Distortions of Subjective Time Perception Within and Across Senses

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

Changes in balance and joint position sense during a 12-day high altitude trek: The British Services Dhaulagiri medical research expedition

<div><p>Postural control and joint position sense are essential for safely undertaking leisure and professional activities, particularly at high altitude. We tested whether exposure to a 12-day trek with a gradual ascent to high altitude impairs postural control and joint position sense. This was a repeated measures observational study of 12 military service personnel (28±4 years). Postural control (sway velocity measured by a portable force platform) during standing balance, a Sharpened Romberg Test and knee joint position sense were measured, in England (113m elevation) and at 3 research camps (3619m, 4600m and 5140m) on a 12-day high altitude trek in the Dhaulagiri region of Nepal. Pulse oximetry, and Lake Louise scores were also recorded on the morning and evening of each trek day. Data were compared between altitudes and relationships between pulse oximetry, Lake Louise score, and sway velocity were explored. Total sway velocity during standing balance with eyes open (p = 0.003, d = 1.9) and during Sharpened Romberg test with eyes open (p = 0.007, d = 1.6) was significantly greater at altitudes of 3619m and 5140m when compared with sea level. Anterior-posterior sway velocity during standing balance with eyes open was also significantly greater at altitudes of 3619m and 5140m when compared with sea level (p = 0.001, d = 1.9). Knee joint position sense was not altered at higher altitudes. There were no significant correlations between Lake Louise scores, pulse oximetry and postural sway. Despite a gradual ascent profile, exposure to 3619 m was associated with impairments in postural control without impairment in knee joint position sense. Importantly, these impairments did not worsen at higher altitudes of 4600 m or 5140 m. The present findings should be considered during future trekking expeditions when developing training strategies targeted to manage impairments in postural control that occur with increasing altitude.</p></div

The non-pathogenic mycobacteria M. smegmatis and M. fortuitum induce rapid host cell apoptosis via a caspase-3 and TNF dependent pathway

<p>Abstract</p> <p>Background</p> <p>The HIV pandemic raised the potential for facultative-pathogenic mycobacterial species like, <it>Mycobacterium kansasii</it>, to cause disseminating disease in humans with immune deficiencies. In contrast, non-pathogenic mycobacterial species, like <it>M. smegmatis</it>, are not known to cause disseminating disease even in immunocompromised individuals. We hypothesized that this difference in phenotype could be explained by the strong induction of an innate immune response by the non-pathogenic mycobacterial species.</p> <p>Results</p> <p>A comparison of two rapid-growing, non-pathogenic species (<it>M. smegmatis </it>and <it>M. fortuitum</it>) with two facultative-pathogenic species (<it>M. kansasii </it>and <it>M. bovis </it>BCG) demonstrated that only the non-pathogenic bacteria induced strong apoptosis in human THP-1 cells and murine bone marrow-derived macrophages (BMDM) and dendritic cells (BMDD). The phospho-<it>myo</it>-inositol modification of lipoarabinomannan (PI-LAM) isolated from non-pathogenic species may be one of the cell wall components responsible for the pro-inflammatory activity of the whole bacteria. Indeed, PI-LAM induces high levels of apoptosis and IL-12 expression compared to the mannosyl modification of LAM isolated from facultative-pathogenic mycobacteria. The apoptosis induced by non-pathogenic <it>M. smegmatis </it>was dependent upon caspase-3 activation and TNF secretion. Consistently, BALB/c BMDM responded by secreting large amounts of TNF upon infection with non-pathogenic but not facultative-pathogenic mycobacteria. Interestingly, C57Bl/6 BMDM do not undergo apoptosis upon infection with non-pathogenic mycobacteria despite the fact that they still induce an increase in TNF secretion. This suggests that the host cell signaling pathways are different between these two mouse genotypes and that TNF is necessary but not sufficient to induce host cell apoptosis.</p> <p>Conclusion</p> <p>These results demonstrate a much stronger induction of the innate immune response by non-pathogenic versus facultative-pathogenic mycobacteria as measured by host cell apoptosis, IL-12 and TNF cytokine induction. These observations lend support to the hypothesis that the strong induction of the innate immune response is a major reason for the lack of pathogenicity in fast-growing mycobacteria.</p

A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice (vol 5, pg e27, 2008)

Background: Stored glycogen is an important source of energy for skeletal muscle. Human genetic disorders primarily affecting skeletal muscle glycogen turnover are well-recognised, but rare. We previously reported that a frameshift/premature stop mutation in PPP1R3A, the gene encoding RGL, a key regulator of muscle glycogen metabolism, was present in 1.36% of participants from a population of white individuals in the UK. However, the functional implications of the mutation were not known. The objective of this study was to characterise the molecular and physiological consequences of this genetic variant. Methods and Findings: In this study we found a similar prevalence of the variant in an independent UK white population of 744 participants (1.46%) and, using in vivo 13C magnetic resonance spectroscopy studies, demonstrate that human carriers (n = 6) of the variant have low basal (65% lower, p = 0.002) and postprandial muscle glycogen levels. Mice engineered to express the equivalent mutation had similarly decreased muscle glycogen levels (40% lower in heterozygous knock-in mice, p < 0.05). In muscle tissue from these mice, failure of the truncated mutant to bind glycogen and colocalize with glycogen synthase (GS) decreased GS and increased glycogen phosphorylase activity states, which account for the decreased glycogen content. Conclusions: Thus, PPP1R3A C1984ΔAG (stop codon 668) is, to our knowledge, the first prevalent mutation described that directly impairs glycogen synthesis and decreases glycogen levels in human skeletal muscle. The fact that it is present in ~1 in 70 UK whites increases the potential biomedical relevance of these observations

