Cellular and molecular mechanisms that regulate mammalian digit tip regeneration

Digit tip regeneration is one of the few examples of true multi-tissue regeneration in an adult mammal. The key step in this process is the formation of the blastema, a transient proliferating cell mass that generates the different cell types of the digit to replicate the original structure. Failure to form the blastema results in a lack of regeneration and has been postulated to be the reason why mammalian limbs cannot regrow following amputation. Understanding how the blastema forms and functions will help us to determine what is required for mammalian regeneration to occur and will provide insights into potential therapies for mammalian tissue regeneration and repair. This review summarizes the cellular and molecular mechanisms that influence murine blastema formation and govern digit tip regeneration.

Modification of conditioned apneas in rats: evidence for cortical involvement

Apneic patterns in breathing can be classically conditioned in rats by brief neonatal exposures to hypoxia, noise, and petting during sleep (A. J. Thomas, W. Austin, L. Friedman, and K. P. Strohl, J. Appl. Physiol. 73: 1530–1536, 1992); thus animals may acquire apneic patterns by exposure to not only respiratory but also nonrespiratory stimuli. We hypothesized that conditioned apneas in these animals can be reduced or abolished by presentation of counterconditioning stimuli, which would prevent the respiratory controller from being influenced by nonrespiratory stimuli and affecting breathing rhythmicity. In five female rats conditioned during neonatal life to exhibit apneic breathing during adulthood and in five female unconditioned control rats, the effect of a brief quiet repetitive auditory stimulus (white noise, 50 Hz, 30 dB) presented for periods of 20 min on and 20 min off was assessed. In conditioned apneic rats, white noise reduced the frequencies of apneas by approximately 79% (P < 0.01) but did not alter the number of apneas in unconditioned control rats. In either group, white noise had no effect on the number of apneas preceded by a sigh. In a second experiment, the effect of Equithesin anesthetic was examined in five female conditioned apneic rats. In contrast to the white noise effect, not only apneic breathing but also apneas preceded by a sign were completely abolished by anesthesia (P < 0.0001). These findings suggest a role for counterconditioning and cortical influences on respiratory rhythm in the adult mammal.