The clinical features in Chinese patients with PRNP D178N mutation.

BACKGROUND AND PURPOSE: Fatal familial insomnia (FFI) is an autosomal dominant disease due to the D178N mutation of PRNP gene coupling with homozygous methionine (Met) at codon 129. It is generally considered that D178N mutation cases with 129 M/M homozygotes present as FFI, and 129 V/V as genetic CJD. However, the frequency of 129 Met alleles in Chinese population is much higher than that in Caucasians. This study aims to investigate the clinical features and genetic characteristics of Chinese D178N mutants in this genetic context. METHODS: We reviewed the clinical and genetic features of seven D178N patients. The clinical data, genetic data, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), polysomnography (PSG), CSF 14-3-3 protein examinations of the seven patients were analyzed. RESULTS: The genotypes at codon 129 were all M/M. Four of the seven cases reported positive family history. Four patients were more likely the CJD phenotype and three were FFI phenotype according to the core clinical features. No major differences were found on the EEG, CSF 14-3-3 protein, and PSG presentations between this study and western studies. Novel neuroimaging findings were two patients had typical neuroimaging abnormalities of CJD and frontotemporal dementia, respectively. CONCLUSIONS: Unlike the western populations, the diverse phenotypical presentations of D178N mutants were not simply determined by the 129 genotypes in Chinese. The underlying modifying factors for phenotypical variations warrant further investigations. For those with atypical clinical and imaging features, genetic testing was important for final diagnosis.

Conventional and generalized efficiencies of flashing and rocking ratchets: analytical comparison of high-efficiency limits.

We consider two basic types of Brownian motors which generate directed motion in a periodic asymmetric piecewise-linear potential as a result of random half-period shifts of the potential relief (flashing ratchets) or due to a temporally asymmetric unbiased force applied to the system (rocking ratchets). Analytical relationships have been derived which enable the comparison of the upper limits for the conventional and generalized energy conversion efficiencies in these motors. As found, the increasing amplitude of a sawtooth potential (or the decreasing temperature) makes the conventional efficiency tend to the unity limit faster for a rocking ratchet (in the absence of temporal asymmetry) than for a flashing ratchet. The inverse is true for the generalized efficiency. The potential amplitude being the same, the generalized efficiency is always less than the conventional efficiency. A decreased asymmetry of the potential always results in the reduction of both efficiencies. The temporal asymmetry of an unbiased force has an opposite effect on the conventional and generalized efficiencies: the former rises and the latter drops as the positive signal component becomes shorter in time and larger in amplitude.