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1.
PLoS One ; 17(6): e0270412, 2022.
Article in English | MEDLINE | ID: covidwho-1933363

ABSTRACT

BACKGROUND: Individuals with respiratory conditions, such as asthma, are particularly susceptible to adverse health effects associated with higher levels of ambient air pollution and temperature. This study evaluates whether hourly levels of fine particulate matter (PM2.5) and dry bulb globe temperature (DBGT) are associated with the lung function of adult participants with asthma. METHODS AND FINDINGS: Global positioning system (GPS) location, respiratory function (measured as forced expiratory volume at 1 second (FEV1)), and self-reports of asthma medication usage and symptoms were collected as part of the Exposure, Location, and Lung Function (ELF) study. Hourly ambient PM2.5 and DBGT exposures were estimated by integrating air quality and temperature public records with time-activity patterns using GPS coordinates for each participant (n = 35). The relationships between acute PM2.5, DBGT, rescue bronchodilator use, and lung function collected in one week periods and over two seasons (summer/winter) were analyzed by multivariate regression, using different exposure time frames. In separate models, increasing levels in PM2.5, but not DBGT, were associated with rescue bronchodilator use. Conversely DBGT, but not PM2.5, had a significant association with FEV1. When DBGT and PM2.5 exposures were placed in the same model, the strongest association between cumulative PM2.5 exposures and the use of rescue bronchodilator was identified at the 0-24 hours (OR = 1.030; 95% CI = 1.012-1.049; p-value = 0.001) and 0-48 hours (OR = 1.030; 95% CI = 1.013-1.057; p-value = 0.001) prior to lung function measure. Conversely, DBGT exposure at 0 hours (ß = 3.257; SE = 0.879; p-value>0.001) and 0-6 hours (ß = 2.885; SE = 0.903; p-value = 0.001) hours before a reading were associated with FEV1. No significant interactions between DBGT and PM2.5 were observed for rescue bronchodilator use or FEV1. CONCLUSIONS: Short-term increases in PM2.5 were associated with increased rescue bronchodilator use, while DBGT was associated with higher lung function (i.e. FEV1). Further studies are needed to continue to elucidate the mechanisms of acute exposure to PM2.5 and DBGT on lung function in asthmatics.


Subject(s)
Air Pollution , Asthma , Adult , Air Pollution/adverse effects , Bronchodilator Agents , Environmental Exposure/adverse effects , Humans , Lung , Temperature
2.
Environ Int ; 163: 107226, 2022 05.
Article in English | MEDLINE | ID: covidwho-1773289

ABSTRACT

During events like the COVID-19 pandemic or a disaster, researchers may need to switch from collecting biological samples to personal exposure samplers that are easy and safe to transport and wear, such as silicone wristbands. Previous studies have demonstrated significant correlations between urine biomarker concentrations and chemical levels in wristbands. We build upon those studies and use a novel combination of descriptive statistics and supervised statistical learning to evaluate the relationship between polycyclic aromatic hydrocarbon (PAH) concentrations in silicone wristbands and hydroxy-PAH (OH-PAH) concentrations in urine. In New York City, 109 participants in a longitudinal birth cohort wore one wristband for 48 h and provided a spot urine sample at the end of the 48-hour period during their third trimester of pregnancy. We compared four PAHs with the corresponding seven OH-PAHs using descriptive statistics, a linear regression model, and a linear discriminant analysis model. Five of the seven PAH and OH-PAH pairs had significant correlations (Pearson's r = 0.35-0.64, p ≤ 0.003) and significant chi-square tests of independence for exposure categories (p ≤ 0.009). For these five comparisons, the observed PAH or OH-PAH concentration could predict the other concentration within a factor of 1.47 for 50-80% of the measurements (depending on the pair). Prediction accuracies for high exposure categories were at least 1.5 times higher compared to accuracies based on random chance. These results demonstrate that wristbands and urine provide similar PAH exposure assessment information, which is critical for environmental health researchers looking for the flexibility to switch between biological sample and wristband collection.


Subject(s)
COVID-19 , Polycyclic Aromatic Hydrocarbons , Environmental Monitoring/methods , Female , Humans , Pandemics , Polycyclic Aromatic Hydrocarbons/analysis , Pregnancy , Silicones
3.
Langmuir ; 37(41): 12089-12097, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1450265

