Effect of magnetic stimulation on the gene expression profile of in vitro cultured neural cells.

Transcranial magnetic stimulation is a non-invasive tool in clinical diagnostics and therapy for physiological and psychological diseases and has an increased application in experimental neurophysiology. Despite this, the mechanisms of magnetic stimulation of the central nervous system remain still unclear. We applied sinus-shaped high frequency magnetic fields in different stimulation patterns and repeated treatments to cell cultures derived from frontal cortex of murine embryos (BALB/cOlaHsd mice) to elucidate the effects of repetitive magnetic stimulation on the gene expression of in vitro cultured neural cells. Gene expression profiling was performed by using qRT-PCR array and single qRT-PCR analyses. Our methodological approach using microelectrode arrays data recording and analysis minimizes variations in transcriptome analysis arising from cell differentiation status and tissue complexity. With 10 significant changes in gene expression out of 171 genes using Alzheimer disease and neurodegeneration related qRT-PCR arrays we demonstrate significant impact of repetitive magnetic stimulation on the mRNA transcript of neural cell cultures. Sixteen candidate genes were analyzed using single qRT-PCR in a replicated statistical design, which provided more precise estimates of differences in expression profiles. We discussed the utility of the experimental methods used for cell culture selection and the changes in gene expression considering physiological aspects.

Altering developmental trajectories in mice by restricted index selection.

A restricted index selection experiment on mice was carried out for 1-4 generations on rate of early postnatal development (growth rate from birth to 10 days of age) vs. rate of development much later in ontogeny (growth rate from 28 to 56 days of age). Early rate of development (E) approximates hyperplasia (changes in cell number) and later rate (L) reflects hypertropy (changes in cell size). The selection criteria were as follows; E+LO was selected to increase early body weight gain while holding late body weight gain constant; E-LO was selected to decrease early body gain while holding late gain constant; EOL+ was selected to increase late gain holding early gain constant; and EOL- was selected to decrease late gain holding early gain constant. After 14 generations of selection, significant divergence among lines has occurred and the changes in the growth trajectories are very close to expectation. The genetic and developmental bases of complex traits are discussed as well as the concept of developmental homoplasy.

Prostheses for primary total hip replacement. A critical appraisal of the literature.

Eighty-one published papers on the performance of prostheses in total hip replacement were appraised. Sound methodology was demonstrated in 1 of 8 randomized controlled trials and 4 of 17 nonrandomized comparative studies. Of 56 case series without controls, 32 met the appraisal criteria, but these are intrinsically less useful. The published literature does not provide solid evidence for the superiority of cement-free or hybrid prostheses over modern cemented types.

The epigenetic influence of growth hormone on skeletal development.

We studied the epigenetic effect of growth hormone using mice that were transgenic for a sheep metallothionein 1a-sheep growth hormone, which was expressed beginning at 21 days postnatal age. The impact of exogenous growth hormone (GH) on various skeletal traits with special emphasis on the mandible was examined by conventional statistical analysis and finite element scaling analysis. In long bones, growth hormone enhances the proliferation rate of cartilage cells in the growth plate and should thus lead to increased lengths. Further, growth hormone is known to increase muscle mass. Our results are consistent with these developmental considerations. We found that the lengths of long bones increased in the transgenic mice compared to the control mice, while the differences in long bone width were less pronounced. In the mandible and skull, the impact of GH is most pronounced in areas of major muscle attachment, i.e., the proximal part of the mandible and the occipital and malar bones in the skull.

Donor and recipient genotype and heterosis effects on survival and prenatal growth of transferred mouse embryos.

Reciprocal embryo transfers amongst two inbred strains (C3HeB/FeJ and SWR/J) and their F1 cross (C3SWF1) were used to examine donor and recipient genotype and heterosis effects on survival and prenatal growth of mouse embryos. Among inbred strains, significant recipient genotype effects were detected for both embryo survival (P less than 0.01) and prenatal growth (P less than 0.05), while no donor genotype effects were observed. The recipient effect on overall embryo survival was due to a higher proportion of C3H recipients maintaining pregnancy to term than SWR recipients (P less than 0.01), rather than survival within litters. Irrespective of their own genotype, embryos developing in C3H uteri achieved larger body weights (P less than 0.01) and longer tail lengths (P less than 0.05) at birth than did embryos developing in SWR uteri. Recipient heterosis was not significant, while donor heterosis was significant for prenatal growth traits (P less than 0.001).

