Comorbid depression and chronic pain are highly prevalent in individuals suffering from physical illness. Here, we critically examine the possibility that inflammation is the common mediator of this ...comorbidity, and we explore the implications of this hypothesis. Inflammation signals the brain to induce sickness responses that include increased pain and negative affect. This is a typical and adaptive response to acute inflammation. However, chronic inflammation induces a transition from these typical sickness behaviors into depression and chronic pain. Several mechanisms can account for the high comorbidity of pain and depression that stem from the precipitating inflammation in physically ill patients. These mechanisms include direct effects of cytokines on the neuronal environment or indirect effects via downregulation of G protein-coupled receptor kinase 2, activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase that generates neurotropic kynurenine metabolites, increased brain extracellular glutamate, and the switch of GABAergic neurotransmission from inhibition to excitation. Despite the existence of many neuroimmune candidate mechanisms for the co-occurrence of depression and chronic pain, little work has been devoted so far to critically assess their mediating role in these comorbid symptoms. Understanding neuroimmune mechanisms that underlie depression and pain comorbidity may yield effective pharmaceutical targets that can treat both conditions simultaneously beyond traditional antidepressants and analgesics.
Abstract
We report the discovery of two ultra-faint satellites in the vicinity of the Large Magellanic Cloud (LMC) in data from the Magellanic Satellites Survey (MagLiteS ). Situated 18 deg (∼20 kpc) ...from the LMC and separated from each other by only 18 arcmin, Carina II and III form an intriguing pair. By simultaneously modelling the spatial and the colour–magnitude stellar distributions, we find that both Carina II and Carina III are likely dwarf galaxies, although this is less clear for Carina III. There are in fact several obvious differences between the two satellites. While both are well described by an old and metal poor population, Carina II is located at ∼36 kpc from the Sun, with MV ∼ −4.5 and rh ∼ 90 pc, and it is further confirmed by the discovery of 3 RR Lyrae at the right distance. In contrast, Carina III is much more elongated, measured to be fainter (MV ∼ −2.4), significantly more compact (rh ∼ 30 pc), and closer to the Sun, at ∼28 kpc, placing it only 8 kpc away from Car II. Together with several other systems detected by the Dark Energy Camera, Carina II and III form a strongly anisotropic cloud of satellites in the vicinity of the Magellanic Clouds.
Monolayers of molybdenum and tungsten dichalcogenides are direct bandgap semiconductors, which makes them promising for optoelectronic applications. In particular, van der Waals heterostructures ...consisting of monolayers of MoS2 sandwiched between atomically thin hexagonal boron nitride (hBN) and graphene electrodes allows one to obtain light emitting quantum wells (LEQWs) with low-temperature external quantum efficiency (EQE) of 1%. However, the EQE of MoS2- and MoSe2-based LEQWs shows behavior common for many other materials: it decreases fast from cryogenic conditions to room temperature, undermining their practical applications. Here we compare MoSe2 and WSe2 LEQWs. We show that the EQE of WSe2 devices grows with temperature, with room temperature EQE reaching 5%, which is 250× more than the previous best performance of MoS2 and MoSe2 quantum wells in ambient conditions. We attribute such different temperature dependences to the inverted sign of spin–orbit splitting of conduction band states in tungsten and molybdenum dichalcogenides, which makes the lowest-energy exciton in WSe2 dark.
Ambient air monitoring as part of the US Environmental Protection Agency's (US EPA's) Clean Air Status and Trends Network (CASTNet) currently uses filter packs to measure weekly integrated ...concentrations. The US EPA is interested in supplementing CASTNet with semi-continuous monitoring systems at select sites to characterize atmospheric chemistry and deposition of nitrogen and sulfur compounds at higher time resolution than the filter pack. The Monitor for AeRosols and GAses in ambient air (MARGA) measures water-soluble gases and aerosols at an hourly temporal resolution. The performance of the MARGA was assessed under the US EPA Environmental Technology Verification (ETV) program. The assessment was conducted in Research Triangle Park, North Carolina, from 8 September to 8 October 2010 and focused on gaseous SO2, HNO3, and NH3 and aerosol SO42-, NO3-, and NH4+. Precision of the MARGA was evaluated by calculating the median absolute relative percent difference (MARPD) between paired hourly results from duplicate MARGA units (MUs), with a performance goal of ≤ 25%. The accuracy of the MARGA was evaluated by calculating the MARPD for each MU relative to the average of the duplicate denuder/filter pack concentrations, with a performance goal of ≤ 40%. Accuracy was also evaluated by using linear regression, where MU concentrations were plotted against the average of the duplicate denuder/filter pack concentrations. From this, a linear least squares line of best fit was applied. The goal was for the slope of the line of best fit to be between 0.8 and 1.2. The MARGA performed well in comparison to the denuder/filter pack for SO2, SO42−, and NH4+, with all three compounds passing the accuracy and precision goals by a significant margin. The performance of the MARGA in measuring NO3- could not be evaluated due to the different sampling efficiency of coarse NO3- by the MUs and the filter pack. Estimates of "fine" NO3- were calculated for the MUs and the filter pack. Using this and results from a previous study, it is concluded that if the MUs and the filter pack were sampling the same particle size, the MUs would have good agreement in terms of precision and accuracy. The MARGA performed moderately well in measuring HNO3 and NH3, though neither met the linear regression slope goals. However, recommendations for improving the measurement of HNO3 and NH3 are discussed. It is concluded that SO42-, SO2, NO3-, HNO3, NH4+, and NH3 concentrations can be measured with acceptable accuracy and precision when the MARGA is operated in conjunction with the recommendations outlined in the manuscript.
