A de novo originated gene depresses budding yeast mating pathway and is repressed by the protein encoded by its antisense strand

Recent transcription profiling studies have revealed an unexpectedly large proportion of antisense transcripts in eukaryotic genomes. These antisense genes seem to regulate gene expression by interacting with sense genes. Previous studies have focused on the non-coding antisense genes, but the possible regulatory role of the antisense protein is poorly understood. In this study, we found that a protein encoded by the antisense gene ADF1 acts as a transcription suppressor, regulating the expression of sense gene MDF1 in Saccharomyces cerevisiae. Based on the evolutionary, genetic, cytological and biochemical evidence, we show that the protein-coding sense gene MDF1 most likely originated de novo from a previously non-coding sequence and can significantly suppress the mating efficiency of baker's yeast in rich medium by binding MAT alpha 2 and thus promote vegetative growth. These results shed new light on several important issues, including a new sense-antisense interaction mechanism, the de novo origination of a functional gene, and the regulation of yeast mating pathway.

RESERPINE IMPAIRS SPATIAL WORKING-MEMORY PERFORMANCE IN MONKEYS - REVERSAL BY THE ALPHA-2-ADRENERGIC AGONIST CLONIDINE

Repeated daily treatment with the catecholamine-depleting agent, reserpine, dramatically reduced performance on the delayed response task, a test of spatial working memory that depends upon the integrity of the prefrontal cortex. Delayed response performance fell from an average of 27.2/30 trials correct before reserpine treatment to an average of 20.4/30 trials correct after repeated reserpine administration. Injection of the alpha2-adrenergic agonist, clonidine (0.0001-0.05 mg/kg), to chronic reserpine-treated monkeys significantly restored performance on the delayed response task; performance after an optimal dose averaged 27.8/30 trials correct. Clonidine's beneficial effects on delayed response performance were longlasting; monkeys remained improved for more than 24 h after a single clonidine injection. The finding that clonidine is efficacious in reserpinized animals supports the hypothesis that alpha2-adrenergic agonists improve cognitive function through actions at postsynaptic, alpha2-adrenergic receptors on non-adrenergic cells. In contrast to the delayed response task, reserpine had little effect on performance of a visual discrimination task, a reference memory task which does not depend on the prefrontal cortex. These results emphasize the importance of postsynaptic alpha2-adrenergic mechanisms in the regulation of working memory,

Transcription rates of yeast genes are influenced by the distribution of introns

A comparative analysis on the intron sequence oligonucleotide usages in two sets of yeast genes with higher and lower transcription frequencies, respectively, has shown that the intron sequence structures of the two sets of genes are different. There are more potential binding sites for transcription factors in the introns of the genes with high transcription frequencies. So it is speculated that introns regulate the transcription of genes. But more evidences are needed to favor this speculation. The detailed comparative analyses on the distribution ( length and position) of introns and exons in the two sets of gene sequences also show that there is an obvious boundary between the lengths of the two sets of introns. There is no boundary between the lengths of the two sets of exons, although the means of their lengths are of discrepancy. The situation of the gene lengths ( length of intron and exon) is similar to exon lengths. As far as the relative position, the introns in two sets of genes all have a bias toward the 5' ends of genes. But as the actual position is considered, more introns in high transcription genes have a tendency to be located toward the 5' ends of genes, some even located at 5'-UTR. These results suggest that the gene transcription rates are related to the length of intron, but not to the lengths of exons and genes sequences. The positions of introns may also influence the transcription rates. The transcriptional regulation of introns may be correlative with the transcriptional regulation of the upstream of genes, or be its continuous action.

Sequential ultrastructural and biochemical changes induced in vivo by the hepatotoxic microcystins in liver of the phytoplanktivorous silver carp Hypophthalmichthys molitrix

