9 research outputs found

    Premature responses in the five-choice serial reaction time task reflect rodents’ temporal strategies: evidence from no-light and pharmacological challenges

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    RATIONALE: The five-choice serial reaction time task (5-CSRTT) is regularly used to study attention and impulsivity. In the 5-CSRTT, rodents initiate a trial, then after an inter-trial interval (ITI), a light appears in one of five holes. Responding in the lit vs. unlit hole reflects attention (accuracy), while responding prematurely before a light appears is suggested to reflect impulsivity/response disinhibition. Comparison of rat and mouse 5-CSRTT performance has raised questions on the validity of premature responses as measuring impulsivity/response inhibition. To minimize effort, rodents may use a temporal strategy, enabling their ‘timing’ of the ITI, minimizing the need to attend during this delay. Greater reliance this strategy could result in premature responses due to “guesses” if their timing was poor/altered. OBJECTIVES: To assess the degree to which rats and/or mice utilize a temporal strategy, we challenged performance using infrequent no-light trials during 5-CSRTT performance. RESULTS: Even when no light appeared when one was expected, rats responded ~60% compared to ~40% in mice, indicating a greater reliance on a temporal strategy by rats than by mice. Consistent with this hypothesis, rats made more premature responses than mice. Additional studies using a temporal discrimination task and a 5-CSRTT variant demonstrated that delta-9-tetrahydrocannabinol, the active ingredient in cannabis, slowed temporal perception and reduced premature responses. CONCLUSIONS: These data provide behavioral and pharmacological evidence indicating that premature responses are heavily influenced by temporal perception. Hence, they may reflect an aspect of waiting impulsivity, but not response disinhibition, an important distinction for translational clinical research

    Comparative validation of the D. melanogaster modENCODE transcriptome annotation

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    Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome annotation by using deep and diverse high-throughput data. Since transcriptional activity that has been evolutionarily conserved is likely to have an advantageous function, we have performed large-scale interspecific comparisons to increase confidence in predicted annotations. To support comparative genomics, we filled in divergence gaps in the Drosophila phylogeny by generating draft genomes for eight new species. For comparative transcriptome analysis, we generated mRNA expression profiles on 81 samples from multiple tissues and developmental stages of 15 Drosophila species, and we performed cap analysis of gene expression in D. melanogaster and D. pseudoobscura. We also describe conservation of four distinct core promoter structures composed of combinations of elements at three positions. Overall, each type of genomic feature shows a characteristic divergence rate relative to neutral models, highlighting the value of multispecies alignment in annotating a target genome that should prove useful in the annotation of other high priority genomes, especially human and other mammalian genomes that are rich in noncoding sequences. We report that the vast majority of elements in the annotation are evolutionarily conserved, indicating that the annotation will be an important springboard for functional genetic testing by the Drosophila community

    Dialect typology: recent advances

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    This chapter provides an overview of recent innovative approaches that focus on the distributional patterns of linguistic phenomena in dialects across different languages. We set the stage by discussing a number of geographical factors that are assumed in the literature to have a bearing on the structural make-up of different languages and dialects such as world region, altitude, contact with speakers of other languages or dialects, etc. We then move on to sketch the extent to which dialects of a language exhibit common features (e.g., “vernacular universals” à la Chambers 2004) and identify structural dichotomies and continua that are regularly invoked when it comes to explaining the structural diversity of languages, namely, analyticity versus syntheticity, explicitness versus economy, complexity versus simplicity, and innovativeness versus conservativeness, all within the context of geographic space

    Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

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    Dissecting fibrosis: therapeutic insights from the small-molecule toolbox

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