91 research outputs found

    Mother mouse sets the circadian clock of pups

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    We report here the ontogeny of a circadian clock of the field mouseMus booduga expressing itself 16 days after parturition in the locomotory activity of neonate pups removed from the mother and held in continuous darkness ever since birth. Locomotion is a 'complex' activity serving such functions as foraging, exploration, and territoriality. Since these functions are not conventionally associated with neonate and altricial animals, it is of interest that this ability has such an early circadian origin. A backward extrapolation of the pups rhythm and the rhythm of the mother strongly implicate maternal synchronization. The period of the circadian rhythm of the pups shortens with age, from birth up to six months

    Identification of candidate regulatory sequences in mammalian 3' UTRs by statistical analysis of oligonucleotide distributions

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    3' untranslated regions (3' UTRs) contain binding sites for many regulatory elements, and in particular for microRNAs (miRNAs). The importance of miRNA-mediated post-transcriptional regulation has become increasingly clear in the last few years. We propose two complementary approaches to the statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of candidate binding sites for regulatory elements. The first method is based on the identification of sets of genes characterized by evolutionarily conserved overrepresentation of an oligonucleotide. The second method is based on the identification of oligonucleotides showing statistically significant strand asymmetry in their distribution in 3' UTRs. Both methods are able to identify many previously known binding sites located in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are proposed for experimental verification.Comment: Added two reference

    Genome-Wide Survey of MicroRNA - Transcription Factor Feed-Forward Regulatory Circuits in Human

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    In this work, we describe a computational framework for the genome-wide identification and characterization of mixed transcriptional/post-transcriptional regulatory circuits in humans. We concentrated in particular on feed-forward loops (FFL), in which a master transcription factor regulates a microRNA, and together with it, a set of joint target protein coding genes. The circuits were assembled with a two step procedure. We first constructed separately the transcriptional and post-transcriptional components of the human regulatory network by looking for conserved over-represented motifs in human and mouse promoters, and 3'-UTRs. Then, we combined the two subnetworks looking for mixed feed-forward regulatory interactions, finding a total of 638 putative (merged) FFLs. In order to investigate their biological relevance, we filtered these circuits using three selection criteria: (I) GeneOntology enrichment among the joint targets of the FFL, (II) independent computational evidence for the regulatory interactions of the FFL, extracted from external databases, and (III) relevance of the FFL in cancer. Most of the selected FFLs seem to be involved in various aspects of organism development and differentiation. We finally discuss a few of the most interesting cases in detail.Comment: 51 pages, 5 figures, 4 tables. Supporting information included. Accepted for publication in Molecular BioSystem

    Modeling tissue-specific structural patterns in human and mouse promoters

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    Sets of genes expressed in the same tissue are believed to be under the regulation of a similar set of transcription factors, and can thus be assumed to contain similar structural patterns in their regulatory regions. Here we present a study of the structural patterns in promoters of genes expressed specifically in 26 human and 34 mouse tissues. For each tissue we constructed promoter structure models, taking into account presences of motifs, their positioning to the transcription start site, and pairwise positioning of motifs. We found that 35 out of 60 models (58%) were able to distinguish positive test promoter sequences from control promoter sequences with statistical significance. Models with high performance include those for liver, skeletal muscle, kidney and tongue. Many of the important structural patterns in these models involve transcription factors of known importance in the tissues in question and structural patterns tend to be conserved between human and mouse. In addition to that, promoter models for related tissues tend to have high inter-tissue performance, indicating that their promoters share common structural patterns. Together, these results illustrate the validity of our models, but also indicate that the promoter structures for some tissues are easier to model than those of others

    I\u27m Controlling and Composing : The Role of Metacognition in The Incredible Machine

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    The mouse sets the bowling ball in motion, which falls and squeezes the bellows, which sends out a puff of air, which sends the balloon into the gears that are connect by a belt to another mouseā€™s exercise wheel. The balloon pops. Having learned how this routine functions, I then move my mouse to connect the rest of the on-screen mice so that the pulleys of all of the caged mice spin with their wheels to punish the puzzle in time allowing me to move to the next level. Eventually, I will be able to make my own versions of Rube Goldberg machines turned into puzzles based on what I have seen and learned in playing through the eighty challenges provided for Mort the mouse, Bob the fish, and me. Although it is more than twenty-five years old, by teaching about games, learning through games, and learning itself, The Incredible Machine (Dynamix, 1992) continues to defy several key deterministic viewpoints about video games. Said another way, The Incredible Machine (TIM) anticipates Hackerā€™s defining study of meta-cognitionā€”i.e., ā€œknowledge of oneā€™s own knowledge processesā€ā€”in games and simulations. As a game about learning, TIM resists the prevailing scholarly notion that pleasurable games must follow the cultural imperative for accumulation, competition, and/or conquest and that pleasurable games are not suitable for teaching. Indeed, Hackerā€™s later work emphasizes so-called ā€œserious games,ā€ which are explicitly and didactically aimed at learning, a process that has ā€œmet with mixed results.ā€ Thus, my paper will examine the metacognition that occurs in and through the very unserious playing TIM

    PDX USE IN CLINICAL TRIALS FOR TREATING COLORECTAL CANCER

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    https://openworks.mdanderson.org/sumexp22/1012/thumbnail.jp
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