Dekker, T. | bioRxiv Science

bioRxiv2019

Loss of adaptive capacity in asthmatics revealed by biomarker fluctuation dynamics on experimental rhinovirus challenge

Asthma is a dynamic disease, in which lung mechanical and inflammatory processes often interact in a complex, unpredictable manner. We hypothesize that this may be explained by respiratory disease-related systems instability and loss of adaptability to changing environmental conditions, resulting in highly fluctuating biomarkers and symptoms. Using time series of inflammatory (eosinophils, neutrophils, FeNO), clinical and lung function biomarkers (PEF, FVC, and FEV1), we estimated this loss of adaptive capacity (AC) during an experimental perturbation with a rhinovirus in 24 healthy and asthmatic volunteers. Loss of AC was estimated by comparing similarities between pre- and post-challenge time series. Unlike healthy participants, the asthmatics post-viral-challenge state resembled significantly more other rhinovirus-infected asthmatics than their own pre-viral-challenge state (hypergeometric-test: p=0.029). This reveals loss of AC, and supports the novel concept that not only single physiological mechanisms, but interacting dynamic disease properties are altered in asthma and contribute to a more vulnerable phenotype.

physiology↗

bioRxiv2018

Trace impurities in test stimuli can seriously compromise chemosensory studies

The discovery of olfactory receptors and major technological advances have greatly accelerated our understanding of chemosensory mechanisms. However, some of this rapid progress may be compromised by inadequate knowledge or characterization of the purity of chemical stimuli used to challenge olfactory or other chemoreceptors when mapping their response profiles. Here, we provide strong evidence that the presence of trace impurities in test stimuli can completely obscure true ligand-receptor relationships. DmOR7a, an olfactory receptor of the vinegar fly (Drosophila melanogaster) has been reported to respond to several long-chain aliphatic ligands such as a putative Drosophila pheromone1, the pheromone of the silkworm moth Bombyx mori2, and a common fatty acid, linoleic acid3. By contrast, we show that DmOR7a responds with high sensitivity to volatile impurities and degradation products present in minute quantities in authentic standards of those compounds, but not to the standards themselves. Responses to impurities can easily go unnoticed due to two main factors. First, the sensitivity of receptors to key ligands may be greater than that of analytical chemistry instruments used to check sample purity. Second, the concentration of highly volatile impurities in an odour puff may be orders of magnitude higher than the main component of a sample, due to the large differences in vapour pressures between the impurities and the main component. Issues concerning impurities are not limited to studies on olfaction that use odour puffs to characterize receptor-ligand interactions, but may affect all studies on chemosensation, from molecular biology and in-silico predictions to behaviour. Purity, which is crucial in receptor-ligand studies, is always implied, but rarely checked rigorously. To avoid misinterpretations, a proper account of all compounds present in test stimuli and an unequivocal confirmation of ligand affinity should accompany chemosensory studies.

neuroscience↗