ABSTRACT

The COVID-19 pandemic has claimed millions of lives worldwide, sickened many more, and has resulted in severe socioeconomic consequences. As society returns to normal, understanding the spread and persistence of SARS CoV-2 on commonplace surfaces can help to mitigate future outbreaks of coronaviruses and other pathogens. We hypothesize that such an understanding can be aided by studying the binding and interaction of viral proteins with nonbiological surfaces. Here, we propose a methodology for investigating the adhesion of the SARS CoV-2 spike glycoprotein on common inorganic surfaces such as aluminum, copper, iron, silica, and ceria oxides as well as metallic gold. Quantitative adhesion was obtained from the analysis of measured forces at the nanoscale using an atomic force microscope operated under ambient conditions. Without imposing further constraints on the measurement conditions, our preliminary findings suggest that spike glycoproteins interact with similar adhesion forces across the majority of the metal oxides tested with the exception to gold, for which attraction forces ∼10 times stronger than all other materials studied were observed. Ferritin, which was used as a reference protein, was found to exhibit similar adhesion forces as SARS CoV-2 spike protein. This study results show that glycoprotein adhesion forces for similar ambient humidity, tip shape, and contact surface are nonspecific to the properties of metal oxide surfaces, which are expected to be covered by a thin water film. The findings suggest that under ambient conditions, glycoprotein adhesion to metal oxides is primarily controlled by the water capillary forces, and they depend on the surface tension of the liquid water. We discuss further strategies warranted to decipher the intricate nanoscale forces for improved quantification of the adhesion.


Subject(s)
COVID-19 , Humans , Microscopy, Atomic Force , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Surface Properties
4.
mBio ; 12(4): e0157221, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1349194

ABSTRACT

Tissue- and cell-specific expression patterns are highly variable within and across individuals, leading to altered host responses after acute virus infection. Unraveling key tissue-specific response patterns provides novel opportunities for defining fundamental mechanisms of virus-host interaction in disease and the identification of critical tissue-specific networks for disease intervention in the lung. Currently, there are no approved therapeutics for Middle East respiratory syndrome coronavirus (MERS-CoV) patients, and little is understood about how lung cell types contribute to disease outcomes. MERS-CoV replicates equivalently in primary human lung microvascular endothelial cells (MVE) and fibroblasts (FB) and to equivalent peak titers but with slower replication kinetics in human airway epithelial cell cultures (HAE). However, only infected MVE demonstrate observable virus-induced cytopathic effect. To explore mechanisms leading to reduced MVE viability, donor-matched human lung MVE, HAE, and FB were infected, and their transcriptomes, proteomes, and lipidomes were monitored over time. Validated functional enrichment analysis demonstrated that MERS-CoV-infected MVE were dying via an unfolded protein response (UPR)-mediated apoptosis. Pharmacologic manipulation of the UPR in MERS-CoV-infected primary lung cells reduced viral titers and in male mice improved respiratory function with accompanying reductions in weight loss, pathological signatures of acute lung injury, and times to recovery. Systems biology analysis and validation studies of global kinetic transcript, protein, and lipid data sets confirmed that inhibition of host stress pathways that are differentially regulated following MERS-CoV infection of different tissue types can alleviate symptom progression to end-stage lung disease commonly seen following emerging coronavirus outbreaks. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe atypical pneumonia in infected individuals, but the underlying mechanisms of pathogenesis remain unknown. While much has been learned from the few reported autopsy cases, an in-depth understanding of the cells targeted by MERS-CoV in the human lung and their relative contribution to disease outcomes is needed. The host response in MERS-CoV-infected primary human lung microvascular endothelial (MVE) cells and fibroblasts (FB) was evaluated over time by analyzing total RNA, proteins, and lipids to determine the cellular pathways modulated postinfection. Findings revealed that MERS-CoV-infected MVE cells die via apoptotic mechanisms downstream of the unfolded protein response (UPR). Interruption of enzymatic processes within the UPR in MERS-CoV-infected male mice reduced disease symptoms, virus-induced lung injury, and time to recovery. These data suggest that the UPR plays an important role in MERS-CoV infection and may represent a host target for therapeutic intervention.


Subject(s)
Acute Lung Injury/pathology , Apoptosis/physiology , Coronavirus Infections/pathology , Unfolded Protein Response/physiology , Acute Lung Injury/virology , Animals , Cell Line , Endothelial Cells/metabolism , Endothelial Cells/virology , Female , Fibroblasts/metabolism , Fibroblasts/virology , Humans , Male , Mice , Middle East Respiratory Syndrome Coronavirus/immunology
5.
BMC Bioinformatics ; 22(1): 287, 2021 May 29.
Article in English | MEDLINE | ID: covidwho-1257920

ABSTRACT

BACKGROUND: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets. RESULTS: We compiled a novel data set of transcriptional host response to pathogenic viral infections and formulated relationships between genes as a hypergraph where hyperedges represent significantly perturbed genes, and vertices represent individual biological samples with specific experimental conditions. We find that hypergraph betweenness centrality is a superior method for identification of genes important to viral response when compared with graph centrality. CONCLUSIONS: Our results demonstrate the utility of using hypergraphs to represent complex biological systems and highlight central important responses in common to a variety of highly pathogenic viruses.


Subject(s)
Algorithms , Models, Biological , Genomics , Proteins
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