Context Is key: Delineating the unique functions of IFNα and IFNβ in disease

Type I interferons (IFNs) are critical effector cytokines of the immune system and were originally known for their important role in protecting against viral infections; however, they have more recently been shown to play protective or detrimental roles in many disease states. Type I IFNs consist of IFNα, IFNβ, IFNϵ, IFNκ, IFNω, and a few others, and they all signal through a shared receptor to exert a wide range of biological activities, including antiviral, antiproliferative, proapoptotic, and immunomodulatory effects. Though the individual type I IFN subtypes possess overlapping functions, there is growing appreciation that they also have unique properties. In this review, we summarize some of the mechanisms underlying differential expression of and signaling by type I IFNs, and we discuss examples of differential functions of IFNα and IFNβ in models of infectious disease, cancer, and autoimmunity

Dismantling, disintegration or continuing stealthy integration in European Union environmental policy?

This symposium assesses the trajectory of European Union (EU) environmental policy and integration in light of the rising pressure for policy dismantling and disintegration. This introductory article discusses the literature and the mixed evidence of EU environmental policy dismantling. Building on the three symposium articles, we investigate the role of the European Commission in this process, evaluating its role as a general ‘motor of integration’ and more specifically as an environmental policy entrepreneur. We find that the current political context does push the Commission to reconsider its entrepreneurial role and adopt the role of a ‘normalised bureaucracy’. Nonetheless, organisational features, such as new organisational hierarchies and presidential leadership, and ideas that frame policy initiatives explain continued policy evolution and resistance to outright dismantling. Scholars also should pay close attention to implementing measures and patterns of enforcement to detect the more subtle policy shifts

Observational Validation of The Compensating Mass Flux Through The Shell Around Cumulus Clouds

The existence of a subsiding shell around cumulus clouds has been observed before in several aircraft measurement campaigns. Recent results from large-eddy simulations (LES) showed that the downward mass flux through the shell compensates for a significant fraction of the upward mass flux through the cloud. In this study, aeroplane measurements from the Rain In Cumulus over the Ocean (RICO) field campaign are used to verify the existence of this compensating mass flux. Just as in the LES results, the in-shell downward mass flux is found to be significant. However, a few differences were found in comparison with the LES results; most of them were explained by taking into account the difference between the two-dimensional slabs in LES and the one-dimensional lines from aeroplane observations

Infection of myofibers contributes to increased pathogenicity during infection with an epidemic strain of chikungunya virus

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes that is known to cause severe arthritis and myositis in affected patients. The ongoing epidemic began in eastern Africa in 2004 and then spread to islands of the Indian Ocean, India, and Southeast Asia, ultimately afflicting millions. During this outbreak, more severe disease manifestations, including fatalities, have been documented. The reasons for this change in pathogenesis are multifactorial but likely include mutations that have arisen in the viral genome which could alter disease pathogenesis. To test this hypothesis, we used a murine model of CHIKV to compare the disease pathogeneses of two recombinant strains of CHIKV, the first derived from the La Reunion outbreak in 2006 (LR2006 OPY1) and the second isolated from Senegal in 1983 (37997). While the two strains exhibited similar growth in mammalian cells in vitro, we observed more severe clinical disease and pathology in mice infected with the LR2006 OPY1 strain of CHIKV, which included prolonged viremia and elevated viral titers and persistence in the muscle, resulting in devastating myonecrosis. Both CHIKV strains infected connective tissue fibroblasts of the muscle, but only the LR2006 OPY1 strain replicated within myofibers in vivo, despite similar growth of the two strains in these cell types in vitro. However, when the 37997 strain was administered directly into muscle, myofiber infection was comparable to that in LR2006 OPY1-infected mice. These results indicate that differences in the ability of the strain of CHIKV to establish infection in myofibers may contribute to the increased disease severity. IMPORTANCE CHIKV is an emerging pathogen that causes significant morbidity. Little is known about the pathogenesis of the disease, and this study suggests that the ability of a recent epidemic strain to infect myofibers results in increased disease severity. Better understanding of how CHIKV causes disease contributes to the ultimate goal of creating therapeutics to alleviate the impact of this debilitating virus

