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.
Local measurements of structural characteristics such as intrinsic microstrain along the c axis of the lattice ε=δc/c and its mean square fluctuation 〈ε〉, oxygen deficiency x, cation composition, etc. were performed on epitaxial YBa2Cu3O7 films grown on various substrates (MgO, BaSrTiO3/MgO, SrTiO3, LaAlO3, ZrO2/Si, Al2O3). A number of film microstrips were fabricated and the normalized flicker noise intensity (Hooge parameter α) and the resistivity ρ at 300 K were measured at each characterized point. A theoretical model was developed that explains the observed first growth of α with 〈ε〉 and the well-known high level of the normal-phase flicker noise in various high temperature superconducting compounds. Comparison of the experimental and simulated dependence of α on 〈ε〉, frequency, and temperature permits one to determine numerically the theoretical parameters of the double-well potential with minima located at the chain (O1) and empty (O5) oxygen lattice positions of the CuO plane.
Superconducting transition edge bolometers on micromachined silicon membranes have been fabricated. The optical response is 580 V/W at a time constant of 0.4 ms. The detectivity D* is 3.8×109 (cm Hz1/2 W−1) at a temperature of 84.5 K and within the frequency regime 100<f<300 Hz. This is one of the fastest composite type bolometers ever reported. Upon thermal optimization, this type of detector should be competitive with state-of-the-art quantum detectors.
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.
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