Selected from the same population in which the cases were identified effectively prevents population stratification

It has been shown that female mice run better than male mice. The mechanisms used by Leu3p as a transcriptional regulator are conserved throughout plants and mammals and could involve TBP. Leu3p is able to transcribe genes solely and specifically in the presence of its effector molecule a-IRM in yeast, in transiently transfected mouse pre-adipocytes and fibroblasts as well as in vitro. Here, we demonstrate that a chromosomally integrated ”Leu3p-a-IRM” can be used as a highly specific inducible gene expression system. Taking advantage of the fact that the leucine biosynthetic pathway exists only in prokaryotes, fungi and superior plants, but not in animals, we EX 527 generated transgenic mice and found that the ”Leu3p-a-IPM” system is a safe and efficient ”OFF-ON” gene switch in double transgenic primary mouse embryo fibroblasts, thus paving the way for a number of applications in gene regulation studies and biomedicine. In our uninfected control mice, we also noticed that the normalized running distance was significantly higher in female mice. Interestingly, female mice also appeared to respond better to AV.RSV.MCAT treatment. Compared with male mice, AV.RSV.MCAT administration resulted in significantly better improvement in both absolute and normalized running distance in female mice. Taken together, our results suggest that the mitochondria may still represent a critical site of free radical production during exhaustive exercise. Further, targeted expression of catalase to the mitochondria may counteract oxidative muscle damage and enhance performance. Normal muscle contraction requires low levels of reactive oxygen species. A complete or near-complete elimination of cellular free radicals may affect force production. To determine whether MCAT overexpression compromises basal muscle contraction, we examined the contract profile of the isolated EDL muscle. Previous studies on the effects of globin reduction from whole blood suggested that globin depletion can introduce transformations to original gene expression profile. On the contrary, our comparative analysis on the different sample types as shown by the Venn diagram clearly demonstrated high fidelity in gene expression with a high degree of overlap between the PAX and PAX-GR samples. The globin depletion process appears to be advantageous as it reduces the variability of data between samples as shown by the scatter plot and the error analyses. More importantly, depletion of globins led to unmasking of more than 3000 transcripts in the whole blood samples which GO analysis indicates have biological process functions such as transcription, intracellular transport and biochemical signaling. This eventually led to an improvement in the degree of overlap between PAX-GR and PBMCs at 73-80%. No difference was observed between AV.RSV.MCAT infected and uninfected controls in terms of twitch force.

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