How Long and Low Can You Go? Effect of Conformation on the Risk of Thoracolumbar Intervertebral Disc Extrusion in Domestic Dogs

Intervertebral disc extrusion (IVDE) is a common neurological disorder in certain dog breeds, resulting in spinal cord compression and injury that can cause pain and neurological deficits. Most disc extrusions are reported in chondrodystrophic breeds (e.g. Dachshunds, Basset Hounds, Pekingese), where selection for ‘long and low’ morphologies is linked with intervertebral discs abnormalities that predispose dogs to IVDE. The aim of this study was to quantify the relationship between relative thoracolumbar vertebral column length and IVDE risk in diverse breeds. A 14 month cross-sectional study of dogs entering a UK small animal referral hospital for diverse disorders including IVDE was carried out. Dogs were measured on breed-defining morphometrics, including back length (BL) and height at the withers (HW). Of 700 dogs recruited from this referral population, measured and clinically examined, 79 were diagnosed with thoracolumbar IVDE following diagnostic imaging ± surgery. The BL:HW ratio was positively associated with IVDE risk, indicating that relatively longer dogs were at increased risk, e.g. the probability of IVDE was 0.30 for Miniature Dachshunds when BL:HW ratio equalled 1.1, compared to 0.68 when BL:HW ratio equalled 1.5. Additionally, both being overweight and skeletally smaller significantly increased IVDE risk. Therefore, selection for longer backs and miniaturisation should be discouraged in high-risk breeds to reduce IVDE risk. In higher risk individuals, maintaining a lean body shape is particularly important to reduce the risk of IVDE. Results are reported as probabilities to aid decision-making regarding breed standards and screening programmes reflecting the degree of risk acceptable to stakeholders

Timing, rates and spectra of human germline mutation.

Germline mutations are a driving force behind genome evolution and genetic disease. We investigated genome-wide mutation rates and spectra in multi-sibling families. The mutation rate increased with paternal age in all families, but the number of additional mutations per year differed by more than twofold between families. Meta-analysis of 6,570 mutations showed that germline methylation influences mutation rates. In contrast to somatic mutations, we found remarkable consistency in germline mutation spectra between the sexes and at different paternal ages. In parental germ line, 3.8% of mutations were mosaic, resulting in 1.3% of mutations being shared by siblings. The number of these shared mutations varied significantly between families. Our data suggest that the mutation rate per cell division is higher during both early embryogenesis and differentiation of primordial germ cells but is reduced substantially during post-pubertal spermatogenesis. These findings have important consequences for the recurrence risks of disorders caused by de novo mutations

Increasing experience in laparoscopic staging of early ovarian cancer

We assessed the effect of increasing experience of a single surgeon (learning curve) in the laparoscopic staging procedure for women with early ovarian cancer and compared the results with the literature. We retrospectively analysed a total of 25 women with apparent early-stage ovarian cancer who underwent a laparoscopic staging procedure by the same surgeon. Three time periods, based on date of surgery, were compared with respect to operating time, amount of lymph nodes harvested and surgical outcome. There was no significant difference in operation time, estimated blood loss and hospital stay between the three periods. There was, however, a significant increase in the median number of pelvic and para-aortal lymph nodes harvested (group1 = 6.5, group 2 = 8.0 and group 3 = 21.0; P < 0.005). For the total period, median operation time was 235 min and median estimated blood loss was 100 ml. The median length of hospital stay was 4.0 days. Two intraoperative and two postoperative complications occurred. The upstaging rate was 32%. The mean interval between initial surgery and laparoscopic staging was 51.2 days. Mean duration of follow-up was 43 months, range (1–116 months). Five (20%) patients had recurrences, and two (8%) patients died of the disease. In conclusion, there is a significant learning curve for the laparoscopic full staging procedure in ovarian cancer. In our study this is mainly reflected in the amount of lymph nodes harvested and not in the total operating time

A Comprehensive Model of Audiovisual Perception: Both Percept and Temporal Dynamics

The sparse information captured by the sensory systems is used by the brain to apprehend the environment, for example, to spatially locate the source of audiovisual stimuli. This is an ill-posed inverse problem whose inherent uncertainty can be solved by jointly processing the information, as well as introducing constraints during this process, on the way this multisensory information is handled. This process and its result - the percept - depend on the contextual conditions perception takes place in. To date, perception has been investigated and modeled on the basis of either one of two of its dimensions: the percept or the temporal dynamics of the process. Here, we extend our previously proposed audiovisual perception model to predict both these dimensions to capture the phenomenon as a whole. Starting from a behavioral analysis, we use a data-driven approach to elicit a Bayesian network which infers the different percepts and dynamics of the process. Context-specific independence analyses enable us to use the model's structure to directly explore how different contexts affect the way subjects handle the same available information. Hence, we establish that, while the percepts yielded by a unisensory stimulus or by the non-fusion of multisensory stimuli may be similar, they result from different processes, as shown by their differing temporal dynamics. Moreover, our model predicts the impact of bottom-up (stimulus driven) factors as well as of top-down factors (induced by instruction manipulation) on both the perception process and the percept itself