137 research outputs found

    Distortions of Subjective Time Perception Within and Across Senses

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    Background: The ability to estimate the passage of time is of fundamental importance for perceptual and cognitive processes. One experience of time is the perception of duration, which is not isomorphic to physical duration and can be distorted by a number of factors. Yet, the critical features generating these perceptual shifts in subjective duration are not understood. Methodology/Findings: We used prospective duration judgments within and across sensory modalities to examine the effect of stimulus predictability and feature change on the perception of duration. First, we found robust distortions of perceived duration in auditory, visual and auditory-visual presentations despite the predictability of the feature changes in the stimuli. For example, a looming disc embedded in a series of steady discs led to time dilation, whereas a steady disc embedded in a series of looming discs led to time compression. Second, we addressed whether visual (auditory) inputs could alter the perception of duration of auditory (visual) inputs. When participants were presented with incongruent audio-visual stimuli, the perceived duration of auditory events could be shortened or lengthened by the presence of conflicting visual information; however, the perceived duration of visual events was seldom distorted by the presence of auditory information and was never perceived shorter than their actual durations. Conclusions/Significance: These results support the existence of multisensory interactions in the perception of duration and, importantly, suggest that vision can modify auditory temporal perception in a pure timing task. Insofar as distortions in subjective duration can neither be accounted for by the unpredictability of an auditory, visual or auditory-visual event, we propose that it is the intrinsic features of the stimulus that critically affect subjective time distortions

    A type 2 diabetes disease module with a high collective influence for Cdk2 and PTPLAD1 is localized in endosomes

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    Despite the identification of many susceptibility genes our knowledge of the underlying mechanisms responsible for complex disease remains limited. Here, we identified a type 2 diabetes disease module in endosomes, and validate it for functional relevance on selected nodes. Using hepatic Golgi/endosomes fractions, we established a proteome of insulin receptor-containing endosomes that allowed the study of physical protein interaction networks on a type 2 diabetes background. The resulting collated network is formed by 313 nodes and 1147 edges with a topology organized around a few major hubs with Cdk2 displaying the highest collective influence. Overall, 88% of the nodes are associated with the type 2 diabetes genetic risk, including 101 new candidates. The Type 2 diabetes module is enriched with cytoskeleton and luminal acidification-dependent processes that are shared with secretion-related mechanisms. We identified new signaling pathways driven by Cdk2 and PTPLAD1 whose expression affects the association of the insulin receptor with TUBA, TUBB, the actin component ACTB and the endosomal sorting markers Rab5c and Rab11a. Therefore, the interactome of internalized insulin receptors reveals the presence of a type 2 diabetes disease module enriched in new layers of feedback loops required for insulin signaling, clearance and islet biology

    Activity in perceptual classification networks as a basis for human subjective time perception

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    Despite being a fundamental dimension of experience, how the human brain generates the perception of time remains unknown. Here, we provide a novel explanation for how human time perception might be accomplished, based on non-temporal perceptual classification processes. To demonstrate this proposal, we build an artificial neural system centred on a feed-forward image classification network, functionally similar to human visual processing. In this system, input videos of natural scenes drive changes in network activation, and accumulation of salient changes in activation are used to estimate duration. Estimates produced by this system match human reports made about the same videos, replicating key qualitative biases, including differentiating between scenes of walking around a busy city or sitting in a cafe or office. Our approach provides a working model of duration perception from stimulus to estimation and presents a new direction for examining the foundations of this central aspect of human experience

    Increased temporal sensitivity for threat: A Bayesian generalized linear mixed modeling approach.

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    People overestimate the duration of threat-related facial expressions, and this effect increases with self-reported fearfulness (Tipples in Emotion, 8, 127-131, 2008, Emotion, 11, 74-80, 2011). One explanation (Cheng, Tipples, Narayanan, & Meck in Timing and Time Perception, 4, 99-122, 2016) for this effect is that emotion increases the rate at which temporal information accumulates. Here I tested whether increased overestimation for threat-related facial expressions in high fearfulness generalizes to pictures of threatening animals. A further goal was to illustrate the use of Bayesian generalized linear mixed modeling (GLMM) to gain more accurate estimates of temporal performance, including estimates of temporal sensitivity. Participants (N = 53) completed a temporal bisection task in which they judged the presentation duration for pictures of threatening animals (poised to attack) and nonthreatening animals. People overestimated the duration of threatening animals, and the effect increased with self-reported fearfulness. In support of increased accumulation of pacemaker ticks due to threat, temporal sensitivity was higher for threat than for nonthreat images. Analyses indicated that temporal sensitivity effects may have been absent in previous research because of the method used to calculate the index of temporal sensitivity. The benefits of using Bayesian GLMM are highlighted, and researchers are encouraged to use this method as the first option for analyzing temporal bisection data