Frequency analysis of air quality time series for traffic related pollutants

In the present work, annual time series of traffic related pollutants (CO and PM10) were considered for frequency analysis (Fourier series) with the aim to understand the underlying physical processes and the influence of emission sources on the variability of the air pollutant concentrations. Several urban traffic and suburban background air quality stations located in Porto metropolitan area (Portugal) were analysed. The results obtained for CO and PM10 reveal the important contributions of short-term fluctuations (12 h and 24 h periods). However, the spectrum signals at low frequencies are significantly different between these pollutants thus stressing that temporal variations of CO and PM10 are influenced by different processes. Cross-spectrum analysis of the air quality time series against wind measurements and traffic counts allowed us to identify the contribution of long-range transport over a period of about 21 days to the PM10 fluctuations. Also, a correlation of over 80% between the pollution levels in the vicinity of traffic sources and suburban background levels are found for these harmonic components in the PM10 spectrum, while correlations for CO is below a significant level. Thus, the spectrum and cross-spectrum analysis performed in this study reveal the distinct influence of local traffic emissions and long-range transport to CO and PM10 fluctuations in the polluted urban area. The methodology shows to be a powerful tool for the analysis of the causes of air pollution

Similarity theory and calculation of turbulent fluxes at the surface for the stably stratified atmospheric boundary layers

In this paper we revise the similarity theory for the stably stratified atmospheric boundary layer (ABL), formulate analytical approximations for the wind velocity and potential temperature profiles over the entire ABL, validate them against large-eddy simulation and observational data, and develop an improved surface flux calculation technique for use in operational models.Comment: The submission to a special issue of the Boundary-Layer Meteorology devoted to the NATO advanced research workshop Atmospheric Boundary Layers: Modelling and Applications for Environmental Securit

Distinct roles of interferon alpha and beta in controlling chikungunya virus replication and modulating neutrophil-mediated inflammation

Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice treated with a pan-IFN-α-blocking antibody). Mice lacking either IFN-α or IFN-β developed severe clinical disease following infection with CHIKV, with a marked increase in foot swelling compared to wild-type mice. Virological analysis revealed that mice lacking IFN-α sustained elevated infection in the infected ankle and in distant tissues. In contrast, IFN-β-KO mice displayed minimal differences in viral burdens within the ankle or at distal sites and instead had an altered cellular immune response. Mice lacking IFN-β had increased neutrophil infiltration into musculoskeletal tissues, and depletion of neutrophils in IFN-β-KO but not IRF7-KO mice mitigated musculoskeletal disease caused by CHIKV. Our findings suggest disparate roles for the IFN subtypes during CHIKV infection, with IFN-α limiting early viral replication and dissemination and IFN-β modulating neutrophil-mediated inflammation

Dynamics and Chemistry of Marine Stratocumulus (DYCOMS) Experiment

A combined atmospheric chemistry-meteorology experiment, the Dynamics and Chemistry of the Marine Stratocumulus (DYCOMS), was carried out during the summer of 1985 over the eastern Pacific Ocean using the NCAR Electra aircraft. The objectives were to 1) study the budgets of several trace reactive species in a relatively pristine, steady-state, horizontally homogeneous, well-mixed boundary layer capped by a strong inversion and 2) study the formation, maintenance and dissipation of marine stratocumulus that persists off the California coast (as well as similar regions elsewhere) in summer. We obtained both mean and turbulence measurements of meteorological variables within and above the cloud-capped boundary layer that is typical of this region. Ozone was used successfully as a tracer for estimating entrainment rate. We found, however, that horizontal variability was large enough for ozone that a correction needs to be included in the ozone budget for the horizontal displacement due to turns even though the airplane was allowed to drift with the wind. The time rate-of-change term was significant in both the ozone and radon budgets; as a result, a considerably longer time interval than the two hours used between sets of flight legs would be desirable to improve the measurement accuracy of this term