A rabbit reticulocyte ubiquitin carrier protein that supports ubiquitin-dependent proteolysis (E214k) is homologous to the yeast DNA repair gene RAD6.

The two isoforms of the 14-kDa ubiquitin carrier protein (E2(14k)) are unique among rabbit E2s in efficiently supporting ubiquitin-protein ligase (E3)-mediated ubiquitination of proteins destined for degradation. To begin determining the structural basis for this property, we have isolated a cDNA encoding the predominant reticulocyte isoform of the E2 from a rabbit skeletal muscle library. The sequence predicts a protein of 152 amino acids with a molecular weight of 17,293. Expression of the cDNA in Escherichia coli and purification of the recombinant protein revealed an E2 with high affinity for E3 and ubiquitin activating enzyme (E1). The latter high affinity interaction appears to be between the ubiquitin charged form of E1 and the uncharged form of E2 and does not result in a stable complex between these two enzymes. The predicted sequence shows regions of strong homology with other sequenced E2s, suggesting that these regions may be involved in binding to E1 and/or in ubiquitin transfer from E1, functions common to all E2s. Surprisingly, the E2(14k)) sequence is markedly more similar to Saccharomyces cerevisiae RAD6 (69% identity) than to its proposed homologs UBC4/UBC5 (38% identity). The sequence is identical to that recently reported for a human 17-kDa E2 which can complement rad6 mutants thereby identifying rabbit E2(14k) as a RAD6 homologue. The biochemical properties of this previously uncharacterized human 17-kDa E2 are now defined and its misassignment as a homologue of rabbit E2(17k) is corrected. Our findings resolve current confusion regarding relationships among E2s and define yeast RAD6, rabbit E2(14k), and the human 17-kDa E2 as a subclass of E2s which biochemically support E3-mediated conjugation and ubiquitin-dependent proteolysis and physiologically play a role in DNA repair

Virtual reality as a new approach to assess cognitive decline in the elderly

Brain aging is a natural process that leads to a change in cognitive functions. Mild Cognitive Impairment (MCI) is a condition in which a person has cognitive functions that are below normal for his age. However, these deficits are not pronounced enough to confirm for the diagnosis of dementia. It is therefore important to develop new ways to assess cognitive functions in the elderly. This would indeed lead to a better identification of the cognitive losses that are related to normal or pathological aging. The objective of this study was to investigate the relevance of virtual reality as a new evaluation approach in psychology. To do this, 10 elderly people with Mild Cognitive Impairment, and 20 elderly people without cognitive problems, were compared using tests of prospective memory that were presented in a traditional way and in virtual reality. The diagnosis of MCI was made using the Montreal Cognitive Assessment (MoCA). Significant differences between the two groups were noted in virtual reality. Nevertheless, no difference was observed between the two groups with the traditional task. A significant positive correlation between the virtual reality task and the MoCA, but not between the traditional task and the MoCA, was observed. An evaluative approach based on virtual reality seems more sensitive to cognitive impairment associated with aging than an approach based on traditional neuropsychological tests.

A New 2D Interaction-based Method for the Behavioral Analysis of Instrumental Activities of Daily Living

In neuropsychology, many computerized solutions have been proposed in order to assess patients’ functioning in activities of daily living, via realistic interactive simulation. In this context, most developed systems are based on simple devices, real time 2D interaction, and monoscopic 3D computer graphics environment. Behavioral analysis has drawn the interest of many domains, such as neuropsychology, ergonomics, web design, or virtual reality. However, advances on this topic remains fragmented in their respective areas. Thus, in computerized solutions applied to neuropsychology, the behavioral analysis does not take into account the data from interaction. The potential interest of computerized solutions is hence underexploited. In this paper, we propose a transdisciplinary solution, based on a finer analysis of 2D interaction data, such as stop duration. This method could reveal interesting aspects of users’ behaviors

Site-specific Mutants of Oncomodulin: 1H NMR and optical stopped-flow studies of the effect on the metal binding properties of an Asp59 → Glu59 substitution in the calcium-specific site