    ChIP-chip versus ChIP-seq: Lessons for experimental design and data analysis

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    <p>Abstract</p> <p>Background</p> <p>Chromatin immunoprecipitation (ChIP) followed by microarray hybridization (ChIP-chip) or high-throughput sequencing (ChIP-seq) allows genome-wide discovery of protein-DNA interactions such as transcription factor bindings and histone modifications. Previous reports only compared a small number of profiles, and little has been done to compare histone modification profiles generated by the two technologies or to assess the impact of input DNA libraries in ChIP-seq analysis. Here, we performed a systematic analysis of a modENCODE dataset consisting of 31 pairs of ChIP-chip/ChIP-seq profiles of the coactivator CBP, RNA polymerase II (RNA PolII), and six histone modifications across four developmental stages of <it>Drosophila melanogaster</it>.</p> <p>Results</p> <p>Both technologies produce highly reproducible profiles within each platform, ChIP-seq generally produces profiles with a better signal-to-noise ratio, and allows detection of more peaks and narrower peaks. The set of peaks identified by the two technologies can be significantly different, but the extent to which they differ varies depending on the factor and the analysis algorithm. Importantly, we found that there is a significant variation among multiple sequencing profiles of input DNA libraries and that this variation most likely arises from both differences in experimental condition and sequencing depth. We further show that using an inappropriate input DNA profile can impact the average signal profiles around genomic features and peak calling results, highlighting the importance of having high quality input DNA data for normalization in ChIP-seq analysis.</p> <p>Conclusions</p> <p>Our findings highlight the biases present in each of the platforms, show the variability that can arise from both technology and analysis methods, and emphasize the importance of obtaining high quality and deeply sequenced input DNA libraries for ChIP-seq analysis.</p

    Motor activity improves temporal expectancy

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    Certain brain areas involved in interval timing are also important in motor activity. This raises the possibility that motor activity might influence interval timing. To test this hypothesis, we assessed interval timing in healthy adults following different types of training. The pre- and post-training tasks consisted of a button press in response to the presentation of a rhythmic visual stimulus. Alterations in temporal expectancy were evaluated by measuring response times. Training consisted of responding to the visual presentation of regularly appearing stimuli by either: (1) pointing with a whole-body movement, (2) pointing only with the arm, (3) imagining pointing with a whole-body movement, (4) simply watching the stimulus presentation, (5) pointing with a whole-body movement in response to a target that appeared at irregular intervals (6) reading a newspaper. Participants performing a motor activity in response to the regular target showed significant improvements in judgment times compared to individuals with no associated motor activity. Individuals who only imagined pointing with a whole-body movement also showed significant improvements. No improvements were observed in the group that trained with a motor response to an irregular stimulus, hence eliminating the explanation that the improved temporal expectations of the other motor training groups was purely due to an improved motor capacity to press the response button. All groups performed a secondary task equally well, hence indicating that our results could not simply be attributed to differences in attention between the groups. Our results show that motor activity, even when it does not play a causal or corrective role, can lead to improved interval timing judgments

    Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

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    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis\textit{cis}-acting variants represent an important source of phenotypic variation. Consequently, cis\textit{cis}-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P\textit{P} = 5.6x106^{-6}). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ\textit{HELQ}, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C\textit{MRPS18C} encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS)\textit{FAM175A (ABRAXAS)}, encoding a BRCA1\textit{BRCA1} BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ \textit{HELQ } (P\textit{P} = 8.28x1014^{-14}), MRPS18C\textit{MRPS18C} (P\textit{P} = 1.94x1027^{-27}) and FAM175A \textit{FAM175A } (P\textit{P} = 3.83x103^{-3}), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.Information regarding funding can be found in the published article or the publisher's website. Funders include Cancer Research UK and the National Institute for Health Research
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