Global observations of tropospheric BrO columns using GOME-2 satellite data

Measurements from the GOME-2 satellite instrument have been analyzed for tropospheric BrO using a residual technique that combines measured BrO columns and estimates of the stratospheric BrO content from a climatological approach driven by O<sub>3</sub> and NO<sub>2</sub> observations. Comparisons between the GOME-2 results and BrO vertical columns derived from correlative ground-based and SCIAMACHY nadir observations, present a good level of consistency. We show that the adopted technique enables separation of stratospheric and tropospheric fractions of the measured total BrO columns and allows quantitative study of the BrO plumes in polar regions. While some satellite observed plumes of enhanced BrO can be explained by stratospheric descending air, we show that most BrO hotspots are of tropospheric origin, although they are often associated to regions with low tropopause heights as well. Elaborating on simulations using the <i>p</i>-TOMCAT tropospheric chemical transport model, this result is found to be consistent with the mechanism of bromine release through sea salt aerosols production during blowing snow events. No definitive conclusion can be drawn however on the importance of blowing snow sources in comparison to other bromine release mechanisms. Outside polar regions, evidence is provided for a global tropospheric BrO background with column of 1–3 × 10<sup>13</sup> molec cm<sup>−2</sup>, consistent with previous estimates

Development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples

Surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. However, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as well as from potential reservoir animals such as bats. In order to address this, we have developed a broadly reactive multiplex microsphere immunoassay (MMIA) for the detection of antibodies against several highly pathogenic viruses from both humans and animals. To this aim, nucleoproteins (NP) of Ebola virus (EBOV), Marburg virus (MARV) and nucleocapsid proteins (NP) of Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus and Dobrava-Belgrade hantavirus were employed in a 5-plex assay for IgG detection. After optimisation, specific binding to each respective NP was shown by testing sera from humans and non-human primates with known infection status. The usefulness of our assay for serosurveillance was shown by determining the immune response against the NP antigens in a panel of 129 human serum samples collected in Guinea between 2011 and 2012 in comparison to a panel of 88 sera from the German blood bank. We found good agreement between our MMIA and commercial or in-house reference methods by ELISA or IIFT with statistically significant higher binding to both EBOV NP and MARV NP coupled microspheres in the Guinea panel. Finally, the MMIA was successfully adapted to detect antibodies from bats that had been inoculated with EBOV- and MARV- virus-like particles, highlighting the versatility of this technique and potentially enabling the monitoring of wildlife as well as human populations with this assay. We were thus able to develop and validate a sensitive and broadly reactive high-throughput serological assay which could be used as a screening tool to detect antibodies against several highly pathogenic viruses

Molecular complexity determines the number of olfactory notes and the pleasantness of smells

One major unresolved problem in olfaction research is to relate the percept to the molecular structure of stimuli. The present study examined this issue and showed for the first time a quantitative structure-odor relationship in which the more structurally complex a monomolecular odorant, the more numerous the olfactory notes it evokes. Low-complexity odorants were also rated as more aversive, reflecting the fact that low molecular complexity may serve as a warning cue for the olfactory system. Taken together, these findings suggest that molecular complexity provides a framework to explain the subjective experience of smells

Extraction of prefronto-amygdalar pathways by combining probability maps

Many recent studies reported altered functional connectivity within the frontolimbic circuitry in a wide range of neuropsychiatric disorders. However, functional connectivity must rely on structural connections. In this study we applied a novel probabilistic fiber tracking method to assess the structural connectivity between the amygdala and different prefrontal brain regions in vivo. Twenty healthy subjects were investigated with diffusion tensor imaging. Probabilistic fiber tracking was started from the amygdala and different prefrontal brain regions. Resulting probability maps were combined using an extended multiplication of probabilistic maps to identify the most probable anatomical pathways connecting these structures. We found one ventral pathway through the uncinate fascicle, connecting the amygdala and the medial and lateral orbitofrontal cortices. In addition to this ventral pathway, we depicted distinct dorsal pathways (medial and lateral), which connect the amygdala with the anterior cingulate cortex and the dorsolateral prefrontal cortex. The dorso-medial pathway proceeds through the inferior thalamic peduncle, while the dorsolateral pathway travels through the external capsule. We believe that our approach provides a promising tool to assess the integrity of specific structural connections in patients with neuropsychiatric disorders. © 2009 Elsevier Ireland Ltd. All rights reserved

Ball and rackets: inferring fiber fanning from diffusion-weighted MRI

A number of methods have been proposed for resolving crossing fibers from diffusion-weighted (DW) MRI. However, other complex fiber geometries have drawn minimal attention. In this study, we focus on fiber orientation dispersion induced by within-voxel fanning. We use a multi-compartment, model-based approach to estimate fiber dispersion. Bingham distributions are employed to represent continuous distributions of fiber orientations, centered around a main orientation, and capturing anisotropic dispersion. We evaluate the accuracy of the model for different simulated fanning geometries, under different acquisition protocols and we illustrate the high SNR and angular resolution needs. We also perform a qualitative comparison between our parametric approach and five popular non-parametric techniques that are based on orientation distribution functions (ODFs). This comparison illustrates how the same underlying geometry can be depicted by different methods. We apply the proposed model on high-quality, post-mortem macaque data and present whole-brain maps of fiber dispersion, as well as exquisite details on the local anatomy of fiber distributions in various white matter regions

Immune dynamics in SARS-CoV-2 experienced immunosuppressed rheumatoid arthritis or multiple sclerosis patients vaccinated with mRNA-1273

BACKGROUND: Patients affected by different types of autoimmune diseases, including common conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants. METHODS: The dynamics of cellular immune reactivation upon vaccination of SARS-CoV-2 experienced MS patients treated with the humanized anti-CD20 monoclonal antibody ocrelizumab (OCR) and RA patients treated with methotrexate (MTX) monotherapy were analyzed at great depth via high-dimensional flow cytometry of whole blood samples upon vaccination with the SARS-CoV-2 mRNA-1273 (Moderna) vaccine. Longitudinal B and T cell immune responses were compared to SARS-CoV-2 experienced healthy controls (HCs) before and 7 days after the first and second vaccination. RESULTS: OCR-treated MS patients exhibit a preserved recall response of CD8(+) T central memory cells following first vaccination compared to HCs and a similar CD4(+) circulating T follicular helper 1 and T helper 1 dynamics, whereas humoral and B cell responses were strongly impaired resulting in absence of SARS-CoV-2-specific humoral immunity. MTX treatment significantly delayed antibody levels and B reactivation following the first vaccination, including sustained inhibition of overall reactivation marker dynamics of the responding CD4(+) and CD8(+) T cells. CONCLUSIONS: Together, these findings indicate that SARS-CoV-2 experienced MS-OCR patients may still benefit from vaccination by inducing a broad CD8(+) T cell response which has been associated with milder disease outcome. The delayed vaccine-induced IgG kinetics in RA-MTX patients indicate an increased risk after the first vaccination, which might require additional shielding or alternative strategies such as treatment interruptions in vulnerable patients. FUNDING: This research project was supported by ZonMw (The Netherlands Organization for Health Research and Development, #10430072010007), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (#792532 and #860003), the European Commission (SUPPORT-E, #101015756) and by PPOC (#20_21 L2506), the NHMRC Leadership Investigator Grant (#1173871)