As always on Fridays, there are new papers published in PLoS Genetics, PLoS Pathogens and PLoS Computational Biology. I like to take my own picks, and today I pick this pre-publication (there is a provisional PDF online) in my own field:
Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the data sets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA based statistical pre-screening, and three separate classes of post-hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described Fast Fourier Transform (FFT) based technique [1-3]. Permutation based statistical tests were used to derive significance measures for all post-hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, to significantly reduce the false discovery rate (FDR) relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. We identify a set of previously found cycling transcripts as well as a set of novel ones. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR), we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.
The other one I chose is this one, as it is related to some stuff I published way back when I was still in the lab:
Food Deprivation Attenuates Seizures through CaMKII and EAG K+ Channels:
Accumulated research has demonstrated the beneficial effects of dietary restriction on extending lifespan and increasing cellular stress resistance. However, reducing nutrient intake has also been shown to direct animal behaviors toward food acquisition. Under food-limiting conditions, behavioral changes suggest that neuronal and muscle activities in circuits that are not involved in nutrient acquisition are down-regulated. These dietary-regulated mechanisms, if understood better, might provide an approach to compensate for defects in molecules that regulate cell excitability. We previously reported that a neuromuscular circuit used in Caenorhabditis elegans male mating behavior is attenuated under food-limiting conditions. During periods between matings, sex-specific muscles that control movements of the male's copulatory spicules are kept inactive by UNC-103 ether-a-go-go-related gene (ERG)-like K+ channels. Deletion of unc-103 causes â¼30%-40% of virgin males to display sex-muscle seizures; however, when food is deprived from males, the incidence of spontaneous muscle contractions drops to 9%-11%. In this work, we used genetics and pharmacology to address the mechanisms that act parallel with UNC-103 to suppress muscle seizures in males that lack ERG-like K+ channel function. We identify calcium/calmodulin-dependent protein kinase II as a regulator that uses different mechanisms in food and nonfood conditions to compensate for reduced ERG-like K+ channel activity. We found that in food-deprived conditions, calcium/calmodulin-dependent protein kinase II acts cell-autonomously with ether-a-go-go K+ channels to inhibit spontaneous muscle contractions. Our work suggests that upregulating mechanisms used by food deprivation can suppress muscle seizures.
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