•Exposure to stress can determine permanent changes in glucocorticoid signalling.•Dysfunctional glucocorticoid signalling may contribute to psychopathology susceptibility.•GR signalling represents a ...convergence point for mechanisms altered in stress disorders.•SGK1 may link exposure to ELS with life-long changes in glucocorticoid function.
Stress represents the main environmental risk factor for mental illness. Exposure to stressful events, particularly early in life, has been associated with increased incidence and susceptibility of major depressive disorders as well as of other psychiatric illnesses. Among the key players in these events are glucocorticoid receptors. Dysfunctional glucocorticoid signalling may indeed contribute to psychopathology through a number of mechanisms that regulate the response to acute or chronic stress and that affect the function of genes and systems known to be relevant for mood disorders. Indeed, exposure to chronic stress early in life as well as in adulthood has been shown to reduce the expression of glucocorticoid receptors (GR), also through epigenetic mechanisms, and to up-regulate the expression of the co-chaperone gene FKBP5, which restrains GR activity by limiting the translocation of the receptor complex to the nucleus. Another mechanism that contributes to changes in GR responsiveness is the state of receptor phosphorylation that controls activation, subcellular localization as well as its transcriptional activity. Moreover, GR phosphorylation may represent an important mechanism for the cross talk between neurotrophic signalling and GR-dependent transcription, bridging two important players for mood disorders. One gene that lies downstream from GR and may contribute to stress-related changes is serum glucocorticoid kinase-1 (SGK1). We have demonstrated that the expression of SGK1 is significantly increased after exposure to chronic stress in rodents as well as in the blood of drug-free depressed patients. We have also shown that SGK1 up-regulation may ultimately reduce hippocampal neurogenesis and contribute to the structural abnormalities that have been reported to occur in depressed patients.
In summary, GR signalling may represent a point of convergence as well as of divergence for defects associated with pathologic conditions characterized by heightened vulnerability to stress. The characterization of these abnormalities is crucial to identify novel targets for therapeutic intervention that may counteract more effectively stress-induced neurobiological abnormalities.
Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. The human BDNF gene consists of 11 exons, and distinct BDNF ...transcripts are produced through the use of alternative promoters and splicing events. The majority of the BDNF transcripts can be detected not only in the brain but also in the blood cells, although no study has yet investigated the differential expression of BDNF transcripts at the peripheral level. This review provides a description of the human BDNF gene structure as well as a summary of clinical and preclinical evidence supporting the role of BDNF in the pathogenesis of psychiatric disorders. We will discuss several mechanisms as possibly underlying BDNF modulation, including epigenetic mechanisms. We will also discuss the potential use of peripheral BDNF as a biomarker for psychiatric disorders, focusing on the factors that can influence BDNF gene expression and protein levels. Within this context, we have also characterized, for we believe the first time, the expression of BDNF transcripts in the blood, with the aim to provide novel insights into the molecular mechanisms and signaling that may regulate peripheral BDNF gene expression levels.
Present‐day mass redistribution increases the total ocean mass and, on average, causes the ocean bottom to subside elastically. Therefore, barystatic sea level rise is larger than the resulting ...global mean geocentric sea level rise, observed by satellite altimetry and GPS‐corrected tide gauges. We use realistic estimates of mass redistribution from ice mass loss and land water storage to quantify the resulting ocean bottom deformation and its effect on global and regional ocean volume change estimates. Over 1993–2014, the resulting globally averaged geocentric sea level change is 8% smaller than the barystatic contribution. Over the altimetry domain, the difference is about 5%, and due to this effect, barystatic sea level rise will be underestimated by more than 0.1 mm/yr over 1993–2014. Regional differences are often larger: up to 1 mm/yr over the Arctic Ocean and 0.4 mm/yr in the South Pacific. Ocean bottom deformation should be considered when regional sea level changes are observed in a geocentric reference frame.