The impact of maternal uterine genotype on postnatal growth and adult body size in mice.

Embryo transfers were used to demonstrate that the genotype of the mother providing the uterine developmental environment significantly influences postnatal growth and adult body size of her progeny. Irrespective of their own genotype, mouse embryos transferred into the uterus of an inbred strain with large body size (C3H) had greater body weights, longer tails and higher growth rates than those transferred into the uterus of a strain with small body size (SWR). Uterine heterosis on body size was smaller than progeny heterosis, and both progeny and uterine heterosis persisted in adult mice. Uterine litter size was significantly negatively associated with body weight, tail length, growth rate and the timing of developmental events. The inbred SWR strain was more sensitive to the embryo transfer procedure than the C3H strain, but effects due to embryo transfer were moderate. Prenatal uterine effects have ramifications for biotechnologies utilizing embryo transfer as well as predictions about evolutionary change by selection.

Genetic divergence in mandible form in relation to molecular divergence in inbred mouse strains.

Genetic divergence in the form of the mandible is examined in ten inbred strains of mice. Several univariate and multivariate genetic distance estimates are given for the morphological data and these estimates are compared to measures of genealogical and molecular divergence. Highly significant divergence occurs among the ten strains in all 11 mandible traits considered individually and simultaneously. Genealogical relationship among strains is highly correlated with genetic divergence in single locus molecular traits. However, the concordance between genealogical relationship and multivariate genetic divergence in morphology is much more complex. Whether there is a significant correlation between morphological divergence and genealogy depends upon the method of analysis and the particular genetic distance statistic being employed.

Quantitative Genetics of Drosophila Melanogaster. II. Heritabilities and Genetic Correlations between Sexes for Head and Thorax Traits.

A quantitative genetic analysis is reported for traits on the head and thorax of adult fruit flies, Drosophila melanogaster. Females are larger than males, and the magnitude of sexual dimorphism is similar for traits derived from the same imaginal disc, but the level of sexual dimorphism varies widely across discs. The greatest difference between males and females occurs for the dimensions of the sclerotized mouthparts of the proboscis. Most of the traits studied are highly heritable with heritabilities ranging from 0.26 to 0.84 for males and 0.27 to 0.81 for females. In general, heritabilities are slightly higher for males, possibly reflecting the effect of dosage compensation on X-linked variance. The X chromosome contributes substantially to variance for many of these traits, and including results reported elsewhere, the variance for over two-thirds of the traits studied includes X-linked variance. The genetic correlations between sexes for the same trait are generally high and close to unity. Coupled with the small differences in the traits between sexes for heritabilities and phenotypic variances, these results suggest that selection would be very slow to change the level of sexual dimorphism in size of various body parts.

Quantitative Genetics of DROSOPHILA MELANOGASTER. I. Sexual Dimorphism in Genetic Parameters for Wing Traits.

Sexual dimorphism in genetic parameters is examined for wing dimensions of Drosophila melanogaster. Data are fit to a quantitative genetic model where phenotypic variance is a linear function of additive genetic autosomal variance (common to both sexes), additive genetic X-linked variances distinct for each sex, variance due to common rearing environment of families, residual environmental variance, random error variance due to replication, and variance due to measurement error and developmental asymmetry (left vs. right sides). Polygenic dosage compensation and its effect on genetic variances and covariances between sexes is discussed. Variance estimates for wing length and other wing dimensions highly correlated with length support the hypothesis that the Drosophila system of dosage compensation will cause male X-linked genetic variance to be substantially larger than female X-linked variance. Results for various wing dimensions differ, suggesting that the level of dosage compensation may differ for different traits. Genetic correlations between sexes for the same trait are presented. Total additive genetic correlations are near unity for most wing traits; this indicates that selection in the same direction in both sexes would have a minor effect on changing the magnitude of difference between sexes. Additive X-linked correlations suggest some genotype x sex interactions for X-linked effects.