Time Distortions in Mind

Time Distortions in Mind brings together current research on temporal processing in clinical populations to elucidate the interdependence between perturbations in timing and disturbances in the mind and brain. For the student, the scientist, and the stepping-stone for further research

Viral complementation allows HIV-1 replication without integration

<p>Abstract</p> <p>Background</p> <p>The integration of HIV-1 DNA into cellular chromatin is required for high levels of viral gene expression and for the production of new virions. However, the majority of HIV-1 DNA remains unintegrated and is generally considered a replicative dead-end. A limited amount of early gene expression from unintegrated DNA has been reported, but viral replication does not proceed further in cells which contain only unintegrated DNA. Multiple infection of cells is common, and cells that are productively infected with an integrated provirus frequently also contain unintegrated HIV-1 DNA. Here we examine the influence of an integrated provirus on unintegrated HIV-1 DNA (uDNA).</p> <p>Results</p> <p>We employed reporter viruses and quantitative real time PCR to examine gene expression and virus replication during coinfection with integrating and non-integrating HIV-1. Most cells which contained only uDNA displayed no detected expression from fluorescent reporter genes inserted into early (Rev-independent) and late (Rev-dependent) locations in the HIV-1 genome. Coinfection with an integrated provirus resulted in a several fold increase in the number of cells displaying uDNA early gene expression and efficiently drove uDNA into late gene expression. We found that coinfection generates virions which package and deliver uDNA-derived genomes into cells; in this way uDNA completes its replication cycle by viral complementation. uDNA-derived genomes undergo recombination with the integrated provirus-derived genomes during second round infection.</p> <p>Conclusion</p> <p>This novel mode of retroviral replication allows survival of viruses which would otherwise be lost because of a failure to integrate, amplifies the effective amount of cellular coinfection, increases the replicating HIV-1 gene pool, and enhances the opportunity for diversification through errors of polymerization and recombination.</p

‘When Birds of a Feather Flock Together’: Synesthetic Correspondences Modulate Audiovisual Integration in Non-Synesthetes

Parise C, Spence C. ‘When Birds of a Feather Flock Together’: Synesthetic Correspondences Modulate Audiovisual Integration in Non-Synesthetes. Presented at the 10th International Multisensory Research Forum (IMRF 2009), New York, NY

No effect of synesthetic congruency on temporal ventriloquism

A sound presented in temporal proximity to a light can alter the perceived temporal occurrence of that light (temporal ventriloquism). Recent studies have suggested that pitch–size synesthetic congruency (i.e., a natural association between the relative pitch of a sound and the relative size of a visual stimulus) might affect this phenomenon. To reexamine this, participants made temporal order judgements about small- and large-sized visual stimuli while high- or low-pitched tones were presented before the first and after the second light. We replicated a previous study showing that, at large sound–light intervals, sensitivity for visual temporal order was better for synesthetically congruent than for incongruent pairs. However, this congruency effect could not be attributed to temporal ventriloquism, since it disappeared at short sound–light intervals, if compared with a synchronous audiovisual baseline condition that excluded response biases. In addition, synesthetic congruency did not affect temporal ventriloquism even if participants were made explicitly aware of congruency before testing. Our results thus challenge the view that synesthetic congruency affects temporal ventriloquism

Audio-Visual Speech Timing Sensitivity Is Enhanced in Cluttered Conditions

Events encoded in separate sensory modalities, such as audition and vision, can seem to be synchronous across a relatively broad range of physical timing differences. This may suggest that the precision of audio-visual timing judgments is inherently poor. Here we show that this is not necessarily true. We contrast timing sensitivity for isolated streams of audio and visual speech, and for streams of audio and visual speech accompanied by additional, temporally offset, visual speech streams. We find that the precision with which synchronous streams of audio and visual speech are identified is enhanced by the presence of additional streams of asynchronous visual speech. Our data suggest that timing perception is shaped by selective grouping processes, which can result in enhanced precision in temporally cluttered environments. The imprecision suggested by previous studies might therefore be a consequence of examining isolated pairs of audio and visual events. We argue that when an isolated pair of cross-modal events is presented, they tend to group perceptually and to seem synchronous as a consequence. We have revealed greater precision by providing multiple visual signals, possibly allowing a single auditory speech stream to group selectively with the most synchronous visual candidate. The grouping processes we have identified might be important in daily life, such as when we attempt to follow a conversation in a crowded room

