pyHVis3D: visualising molecular simulation deduced H-bond networks in 3D: application to T-cell receptor interactions.

Motivation: Hydrogen bonds (H-bonds) play an essential role for many molecular interactions but are also often transient, making visualising them in a flexible system challenging. Results: We provide pyHVis3D which allows for an easy to interpret 3D visualisation of H-bonds resulting from molecular simulations. We demonstrate the power of pyHVis3D by using it to explain the changes in experimentally measured binding affinities for three T-cell receptor/peptide/MHC complexes and mutants of each of these complexes. Availability and implementation: pyHVis3D can be downloaded for free from http://opig.stats.ox.ac.uk/resources. Contact: science.bernhard.knapp@gmail.com. Supplementary information: Supplementary data are available at Bioinformatics online.

Ulipristal Acetate Improves Clinical Symptoms in Women with Adenomyosis and Uterine Myomas.

STUDY OBJECTIVE: To study the effects of ulipristal acetate (UPA) on adenomyosis-associated clinical symptoms. DESIGN: A retrospective, single-center observational study (Canadian Task Force classification II-2). SETTING: A university tertiary referral center. PATIENTS: Premenopausal women (163) with adenomyosis and symptomatic uterine myomas (41 patients, A + F group) versus a control group with only myomas (122 patients, F group) treated with the first course of UPA. INTERVENTIONS: This was a retrospective study to assess the effects of a 12-week course of UPA (5 mg/d). MEASUREMENTS AND MAIN RESULTS: Clinical symptoms including bleeding control, amenorrhea, pain outcomes, and self-perceived severity of the disease and quality of life. Amenorrhea was present in 90.4% of the A + F group compared with 77.6% in the F group (p = .0017). Optimal bleeding control was significantly higher in the adenomyosis group (pictorial blood loss assessment chart < 75) than in the F group (90.2% vs 73.8%, p = .028). At the end of the first UPA course, the self-reported visual analog scale scores in the A + F group were significantly higher than in the F group (p = .017), reflecting greater improvement in pain outcomes for women with adenomyosis. UPA treatment improved the quality of life in both study groups. Most of the women rated their global health status as "better" after the first UPA course than before the treatment (A + F group: 67.00% and F group: 80.50%, p = .223). CONCLUSION: Treatment with UPA led to a significant reduction in the clinical symptoms of adenomyosis (bleeding and pain) and achieved a high rate of amenorrhea in a cohort of women with concomitant uterine myomas. Despite the limitations of the study, our results showed that UPA might be a good alternative treatment for adenomyosis.

Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context.

Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

Variable Regions of Antibodies and T-Cell Receptors May Not Be Sufficient in Molecular Simulations Investigating Binding.

Antibodies and T-cell receptors are important proteins of the immune system that share similar structures. Both contain variable and constant regions. Insight into the dynamics of their binding can be provided by computational simulations. For these simulations the constant regions are often removed to save runtime as binding occurs in the variable regions. Here we present the first study to investigate the effect of removing the constant regions from antibodies and T-cell receptors on such simulations. We performed simulations of an antibody/antigen and T-cell receptor/MHC system with and without constant regions using 10 replicas of 100 ns of each of the four setups. We found that simulations without constant regions show significantly different behavior compared to simulations with constant regions. If the constant regions are not included in the simulations alterations in the binding interface hydrogen bonds and even partial unbinding can occur. These results indicate that constant regions should be included in antibody and T-cell receptor simulations for reliable conclusions to be drawn.