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Register a new userInternal friction as possible key factor governing the thermosensitivity of TRP channels
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Six thermo-activated transient receptor potential (TRP) channels are the molecular basis of the thermosensation for mammals. But the molecular source of their gating remains unknown. In the Letter, we suggest a physically based model for the TRP channels and show that the temperature dependence of the internal friction can be a key factor governing the ion channels gating. Results of the computer modeling allowed us to successfully reproduce the experimental data for the open probability Popen of the TRPV1 and TRPM8 channels at different temperatures and voltages.
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Genetic and environmental factors are traditionally seen as the sole causes of congenital anomalies. In this paper we introduce a third possible cause, namely random manufacturing discrepancies with respect to ``design values. A clear way to demonstrate the existence of this component is to ``shut the two others and to see whether or not there is remaining variability. Perfect clones raised under well controlled laboratory conditions fulfill the conditions for such a test. Carried out for four different species, the test reveals a variability remainder of the order of 10%-20% in terms of coefficient of variation. As an example, the CV of the volume of E.coli bacteria immediately after binary fission is of the order of 10%. In short, ``manufacturing discrepancies occur randomly, even when no harmful mutation or environmental factors are involved. Not surprisingly, there is a strong connection between congenital defects and infant mortality. In the wake of birth there is a gradual elimination of defective units and this screening accounts for the post-natal fall of infant mortality. Apart from this trend, post-natal death rates also have humps and peaks associated with various inabilities and defects.qL In short, infant mortality rates convert the case-by-case and mostly qualitative problem of congenital malformations into a global quantitative effect which, so to say, summarizes and registers what goes wrong in the embryonic phase. Based on the natural assumption that for simple organisms (e.g. rotifers) the manufacturing processes are shorter than for more complex organisms (e.g. mammals), fewer congenital anomalies are expected. Somehow, this feature should be visible on the infant mortality rate. How this conjecture can be tested is outlined in our conclusion.
The term In Silico Trial indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process. As In Silico Trials are a disruptively innovative class of new methodologies, it is important to have a list of possible CoUs highlighting potential applications for the development of the relative regulatory science. This review paper presents the result of a consensus process that took place in the InSilicoWorld Community of Practice, an online forum for experts in in silico medicine. The experts involved identified 46 descriptions of possible CoUs which were organised into a candidate taxonomy of nine CoU categories. Examples of 31 CoUs were identified in the available literature; the remaining 15 should, for now, be considered speculative.
The delayed luminescence of biological tissues is an ultraweak reemission of absorbed photons after exposure to external monochromatic or white light illumination. Recently, Wang, Bokkon, Dai and Antal (Brain Res. 2011) presented the first experimental proof of the existence of spontaneous ultraweak biophoton emission and visible light induced delayed ultraweak photon emission from in vitro freshly isolated rats whole eye, lens, vitreous humor and retina. Here, we suggest that the photobiophysical source of negative afterimage can also occur within the eye by delayed bioluminescent photons. In other words, when we stare at a colored (or white) image for few seconds, external photons can induce excited electronic states within different parts of the eye that is followed by a delayed reemission of absorbed photons for several seconds. Finally, these reemitted photons can be absorbed by nonbleached photoreceptors that produce a negative afterimage. Although this suggests the photobiophysical source of negative afterimages is related retinal mechanisms, cortical neurons have also essential contribution in the interpretation and modulation of negative afterimages.
Electrostatic interaction between ions in an ionic channel and the charge fluctuations in the channel mouth are considered. It is shown that the charge fluctuations can be enhanced in the channels with low dielectric constant and result in strong modulation of the potential barrier at the selectivity site. The effect of charge fluctuational on transition probabilities in other molecular dynamical systems is briefly discussed.
We investigate the role of the noise in the mating behavior between individuals of Nezara viridula (L.), by analyzing the temporal and spectral features of the non-pulsed type female calling song emitted by single individuals. We have measured the threshold level for the signal detection, by performing experiments with the calling signal at different intensities and analyzing the insect response by directionality tests performed on a group of male individuals. By using a sub-threshold signal and an acoustic Gaussian noise source, we have investigated the insect response for different levels of noise, finding behavioral activation for suitable noise intensities. In particular, the percentage of insects which react to the sub-threshold signal, shows a non-monotonic behavior, characterized by the presence of a maximum, for increasing levels of the noise intensity. This constructive interplay between external noise and calling signal is the signature of the non-dynamical stochastic resonance phenomenon. Finally, we describe the behavioral activation statistics by a soft threshold model which shows stochastic resonance. We find that the maximum of the ensemble average of the input-output cross-correlation occurs at a value of the noise intensity very close to that for which the behavioral response has a maximum.
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