Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy

The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids

Planar Dominance in Non-commutative Field Theories at Infinite External Momentum

In perturbative expansion of field theories on a non-commutative geometry, it is known that planar diagrams dominate when the non-commutativity parameter $\theta$ goes to infinity. We discuss whether the ``planar dominance'' occurs also in the case where $\theta$ is finite, but the external momentum goes to infinity instead. While this holds trivially at the one-loop level, it is not obvious at the two-loop level in particular in the presence of UV divergences. We perform explicit two-loop calculations in the six-dimensional $\phi^3$ theory, and confirm that nonplanar diagrams after renormalization do vanish in the above limit.Comment: 14 pages, 7 Figure

A possible role for endogenous glucocorticoids in orchiectomy-induced atrophy of the rat levator ani muscle: Studies with RU38486, a potent and selective antiglucocorticoid

RU38486, a potent and selective antiglucocorticoid, was employed to study a possible role for endogenous glucocorticoids in atrophy of the levator ani muscle secondary to castration of male rats. RU38486 was shown to block (3H) triamcinolone acetonide binding to cytosol from levator ani muscle. Daily oral administration of RU38486 to castrated rats partially prevented atrophy of the levator ani muscle, as well as a decrease in RNA concentration. In a control group receiving RU38486 alone, the levator ani underwent significant (20%) hypertrophy. Administration of exogenous dexamethasone also caused pronounced atrophy of the levator ani muscle. This atrophy was prevented, to a significant degree, by simultaneous oral administration of RU38486. It is concluded that endogenous glucocorticoids, the actions of which are blocked by RU38486, may be involved in regulation of the mass of the levator ani muscle in intact rats

Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy

Selecting effective siRNA sequences by using radial basis function network and decision tree learning

BACKGROUND: Although short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells, its gene silencing efficacy varies markedly and there are only a few consistencies among the recently reported design rules/guidelines for selecting siRNA sequences effective for mammalian genes. Another shortcoming of the previously reported methods is that they cannot estimate the probability that a candidate sequence will silence the target gene. RESULTS: We propose two prediction methods for selecting effective siRNA target sequences from many possible candidate sequences, one based on the supervised learning of a radial basis function (RBF) network and other based on decision tree learning. They are quite different from the previous score-based siRNA design techniques and can predict the probability that a candidate siRNA sequence will be effective. The proposed methods were evaluated by applying them to recently reported effective and ineffective siRNA sequences for various genes (15 genes, 196 siRNA sequences). We also propose the combined prediction method of the RBF network and decision tree learning. As the average prediction probabilities of gene silencing for the effective and ineffective siRNA sequences of the reported genes by the proposed three methods were respectively 65% and 32%, 56.6% and 38.1%, and 68.5% and 28.1%, the methods imply high estimation accuracy for selecting candidate siRNA sequences. CONCLUSION: New prediction methods were presented for selecting effective siRNA sequences. As the proposed methods indicated high estimation accuracy for selecting candidate siRNA sequences, they would be useful for many other genes