Biology subjects

Smith, G. J.

Publications and source records attributed to Smith, G. J..

22 records · Page 2Linked to original sources

bioRxiv2020

Early induction of SARS-CoV-2 specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients

Virus-specific humoral and cellular immunity act synergistically to protect the host from viral infection. We interrogated the dynamic changes of virological and immunological parameters in 12 patients with symptomatic acute SARS-CoV-2 infection from disease onset to convalescence or death. We quantified SARS-CoV-2 viral RNA in the respiratory tract in parallel with antibodies and circulating T cells specific for various structural (NP, M, ORF3a and spike) and non-structural proteins (ORF7/8, NSP7 and NSP13). We observed that while rapid induction and quantity of humoral responses were associated with increased disease severity, an early induction of SARS-CoV-2 specific T cells was present in patients with mild disease and accelerated viral clearance. These findings provide further support for a protective role of SARS-CoV-2 specific T cells over antibodies during SARS-CoV-2 infection with important implications in vaccine design and immune-monitoring.

immunology↗

bioRxiv2020

DRAM for distilling microbial metabolism to automate the curation of microbiome function

Microbial and viral communities transform the chemistry of Earths ecosystems, yet the specific reactions catalyzed by these biological engines are hard to decode due to the absence of a scalable, metabolically resolved, annotation software. Here, we present DRAM (Distilled and Refined Annotation of Metabolism), a framework to translate the deluge of microbiome-based genomic information into a catalog of microbial traits. To demonstrate the applicability of DRAM across metabolically diverse genomes, we evaluated DRAM performance on a defined, in silico soil community and previously published human gut metagenomes. We show that DRAM accurately assigned microbial contributions to geochemical cycles, and automated the partitioning of gut microbial carbohydrate metabolism at substrate levels. DRAM-v, the viral mode of DRAM, established rules to identify virally-encoded auxiliary metabolic genes (AMGs), resulting in the metabolic categorization of thousands of putative AMGs from soils and guts. Together DRAM and DRAM-v provide critical metabolic profiling capabilities that decipher mechanisms underpinning microbiome function.

microbiology↗

bioRxiv2019

Transcriptional profiling of the murine airway response to acute ozone exposure

Exposure to ambient ozone (O3) pollution causes airway inflammation, epithelial injury, and decreased lung function. Long-term exposure is associated with increased mortality and exacerbations of respiratory conditions. While the adverse health effects of O3 exposure have been thoroughly described, less is known about the molecular processes that drive these outcomes. The aim of this study was to describe the cellular and molecular alterations observed in murine airways after exposure to either 1 or 2 ppm O3. After exposing adult, female C57BL/6J mice to filtered air, 1 or 2 ppm O3 for 3 hours, we assessed hallmark responses including airway inflammatory cell counts, epithelial permeability, cytokine secretion, and morphological alterations of the large airways. Further, we performed RNA-seq to profile gene expression in two critical tissues involved in O3 responses: conducting airways (CA) and airway macrophages (AM). We observed a concentration-dependent increase in airway inflammation and injury, and a large number of genes were differentially expressed in both target tissues at both concentrations of O3. Genes that were differentially expressed in CA were generally associated with barrier function, detoxification processes, and cellular proliferation. The differentially expressed genes in AM were associated with innate immune signaling, cytokine production, and extracellular matrix remodeling. Overall, our study has described transcriptional responses to acute O3 exposure, revealing both shared and unique gene expression patterns across multiple concentrations of O3 and in two important O3-responsive tissues. These profiles provide broad mechanistic insight into pulmonary O3 toxicity, and reveal a variety of targets for refined follow-up studies.

pharmacology and toxicology↗

bioRxiv2018

Development of a large-scale computer-controlled ozone inhalation exposure system for rodents

Complete systems for laboratory-based inhalation toxicology studies are typically not commercially available; therefore, inhalation toxicologists utilize custom-made exposure systems. Here we report on the design, construction, testing, operation, and maintenance of a newly developed in vivo rodent ozone inhalation exposure system. Key design requirements for the system included large-capacity exposure chambers to facilitate studies with large sample sizes, automatic and precise control of chamber ozone concentrations, as well as automated data collection on airflow and environmental conditions. The exposure system contains two Hazelton H-1000 stainless steel and glass exposure chambers, each providing capacity for up to 180 mice or 96 rats. We developed an empirically tuned proportional-integral-derivative (PID) control loop that provides stable ozone concentrations throughout the exposure period (typically 3h), after a short ramp time ([~]8 minutes), and across a tested concentration range of 0.2 to 2 ppm. Specific details on the combination analog and digital input/output system for environmental data acquisition, control, and safety systems are provided, and we outline the steps involved in maintenance and calibration of the system. We show that the exposure system produces consistent ozone exposures both within and across experiments, as evidenced by low coefficients of variation in chamber ozone concentration and consistent biological responses (airway inflammation) in mice, respectively. Thus, we have created a large and robust ozone exposure system, facilitating future studies on the health effects of ozone in rodents.

pharmacology and toxicology↗