Abstract Large Igneous Provinces (LIPs) are associated with global warming and carbon cycle perturbations during Oceanic Anoxic Event 2 (OAE2, ~94 Ma) and the Mid-Cenomanian Event (MCE, ~96.5 Ma). ...However, there is still no consensus on the role volcanism played as a trigger, or its source – previously ascribed to the Caribbean LIP or High Arctic LIP. Here, we use Mentelle Basin sedimentary mercury (Hg) concentrations to determine the timing of volcanism, and neodymium (Nd) and strontium (Sr) isotopes for sedimentary provenance. High Hg concentrations compared to Northern Hemisphere records, and a shift to radiogenic Nd isotopes, indicates Kerguelen LIP volcanic activity and plateau uplift occurred in the lead up to and within OAE2. Whilst we find limited evidence that a volcanic event caused the MCE, pulsed Hg spikes before and during OAE2 imply volcanic emissions were key in driving climate and carbon cycle changes and triggering OAE2.
Sharp rises in the atmospheric abundance of ethane (C2H6) have been detected from 2009 onwards in the Northern Hemisphere as a result of the unprecedented growth in the exploitation of shale gas and ...tight oil reservoirs in North America. Using time series of C2H6 total columns derived from ground-based Fourier transform infrared (FTIR) observations made at five selected Network for the Detection of Atmospheric Composition Change sites, we characterize the recent C2H6 evolution and determine growth rates of ∼5% yr−1 at mid-latitudes and of ∼3% yr−1 at remote sites. Results from CAM-chem simulations with the Hemispheric Transport of Air Pollutants, Phase II bottom-up inventory for anthropogenic emissions are found to greatly underestimate the current C2H6 abundances. Doubling global emissions is required to reconcile the simulations and the observations prior to 2009. We further estimate that North American anthropogenic C2H6 emissions have increased from 1.6 Tg yr−1 in 2008 to 2.8 Tg yr−1 in 2014, i.e. by 75% over these six years. We also completed a second simulation with new top-down emissions of C2H6 from North American oil and gas activities, biofuel consumption and biomass burning, inferred from space-borne observations of methane (CH4) from Greenhouse Gases Observing SATellite. In this simulation, GEOS-Chem is able to reproduce FTIR measurements at the mid-latitudinal sites, underscoring the impact of the North American oil and gas development on the current C2H6 abundance. Finally we estimate that the North American oil and gas emissions of CH4, a major greenhouse gas, grew from 20 to 35 Tg yr−1 over the period 2008-2014, in association with the recent C2H6 rise.
Within the SPARC Data Initiative, the first comprehensive assessment of the quality of 13 water vapor products from 11 limb‐viewing satellite instruments (LIMS, SAGE II, UARS‐MLS, HALOE, POAM III, ...SMR, SAGE III, MIPAS, SCIAMACHY, ACE‐FTS, and Aura‐MLS) obtained within the time period 1978–2010 has been performed. Each instrument's water vapor profile measurements were compiled into monthly zonal mean time series on a common latitude‐pressure grid. These time series serve as basis for the “climatological” validation approach used within the project. The evaluations include comparisons of monthly or annual zonal mean cross sections and seasonal cycles in the tropical and extratropical upper troposphere and lower stratosphere averaged over one or more years, comparisons of interannual variability, and a study of the time evolution of physical features in water vapor such as the tropical tape recorder and polar vortex dehydration. Our knowledge of the atmospheric mean state in water vapor is best in the lower and middle stratosphere of the tropics and midlatitudes, with a relative uncertainty of ±2–6% (as quantified by the standard deviation of the instruments' multiannual means). The uncertainty increases toward the polar regions (±10–15%), the mesosphere (±15%), and the upper troposphere/lower stratosphere below 100 hPa (±30–50%), where sampling issues add uncertainty due to large gradients and high natural variability in water vapor. The minimum found in multiannual (1998–2008) mean water vapor in the tropical lower stratosphere is 3.5 ppmv (±14%), with slightly larger uncertainties for monthly mean values. The frequently used HALOE water vapor data set shows consistently lower values than most other data sets throughout the atmosphere, with increasing deviations from the multi‐instrument mean below 100 hPa in both the tropics and extratropics. The knowledge gained from these comparisons and regarding the quality of the individual data sets in different regions of the atmosphere will help to improve model‐measurement comparisons (e.g., for diagnostics such as the tropical tape recorder or seasonal cycles), data merging activities, and studies of climate variability.
