Early life exposure to nicotine modifies lung gene response after elastase-induced emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is among the top 5 causes of mortality in the world and can develop as a consequence of genetic and/or environmental factors. Current efforts are focused on identifying early life insults and how these contribute to COPD development. In line with this, our study focuses on the influence of early life nicotine exposure and its potential impact on (a) lung pulmonary functions, and (b) elastase-induced emphysema in adulthood. METHODS: To address this hypothesis, we developed a model of 2 hits, delivered at different time points: mouse pups were first exposed to nicotine/placebo in utero and during lactation, and then subsequently received elastase/placebo at the age of 11 weeks. The effect of nicotine pretreatment and elastase instillation was assessed by (a) measurement of pulmonary function at post-elastase day (ped) 21, and (b) transcriptomic profiling at ped3 and 21, and complementary protein determination. Statistical significance was determined by 3- and 2-way ANOVA for pulmonary functions, and RNAseq results were analyzed using the R project. RESULTS: We did not observe any impact of nicotine pre- and early post-natal exposure compared to control samples on lung pulmonary functions in adulthood, as measured by FLEXIVENT technology. After elastase instillation, substantial lung damage was detected by x-ray tomography and was accompanied by loss in body weight at ped3 as well as an increase in cell numbers, inflammatory markers in BAL and lung volume at ped21. Lung functions showed a decrease in elastance and an increase in deep inflation volume and pressure volume (pv) loop area in animals with emphysema at ped21. Nicotine had no effect on elastance and deep inflation volume, but did affect the pv loop area in animals with emphysema at ped21. Extensive transcriptomic changes were induced by elastase at ped3 both in the nicotine-pretreated and the control samples, with several pathways common to both groups, such as for cell cycle, DNA adhesion and DNA damage. Nicotine pretreatment affected the number of lymphocytes present in BAL after elastase instillation and some of the complement pathway related proteins, arguing for a slight modification of the immune response, as well as changes related to general body metabolism. The majority of elastase-induced transcriptomic changes detected at ped3 had disappeared at ped21. In addition, transcriptomic profiling singled out a common gene pool that was independently activated by nicotine and elastase. CONCLUSIONS: Our study reports a broad spectrum of transient transcriptomic changes in mouse emphysema and identifies nicotine as influencing the emphysema-associated immune system response.

Tomoscopy: Time-Resolved Tomography for Dynamic Processes in Materials.

The structure and constitution of opaque materials can be studied with X-ray imaging methods such as 3D tomography. To observe the dynamic evolution of their structure and the distribution of constituents, for example, during processing, heating, mechanical loading, etc., 3D imaging has to be fast enough. In this paper, the recent developments of time-resolved X-ray tomography that have led to what one now calls "tomoscopy" are briefly reviewed A novel setup is presented and applied that pushes temporal resolution down to just 1 ms, that is, 1000 tomograms per second (tps) are acquired, while maintaining spatial resolutions of micrometers and running experiments for minutes without interruption. Applications recorded at different acquisition rates ranging from 50 to 1000 tps are presented. The authors observe and quantify the immiscible hypermonotectic reaction of AlBi10 (in wt%) alloy and dendrite evolution in AlGe10 (in wt%) casting alloy during fast solidification. The combustion process and the evolution of the constituents are analyzed in a burning sparkler. Finally, the authors follow the structure and density of two metal foams over a long period of time and derive details of bubble formation and bubble ageing including quantitative analyses of bubble parameters with millisecond temporal resolution.

Using X-ray tomoscopy to explore the dynamics of foaming metal.

The complex flow of liquid metal in evolving metallic foams is still poorly understood due to difficulties in studying hot and opaque systems. We apply X-ray tomoscopy -the continuous acquisition of tomographic (3D) images- to clarify key dynamic phenomena in liquid aluminium foam such as nucleation and growth, bubble rearrangements, liquid retraction, coalescence and the rupture of films. Each phenomenon takes place on a typical timescale which we cover by obtaining 208 full tomograms per second over a period of up to one minute. An additional data processing algorithm provides information on the 1 ms scale. Here we show that bubble coalescence is not only caused by gravity-induced drainage, as experiments under weightlessness show, and by stresses caused by foam growth, but also by local pressure peaks caused by the blowing agent. Moreover, details of foam expansion and phenomena such as rupture cascades and film thinning before rupture are quantified. These findings allow us to propose a way to obtain foams with smaller and more equally sized bubbles.