21 research outputs found

    Aging, working memory capacity and the proactive control of recollection:An event-related potential study

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    The present study investigated the role of working memory capacity (WMC) in the control of recollection in young and older adults. We used electroencephalographic event-related potentials (ERPs) to examine the effects of age and of individual differences in WMC on the ability to prioritize recollection according to current goals. Targets in a recognition exclusion task were words encoded using two alternative decisions. The left parietal ERP old/new effect was used as an electrophysiological index of recollection, and the selectivity of recollection measured in terms of the difference in its magnitude according to whether recognized items were targets or non-targets. Young adults with higher WMC showed greater recollection selectivity than those with lower WMC, while older adults showed nonselective recollection which did not vary with WMC. The data suggest that aging impairs the ability to engage cognitive control effectively to prioritize what will be recollected

    In vitro nuclear interactome of the HIV-1 Tat protein

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    <p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

    Molecular insights into the premature aging disease progeria

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    Potential therapeutic approaches for modulating expression and accumulation of defective lamin A in laminopathies and age-related diseases

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