Inverted Alu repeats unstable in yeast are excluded from the human genome

The nearly one million ALU: repeats in human chromosomes are a potential threat to genome integrity. ALU:s form dense clusters where they frequently appear as inverted repeats, a sequence motif known to cause DNA rearrangements in model organisms. Using a yeast recombination system, we found that inverted ALU: pairs can be strong initiators of genetic instability. The highly recombinagenic potential of inverted ALU: pairs was dependent on the distance between the repeats and the level of sequence divergence. Even inverted ALU:s that were 86% homologous could efficiently stimulate recombination when separated by <20 bp. This stimulation was independent of mismatch repair. Mutations in the DNA metabolic genes RAD27 (FEN1), POL3 (polymerase delta) and MMS19 destabilized widely separated and diverged inverted ALU:s. Having defined factors affecting inverted ALU: repeat stability in yeast, we analyzed the distribution of ALU: pairs in the human genome. Closely spaced, highly homologous inverted ALU:s are rare, suggesting that they are unstable in humans. ALU: pairs were identified that are potential sites of genetic change.     

Agonist of TRPM8 channel,menthol, facilitates the initiation of thermoregulatory responses to external cooling

The effects of activation of the cold and menthol sensitive TRPM8 ion channel on different thermoregulatory parameters (total oxygen consumption, carbon dioxide release, respiratory coefficient, vasoconstriction response of skin blood vessels and shivering) were studied in anaesthetized rats subjected to two types of external cooling—rapid and slow.     

The influence of TRPM8 ion channel activation on immune response at different temperature conditions

In experiments on rats it was shown that it is possible to modulate the immune response in a whole organism by activating cold-sensitive TRPM8 ion channel by its agonist menthol. The most pronounced changes in the conditions without external temperature stimulation were related to immune parameters for the spleen cells and immunoglobulin level in blood: the activation of TRPM8 ion channel by menthol enhances antigen binding and inhibits antibody formation in spleen, significantly reduces the level of IgG in blood. Activation of TRPM8 ion channel changes the effect of subsequent temperature exposure—cooling or heating. Preliminary application of menthol eliminates the inhibitory effect of deep cooling on immune response. Stimulation of the antigen binding in spleen at deep heating is inversed to suppression in case of heating on the background of TRPM8 activation by menthol. On the contrary, suppression of antibody formation caused by deep heating is eliminated if heating is carried out on the background of TRPM8 stimulation.     

Changes in Spirometric Parameters upon Local Heating of Forearm or Hand Skin

Local heating of the forearm or hand moderately decreases the respiratory volume parameters without changing bronchoconstriction. At the same time, a significant increase in the maximal expiratory flow (MEF₅₀ and MEF₇₅) indicates a limited enhancement of expiration upon local heating. In contrast, local cooling limits the maximum inspiration without affecting expiration.     

Temperature sensitivity and the indicators of respiration in humans in the normal state and during local cooling

The examination has shown that people who have many cold spots on the forearm possess high ventilation volume and breathing frequency and low value of oxygen utilization. These facts can evidence for the effect of cold skin receptors on the respiratory patterns. The skin temperature, at which the maximal cooling-induced changes of respiratory parameters are observed depends on the dynamic activity of cold skin thermoreceptors: the greater number of cold spots in the hand and forearm, the lesser cooling is necessary to cause the maximal increase of oxygen consumption and change of respiratory volume. The latter increased in the case of hand cooling and decreased in the case of the forearm cooling.