Correlations Between Gene Expression and Mercury Levels in Blood of Boys With and Without Autism

Gene expression in blood was correlated with mercury levels in blood of 2- to 5-year-old boys with autism (AU) compared to age-matched typically developing (TD) control boys. This was done to address the possibility that the two groups might metabolize toxicants, such as mercury, differently. RNA was isolated from blood and gene expression assessed on whole genome Affymetrix Human U133 expression microarrays. Mercury levels were measured using an inductively coupled plasma mass spectrometer. Analysis of covariance (ANCOVA) was performed and partial correlations between gene expression and mercury levels were calculated, after correcting for age and batch effects. To reduce false positives, only genes shared by the ANCOVA models were analyzed. Of the 26 genes that correlated with mercury levels in both AU and TD boys, 11 were significantly different between the groups (P(Diagnosis*Mercury) ≤ 0.05). The expression of a large number of genes (n = 316) correlated with mercury levels in TD but not in AU boys (P ≤ 0.05), the most represented biological functions being cell death and cell morphology. Expression of 189 genes correlated with mercury levels in AU but not in TD boys (P ≤ 0.05), the most represented biological functions being cell morphology, amino acid metabolism, and antigen presentation. These data and those in our companion study on correlation of gene expression and lead levels show that AU and TD children display different correlations between transcript levels and low levels of mercury and lead. These findings might suggest different genetic transcriptional programs associated with mercury in AU compared to TD children

A comparison of models of the isometric force of locust skeletal muscle in response to pulse train inputs

Muscle models are an important tool in thedevelopment of newrehabilitation and diagnostic techniques.Many models have been proposed in the past, but little workhas been done on comparing the performance of models. Inthis paper, seven models that describe the isometric forceresponse to pulse train inputs are investigated. Five of themodels are from the literature while two new models are alsopresented. Models are compared in terms of their ability to fitto isometric force data, using Akaike’s and Bayesian informationcriteria and by examining the ability of each model todescribe the underlying behaviour in response to individualpulses. Experimental data were collected by stimulating thelocust extensor tibia muscle and measuring the force generatedat the tibia. Parameters in each model were estimated byminimising the error between the modelled and actual forceresponse for a set of training data. A separate set of test data, which included physiological kick-type data, was used to assess the models. It was found that a linear model performed the worst whereas a new model was found to perform the best. The parameter sensitivity of this new model was investigated using a one-at-a-time approach, and it found that the force response is not particularly sensitive to changes in anyparameter