Experimental Charcot-Marie-Tooth type 1A: A cDNA microarrays analysis

summary:The paper presents a careful analysis of the Cantor-Zassenhaus polynomial factorization algorithm, thus obtaining tight bounds on the performances, and proposing useful improvements. In particular, a new simplified version of this algorithm is described, which entails a lower computational cost. The key point is to use linear test polynomials, which not only reduce the computational burden, but can also provide good estimates and deterministic bounds of the number of operations needed for factoring. Specifically, the number of attempts needed to factor a given polynomial, and the least degree of a polynomial such that a factor is found with at most a fixed number of attempts, are computed. Interestingly, the results obtained demonstrate the existence of some sort of duality relationship between these two problems

Early abnormalities in sciatic nerve function and structure in a rat model of Charcot-Marie-Tooth type 1A disease.

We investigated early peripheral nervous system impairment in PMP22-transgenic rats ("CMT rat"), an established animal model for Charcot-Marie-Tooth disease 1A, at postnatal day 30 (P30), when the clinical phenotype is not yet apparent. Hemizygous CMT1A rats and wildtype littermates were studied by means of behavioral examination, electrophysiology, molecular biology, and light microscopy analysis. Behavioral studies only showed, a mild, but significant, decrease in toe spread 1-5, suggesting a weakness of distal foot muscles in CMT1A rats compared with normal littermates. Nerve conduction studies disclosed a severe slowing in motor conduction velocity, a temporal dispersion and a dramatic decrease of amplitude of motor waves in P30 transgenic animals. Coherently with a demyelinating process, affected nerves showed a significant thinning of myelin. Interestingly, axonal diameter and area were unchanged, but expression of non-phosphorylated neurofilaments was increased in CMT1A rats compared with normal controls. Our results confirm the fidelity of this animal model to human disease. Similarly, in young CMT1A patients, the MCV is significantly reduced and the muscle weakness is confined to distal segments, whereas morphological and morphometrical signs of axonal atrophy are absent. However, the presence of a molecular and functional damage of the axons suggests that this may be the correct moment to start neuroprotective therapies

Electrophysiological comparison between males and females in HNPP

Some evidences highlighted a higher clinical expression of hereditary neuropathy with liability to pressure palsy (HNPP) in males, and a higher load of traumatic nerve injuries due to different occupational activity has been invoked to explain this observation. It is unknown whether this increased clinical impairment corresponds to a greater electrophysiological involvement. Thus, we compared clinical and electrophysiological features between men and women in a large cohort of HNPP patients. Nerve palsies and electrophysiological abnormalities were more frequent in men, and electrophysiological findings which differentiated males from females did not show any age-related worsening. In conclusion, our findings showed a higher clinical and electrophysiological involvement in males which does not seem related to different cumulative nerve damage over time. We believe that the higher disease expression may increase the chance to detect the disease in males and, thereby, to underestimate the HNPP diagnosis in female