A note on fitting one-compartment models: non-linear least squares versus linear least squares using transformed data

Drug concentrations in one-compartment systems are frequently modeled using a single exponential function. Two methods of estimation are commonly used for determining the parameters of such a model. In the first method, non-linear least-squares regression is used to calculate the parameters. In the second method, the data are first transformed by a logarithmic function, and then the log-concentration data are fit using linear least-squares regression. The assumptions for fitting these models are discussed with special emphasis on which data points are most influential in determining parameter values. The similarities between fitting a linear regression model to the log-concentration data and fitting a weighted regression model to the original data are noted. An example is presented that illustrates the differences in fitting a model to the log-transformed data versus fitting unweighted and weighted models to the original-scale data.     

Neuronal cytoskeleton: structural, functional and dynamic aspects]

The cytoskeleton of practically every type of cell is constituted by 3 types of filaments: microfilaments, microtubules and intermediate filaments. The latter are cell-type specific and are represented in neurons by neurofilaments accompanied by other intermediate filaments, which have recently been described and whose nature depends on the period of development and on the neuronal type. Numerous studies demonstrate that many proteins are associated with microfilaments and microtubules and that they are responsible not only for the structure of the lattices but also for their function and dynamics. Moreover, these proteins can link one type of filament to another, and the network thus constituted, to the plasmic membrane and probably also to the nuclear membrane. The neuronal cytoskeleton is not static; it has, of course, a very important role in the maintenance of the structural integrity of the neuron, but it is also the promoter of axonal growth, the substratum against which many organelles move and thus has an essential role in axonal transport. In a few neuropathies chosen as examples for a disturbed axonal transport, abnormal bundles of filaments are observed; they are probably the end product of a primary disorder which has still to be analyzed.     

Two large French pedigrees with non syndromic sensorineural deafness and the mitochondrial DNA T7511C mutation: evidence for a modulatory factor

Hearing impairment is the most frequent sensory defect in children, with a genetic basis in about 50% of cases. Several point mutations and deletions in mitochondrial DNA (mtDNA) have been identified in non-syndromic sensorineural hearing loss (NSSNHL). Beside the frequent A1555G mutation, a number of mutations in tRNAs have been reported recently, but their incidence remains unknown. We identified the T7511C mutation in the tRNASer(UCN) gene in two French families with isolated deafness. Maternal transmission was obvious in both. The 15 patients with hearing impairment exhibited a variable disease phenotype in terms of onset, severity, and progression. T7511C was present in all the patients screened. Homoplasmic and heteroplasmic levels were observed and did not correlate with the severity of the disease. T7511C was also present in 12 hearing offspring of the oldest deaf mothers, confirming the existence of modulatory factors. Our data suggest that this mtDNA mutation should be screened for in all cases of familial NSSNHL compatible with maternal transmission.