New insights into the impact of neuro-inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA

A portable dual-smog-chamber system for atmospheric aerosol field studies

Smog chamber experiments using ambient air as a starting point can improve our understanding of the evolution of atmospheric particulate matter at timescales longer than those achieved by traditional laboratory experiments. These types of studies can take place under more realistic environmental conditions addressing the interactions among multiple pollutants. The use of two identical smog chambers, with the first serving as the baseline chamber and the second as the perturbation chamber (in which addition or removal of pollutants, addition of oxidants, change in the relative humidity, etc.), can facilitate the interpretation of the results in such inherently complex experiments. The differences of the measurements in the two chambers can be used as the basis for the analysis of the corresponding chemical or physical processes of ambient air. A portable dual-smog-chamber system was developed using two identical pillow-shaped smog chambers (1.5&thinsp;m3 each). The two chambers are surrounded by UV lamps in a hexagonal arrangement yielding a total JNO2 of 0.1&thinsp;min−1. The system can be easily disassembled and transported, enabling the study of various atmospheric environments. Moreover, it can be used with natural sunlight. The results of test experiments using ambient air as the starting point are discussed as examples of applications of this system.</p

TNFR1 inhibition with a nanobody protects against EAE development in mice

TNF has as detrimental role in multiple sclerosis (MS), however, anti-TNF medication is not working. Selective TNF/TNFR1 inhibition whilst sparing TNFR2 signaling reduces the pro-inflammatory effects of TNF but preserves the important neuroprotective signals via TNFR2. We previously reported the generation of a Nanobody-based selective inhibitor of human TNFR1, TROS that will be tested in experimental autoimmune encephalomyelitis (EAE). We specifically antagonized TNF/TNFR1 signaling using TROS in a murine model of MS, namely MOG(35-55)-induced EAE. Because TROS does not cross-react with mouse TNFR1, we generated mice expressing human TNFR1 in a mouse TNFR1-knockout background (hTNFR1 Tg), and we determined biodistribution of Tc-99m-TROS and effectiveness of TROS in EAE in those mice. Biodistribution analysis demonstrated that intraperitoneally injected TROS is retained more in organs of hTNFR1 Tg mice compared to wild type mice. TROS was also detected in the cerebrospinal fluid (CSF) of hTNFR1 Tg mice. Prophylactic TROS administration significantly delayed disease onset and ameliorated its symptoms. Moreover, treatment initiated early after disease onset prevented further disease development. TROS reduced spinal cord inflammation and neuroinflammation, and preserved myelin and neurons. Collectively, our data illustrate that TNFR1 is a promising therapeutic target in MS

Rapid dark aging of biomass burning as an overlooked source of oxidized organic aerosol

To quantify the full implications of biomass burning emissions on the atmosphere, it is essential to accurately represent the emission plume after it has undergone chemical aging in the atmosphere. Atmospheric models typically consider the predominant aging pathway of biomass burning emissions to take place in the presence of sunlight (via the OH radical); however, this mechanism leads to consistent underpredictions of oxidized organic aerosol in wintertime urban areas. Here, we show, through a combination of laboratory experiments, ambient field measurements, and chemical transport modeling, that biomass burning emission plumes exposed to NO2 and O3 age rapidly without requiring any sunlight, thus providing an overlooked source of oxidized organic aerosol previously not accounted for in models

