RESUMO
The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
Assuntos
Evolução Molecular , Genoma , Genômica , Ratos Endogâmicos BN/genética , Animais , Composição de Bases , Centrômero/genética , Cromossomos de Mamíferos/genética , Ilhas de CpG/genética , Elementos de DNA Transponíveis/genética , DNA Mitocondrial/genética , Duplicação Gênica , Humanos , Íntrons/genética , Masculino , Camundongos , Modelos Moleculares , Mutagênese , Polimorfismo de Nucleotídeo Único/genética , Sítios de Splice de RNA/genética , RNA não Traduzido/genética , Ratos , Sequências Reguladoras de Ácido Nucleico/genética , Retroelementos/genética , Análise de Sequência de DNA , Telômero/genéticaRESUMO
The main goal of the present study was to explore the role of sleep in the process of ill-defined problem solving. The results of previous studies indicate that various cognitive processes are largely dependent on the quality and quantity of sleep. However, while sleep-related memory consolidation seems to be well-grounded, with regard to the impact of sleep on problem solving, existing research yields mixed and rather inconclusive results. Moreover, this effect has been mainly tested using simple and well-defined, common laboratory problems, such as the remote associate test (RAT), crossword and anagram puzzles, numeric and logic problems, etc. What is lacking is research on the effect of sleep on solving more complex and more real-life oriented ill-defined problems. In the present study, we hypothesized that sleep can improve performance in solving this kind of problems. The study involved 40 participants, randomly assigned to two experimental conditions: sleep group and waking group. The experimental protocol comprised three stages: problem presentation, retention interval, and testing stage. The problem was presented to the participants in the form of an interactive computer game concerning a complex, elaborate crime story. During the retention interval, the participants-depending on the condition-took a nap or stayed awake; sleeping participants underwent polysomnography recording, while waking participants performed activities not related to the experimental problem. In the testing stage, participants tried to solve the presented problem. The solutions generated were assessed both for quality (reasonableness, consistency, and story recall) and creativity (fluency, flexibility, originality, and elaboration). Contrary to expectations, we found no effect of sleep on ill-defined problem solving. Neither quality nor creativity of the solutions generated by the participants was higher in the nap group than in the waking group. There were also no performance improvements with regard to any sleep stage or incidence of dreams. Our study adds to a growing body of evidence that sleep probably might provide an incubation gap, but not a facilitating environment serving the purpose of problem solving, at least with regard to ill-defined problems.
RESUMO
Multiple lines of evidence suggest that inhibition of Type I Interferons, including IFN-alpha, may provide a therapeutic benefit for autoimmune diseases. Using a chemical genomics approach integrated with cellular and in vivo assays, we screened a small compound library to identify modulators of IFN-alpha biological effects. A genomic fingerprint was developed from both ex vivo patient genomic information and in vitro gene modulation from IFN-alpha cell-based stimulation. A high throughput genomic-based screen then was applied to prioritize 268 small molecule inhibitors targeting 41 different intracellular signaling pathways. Active compounds were profiled further for their ability to inhibit the activation and differentiation of human monocytes using disease-related stimuli. Inhibitors targeting NF-kappaB or Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling emerged as "dissociated inhibitors" because they did not modulate IFN-alpha anti-viral effects against HSV-1 but potently inhibited other immune-related functions. This work describes a novel strategy to identify small molecule inhibitors for the treatment of autoimmune disorders.