Up to now, in vivo studies on the toxic effects of microcystins (MCs) on the ultrastructures of fish liver have been very limited. The phytoplanktivorous silver carp was injected i.p. with extracted hepatotoxic microcystins (mainly MC-RR and -LR) at a dose of 1000 mu g MC-LReq. kg(-1) body weight, showing a time-dependent ultrastructural change in liver as well as significant increases in enzyme activity of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). We observed for the first time the occurrence of a large amount of activated secondary lysosomes, which might be an adaptive mechanism to eliminate or lessen cell damage caused by MCs through lysosome activation. Quantitative and qualitative determinations of MCs in the liver were conducted by HPLC and LC-MS2, respectively. MCs concentration in the liver reached the maximum (114.20 mu g g(-1) dry weight) after 3 h post-injection, and then rapidly dropped to 7.57 mu g g(-1) dry weight at 48 h, indicating a deputation of 99% accumulated MC-LReq. On the other hand, a decrease trend in glutathione (GSH) concentration was observed in the liver of silver carp while the activity of glutathione S-transferase (GST) increased significantly after injection. The high tolerance of silver carp to MCs might be due to the high basic GSH level in their liver, and/or an increased GSH synthesis. (C) 2007 Elsevier Inc. All rights reserved.

Conservation strategies for endemic fish species threatened by the Three Gorges Dam

The largest damming project to date, the Three Gorges Dam has been built along the Yangtze River (China), the most species-rich river in the Palearctic region. Among 162 species of fish inhabiting the main channel of the upper Yangtze, 44 are endemic and are therefore under serious threat of global extinction from the dam. Accordingly, it is urgently necessary to develop strategies to minimize the impacts of the drastic environmental changes associated with the dam. We sought to identify potential reserves for the endemic species among the 17 tributaries in the upper Yangtze, based on presence/absence data for the 44 endemic species. Potential reserves for the endemic species were identified by characterizing the distribution patterns of endemic species with an adaptive learning algorithm called a "self-organizing map" (SOM). Using this method, we also predicted occurrence probabilities of species in potential reserves based on the distribution patterns of communities. Considering both SOM model results and actual knowledge of the biology of the considered species, our results suggested that 24 species may survive in the tributaries, 14 have an uncertain future, and 6 have a high probability of becoming extinct after dam filling.

Gene transfer into genomes of human cells by the sleeping beauty transposon system

The Sleeping Beauty (SB) transposon system, derived from teleost fish sequences, is extremely effective at delivering DNA to vertebrate genomes, including those of humans. We have examined several parameters of the SB system to improve it as a potential, nonviral vector for gene therapy. Our investigation centered on three features: the carrying capacity of the transposon for efficient integration into chromosomes of HeLa cells, the effects of overexpression of the SB transposase gene on transposition rates, and improvements in the activity of SB transposase to increase insertion rates of transgenes into cellular chromosomes. We found that SB transposons of about 6 kb retained 50% of the maximal efficiency of transposition, which is sufficient to deliver 70-80% of identified human cDNAs with appropriate transcriptional regulatory sequences. Overexpression inhibition studies revealed that there are optimal ratios of SB transposase to transposon for maximal rates of transposition, suggesting that conditions of delivery of the two-part transposon system are important for the best gene-transfer efficiencies. We further refined the SB transposase to incorporate several amino acid substitutions, the result of which led to an improved transposase called SB11. With SB11 we are able to achieve transposition rates that are about 100-fold above those achieved with plasmids that insert into chromosomes by random recombination. With the recently described improvements to the transposon itself, the SB system appears to be a potential gene-transfer tool for human gene therapy.

Enhancement of Moina micrura by the filter-feeding silver and bighead carps in a subtropical Chinese lake

The changes of cladoceran zooplankton from 1980 to 1996 were studied in a hypereutrophic subtropical Chinese lake, Lake Donghu, and an enclosure experiment was conducted to examine the possible role of the increased fish production in the enhancement of Moina micrura in the lake after mid-1980s. During the 1980s, the most striking event of the cladoceran community in the lake was that dominance of Daphnia was replaced by Moina following a steady increase in the production of planktivorous fish. This replacement was a direct result of increased fish predation, since our enclosure experiment indicates that Moina are less vulnerable to fish predation than Daphnia, and that increase in fish-stocking rate favors the development of M. micrura. The stronger resistance of M. micrura to fish predation may be attributed to its smaller body size and higher intrinsic growth rate than the daphnids. The present study has a strong parallel with the responses of zooplankton community to predators observed in many temperate lakes, and perhaps the only real difference is that in our lake the small rapidly growing cladoceran is Moina, rather than Bosmina or some other typical temperate take species. In the present study, the strong fish predation caused a shift from Daphnia to small zooplankton but not a corresponding increase in phytoplankton, which is in sharp contrast to what is expected with the classic "trophic cascade" process.