More than twenty years ago, a biological regulation of climate was proposed whereby emissions of dimethyl sulphide from oceanic phytoplankton resulted in the formation of aerosol particles that acted ...as cloud condensation nuclei in the marine boundary layer. In this hypothesis--referred to as CLAW--the increase in cloud condensation nuclei led to an increase in cloud albedo with the resulting changes in temperature and radiation initiating a climate feedback altering dimethyl sulphide emissions from phytoplankton. Over the past two decades, observations in the marine boundary layer, laboratory studies and modelling efforts have been conducted seeking evidence for the CLAW hypothesis. The results indicate that a dimethyl sulphide biological control over cloud condensation nuclei probably does not exist and that sources of these nuclei to the marine boundary layer and the response of clouds to changes in aerosol are much more complex than was recognized twenty years ago. These results indicate that it is time to retire the CLAW hypothesis.
Exploring large environmental datasets generated by high-throughput DNA sequencing technologies requires new analytical approaches to move beyond the basic inventory descriptions of the composition ...and diversity of natural microbial communities. In order to investigate potential interactions between microbial taxa, network analysis of significant taxon co-occurrence patterns may help to decipher the structure of complex microbial communities across spatial or temporal gradients. Here, we calculated associations between microbial taxa and applied network analysis approaches to a 16S rRNA gene barcoded pyrosequencing dataset containing >160 000 bacterial and archaeal sequences from 151 soil samples from a broad range of ecosystem types. We described the topology of the resulting network and defined operational taxonomic unit categories based on abundance and occupancy (that is, habitat generalists and habitat specialists). Co-occurrence patterns were readily revealed, including general non-random association, common life history strategies at broad taxonomic levels and unexpected relationships between community members. Overall, we demonstrated the potential of exploring inter-taxa correlations to gain a more integrated understanding of microbial community structure and the ecological rules guiding community assembly.
Flagellin is a potent activator of a broad range of cell types involved in innate and adaptive immunity. An increasing number of studies have demonstrated the effectiveness of flagellin as an ...adjuvant, as well as its ability to promote cytokine production by a range of innate cell types, trigger a generalized recruitment of T and B lymphocytes to secondary lymphoid sites, and activate TLR5(+)CD11c(+) cells and T lymphocytes in a manner that is distinct from cognate Ag recognition. The plasticity of flagellin has allowed for the generation of a range of flagellin-Ag fusion proteins that have proven to be effective vaccines in animal models. This review summarizes the state of our current understanding of the adjuvant effect of flagellin and addresses important areas of current and future research interest.
The nasal-associated lymphoid tissues (NALT) are generally accepted as an immune induction site, but the activation of naïve T-cells in that compartment has not been well-characterized. I wanted to ...determine if early events in naïve CD4
T cell activation and the extent of antigen specific cell division are similar in NALT to that observed in other secondary lymphoid compartments. I performed antigen tracking experiments and analyzed the activation of naïve antigen-specific CD4
T cells in the nasal-associated lymphoid tissues (NALT). I directly observed transepithelial transport of fluorescently labeled antigen from the lumen of the airway to the interior of the NALT two hours following immunization. One day following intranasal (i.n.) immunization with antigen and adjuvant, antigen-specific CD4
T cells in the NALT associated as clusters, while antigen-specific CD4
T cells in control mice immunized with adjuvant only remained dispersed. The antigen-specific CD4
populations in the NALT and cranial deep cervical lymph nodes of immunized mice expanded significantly by day three following immunization. These findings are consistent with initial activation of naïve CD4
T cells in the NALT and offer insight into adjuvant mechanism of flagellin in the upper respiratory compartment.
Early stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement. Although speculated that such ...paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. Herein, a mathematical model demonstrates that the large amount of pulmonary venous admixture observed in patients with early COVID-19 can be reasonably explained by a combination of pulmonary embolism, ventilation-perfusion mismatching in the noninjured lung, and normal perfusion of the relatively small fraction of injured lung. Although underlying perfusion heterogeneity exacerbates existing shunt and ventilation-perfusion mismatch in the model, the reported hypoxemia severity in early COVID-19 patients is not replicated without either extensive perfusion defects, severe ventilation-perfusion mismatch, or hyperperfusion of nonoxygenated regions.
The ability of certain components of particulate matter to induce oxidative stress through the generation of reactive oxygen species (ROS) in vivo may be one mechanism accounting for observed ...linkages between ambient aerosols and adverse health outcomes. A variety of assays have been used to measure this so-called aerosol oxidative potential. We developed a semi-automated system to quantify oxidative potential of filter aqueous extracts utilizing the dithiothreitol (DTT) assay and report here the development of a similar semi-automated system for the ascorbic acid (AA) assay. Approximately 500 PM2.5 filter samples collected in contrasting locations in the southeastern US were analyzed for a host of aerosol species, along with AA and DTT activities. We present a detailed contrast in findings from these two assays. Water-soluble AA activity was higher in summer and fall than in winter, with highest levels near heavily trafficked highways, whereas DTT activity was higher in winter compared to summer and fall and more spatially homogeneous. AA activity was nearly exclusively correlated with water-soluble Cu (r- = -0.70-0.94 at most sites), whereas DTT activity was correlated with organic and metal species. Source apportionment models, positive matrix factorization (PMF) and a chemical mass balance method with ensemble-averaged source impact profiles (CMB-E), suggest a strong contribution from traffic emissions and secondary processes (e.g., organic aerosol oxidation or metals mobilization by secondary acids) to both AA and DTT activities in urban Atlanta. In contrast, biomass burning was a large source for DTT activity, but insignificant for AA. AA activity was not correlated with PM2.5 mass, while DTT activity co-varied strongly with mass (r- = -0.49-0.86 across sites and seasons). Various linear models were developed to estimate AA and DTT activities for the central Atlanta Jefferson Street site, based on the CMB-E sources. The models were then used to estimate daily oxidative potential at this site over the 1998-2009 period. Time series epidemiological analyses were conducted to assess daily emergency department (ED) visits data for the five-county Atlanta metropolitan area based on the estimated 10-year backcast oxidative potential. Estimated AA activity was not statistically associated with any tested health outcome, while DTT activity was associated with ED visits for both asthma or wheeze and congestive heart failure. The findings point to the importance of both organic components and transition metals from biomass burning and mobile sources to adverse health outcomes in this region.