Key Points
Validation of H2O climatologies from limb‐viewing satellite instruments
Key information on uncertainty for data merging or climate variability studies
Best quality of H2O in middle stratosphere, worst in UTLS
Industrial processes such as spray drying of pharmaceutical and food products often involve the drying of aerosol droplets containing colloidal suspensions into powdered microparticles of desired ...properties. The morphology and surface properties of the final dry products/microparticles obtained after the drying process are strongly influenced by the parameters of the initial aerosol droplet composition and the drying conditions. In particular, the final dry microparticle morphology can be dependent on the dimensionless Péclet number (Pe), which expresses the relative competition between the diffusion of the dispersed particles within the droplet and the rate of solvent loss via evaporation. In this work, we examine how control over the gas phase drying conditions and initial aerosol droplet composition can be used to influence the aerosol droplet drying kinetics in the gas phase for a range of Péclet numbers. We used a single-particle levitation instrument, the electrodynamic balance, to measure the drying kinetics of colloidal silica droplets (0.10–0.60% v/v) under controlled gas phase drying conditions of temperature (263–326 K) and relative humidity (0–90%) and obtained Péclet numbers ranging from 4.05 to 184.5. We demonstrate that, for aerosol droplets with initially dilute feed colloid concentrations and within the constant evaporation regime, the starting composition does not strongly influence the solvent evaporation rate with the included nanoparticles (NPs) acting as spectators. However, the gas phase drying conditions, temperature, and relative humidity, directly influence the droplet temperature via evaporative cooling as well as the droplet drying kinetics and the final dry microparticle properties. With a priori knowledge of the droplet drying kinetics from the single droplet measurements, we further demonstrate the possibility of tailoring the morphology of the dried microparticles. Dried silica microparticles collected at Pe = 23.8 had dense spherical morphologies, while those at the highest Pe = 180.0 had crumpled surface morphologies with a transition in morphology between these limiting Pe values. Our results extend the fundamental understanding of the mechanisms controlling the drying of aerosol droplets in colloidal suspensions across a wide range of application areas extending from spray drying to the drying of respiratory fluid droplets containing bacteria and viruses and the drying of atmospheric aerosol droplets.
The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2 years due to the Covid pandemic, was organised to debate and discuss the future of ...Remote Ischaemic Conditioning (RIC). This evolved from the large multicentre CONDI-2–ERIC–PPCI outcome study which demonstrated no additional benefit when using RIC in the setting of ST-elevation myocardial infarction (STEMI). The workshop discussed how conditioning has led to a significant and fundamental understanding of the mechanisms preventing cell death following ischaemia and reperfusion, and the key target cyto-protective pathways recruited by protective interventions, such as RIC. However, the obvious need to translate this protection to the clinical setting has not materialised largely due to the disconnect between preclinical and clinical studies. Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the potential for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify so-called responders vs. non-responders in both the preclinical and clinical settings.
Augmenting hippocampal neurogenesis represents a potential new strategy for treating depression. Here we test this possibility by comparing hippocampal neurogenesis in depression-prone ghrelin ...receptor (Ghsr)-null mice to that in wild-type littermates and by determining the antidepressant efficacy of the P7C3 class of neuroprotective compounds. Exposure of Ghsr-null mice to chronic social defeat stress (CSDS) elicits more severe depressive-like behavior than in CSDS-exposed wild-type littermates, and exposure of Ghsr-null mice to 60% caloric restriction fails to elicit antidepressant-like behavior. CSDS resulted in more severely reduced cell proliferation and survival in the ventral dentate gyrus (DG) subgranular zone of Ghsr-null mice than in that of wild-type littermates. Also, caloric restriction increased apoptosis of DG subgranular zone cells in Ghsr-null mice, although it had the opposite effect in wild-type littermates. Systemic treatment with P7C3 during CSDS increased survival of proliferating DG cells, which ultimately developed into mature (NeuN+) neurons. Notably, P7C3 exerted a potent antidepressant-like effect in Ghsr-null mice exposed to either CSDS or caloric restriction, while the more highly active analog P7C3-A20 also exerted an antidepressant-like effect in wild-type littermates. Focal ablation of hippocampal stem cells with radiation eliminated this antidepressant effect, further attributing the P7C3 class antidepressant effect to its neuroprotective properties and resultant augmentation of hippocampal neurogenesis. Finally, P7C3-A20 demonstrated greater proneurogenic efficacy than a wide spectrum of currently marketed antidepressant drugs. Taken together, our data confirm the role of aberrant hippocampal neurogenesis in the etiology of depression and suggest that the neuroprotective P7C3-compounds represent a novel strategy for treating patients with this disease.
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