Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease

Background

There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.

Methods

We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012. Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.

Results

Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively). Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05). Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads. Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs. No association was observed between inflammation and health status (p > 0.05).

Conclusions

Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique. The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae. However, discordance between inflammation and health status was observed.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users.     

Inferring the number of evolutionary events from DNA coding sequence differences

The estimation of the amount of evolutionary divergence that has taken place between two DNA coding sequences depends strongly on the degree of constraint on amino acid replacements. If amino acid replacements are relatively unconstrained, the individual nucleotide is the appropriate unit of analysis and the method of Tajima and Nei can be used. If amino acid replacements are constrained, however, this method is shown to be inapplicable. For sequences with strong amino acid constraints, a method is outlined analogous to the Tajima and Nei method using codons as the unit of analysis. Only synonymous substitutions are used. Codon usage data can be employed to estimate the necessary parameters of the calculation, or a priori models of substitution may be employed. Sequences with significant but intermediate constraints on amino acid replacements are, in principle, unanalyzable.      

Visual control of steering in locust flight: the effects of head movement on responses to roll stimuli

The contribution of head movement to the control of roll responses in flying locusts (Locusta migratoria) has been examined (i) on a flight balance, recording the angles through which the locust turns when following an artificial horizon; (ii) by recording activity in a pair of flight muscles in restrained conditions; and (iii) by observations on free flying locusts. Responses were compared when the head was free to turn about the thorax, as normal, and when the head was waxed to the thorax, blocking any relative motion between the two (head-fixed). These experiments suggest that the major signal generating corrective roll manoeuvres is the visual error between the angle of the head and the horizon, rather than a signal that includes a measure of the head-thorax angle.

Mitogenic activity of pituitary hormones on cell cultures of normal and carcinogen-induced tumor epithelium from rat mammary glands

Cell suspension containing normal or tumor epithelium were readily obtained by enzymatically digesting rat mammary glands from perphenazine-treated (prolactin-hypersecreting) cycling, female virgin animals or hormone- responsive mammary tumors from animal treated with dimethylbenzanthracene. Cell suspensions were fractioned into predominantly epithelial and predominantly stromal cells by their differential rates of attachment to culture dishes. Both normal mammary and tumor epithelial cells were characterized by the presence of specific cell-junctional complexes, desmosome-like structures, surface microvilli, and their ability to synthesize casein. Serum-dependent protease activity was greater in cultures derived from tumors, and cells from such cultures grew in agarose whereas those from the non-neoplastic gland did not. The addition of prolactin to the culture medium stimulated DNA synthesis in primary or secondary epithelial cultures from tumors, whereas additional insulin and hydrocortisone with prolactin were required for similar levels of DNA synthesis in cultures from non-neoplastic glands. The fraction of cells synthesizing DNA was, however, smaller than that with 10 percent serum measured in the same time period. Both growth hormone and epidermal growth factor stimulated DNA synthesis but to a lesser extent than did prolactin. Prolactin with hydrocortisone and insulin were relatively inactive in promoting DNA synthesis of the nonepithelial cells whereas pituitary fibroblast growth factor was more active. These mitogenic effects were obtained when the hormones were added to the medium at near physiological concentrations, and paralleled the known activities of the hormones in control of mammary gland growth and development in the rat.     

Disruption of state estimation in the human lateral cerebellum

The cerebellum has been proposed to be a crucial component in the state estimation process that combines information from motor efferent and sensory afferent signals to produce a representation of the current state of the motor system. Such a state estimate of the moving human arm would be expected to be used when the arm is rapidly and skillfully reaching to a target. We now report the effects of transcranial magnetic stimulation (TMS) over the ipsilateral cerebellum as healthy humans were made to interrupt a slow voluntary movement to rapidly reach towards a visually defined target. Errors in the initial direction and in the final finger position of this reach-to-target movement were significantly higher for cerebellar stimulation than they were in control conditions. The average directional errors in the cerebellar TMS condition were consistent with the reaching movements being planned and initiated from an estimated hand position that was 138 ms out of date. We suggest that these results demonstrate that the cerebellum is responsible for estimating the hand position over this time interval and that TMS disrupts this state estimate.     

Fertilization effects with P on accumulated leaf area duration,biomass and yield of three cultivars of maize in Toluca,Mexico

The effect of six phosphorus levels (0, 40, 80, 120, 160 and 200 kg/ha) on the duration of cumulative leaf area, biomass and agronomic yield was determined in the maize cultivars: Amarillo Almoloya, Cacahuacintle and Condor in 2010 and 2011. Such cultivars were sown in the Cerrillo Piedras Blancas Mexico. A completely randomized complete block design with factorial arrangement was utilized. High phosphorus levels (120, 160 and 200 kg/ha) positively affected the duration of cumulative leaf area; greatest values were obtained in Cacahuacintle. A greater duration of accumulated leaf area contributes to determine high values of biomass accumulation and grain yield in this cultivar. Leaf area duration appeared to be a useful tool for evaluating different genotypes in a given environment.     

A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors

Bacterial pathogens often subvert the innate immune system to establish a successful infection. The direct inhibition of downstream components of innate immune pathways is particularly well documented but how bacteria interfere with receptor proximal events is far less well understood. Here, we describe a Toll/interleukin 1 receptor (TIR) domain‐containing protein (PumA) of the multi‐drug resistant Pseudomonas aeruginosa PA7 strain. We found that PumA is essential for virulence and inhibits NF‐κB, a property transferable to non‐PumA strain PA14, suggesting no additional factors are needed for PumA function. The TIR domain is able to interact with the Toll‐like receptor (TLR) adaptors TIRAP and MyD88, as well as the ubiquitin‐associated protein 1 (UBAP1), a component of the endosomal‐sorting complex required for transport I (ESCRT‐I). These interactions are not spatially exclusive as we show UBAP1 can associate with MyD88, enhancing its plasma membrane localization. Combined targeting of UBAP1 and TLR adaptors by PumA impedes both cytokine and TLR receptor signalling, highlighting a novel strategy for innate immune evasion.