Nutrient scarcity is pervasive for natural microbial communities, affecting species reproduction and co-existence. However, it remains unclear whether there are general rules of how microbial species ...abundances are shaped by biotic and abiotic factors. Here we show that the ribosomal RNA gene operon (rrn) copy number, a genomic trait related to bacterial growth rate and nutrient demand, decreases from the abundant to the rare biosphere in the nutrient-rich coastal sediment but exhibits the opposite pattern in the nutrient-scarce pelagic zone of the global ocean. Both patterns are underlain by positive correlations between community-level rrn copy number and nutrients. Furthermore, inter-species co-exclusion inferred by negative network associations is observed more in coastal sediment than in ocean water samples. Nutrient manipulation experiments yield effects of nutrient availability on rrn copy numbers and network associations that are consistent with our field observations. Based on these results, we propose a "hunger games" hypothesis to define microbial species abundance rules using the rrn copy number, ecological interaction, and nutrient availability.
We spend the majority of our lives indoors where we are constantly exposed to bacteria residing on surfaces. However, the diversity of these surface-associated communities is largely unknown. We ...explored the biogeographical patterns exhibited by bacteria across ten surfaces within each of twelve public restrooms. Using high-throughput barcoded pyrosequencing of the 16 S rRNA gene, we identified 19 bacterial phyla across all surfaces. Most sequences belonged to four phyla: Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria. The communities clustered into three general categories: those found on surfaces associated with toilets, those on the restroom floor, and those found on surfaces routinely touched with hands. On toilet surfaces, gut-associated taxa were more prevalent, suggesting fecal contamination of these surfaces. Floor surfaces were the most diverse of all communities and contained several taxa commonly found in soils. Skin-associated bacteria, especially the Propionibacteriaceae, dominated surfaces routinely touched with our hands. Certain taxa were more common in female than in male restrooms as vagina-associated Lactobacillaceae were widely distributed in female restrooms, likely from urine contamination. Use of the SourceTracker algorithm confirmed many of our taxonomic observations as human skin was the primary source of bacteria on restroom surfaces. Overall, these results demonstrate that restroom surfaces host relatively diverse microbial communities dominated by human-associated bacteria with clear linkages between communities on or in different body sites and those communities found on restroom surfaces. More generally, this work is relevant to the public health field as we show that human-associated microbes are commonly found on restroom surfaces suggesting that bacterial pathogens could readily be transmitted between individuals by the touching of surfaces. Furthermore, we demonstrate that we can use high-throughput analyses of bacterial communities to determine sources of bacteria on indoor surfaces, an approach which could be used to track pathogen transmission and test the efficacy of hygiene practices.
Archaea, primarily Crenarchaeota, are common in soil; however, the structure of soil archaeal communities and the factors regulating their diversity and abundance remain poorly understood. Here, we ...used barcoded pyrosequencing to comprehensively survey archaeal and bacterial communities in 146 soils, representing a multitude of soil and ecosystem types from across the globe. Relative archaeal abundance, the percentage of all 16S rRNA gene sequences recovered that were archaeal, averaged 2% across all soils and ranged from 0% to >10% in individual soils. Soil C:N ratio was the only factor consistently correlated with archaeal relative abundances, being higher in soils with lower C:N ratios. Soil archaea communities were dominated by just two phylotypes from a constrained clade within the Crenarchaeota, which together accounted for >70% of all archaeal sequences obtained in the survey. As one of these phylotypes was closely related to a previously identified putative ammonia oxidizer, we sampled from two long-term nitrogen (N) addition experiments to determine if this taxon responds to experimental manipulations of N availability. Contrary to expectations, the abundance of this dominant taxon, as well as archaea overall, tended to decline with increasing N. This trend was coupled with a concurrent increase in known N-oxidizing bacteria, suggesting competitive interactions between these groups.
Female smokers have increased risk of chronic obstructive pulmonary disease (COPD) compared with male smokers who have a similar history of cigarette smoke exposure. We have shown previously that ...chronic smoke exposure for 6 months leads to increased airway wall remodeling in female C57BL/6 mice compared with male C57BL/6 mice. These differences, however, were not evident in female ovariectomized mice exposed to cigarette smoke. Herein, we report on the pulmonary function test results from the flexiVent system, which was used to determine the potential functional consequences of the histologic changes observed in these mice. We found that tissue damping (G) was increased in female compared to male or ovariectomized female mice after smoke exposure. At low oscillating frequencies, complex input resistance (Zrs) and impedance (Xrs) of the respiratory system was increased and decreased, respectively, in female but not in male or ovariectomized female mice after smoke exposure. Quasistatic pressure-volume curves revealed a reduction in inspiratory capacity in female mice but not in male or ovariectomized female mice after smoke exposure. The remaining lung function measurements including quasistatic compliance were similar amongst all groups. This is the first study characterizing a sexual dimorphism in respiratory functional properties in a mouse model of COPD. These findings demonstrate that increased airway remodeling in female mice following chronic smoke exposure is associated with increased tissue resistance in the peripheral airways. These data may explain the importance of female sex hormones and the increased risk of airway disease in female smokers.
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