Oxidative Potential of Atmospheric Particles at an Eastern Mediterranean Site

Aerosol oxidative potential (OP; the inherent ability of ambient particles to generate reactive oxygen species in vivo) may be linked to the health effects of population exposure to aerosol and is a metric of their toxicity. The goal of this work was to quantify the water-soluble OP of particles in an urban area in Patras, Greece and to investigate its links with source emissions or components of this particulate matter (PM). A field campaign was conducted during a monthlong wintertime period in 2020 (January 10 to February 13) on the campus of the University of Peloponnese in the southwest of Patras. During this time, ambient filter samples (a total of 35 filters) were collected. To measure the water-soluble OP we used a semiautomated system similar to Fang et al. (2015) based on the dithiothreitol (DTT) assay. The accuracy of our system was validated by measuring the DTT activity of 11 phenanthrequinone (PQN) solutions on both our system and the identical semi-automated validated system at the National Observatory of Athens (NOA). These two sets of analysed DTT activities (current vs. NOA system) were significantly correlated (R2=0.99) with a slope of 1.15 ± 0.04 and an intercept close to zero. We found that the average water-soluble OP in Patras was 1.5 ± 0.3 nmol min-1 m-3, ranging from 0.7 to 2 nmol min-1 m-3. The OP measured in Patras during the campaign is higher than reported values from similar wintertime studies in other urban areas such as Athens (Paraskevopoulou et al., 2019). The average watersoluble OP during a summer study for Patras was significantly lower and equal to 0.18 ± 0.02 nmol min-1 m- 3. Taking into account the average PM1 mass concentrations for these two periods (summer: 6 μg m-3 and winter: 23 μg m-3) it is clear that the increase in OP was two times the increase in PM mass making the wintertime aerosol more toxic. Additionally, the water-soluble brown carbon (BrC) was determined using an offline semi-automated system, where absorption was measured over a 1 m path length. The average BrC absorption in Patras at a wavelength of 365 nm was 8.6 ± 3.9 Mm-1 suggesting that there was significant BrC in the organic aerosol during this period. The coefficients of determination, R2, in Table 1 are used as a metric of the potential relationships between the various carbonaceous aerosol components and the DTT activity. The results suggest that the OP is not dominated by a single source or component, but that there are multiple components contributing to it during the study period. Interestingly, the highest correlation coefficient (R2 = 0.46) was found between the OP and Brown Carbon. This is consistent with recently published results for an urban site in Atlanta where the oxidative potential measured with the DTT method also had stronger correlations with BrC during the winter (Gao et al., 2020)

Sources of water-soluble Brown Carbon at a South-Eastern European Site

Atmospheric brown carbon (BrC) is a highly uncertain, but potentially important contributor to light absorption in the atmosphere. Laboratory and field studies have shown that BrC can be produced from multiple sources, including primary emissions from fossil fuel combustion and biomass burning (BB), as well as secondary formation through a number of reaction pathways. It is currently thought that the dominant source of atmospheric BrC is primary emissions from BB, but relatively few studies demonstrate this in environments with complex source profiles. A field campaign was conducted during a month-long wintertime period in 2020 on the campus of the University of Peloponnese in the southwest of Patras, Greece which represents an urban site. During this time, ambient filter samples (a total of 35 filters) were collected from which the water-soluble BrC was determined using a semi-automated system similar to Hecobian et al. (2010), where absorption was measured over a 1 m path length. To measure the BrC, a UV-Vis Spectrophotometer was coupled to a Liquid Waveguide Capillary Cell and the light absorption intensity was recorded at 365 and 700 nm. The latter was used as a reference wavelength. We found that the average BrC absorption in Patras at a wavelength of 365 nm was 8.5 ± 3.9 Mm-1 suggesting that there was significant BrC in the organic aerosol during this period. Attribution of sources of BrC was done using simultaneous chemical composition data observations (primarily organic carbon, black carbon, and nitrate) combined with Positive Matrix Factorization analysis. This analysis showed that in addition to the important role of biomass burning (a contribution of about 20%) and other combustion emissions (also close to 20%), oxidized organic aerosol (approximately 40%) is also a significant contributor to BrC in the study area. Reference Hecobian, A., Zhang, X., Zheng, M., Frank, N., Edgerton, E.S., Weber, R.J., 2010. Water-soluble organic aerosol material and the light-absorption characteristics of aqueous extracts measured over the Southeastern United States. Atmos. Chem. Phys. 10, 5965–5977. https://doi.org/10.5194/acp-10-5965-201

Chemical evolution of primary and secondary biomass burning aerosols during daytime and nighttime