Key Points
The effect of present‐day mass redistribution on ocean bottom deformation is studied
A global mean ocean bottom subsidence of 0.1 mm/yr was caused by surface mass redistribution over 1993–2014
Mean ocean basin deformations are 1 mm/yr in the Arctic Ocean and up to 0.4 mm/yr elsewhere
Sea-level change is often considered to be globally uniform in sea-level projections. However, local relative sea-level (RSL) change can deviate substantially from the global mean. Here, we present ...maps of twenty-first century local RSL change estimates based on an ensemble of coupled climate model simulations for three emission scenarios. In the Intergovernmental Panel on Climate Change Fourth Assessment Report (IPCC AR4), the same model simulations were used for their projections of global mean sea-level rise. The contribution of the small glaciers and ice caps to local RSL change is calculated with a glacier model, based on a volume-area approach. The contributions of the Greenland and Antarctic ice sheets are obtained from IPCC AR4 estimates. The RSL distribution resulting from the land ice mass changes is then calculated by solving the sea-level equation for a rotating, elastic Earth model. Next, we add the pattern of steric RSL changes obtained from the coupled climate models and a model estimate for the effect of Glacial Isostatic Adjustment. The resulting ensemble mean RSL pattern reveals that many regions will experience RSL changes that differ substantially from the global mean. For the A1B ensemble, local RSL change values range from −3.91 to 0.79 m, with a global mean of 0.47 m. Although the RSL amplitude differs, the spatial patterns are similar for all three emission scenarios. The spread in the projections is dominated by the distribution of the steric contribution, at least for the processes included in this study. Extreme ice loss scenarios may alter this picture. For individual sites, we find a standard deviation for the combined contributions of approximately 10 cm, regardless of emission scenario.
We propose a set of new indices to assist global sensitivity analysis in the presence of data allowing for interpretations based on a collection of diverse models whose parameters could be affected ...by uncertainty. Our global sensitivity analysis metrics enable us to assess the sensitivity of various features (as rendered through statistical moments) of the probability density function of a quantity of interest with respect to imperfect knowledge of (i) the interpretive model employed to characterize the system behavior and (ii) the ensuing model parameters. We exemplify our methodology for the case of heavy metal sorption onto soil, for which we consider three broadly used (equilibrium isotherm) models. Our analyses consider (a) an unconstrained case, i.e., when no data are available to constrain parameter uncertainty and to evaluate the (relative) plausibility of each considered model, and (b) a constrained case, i.e., when the analysis is constrained against experimental observations. Our moment‐based indices are structured according to two key components: (a) a model‐choice contribution, associated with the possibility of analyzing the system of interest by taking advantage of multiple model conceptualizations (or mathematical renderings); and (b) a parameter‐choice contribution, related to the uncertainty in the parameters of a selected model. Our results indicate that a given parameter can be associated with diverse degrees of importance, depending on the considered statistical moment of the target model output. The influence on the latter of parameter and model uncertainty evolves as a function of the available level of information about the modeled system behavior.
Plain Language Summary
The quality and amount of data available in many practical situations justify the interpretation of the system under investigation through a collection of alternative interpretative models. This is reflected by the observation that there is uncertainty about model structure/format. The situation is exacerbated by the observation that parameters associated with each model could also be affected by uncertainty. In this context, quantification of the influence of these multiple sources of uncertainties on environmental quantities of interest is key to increase our understanding and confidence on model(s) functioning and guide further actions (including, e.g., model calibration or collection of new data). We propose an original global sensitivity analysis approach that enables us to quantify the sensitivity of a target quantity with respect to each of the parameters stemming from situations where multiple interpretative models have been formulated. The proposed global sensitivity analysis allows (i) investigating the sensitivity of model outputs through diverse aspects of uncertainty (i.e., focusing on various statistical moments of the probability density function of the target output) as well as (ii) discriminating between contributions to sensitivity due to our lack of knowledge in (a) model format and (b) parameter values.
Key Points
A novel global sensitivity analysis in case of multiple alternative interpretive models is proposed
The approach allows discriminating between contributions to sensitivity due to our lack of knowledge in (a) model format and (b) parameter values
We analyze the evolution of the proposed sensitivity metrics as observations about the system under investigation become available
In next fall and winter, SARS-CoV-2 could circulate in parallel with seasonal influenza. The dual epidemics will result in considerable morbidity and mortality; therefore, influenza vaccination may ...be essential. Recent studies found increased risk of coronavirus in individuals receiving influenza vaccination.
Our aim is to analyse the association between influenza vaccination and COVID-19 in a population of healthcare workers (HCWs).
IgG antibodies against SARS-CoV-2 were detected in 3520 HCWs at a large hospital in Northern Italy. For each participant, we collected data on flu immunization status for the last five flu seasons. Logistic regression was used to test associations between seasonal flu vaccination status and a positive serology tests for COVID-19.
During the last five flu seasons, 2492 vaccinations were administered. Serology tests were negative for 3196 (91%) HCWs and residents and only 21 (1%) people had an equivocal test (12.0-15.0 AU/mL). Only 128 (4%) people received a diagnosis of COVID-19, with a positive swab test. No flu vaccinations for the last five flu seasons were specifically associated with diagnosis of COVID-19 or with positive results of serology tests.
Flu vaccinations did not appear to be associated with SARS-CoV-2 infection. Influenza vaccination should continue to be recommended for HCWs and for individuals at increased risk for severe illness from respiratory infection.
Substantial amounts of secondary organic aerosol (SOA) can be formed from isoprene epoxydiols (IEPOX), which are oxidation products of isoprene mainly under low-NO conditions. Total IEPOX-SOA, which ...may include SOA formed from other parallel isoprene oxidation pathways, was quantified by applying positive matrix factorization (PMF) to aerosol mass spectrometer (AMS) measurements. The IEPOX-SOA fractions of organic aerosol (OA) in multiple field studies across several continents are summarized here and show consistent patterns with the concentration of gas-phase IEPOX simulated by the GEOS-Chem chemical transport model. During the Southern Oxidant and Aerosol Study (SOAS), 78 % of PMF-resolved IEPOX-SOA is accounted by the measured IEPOX-SOA molecular tracers (2-methyltetrols, C5-Triols, and IEPOX-derived organosulfate and its dimers), making it the highest level of molecular identification of an ambient SOA component to our knowledge. An enhanced signal at C5H6O+ (m/z 82) is found in PMF-resolved IEPOX-SOA spectra. To investigate the suitability of this ion as a tracer for IEPOX-SOA, we examine fC5H6O (fC5H6O= C5H6O+/OA) across multiple field, chamber, and source data sets. A background of ~ 1.7 ± 0.1 ‰ (‰ = parts per thousand) is observed in studies strongly influenced by urban, biomass-burning, and other anthropogenic primary organic aerosol (POA). Higher background values of 3.1 ± 0.6 ‰ are found in studies strongly influenced by monoterpene emissions. The average laboratory monoterpene SOA value (5.5 ± 2.0 ‰) is 4 times lower than the average for IEPOX-SOA (22 ± 7 ‰), which leaves some room to separate both contributions to OA. Locations strongly influenced by isoprene emissions under low-NO levels had higher fC5H6O (~ 6.5 ± 2.2 ‰ on average) than other sites, consistent with the expected IEPOX-SOA formation in those studies. fC5H6O in IEPOX-SOA is always elevated (12–40 ‰) but varies substantially between locations, which is shown to reflect large variations in its detailed molecular composition. The low fC5H6O (< 3 ‰) reported in non-IEPOX-derived isoprene-SOA from chamber studies indicates that this tracer ion is specifically enhanced from IEPOX-SOA, and is not a tracer for all SOA from isoprene. We introduce a graphical diagnostic to study the presence and aging of IEPOX-SOA as a triangle plot of fCO2 vs. fC5H6O. Finally, we develop a simplified method to estimate ambient IEPOX-SOA mass concentrations, which is shown to perform well compared to the full PMF method. The uncertainty of the tracer method is up to a factor of ~ 2, if the fC5H6O of the local IEPOX-SOA is not available. When only unit mass-resolution data are available, as with the aerosol chemical speciation monitor (ACSM), all methods may perform less well because of increased interferences from other ions at m/z 82. This study clarifies the strengths and limitations of the different AMS methods for detection of IEPOX-SOA and will enable improved characterization of this OA component.
Highlights ► Environmental enrichment rescues BDNF expression and 5HT metabolism in BDNF+/− mice. ► Environmental enrichment did not affect BDNF expression and 5HT In female mice. ► Thus, rescue ...effects of emotional phenotype by enrichment are gender-specific.
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