Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage

SUMO and ubiquitin play important roles in the response of cells to DNA damage. These pathways are linked by the SUMO Targeted ubiquitin Ligase Rnf4 that catalyses transfer of ubiquitin from a ubiquitin loaded E2 conjugating enzyme to a polySUMO modified substrate. Rnf4 can functionally interact with multiple E2s, including Ube2w, in vitro. Chicken cells lacking Rnf4 are hypersensitive to hyroxyurea, DNA alkylating drugs and DNA crosslinking agents, but this sensitivity is suppressed by simultaneous depletion of Ube2w. Cells depleted of Ube2w alone are not hypersensitive to the same DNA damaging agents. Similar results were also obtained in human cells. These data indicate that Ube2w does not have an essential role in the DNA damage response, but is deleterious in the absence of Rnf4. Thus, although Rnf4 and Ube2w functionally interact in vitro, our genetic experiments indicate that in response to DNA damage Ube2w and Rnf4 function in distinct pathways

Effects of seasonal allergic rhinitis on driving performance, memory functioning, psychomotor performance and quality of life

Background: Seasonal allergic rhinitis (SAR) has shown to affect quality of life and impair cognitive functioning. Objective: The objective of this study was to compare driving ability, memory, and psychomotor performance during grass pollen season with winter season in untreated patients with SAR. Methods: Patients with SAR were trained and tested during the grass pollen season (summer) and winter. An on-the-road driving test during normal traffic conditions was performed. Primary parameter is the Standard Deviation of Lateral Position (SDLP), i.e. the weaving of the car. In addition, a word learning test and continuous performance test were performed and quality of life was assessed. Patients were included if in winter the Total 5-Symptoms Score (T5SS) was 3. Results: 70 patients were recruited of which 22 started the study. Fifteen patients completed the study of which 11 met the inclusion criteria. These 11 patients had a mean T5SS of 6.8 in summer and 0.6 in winter. Patient reported a significantly reduced overall quality of life during grass pollen season (p<0.0001). No significant effects were found on the driving test, except a significant (but not relevant) decrease in mean speed during the grass pollen season (p<0.035). No significant effects were found on the word learning test and continuous performance test. Conclusion: Our data suggest that moderate SAR symptoms do not impair driving ability, memory functioning and continuous performance. However, given the small sample size future studies should confirm these findings

Effects of seasonal allergic rhinitis on driving performance, memory functioning, psychomotor performance and quality of life

Background: Seasonal allergic rhinitis (SAR) has shown to affect quality of life and impair cognitive functioning. Objective: The objective of this study was to compare driving ability, memory, and psychomotor performance during grass pollen season with winter season in untreated patients with SAR. Methods: Patients with SAR were trained and tested during the grass pollen season (summer) and winter. An on-the-road driving test during normal traffic conditions was performed. Primary parameter is the Standard Deviation of Lateral Position (SDLP), i.e. the weaving of the car. In addition, a word learning test and continuous performance test were performed and quality of life was assessed. Patients were included if in winter the Total 5-Symptoms Score (T5SS) was 3. Results: 70 patients were recruited of which 22 started the study. Fifteen patients completed the study of which 11 met the inclusion criteria. These 11 patients had a mean T5SS of 6.8 in summer and 0.6 in winter. Patient reported a significantly reduced overall quality of life during grass pollen season (p<0.0001). No significant effects were found on the driving test, except a significant (but not relevant) decrease in mean speed during the grass pollen season (p<0.035). No significant effects were found on the word learning test and continuous performance test. Conclusion: Our data suggest that moderate SAR symptoms do not impair driving ability, memory functioning and continuous performance. However, given the small sample size future studies should confirm these findings

Amplified Vibrational Circular Dichroism as a Probe of Local Biomolecular Structure

We show that the VCD signal intensities of amino acids and oligopeptides can be enhanced by up to 2 orders of magnitude by coupling them to a paramagnetic metal ion. If the redox state of the metal ion is changed from paramagnetic to diamagnetic the VCD amplification vanishes completely. From this observation and from complementary quantum-chemical calculations we conclude that the observed VCD amplification finds its origin in vibronic coupling with low-lying electronic states. We find that the enhancement factor is strongly mode dependent and that it is determined by the distance between the oscillator and the paramagnetic metal ion. This localized character of the VCD amplification provides a unique tool to specifically probe the local structure surrounding a paramagnetic ion and to zoom in on such local structure within larger biomolecular systems