Noninvasive real-time breath test for controlling hormonal background of the human body: detection of serotonin and melatonin with quantum point-contact sensors.

Significant progress in development of noninvasive diagnostic tools based on breath analysis can be expected if one employs a real-time detection method based on finding a spectral breath profile which would contain some energy characteristics of the analyzed gas mixture. Using the fundamental energy parameters of a quantum system, it is possible to determine with a high accuracy its quantitative and qualitative composition. Among the most efficient tools to measure energy characteristics of quantum systems are sensors based on Yanson point contacts. This paper reports the results of serotonin and melatonin detection as an example of testing the human hormonal background with point-contact sensors, which have already demonstrated their high efficiency in detecting carcinogenic strains ofHelicobacter pyloriand selective detection of complex gas mixtures. When comparing the values of serotonin and melatonin with the characteristic parameters of the spectral profile of the exhaled breath of each patient, high correlation dependences of the concentration of serotonin and melatonin with a number of characteristic parameters of the response curve of the point-contact sensor were found. The performed correlation analysis was complemented with the regression analysis. As a result, empiric regression relations were proposed to realize in practice the new non-invasive breath test for evaluation of the human hormonal background. Registration of the patient's breath profile using point-contact sensors makes it possible to easily monitor the dynamics of changes in the human hormonal background and perform a quantitative evaluation of serotonin and melatonin levels in the human body in real time without invasive interventions (blood collection) and expensive equipment or reagents.

Activation of the cold-receptor TRPM8 by low levels of menthol in tobacco products.

Activation of the cold-receptor TRPM8 by menthol or other tobacco additives can suppress natural defense reactions such as coughing that usually would become effective as involuntary resistance against the inhalation of fumes. In Europe menthol is only regulated as flavor, but can be used as additive as long as no characteristic mint-like aroma will become noticeable in the end-product tobacco. The question needs to be addressed of whether such comparatively minor contents would be sufficient to trigger a measurable activation of TRPM8. In this study, we have analyzed both the contents of menthol and other natural TRPM8 agonists in tobacco products and developed a bioassay to determine the minimum concentrations of selected agonists to activate the TRPM8 receptor in cultured cells. The data confirm menthol as strongest natural agonist investigated. Based on these experiments and previously published data, we have estimated both the minimum menthol concentrations in cigarette smoke and in tobacco that are expected to trigger measurable physiological effects. According to our assessments, TRPM8 activation is likely to occur when cigarettes contain more than 50 micrograms of menthol. Importantly, menthol contents in cigarettes far below the typical levels that require declaration as "mentholated" would be sufficient to activate sensory receptors.

The Q-rich/PST domain of the AHR regulates both ligand-induced nuclear transport and nucleocytoplasmic shuttling.

The aryl hydrocarbon receptor (AHR) shuttles continuously between cytoplasm and nucleus, unless ligand-binding triggers association with the AHR nuclear translocator (ARNT) and subsequent binding to cognate DNA motifs. We have now identified Val 647 as mandatory residue for export from the nucleus and AHR-function. This residue prevents inactivation of the receptor as a consequence of nuclear sequestration via constitutive import. Concomitantly mutants lacking this residue are exclusively localised in the nucleus. Although ligands accelerate nuclear import transiently, stable nuclear transition depends on a motif adjacent to Val 647 that comprises residues 650-661. Together, this defined region within the Q-rich domain regulates intracellular trafficking of the AHR in context of both nucleocytoplasmic shuttling and receptor activation. Nuclear export therefore depends on the previously characterised N-terminal NES and the newly identified motif that includes V647. Nucleocytoplasmic distribution of full-length human AHR is further affected by a section of the PST domain that shows sequence similarities with nuclear export signals. In concert, these motifs maintain a predominant cytoplasmic compartmentalisation, receptive for ligand binding.