Predicting the influence of a p2-symmetric substrate on molecular self-organization with an interaction-site model

An interaction-site model can a priori predict molecular selforganisation on a new substrate in Monte Carlo simulations. This is experimentally confirmed with scanning tunnelling microscopy on Fre´chet dendrons of a pentacontane template. Local and global ordering motifs, inclusion molecules and a rotated unit cell are correctly predicted

Aha1 regulates Hsp90's conformation and function in a stoichiometry-dependent way

The heat shock protein 90 (Hsp90) is a molecular chaperone, which plays a key role in eukaryotic protein homeostasis. Co-chaperones assist Hsp90 in client maturation and in regulating essential cellular processes such as cell survival, signal transduction, gene regulation, hormone signaling and neurodegeneration. Aha1 (activator of Hsp90 ATPase) is a unique co-chaperone known to stimulate the ATP hydrolysis of Hsp90, but the mechanism of their interaction is still unclear. In this report, we show that one or two Aha1 can bind to one Hsp90 dimer and that the binding stoichiometry affects Hsp90's conformation, kinetics, ATPase activity and stability. In particular, a coordination of two Aha1 molecules can be seen in stimulating the ATPase activity of Hsp90 and the unfolding of the middle domain, while the conformational equilibrium and kinetics are hardly affected by the stoichiometry of bound Aha1. Altogether, we show a regulation mechanism through the stoichiometry of Aha1 going far beyond a regulation of Hsp90's conformation.</p

Evolution of Neuropsychological Deficits in First-Ever Isolated Ischemic Thalamic Stroke and Their Association With Stroke Topography: A Case-Control Study.

BACKGROUND The thalamus plays an essential role in cognition. Cognitive deficits have to date mostly been studied retrospectively in chronic thalamic stroke in small cohorts. Studies prospectively evaluating the evolution of cognitive deficits and their association with thalamic stroke topography are lacking. This knowledge is relevant for targeted patient diagnostics and rehabilitation. METHODS Thirty-seven patients (57.5±17.5 [mean±SD] years, 57% men) with first-ever acute isolated ischemic stroke covering the anterior (n=5), paramedian (n=12), or inferolateral (n=20) thalamus and 37 in-patient controls without stroke with similar vascular risk factors matched for age and sex were prospectively studied. Cognition was evaluated using predefined tests at 1, 6, 12, and 24 months. Voxel-based lesion-symptom mapping was used to determine associations between neuropsychological deficits and stroke topography. RESULTS Patients with anterior thalamic stroke revealed severe deficits in verbal memory (median T score [Q1-Q3]: 39.1 [36.1-44.1]), language (31.8 [31.0-43.8]), and executive functions (43.8 [35.5-48.1]) at 1 month compared with controls (verbal memory: 48.5 [43.6-61.0], language: 55.7 [42.3-61.1], executive functions: 51.3 [50.1-56.8]). Patients with paramedian thalamic stroke showed moderate language (44.7 [42.8-55.9]) and executive (49.5 [44.3-55.1]) deficits and no verbal memory deficits (48.1 [42.5-54.7]) at 1 month compared with controls (59.0 [47.0-64.5]; 59.6 [51.1-61.3]; 52.5 [44.2-55.3]). The language and executive deficits in paramedian thalamic stroke patients almost completely recovered during follow-up. Intriguingly, significant deficits in verbal memory (44.7 [41.5-51.9]), language (47.5 [41.8-54.1]), and executive functions (48.2 [46.2-59.7]) were found in inferolateral thalamic stroke patients at 1 month compared with controls (50.5 [46.7-59.9]; 57.0 [51.2-62.9]; 57.4 [51.2-60.7]). Language, but not executive deficits persisted during follow-up. Voxel-based lesion-symptom mapping revealed an association of verbal memory deficits with anterior thalamus lesions and an association of non-verbal memory, language, and executive deficits with lesions at the anterior/paramedian/inferolateral border. CONCLUSIONS All 3 stroke topographies exhibited significant deficits in diverse cognitive domains, which recovered to a different degree depending on the stroke localization. Our study emphasizes the need for comprehensive neuropsychological diagnostics to secure adequate patient rehabilitation

Differential associations of emotional and physical domains of the MacNew Heart with changes in 6-min walking test

Aims Cardiac rehabilitation (CR), a key component of secondary prevention in cardiac patients, contributes fundamentally to improved cardiovascular health outcomes. Health-related quality of life (HRQOL) represents a widely employed outcome measure in CR, yet, its predictive properties on exercise capacity change during CR are poorly understood. Aim of this study was to examine the association between baseline HRQOL and its subdomains on improvement of exercise capacity during CR. Methods Study participants were 13,717 inpatients of six Swiss CR clinics from 2012 to 2018. We measured HRQOL at admission to CR with the MacNew Heart (MNH) questionnaire and exercise capacity at admission and discharge using the six minutes walking test (6MWT). Following factorial analyses, we performed univariate and multivariate analyses to test the predictive properties of baseline global HRQOL and its domains for improvement in exercise capacity, adjusting for demographic and clinical characteristics. Results Mean improvement in 6MWT was 114 m (SD = 90), achieved after 17.4 days (SD = 5.5). Lower emotional HRQOL (b = 7.85, p =  < .001, 95% CI [− 5.67, 10.03]) and higher physical HRQOL (b =  − 5.23, p < .001, 95% CI [− 6.56, − 3.90]) were associated with less improvement in the 6MWT. Global MNH and social HRQOL showed no association with exercise capacity improvement. Conclusion Patients entering CR with low emotional and high physical HRQOL are at risk for a lower gain in exercise capacity during CR. Global MNH alone does not provide a reliable assessment of HRQOL; thus a focus on specific domains of HRQOL is needed