67 research outputs found
Functional Characterization of Transcription Factor Motifs Using Cross-species Comparison across Large Evolutionary Distances
We address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription factors. We develop a computational framework for this task, whose features include a new statistical score for motif scanning, the use of different scores for predicting targets of different motifs, and new ways to deal with redundancies among significant motifβfunction associations. This framework is applied to the recently sequenced genome of the jewel wasp, Nasonia vitripennis, making use of the existing knowledge of motifs and gene annotations in another insect genome, that of the fruitfly. The framework uses cross-species comparison to improve the specificity of its predictions, and does so without relying upon non-coding sequence alignment. It is therefore well suited for comparative genomics across large evolutionary divergences, where existing alignment-based methods are not applicable. We also apply the framework to find motifs associated with socially regulated gene sets in the honeybee, Apis mellifera, using comparisons with Nasonia, a solitary species, to identify honeybee-specific associations
Selective phosphodiesterase inhibitors: a promising target for cognition enhancement
# The Author(s) 2008. This article is published with open access at Springerlink.com Rationale One of the major complaints most people face during aging is an impairment in cognitive functioning. This has a negative impact on the quality of daily life and is even more prominent in patients suffering from neurodegenerative and psychiatric disorders including Alzheimerβs disease, schizophrenia, and depression. So far, the majority of cognition enhancers are generally targeting one particular neurotransmitter system. However, recently phosphodiesterases (PDEs) have gained increased attention as a potential new target for cognition enhancement. Inhibition of PDEs increases the intracellular availability of the second messengers cGMP and/or cAMP. Objective The aim of this review was to provide an overvie
Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption
Dissection of memory formation: from behavioral pharmacology to molecular genetics
Behavioral pharmacology has suggested an intricate, multiphasic pathway of memory consolidation. An integrated molecular pharmacological approach in Drosophila has lent support to this theory recently by dissecting consolidated memory into two genetically distinct components: a cycloheximide-insensitive, anesthesia-resistant memory and a cycloheximide-sensitive long-term memory. In addition, experiments using inducible dominant-negative transgenes in Drosophila or gene knockouts in mice demonstrate a role for cAMP-responsive transcription factors in formation of long-term memory. These studies support the application of reverse-genetic strategies, including the use of temporally specific agonists and antagonists, to advance the functional dissection of memory formation
Involvement of long terminal repeat U3 sequences overlapping the transcription control region in human immunodeficiency virus type 1 mRNA 3' end formation.
Relative roles of signals upstream of AAUAAA and promoter proximity in regulation of human immunodeficiency virus type 1 mRNA 3' end formation.
Sequences regulating temporal poly(A) site switching in the adenovirus major late transcription unit.
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