Project description:The study aimed at evaluation and comparison of airway epithelium mRNA profile in response to airborne particulate matter presented by macrophages using in vitro triple cell co-culture model.
Project description:New respiratory diseases in personnel deployed to Southwest Asia after September 11th raise major concerns about the impacts of airborne particulate matter. Although regulations exist, the knowledge about how particulates influence disease states is limited, precluding the appropriate recognition, prevention and treatment of deployment-related lung diseases. We applied two genomics assays, Precision Run-on sequencing (PRO-seq) and the assay for transposase accessible chromatin with sequencing (ATAC-seq), to characterize the small airway epithelial cell response to Afghan desert particulate matter (APM).
Project description:New respiratory diseases in personnel deployed to Southwest Asia after September 11th raise major concerns about the impacts of airborne particulate matter. Although regulations exist, the knowledge about how particulates influence disease states is limited, precluding the appropriate recognition, prevention and treatment of deployment-related lung diseases. We applied two genomics assays, Precision Run-on sequencing (PRO-seq) and the assay for transposase accessible chromatin with sequencing (ATAC-seq), to characterize the small airway epithelial cell response to Afghan desert particulate matter (APM).
Project description:To seek whether seasonal variation in environmental particulate matter composition affected the global gene response patterns in cultured human cells representing pulmonary and systemic vascular targets. We used microarrays to detail the global program of gene expression affected on different cells type by different seasonal collections of Ambient Particulate Matter.
Project description:Particulate Matter Triggers Carotid Body Dysfunction, Respiratory Dysynchrony and Cardiac Arrhythmias in Mice with Cardiac Failure; The mechanistic link between human exposure to airborne particulate matter (PM) pollution and the increased cardiovascular morbidity and mortality observed in people with congestive heart failure (CHF) is unknown. We now show that exposure of genetically-engineered mice with CHF (expressing a cardiac-specific CREB mutant transcription factor) to ambient PM (collected in Baltimore, mean aerodynamic diameter 1.9 um) unmasks severe autonomic morbidities manifested as significant reductions in heart rate variability, respiratory dysynchrony and increased frequency of serious ventricular arrhythmias, features not observed in PM-challenged wild type mice without CHF. PM exposure in CREB mice with CHF reflexly triggers autonomic dysfunction via heightened carotid body function as evidenced by pronounced afferent nerve responses to hypoxia and marked depression of breathing by hyperoxia challenge. Genomic analyses of lung and ventricular tissues revealed PM-induced molecular signatures of inflammation and oxidative stress. These findings in a murine model of cardiac failure provide the first direct assessment of autonomic function in response to PM challenge and are highly consistent with current epidemiologic findings on cardiovascular morbidity in susceptible PM-exposed human populations. We utilized a murine model of dilated cardiomyopathy to address potential mechanistic links between PM exposure and the development of life-threatening cardiac dysrhythmias. Experiment Overall Design: four group (n=3) of animals were treated by PBS or particulate matter (20mg/kg 1.9µm particulate matter) in Wild type or CD-1 dominate negative mice
Project description:To seek whether seasonal variation in environmental particulate matter composition affected the global gene response patterns in cultured human cells representing pulmonary and systemic vascular targets. We used microarrays to detail the global program of gene expression affected on different cells type by different seasonal collections of Ambient Particulate Matter. After treatment with 10 ug/mL either summer2006 or winter2007APM, endothelial or bronchail epithelial cells were isolated by RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the genes responses correlated with current concepts of systemic inflammation in cardiovascular effects of particulate air pollution.
Project description:Antibiotic resistance is exacerbated by the exchange of antibiotic resistance genes (ARGs) between microbes from diverse habitats. Plasmids are important ARGs mobile elements and are spread by horizontal gene transfer (HGT). In this study, we demonstrated the presence of multi-resistant plasmids from inhalable particulate matter (PM) and its effect on gene horizontal transfer. Three transferable multi-resistant plasmids were identified from PM in a hospital, using conjugative mating assays and nanopore sequencing. pTAir-3 contained 26 horizontal transfer elements and 10 ARGs. Importantly pTAir-5 harbored carbapenem resistance gene (blaOXA) which shows homology to plasmids from human and pig commensal bacteria, thus indicating that PM is a media for antibiotic resistant plasmid spread. In addition, 125 μg/mL PM2.5 and PM10 significantly increased the conjugative transfer rate by 110% and 30%, respectively, and augmented reactive oxygen species (ROS) levels. Underlying mechanisms were revealed by identifying the upregulated expressional levels of genes related to ROS, SOS, cell membranes, pilus generation, and transposition via genome-wide RNA sequencing. The study highlights the airborne spread of multi-resistant plasmids and the impact of inhalable PM on the horizontal transfer of antibiotic resistance.
Project description:Epidemiological studies have demonstrated that exposure to particulate matter (PM) ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Fine airborne particles <2.5 µm (PM2.5) are the most harmful of the urban pollutants, and the most closely linked to respiratory disease. Based on the knowledge that the small airway epithelium (SAE) plays a central role in pathogenesis of smoking-related lung disease, we hypothesized that elevated PM2.5 levels are associated with dysregulation of SAE gene expression.
Project description:Purpose: Determine the mechanism of particulate matter-induced signaling in melanocytes. Method: Primary human epidermal melanocytes were treated with particulate matter (5 μg/cm2) and incubated for 24 h. Total RNA (1 ug) from melanocytes were extracted and subjected to library synthesis. Results: Particulate matter-treated melanocytes exhibited upregulation of ER stress, unfolded protein response, and melanogenesis-related molecules. Conclusion: Particulate matter-induced melanocyte signaling was well evaluated using RNA sequencing.
