix

Enhanced Rock Weathering is a proposed Carbon Dioxide Removal technology involving the application of crushed silicate rocks, such as basalt, to agricultural soils with potential co-benefits for crops and soils, and mitigation of ocean acidification. Here we address the requirement of diverse stakeholders for informative studies quantifying possible environmental and health risks of Enhanced Rock Weathering. Using life-cycle assessment modelling of potential supply chain impacts for twelve nations undertaking Enhanced Rock Weathering deployment to deliver up to net 2 Gt CO2 yr−1 CDR, we find that rock grinding rather than mining exerts the dominant influence on environmental impacts. This finding holds under both a business-as-usual and clean energy mix scenario to 2050 but transitioning to undertaking Enhanced Rock Weathering in the future with low carbon energy systems improves the sustainability of the Enhanced Rock Weathering supply chain. We find that Enhanced Rock Weathering is competitive with other large-scale Carbon Dioxide Removal strategies in terms of energy and water demands

Worldwide impacts of climate change on energy for heating and cooling

The energy sector is not only a major contributor to greenhouse gases, it is also vulnerable to climate change and will have to adapt to future climate conditions. The objective of this study is to analyze the impacts of changes in future temperatures on the heating and cooling services of buildings and the resulting energy and macro-economic effects at global and regional levels. For this purpose, the techno-economic TIAM-WORLD (TIMES Integrated Assessment Model) and the general equilibrium GEMINI-E3 (General Equilibrium Model of International-National Interactions between Economy, Energy and Environment) models are coupled with a climate model, PLASIM-ENTS (Planet-Simulator - Efficient Numerical Terrestrial Scheme). The key results are as follows. At the global level, the climate feedback induced by adaptation of the energy system to heating and cooling is found to be insignificant, partly because heating and cooling-induced changes compensate and partly because they represent a limited share of total final energy consumption. However, significant changes are observed at regional levels, more particularly in terms of addi- tional power capacity required to satisfy additional cooling services, resulting in increases in electricity prices. In terms of macro-economic impacts, welfare gains and losses are associated more with changes in energy exports and imports than with changes in energy consumption for heating and cooling. The rebound effect appears to be non-negligible. To conclude, the coupling of models of different nature was successful and showed that the energy and economic impacts of climate change on heating and cooling remain small at the global level, but changes in energy needs will be visible at more local scale

Gender Differences in Publication Output: Towards an Unbiased Metric of Research Performance

We examined the publication records of a cohort of 168 life scientists in the field of ecology and evolutionary biology to assess gender differences in research performance. Clear discrepancies in publication rate between men and women appear very early in their careers and this has consequences for the subsequent citation of their work. We show that a recently proposed index designed to rank scientists fairly is in fact strongly biased against female researchers, and advocate a modified index to assess men and women on a more equitable basis

Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors

In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kγ inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kγ inhibitor with ADME properties suitable for oral administration. Compound 15 was advanced into in vivo studies showing dose-dependent inhibition of LPS-induced airway neutrophilia in rats when administered orally

World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [-13910*T (rs4988235), -13907*G (rs41525747), -13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection