Understanding the impact of recent advances in isoprene photooxidation on simulations of regional air quality

The CMAQ (Community Multiscale Air Quality) us model in combination with observations for INTEX-NA/ICARTT (Intercontinental Chemical Transport Experiment–North America/International Consortium for Atmospheric Research on Transport and Transformation) 2004 are used to evaluate recent advances in isoprene oxidation chemistry and provide constraints on isoprene nitrate yields, isoprene nitrate lifetimes, and NO_x recycling rates. We incorporate recent advances in isoprene oxidation chemistry into the SAPRC-07 chemical mechanism within the US EPA (United States Environmental Protection Agency) CMAQ model. The results show improved model performance for a range of species compared against aircraft observations from the INTEX-NA/ICARTT 2004 field campaign. We further investigate the key processes in isoprene nitrate chemistry and evaluate the impact of uncertainties in the isoprene nitrate yield, NO_x (NO_x = NO + NO_2) recycling efficiency, dry deposition velocity, and RO_2 + HO_2 reaction rates. We focus our examination on the southeastern United States, which is impacted by both abundant isoprene emissions and high levels of anthropogenic pollutants. We find that NO_x concentrations increase by 4–9% as a result of reduced removal by isoprene nitrate chemistry. O3 increases by 2 ppbv as a result of changes in NO_x. OH concentrations increase by 30%, which can be primarily attributed to greater HO_x production. We find that the model can capture observed total alkyl and multifunctional nitrates (∑ANs) and their relationship with O_3 by assuming either an isoprene nitrate yield of 6% and daytime lifetime of 6 hours or a yield of 12% and lifetime of 4 h. Uncertainties in the isoprene nitrates can impact ozone production by 10% and OH concentrations by 6%. The uncertainties in NO_x recycling efficiency appear to have larger effects than uncertainties in isoprene nitrate yield and dry deposition velocity. Further progress depends on improved understanding of isoprene oxidation pathways, the rate of NOx recycling from isoprene nitrates, and the fate of the secondary, tertiary, and further oxidation products of isoprene

Epoxide as a precursor to secondary organic aerosol formation from isoprene photooxidation in the presence of nitrogen oxides

Isoprene is a substantial contributor to the global secondary organic aerosol (SOA) burden, with implications for public health and the climate system. The mechanism by which isoprene-derived SOA is formed and the influence of environmental conditions, however, remain unclear. We present evidence from controlled smog chamber experiments and field measurements that in the presence of high levels of nitrogen oxides (NOx = NO + NO2) typical of urban atmospheres, 2-methyloxirane-2-carboxylic acid (methacrylic acid epoxide, MAE) is a precursor to known isoprene-derived SOA tracers, and ultimately to SOA. We propose that MAE arises from decomposition of the OH adduct of methacryloylperoxynitrate (MPAN). This hypothesis is supported by the similarity of SOA constituents derived from MAE to those from photooxidation of isoprene, methacrolein, and MPAN under high-NOx conditions. Strong support is further derived from computational chemistry calculations and Community Multiscale Air Quality model simulations, yielding predictions consistent with field observations. Field measurements taken in Chapel Hill, North Carolina, considered along with the modeling results indicate the atmospheric significance and relevance of MAE chemistry across the United States, especially in urban areas heavily impacted by isoprene emissions. Identification of MAE implies a major role of atmospheric epoxides in forming SOA from isoprene photooxidation. Updating current atmospheric modeling frameworks with MAE chemistry could improve the way that SOA has been attributed to isoprene based on ambient tracer measurements, and lead to SOA parameterizations that better capture the dependency of yield on NOx

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis

Is social stress in the first half of life detrimental to later physical and mental health in both men and women?

This study examined gender differences in the associations between affection- and status-related stressors encountered in the first half of life and physical and mental health problems later on. Based on the theory of Social Production Functions (SPF) two hypotheses have been formulated, which were tested in a representative sample of 446 men and 514 women (aged 40–79). Main outcome measures were number of chronic somatic diseases and level of psychological distress. As expected, regression analyses showed no gender differences in the associations between affection-related stressors and physical and mental health problems later on. In contrast, but as also expected, status-related stressors encountered in the first half of life were associated with later physical and mental health for men only. It is concluded that the gender differences in the associations between earlier social stressors and later health problems may be more complex than the common assumption that men are only affected by status stress and women only by affection stress. This study contributes to the knowledge on gender differences concerning the link between social stress and health, and it indicates that social experiences encountered earlier in life are of importance for being healthy and happy in later life

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention

The discovAIR project: a roadmap towards the Human Lung Cell Atlas

The Human Cell Atlas (HCA) consortium aims to establish an atlas of all organs in the healthy human body at single-cell resolution to increase our understanding of basic biological processes that govern development, physiology and anatomy, and to accelerate diagnosis and treatment of disease. The Lung Biological Network of the HCA aims to generate the Human Lung Cell Atlas as a reference for the cellular repertoire, molecular cell states and phenotypes, and cell–cell interactions that characterise normal lung homeostasis in healthy lung tissue. Such a reference atlas of the healthy human lung will facilitate mapping the changes in the cellular landscape in disease. The discovAIR project is one of six pilot actions for the HCA funded by the European Commission in the context of the H2020 framework programme. discovAIR aims to establish the first draft of an integrated Human Lung Cell Atlas, combining single-cell transcriptional and epigenetic profiling with spatially resolving techniques on matched tissue samples, as well as including a number of chronic and infectious diseases of the lung. The integrated Human Lung Cell Atlas will be available as a resource for the wider respiratory community, including basic and translational scientists, clinical medicine, and the private sector, as well as for patients with lung disease and the interested lay public. We anticipate that the Human Lung Cell Atlas will be the founding stone for a more detailed understanding of the pathogenesis of lung diseases, guiding the design of novel diagnostics and preventive or curative interventions

An integrated cell atlas of the lung in health and disease

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas

Enhanced Auditory Brainstem Response and Parental Bonding Style in Children with Gastrointestinal Symptoms

The electrophysiological properties of the brain and influence of parental bonding in childhood irritable bowel syndrome (IBS) are unclear. We hypothesized that children with chronic gastrointestinal (GI) symptoms like IBS may show exaggerated brainstem auditory evoked potential (BAEP) responses and receive more inadequate parental bonding. = 0.024). Multiple regression analysis in females also supported these findings.It is suggested that children with chronic GI symptoms have exaggerated brainstem responses to environmental stimuli and inadequate parental behaviors aggravate these symptoms