Nicotine Inhibits Memory CTL Programming

Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs) and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development.     

Long-term effects of timber harvesting on hemicellulolytic microbial populations in coniferous forest soils

Forest ecosystems need to be sustainably managed, as they are major reservoirs of biodiversity, provide important economic resources and modulate global climate. We have a poor knowledge of populations responsible for key biomass degradation processes in forest soils and the effects of forest harvesting on these populations. Here, we investigated the effects of three timber-harvesting methods, varying in the degree of organic matter removal, on putatively hemicellulolytic bacterial and fungal populations 10 or more years after harvesting and replanting. We used stable-isotope probing to identify populations that incorporated ¹³C from labeled hemicellulose, analyzing ¹³C-enriched phospholipid fatty acids, bacterial 16 S rRNA genes and fungal ITS regions. In soil microcosms, we identified 104 bacterial and 52 fungal hemicellulolytic operational taxonomic units (OTUs). Several of these OTUs are affiliated with taxa not previously reported to degrade hemicellulose, including the bacterial genera Methylibium, Pelomonas and Rhodoferax, and the fungal genera Cladosporium, Pseudeurotiaceae, Capronia, Xenopolyscytalum and Venturia. The effect of harvesting on hemicellulolytic populations was evaluated based on in situ bacterial and fungal OTUs. Harvesting treatments had significant but modest long-term effects on relative abundances of hemicellulolytic populations, which differed in strength between two ecozones and between soil layers. For soils incubated in microcosms, prior harvesting treatments did not affect the rate of incorporation of hemicellulose carbon into microbial biomass. In six ecozones across North America, distributions of the bacterial hemicellulolytic OTUs were similar, whereas distributions of fungal ones differed. Our work demonstrates that diverse taxa in soil are hemicellulolytic, many of which are differentially affected by the impact of harvesting on environmental conditions. However, the hemicellulolytic capacity of soil communities appears resilient.     

Using Drugs to Probe the Variability of Trans-Epithelial Airway Resistance

Background

Precision medicine aims to combat the variability of the therapeutic response to a given medicine by delivering the right medicine to the right patient. However, the application of precision medicine is predicated on a prior quantitation of the variance of the reference range of normality. Airway pathophysiology provides a good example due to a very variable first line of defence against airborne assault. Humans differ in their susceptibility to inhaled pollutants and pathogens in part due to the magnitude of trans-epithelial resistance that determines the degree of epithelial penetration to the submucosal space. This initial ‘set-point’ may drive a sentinel event in airway disease pathogenesis. Epithelia differentiated in vitro from airway biopsies are commonly used to model trans-epithelial resistance but the ‘reference range of normality’ remains problematic. We investigated the range of electrophysiological characteristics of human airway epithelia grown at air-liquid interface in vitro from healthy volunteers focusing on the inter- and intra-subject variability both at baseline and after sequential exposure to drugs modulating ion transport.

Methodology/Principal Findings

Brushed nasal airway epithelial cells were differentiated at air-liquid interface generating 137 pseudostratified ciliated epithelia from 18 donors. A positively-skewed baseline range exists for trans-epithelial resistance (Min/Max: 309/2963 Ω·cm²), trans-epithelial voltage (-62.3/-1.8 mV) and calculated equivalent current (-125.0/-3.2 μA/cm²; all non-normal, P<0.001). A minority of healthy humans manifest a dramatic amiloride sensitivity to voltage and trans-epithelial resistance that is further discriminated by prior modulation of cAMP-stimulated chloride transport.

Conclusions/Significance

Healthy epithelia show log-order differences in their ion transport characteristics, likely reflective of their initial set-points of basal trans-epithelial resistance and sodium transport. Our data may guide the choice of the background set point in subjects with airway diseases and frame the reference range for the future delivery of precision airway medicine.     

A Framework to Assess Biogeochemical Response to Ecosystem Disturbance Using Nutrient Partitioning Ratios

Disturbances affect almost all terrestrial ecosystems, but it has been difficult to identify general principles regarding these influences. To improve our understanding of the long-term consequences of disturbance on terrestrial ecosystems, we present a conceptual framework that analyzes disturbances by their biogeochemical impacts. We posit that the ratio of soil and plant nutrient stocks in mature ecosystems represents a characteristic site property. Focusing on nitrogen (N), we hypothesize that this partitioning ratio (soil N: plant N) will undergo a predictable trajectory after disturbance. We investigate the nature of this partitioning ratio with three approaches: (1) nutrient stock data from forested ecosystems in North America, (2) a process-based ecosystem model, and (3) conceptual shifts in site nutrient availability with altered disturbance frequency. Partitioning ratios could be applied to a variety of ecosystems and successional states, allowing for improved temporal scaling of disturbance events. The generally short-term empirical evidence for recovery trajectories of nutrient stocks and partitioning ratios suggests two areas for future research. First, we need to recognize and quantify how disturbance effects can be accreting or depleting, depending on whether their net effect is to increase or decrease ecosystem nutrient stocks. Second, we need to test how altered disturbance frequencies from the present state may be constructive or destructive in their effects on biogeochemical cycling and nutrient availability. Long-term studies, with repeated sampling of soils and vegetation, will be essential in further developing this framework of biogeochemical response to disturbance.     

Cell Boundary Confinement Sets the Size and Position of the E. coli Chromosome

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Polymodal Nociception in Drosophila Requires Alternative Splicing of TrpA1

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The Structural Basis of the Farnesylated and Methylated KRas4B Interaction with Calmodulin

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Potential Facilitation Between a Commensal and a Pathogenic Microbe in a Wildlife Disease

We assessed the potential for microbial interactions influencing a well-documented host–pathogen system. Mycoplasma agassizii is the known etiological agent of upper respiratory tract disease in Mojave desert tortoises (Gopherus agassizii), but disease in wild animals is extremely heterogeneous. For example, a much larger proportion of animals harbor M. agassizii than those that develop disease. With the availability of a new quantitative PCR assay for a microbe that had previously been implicated in disease, Pasteurella testudinis, we tested 389 previously collected samples of nasal microbes from tortoise populations across the Mojave desert. We showed that P. testudinis is a common commensal microbe. However, we did find that its presence was associated with higher levels of M. agassizii among the tortoises positive for this pathogen. The best predictor of P. testudinis prevalence in tortoise populations was average size of tortoises, suggesting that older populations have higher levels of P. testudinis. The prevalence of co-infection in populations was associated with the prevalence of URTD, providing additional evidence for an indirect interaction between the two microbes and inflammatory disease. We showed that URTD, like many chronic, polymicrobial diseases involving mucosal surfaces, shows patterns of a polymicrobial etiology.