Exposure to delayed visual feedback of the hand changes motor-sensory synchrony perception

We examined whether the brain can adapt to temporal delays between a self-initiated action and the naturalistic visual feedback of that action. During an exposure phase, participants tapped with their index finger while seeing their own hand in real time (~0 ms delay) or delayed at 40, 80, or 120 ms. Following exposure, participants were tested with a simultaneity judgment (SJ) task in which they judged whether the video of their hand was synchronous or asynchronous with respect to their finger taps. The locations of the seen and the real hand were either different (Experiment 1) or aligned (Experiment 2). In both cases, the point of subjective simultaneity (PSS) was uniformly shifted in the direction of the exposure lags while sensitivity to visual-motor asynchrony decreased with longer exposure delays. These findings demonstrate that the brain is quite flexible in adjusting the timing relation between a motor action and the otherwise naturalistic visual feedback that this action engenders

Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells

The goal of cancer immunotherapy is the generation of an effective, stable, and self-renewing antitumor T-cell population. One such approach involves the use of high-affinity cancer-specific T-cell receptors in gene-therapy protocols. Here, we present the generation of functional tumor-specific human T cells in vivo from genetically modified human hematopoietic stem cells (hHSC) using a human/mouse chimera model. Transduced hHSC expressing an HLA-A*0201–restricted melanoma-specific T-cell receptor were introduced into humanized mice, resulting in the generation of a sizeable melanoma-specific naïve CD8^+ T-cell population. Following tumor challenge, these transgenic CD8^+ T cells, in the absence of additional manipulation, limited and cleared human melanoma tumors in vivo. Furthermore, the genetically enhanced T cells underwent proper thymic selection, because we did not observe any responses against non–HLA-matched tumors, and no killing of any kind occurred in the absence of a human thymus. Finally, the transduced hHSC established long-term bone marrow engraftment. These studies present a potential therapeutic approach and an important tool to understand better and to optimize the human immune response to melanoma and, potentially, to other types of cancer

Sound Frequency and Aural Selectivity in Sound-Contingent Visual Motion Aftereffect

BACKGROUND: One possible strategy to evaluate whether signals in different modalities originate from a common external event or object is to form associations between inputs from different senses. This strategy would be quite effective because signals in different modalities from a common external event would then be aligned spatially and temporally. Indeed, it has been demonstrated that after adaptation to visual apparent motion paired with alternating auditory tones, the tones begin to trigger illusory motion perception to a static visual stimulus, where the perceived direction of visual lateral motion depends on the order in which the tones are replayed. The mechanisms underlying this phenomenon remain unclear. One important approach to understanding the mechanisms is to examine whether the effect has some selectivity in auditory processing. However, it has not yet been determined whether this aftereffect can be transferred across sound frequencies and between ears. METHODOLOGY/PRINCIPAL FINDINGS: Two circles placed side by side were presented in alternation, producing apparent motion perception, and each onset was accompanied by a tone burst of a specific and unique frequency. After exposure to this visual apparent motion with tones for a few minutes, the tones became drivers for illusory motion perception. However, the aftereffect was observed only when the adapter and test tones were presented at the same frequency and to the same ear. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the auditory processing underlying the establishment of novel audiovisual associations is selective, potentially but not necessarily indicating that this processing occurs at an early stage

Adaptation to motor-visual and motor-auditory temporal lags transfer across modalities

Previous research has shown that the timing of a sensor-motor event is recalibrated after a brief exposure to a delayed feedback of a voluntary action (Stetson et al. 2006). Here, we examined whether it is the sensory or motor event that is shifted in time. We compared lag adaption for action-feedback in visuo-motor pairs and audio-motor pairs using an adaptation-test paradigm. Participants were exposed to a constant lag (50 or 150 ms) between their voluntary action (finger tap) and its sensory feedback (flash or tone pip) during an adaptation period (~3 min). Immediately after that, they performed a temporal order judgment (TOJ) task about the tap-feedback test stimulus pairings. The modality of the feedback stimulus was either the same as the adapted one (within-modal) or different (cross-modal). The results showed that the point of subjective simultaneity (PSS) was uniformly shifted in the direction of the exposed lag within and across modalities (motor-visual, motor-auditory). This suggests that the TRE of sensor-motor events is mainly caused by a shift in the motor component