Primary emissions from wood and pellet stoves were aged in an atmospheric simulation chamber under daytime and nighttime conditions. The aerosol was analyzed with the online Aerosol Mass Spectrometer (AMS) and offline Fourier transform infrared spectroscopy (FTIR). Measurements using the two techniques agreed reasonably well in terms of the organic aerosol (OA) mass concentration, OA:OC trends, and concentrations of biomass burning markers – lignin-like compounds and anhydrosugars. Based on the AMS, around 15 % of the primary organic aerosol (POA) mass underwent some form of transformation during daytime oxidation conditions after 6–10 hours of atmospheric exposure. A lesser extent of transformation was observed during the nighttime oxidation. The decay of certain semi-volatile (e.g., levoglucosan) and less volatile (e.g., lignin-like) POA components was substantial during aging, highlighting the role of heterogeneous reactions and gas-particle partitioning. Lignin-like compounds were observed to degrade under both daytime and nighttime conditions, whereas anhydrosugars degraded only under daytime conditions. Among the marker mass fragments of primary biomass burning OA (bbPOA), heavy ones (higher m/z) were relatively more stable during aging. The biomass burning secondary OA (bbSOA) became more oxidized with continued aging and resembled those of aged atmospheric organic aerosols. The bbSOA formed during daytime oxidation was dominated by acids. Organonitrates were an important product of nighttime reactions in both humid and dry conditions. Our results underline the importance of changes to both the primary and secondary biomass burning aerosols during their atmospheric aging. Heavier AMS fragments seldomly used in atmospheric chemistry can be used as more stable tracers of bbPOA and in combination with the established levoglucosan marker, can provide an indication of the extent of bbPOA aging

Drivers of droplet formation in east Mediterranean orographic clouds

The purpose of this study is to understand the drivers of cloud droplet formation in orographic clouds. We used a combination of modeling, in situ, and remote sensing measurements at the high-Altitude Helmos Hellenic Atmospheric Aerosol and Climate Change ((HAC)2) station, which is located at the top of Mt. Helmos (1314 m above sea level), Greece, during the Cloud-AerosoL InteractionS in the Helmos Background TropOsphere (CALISHTO) campaign in fall 2021 (https://calishto.panacea-ri.gr/, last access: 1 August 2024) to examine the origins of the aerosols (i.e., local aerosol from the planetary boundary layer (PBL) or long-range-Transported aerosol from the free-Tropospheric layer (FTL) contributing to the cloud condensation nuclei (CCN)), their characteristics (hygroscopicity, size distribution, and mixing state), and the vertical velocity distributions and resulting supersaturations. We found that the characteristics of the PBL aerosol were considerably different from FTL aerosol and use the aerosol particle number and equivalent mass concentration of the black carbon (eBC) in order to determine when (HAC)2 was within the FTL or PBL based on time series of the height of the PBL. During the (HAC)2 cloud events we sample a mixture of interstitial aerosol and droplet residues, which we characterize using a new approach that utilizes the in situ droplet measurements to determine time periods when the aerosol sample is purely interstitial. From the dataset we determine the properties (size distribution and hygroscopicity) of the pre-cloud, activated, and interstitial aerosol. The hygroscopicity of activated aerosol is found to be higher than that of the interstitial or pre-cloud aerosol. A series of closure studies with the droplet parameterization shows that cloud droplet concentration (Nd) and supersaturation can be predicted to within 25 % of observations when the aerosol size distributions correspond to pre-cloud conditions. The analysis of the characteristic supersaturation of each aerosol population indicates that droplet formation in clouds is aerosol-limited when formed in FTL air masses-hence droplet formation is driven by aerosol variations, while clouds formed in the PBL tend to be velocity-limited and droplet variations are driven by fluctuations in vertical velocity. Given that the cloud dynamics do not vary significantly between air masses, the variation in aerosol concentration and type is mostly responsible for these shifts in cloud microphysical state and sensitivity to aerosol. With these insights, the remote sensing of cloud droplets in such clouds can be used to infer either CCN spectra (when in the FTL) or vertical velocity (when in the PBL). In conclusion, we show that a coordinated measurement of aerosol and cloud properties, together with the novel analysis approaches presented here, allows for the determination of the drivers of droplet formation in orographic clouds and their sensitivity to aerosol and vertical velocity variations.</p