Abstract High resolution 1H nuclear magnetic resonance spectroscopy and optical stopped-flow techniques have been used to study the metal binding properties of a site-specific mutant of bacterial recombinant oncomodulin in which glutamate has replaced a liganding aspartate at position 59 in the CD calcium-binding site. In particular we have followed the replacement of calcium by lutetium in bacterial recombinant oncomodulin and D59E oncomodulin to provide a measure of the protein's preferences for metal ions of different ionic radii. The result of the Asp----Glu substitution is to make the mutant oncomodulin more similar to rat parvalbumin in terms of its relative CD- and EF-domain affinities for lutetium(III), that is to increase its affinity for metal ions with smaller ionic radii. This finding supports the original hypothesis that the presence of Asp at sequence position 59 is an important factor in the reduced preference of the CD site of oncomodulin for smaller metals such as magnesium (Williams, T. C., Corson, D. C., Sykes, B. D., and MacManus, J. P. (1987) J. Biol. Chem. 262, 6248-6256). However, our studies show that both the CD and the EF sites are affected by this single residue substitution suggesting that many factors play a role in the metal binding affinity and interaction between the two sites

Virtual reality and neuropsychological assessment: The reliability of a virtual kitchen to assess daily-life activities in victims of traumatic brain injury.

Traumatic brain injury (TBI) causes impairments affecting instrumental activities of daily living (IADL). However, few studies have considered virtual reality as an ecologically valid tool for the assessment of IADL in patients who have sustained a TBI. The main objective of the present study was to examine the use of the Nonimmersive Virtual Coffee Task (NI-VCT) for IADL assessment in patients with TBI. We analyzed the performance of 19 adults suffering from TBI and 19 healthy controls (HCs) in the real and virtual tasks of making coffee with a coffee machine, as well as in global IQ and executive functions. Patients performed worse than HCs on both real and virtual tasks and on all tests of executive functions. Correlation analyses revealed that NI-VCT scores were related to scores on the real task. Moreover, regression analyses demonstrated that performance on NI-VCT matched real-task performance. Our results support the idea that the virtual kitchen is a valid tool for IADL assessment in patients who have sustained a TBI

Using Virtual Reality to Assess the Elderly: The Impact of Human-Computer Interfaces on Cognition

Prospective memory (PM) is defined be the capacity to remember to realize an intended action in the future. This is a very important cognitive function that permit to maximize autonomy in everyday life. Unfortunately, few assessment tool, valid, reliable and ecological is accessible for clinicians. To obtain a verisimilar and ecologically prospective memory assessment tool, virtual reality seems to be a promising way. A specific and sensible tool could help the clinician to detect subtle changes in the cognition of the elderly and, ideally detect pathological aging soon before the beginning of decline. Because older adults are not really at ease with technology, these (dis)abilities could be confounded with cognitive inefficacy and lead to false positives diagnostics. To avoid this, the psychometrician must consider the impact of human-computer interfaces (HMI) on cognition. This paper present three experiments that show the impact of HMI on stress, capacity to achieve a task and on cognitive load. The first pilot study shown that a “heavy to use” HMI generated stress and difficulty to achieve the task with healthy adults. The second pilot study revealed that VMT-2 is judged moderately challenging cognitively and it seems to be more for older participants. The third pilot study shown that a complex virtual environment (in terms of navigation and interaction) is more cognitively challenging than a simple virtual environment for older peoples compared to young participants. These results indicated the importance of considering HMI as a potential variable that could create bias in the cognitive measurement

Navigation Patterns in Ederly During Multitasking in Virtual Environnment

Cognitive assessment and screening can be realized with virtual environments (VE). These VE reproduce ecological situation and give an overview of participants difficulties through scoring systems. The most variables used to qualify participants performance are number of errors and time completion. These variables are link to cognition and navigation skill in VEs. We assessed navigation of adult and elderly in a multitasking VE. Navigation patterns were elaborate with diagram to visually detect differences between the two age groups. Elderly have poorer performance than adults

Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve