The architectural alteration of proliferating cell and stem cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of oral epithelial dysplasias.

In our previous study, Dark-Agouti (DA) rats were found to be highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue carcinoma (TC), whereas Wistar/Furth (WF) rats were barely susceptible. Interval mapping analysis of reciprocal backcross rats showed two quantitative trait loci (QTL) on rat chromosomes (RNO) 1 and 19. In the present study, a composite interval mapping analysis was applied to 4NQO-induced TC in 130 (DA × × × ×WF) F2 rats, demonstrating five independent QTL, Tongue squamous cell carcinoma 1-5 (Tscc1-5), responsible for phenotypic differences in the size and number of TCs in the two strains. Two of these QTL were mapped on RNO1, and the others were mapped on RNO4, 14, and 19. The DA allele at these loci consistently yielded semidominant susceptibility to TC. Out of the five loci detected in this F2 generation, Tscc1 and 2 were identical to Stc1 and Rtc1 described in our previous study, but the other three were novel. We propose a new nomenclature consistent with their function. Genome-wide screening of the F2 progeny also suggested the presence of three additional QTL on RNO5, 6, and 10. The possible roles of these loci in tongue carcinogenesis are discussed. Key words: Genetic susceptibility -QTL -Tongue cancer -Rat -4-Nitroquinoline 1-oxideTongue carcinoma (TC) is one of the most frequent malignancies in the head and neck region. An increase in TC has been reported in the Western world over the past ten years. TC has a poor prognosis because therapeutic strategies provide limited effects.1-4) For effective prevention of TC, it would be necessary to identify the genetically predisposed risk group. However, virtually nothing is known about the genetic predisposition to TC.Recently, we found that the Dark-Agouti (DA) strain of rats had an extremely high susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced squamous cell carcinoma of the tongue. Virtually 100% of DA rats given drinking water containing 0.001% 4NQO developed one or more large TC within 180 days of administration, whereas the Wistar/Furth (WF) strain of rats was much less susceptible. [5][6][7][8] In the previous study with reciprocal backcrosses between DA and WF rats, 7,8) DA rats were shown to have a semidominant susceptibility locus, Stc1 (Susceptibility to TC-1) on rat chromosome (RNO) 19, and WF rats, another semidominant resistance gene Rtc1 (Resistance to TC-1) on RNO1.In this study, to scrutinize further the genetic predisposition to TC in the rat, we studied F2 progeny between DA and WF strains by means of a composite interval mapping analysis. After several statistical trials, we employed a quantitative parameter for tumor number, TC >3 mm in diameter, rather than TC >5 mm. In addition to two quantitative trait loci (QTL) described in the previous study, three novel QTL have been found to affect TC susceptibility. These five QTL explain almost all phenotypic variations between the two strains. MATERIALS AND METHODS Animals and phenotypeThe origin of DA rats is related to Copenhagen rats, although there is n...

Somatosensory signals play roles in the fine control of dexterous movements through a somatosensory–motor integration mechanism. While skilled individuals are typically characterized by fine-tuned somatosensory functions and dexterous motor skills, it remains unknown whether and in what manner their bridging mechanism, the tactile–motor and proprioceptive–motor integration functions, plastically changes through extensive sensorimotor experiences. Here, we addressed this issue by comparing physiological indices of these functions between pianists and nonmusicians. Both tactile and proprioceptive stimuli to the right index finger inhibited corticospinal excitability measured by a transcranial magnetic stimulation method. However, the tactile and proprioceptive stimuli exerted weaker and stronger inhibitory effects, respectively, on corticospinal excitability in pianists than in nonmusicians. The results of the electroencephalogram measurements revealed no significant group difference in the amplitude of cortical responses to the somatosensory stimuli around the motor and somatosensory cortices, suggesting that the group difference in the inhibitory effects reflects neuroplastic adaptation of the somatosensory–motor integration functions in pianists. Penalized regression analyses further revealed an association between these integration functions and motor performance in the pianists, suggesting that extensive piano practice reorganizes somatosensory–motor integration functions so as to enable fine control of dexterous finger movements during piano performances.

One of the most challenging issues among experts is how to improve motor skills that have already been highly trained. Recent studies have proposed importance of both genetic predisposition and accumulated amount of practice for standing at the top of fields of sports and performing arts. In contrast to the two factors, what is unexplored is how one practices impacts on experts’ expertise. Here, we show that training of active somatosensory function (active haptic training) enhances precise force control in the keystrokes and somatosensory functions specifically of expert pianists, but not of untrained individuals. By contrast, training that merely repeats the task with provision of error feedback, which is a typical training method, failed to improve the force control in the experts, but not in the untrained. These findings provide evidence that the limit of highly trained motor skills could be overcome by optimizing training methods.