Comparison of statistical methods for the analysis of limiting dilution assays

Summary This study reports the results of a critical comparison of five statistical methods for estimating the density of viable cells in a limiting dilution assay (LDA). Artificial data were generated using Monte Carlo simulation. The performance of each statistical method was examined with respect to the accuracy of its estimator and, most importantly, the accuracy of its associated estimated standard error (SE). The regression method was found to perform at a level that is unacceptable for scientific research, due primarily to gross underestimation of the SE. The maximum likelihood method exhibited the best overall performance. A corrected version of Taswell's weighted-mean method, which provides the best performance among all noniterative methods examined, is also presented.     

Patterns of selection against centrosome amplification in human cell lines

The presence of extra centrioles, termed centrosome amplification, is a hallmark of cancer. The distribution of centriole numbers within a cancer cell population appears to be at an equilibrium maintained by centriole overproduction and selection, reminiscent of mutation-selection balance. It is unknown to date if the interaction between centriole overproduction and selection can quantitatively explain the intra- and inter-population heterogeneity in centriole numbers. Here, we define mutation-selection-like models and employ a model selection approach to infer patterns of centriole overproduction and selection in a diverse panel of human cell lines. Surprisingly, we infer strong and uniform selection against any number of extra centrioles in most cell lines. Finally we assess the accuracy and precision of our inference method and find that it increases non-linearly as a function of the number of sampled cells. We discuss the biological implications of our results and how our methodology can inform future experiments.     

Effect of mitochondrial toxins on evoked somatosensory activity in rats

Mitochondrial toxins represent an interesting group of neurotoxicants related both to causation and modelling of central nervous damage. 3-nitropropionic acid (3NP), a neurotoxin of herbal and microfungal origin, inhibits succinate dehydrogenase leading thereby to various biochemical and morphological alterations in the brain. Experimental animals treated by 3NP are used to model Huntington’s disease. Manganese, often present in occupational settings and as environmental pollutant, inhibits complex II and III of the mitochondria and is known to cause Parkinson-like CNS damage. In this work, rats were administered a single acute dose of Mn (50 mg Mn²⁺/kg body weight) or 3-NP (20 mg/kg b.w.) and the alterations of the somatosensory cortical evoked potential elicited by stimulation of the whisker pad and the tail base were observed, together with the changes of the action potential in the tail nerve. Latency and amplitude of the two cortical responses changed in parallel, while those of the tail nerve response remained more or less unaltered. The two mitochondrial toxins studied seem to exert their action centrally, primarily on synaptic transmission, rather than peripherally. Recording of evoked activity could be used to follow-up the nervous system effects of mitochondrial toxins, but it requires further investigation.     

Zur Analyse des Verhältnisses Gewicht/Länge bei Fischen

Ohne Zusammenfassung     

Enzyme polymorphism in the freshwater mussel species, Aspatharia pfeifferiana (Mollusca, Lamellibranchiata) from southern Africa

Gene products of 31 protein coding loci in Aspatharia pfeifferiana examined by horizontal starch gel electrophoresis revealed genetic variation at 10 (32.26%) of the loci studied. The mean number of alleles per locus was 1±39 (±0±11), and the average heterozygosity value was 0±074 (±0±026). Not only is this the first account of electrophoretic variants of this species, but also the results show that the species has less genetic variation than most other molluscs. Genetic variation compares favourably with values obtained for other invertebrate species and for fish from the same geographical region. A. pfeifferiana has sufficient variation to adapt to environmental changes or to be used in selection programmes. The results are useful for conservation stocking and it will undoubtedly aid in improving the systematics and phylogeny of freshwater clams in general.