Cognitive aging at work and in daily life—a narrative review on challenges due to age-related changes in central cognitive functions

Demographic change is leading to an increasing proportion of older employees in the labor market. At the same time, work activities are becoming more and more complex and require a high degree of flexibility, adaptability, and cognitive performance. Cognitive control mechanism, which is subject to age-related changes and is important in numerous everyday and work activities, plays a special role. Executive functions with its core functions updating, shifting, and inhibition comprises cognitive control mechanisms that serve to plan, coordinate, and achieve higher-level goals especially in inexperienced and conflicting actions. In this review, influences of age-related changes in cognitive control are demonstrated with reference to work and real-life activities, in which the selection of an information or response in the presence of competing but task-irrelevant stimuli or responses is particularly required. These activities comprise the understanding of spoken language under difficult listening conditions, dual-task walking, car driving in critical traffic situations, and coping with work interruptions. Mechanisms for compensating age-related limitations in cognitive control and their neurophysiological correlates are discussed with a focus on EEG measures. The examples illustrate how to access influences of age and cognitive control on and in everyday and work activities, focusing on its functional role for the work ability and well-being of older people

pH-dependent structural transitions in cationic ionizable lipid mesophases are critical for lipid nanoparticle function

Lipid nanoparticles (LNPs) are advanced core-shell particles for messenger RNA (mRNA) based therapies that are made of polyethylene glycol (PEG) lipid, distearoylphosphatidylcholine (DSPC), cationic ionizable lipid (CIL), cholesterol (chol), and mRNA. Yet the mechanism of pH-dependent response that is believed to cause endosomal release of LNPs is not well understood. Here, we show that eGFP (enhanced green fluorescent protein) protein expression in the mouse liver mediated by the ionizable lipids DLin-MC3-DMA (MC3), DLin-KC2-DMA (KC2), and DLinDMA (DD) ranks MC3 ≥ KC2 > DD despite similar delivery of mRNA per cell in all cell fractions isolated. We hypothesize that the three CIL-LNPs react differently to pH changes and hence study the structure of CIL/chol bulk phases in water. Using synchrotron X-ray scattering a sequence of ordered CIL/chol mesophases with lowering pH values are observed. These phases show isotropic inverse micellar, cubic Fd3m inverse micellar, inverse hexagonal and bicontinuous cubic Pn3m symmetry. If polyadenylic acid, as mRNA surrogate, is added to CIL/chol, excess lipid coexists with a condensed nucleic acid lipid phase. The next-neighbor distance in the excess phase shows a discontinuity at the Fd3m inverse micellar to inverse hexagonal transition occurring at pH 6 with distinctly larger spacing and hydration for DD vs. MC3 and KC2. In mRNA LNPs, DD showed larger internal spacing, as well as retarded onset and reduced level of DD-LNP-mediated eGFP expression in vitro compared to MC3 and KC2. Our data suggest that the pH-driven Fd3m- transition in bulk phases is a hallmark of CIL-specific differences in mRNA LNP efficacy.publishedVersio

Measuring Correlates of Mental Workload During Simulated Driving Using cEEGrid Electrodes: A Test–Retest Reliability Analysis

The EEG reflects mental processes, especially modulations in the alpha and theta frequency bands are associated with attention and the allocation of mental resources. EEG has also been used to study mental processes while driving, both in real environments and in virtual reality. However, conventional EEG methods are of limited use outside of controlled laboratory settings. While modern EEG technologies offer hardly any restrictions for the user, they often still have limitations in measurement reliability. We recently showed that low-density EEG methods using film-based round the ear electrodes (cEEGrids) are well-suited to map mental processes while driving a car in a driving simulator. In the present follow-up study, we explored aspects of ecological and internal validity of the cEEGrid measurements. We analyzed longitudinal data of 127 adults, who drove the same driving course in a virtual environment twice at intervals of 12–15 months while the EEG was recorded. Modulations in the alpha and theta frequency bands as well as within behavioral parameters (driving speed and steering wheel angular velocity) which were highly consistent over the two measurement time points were found to reflect the complexity of the driving task. At the intraindividual level, small to moderate (albeit significant) correlations were observed in about 2/3 of the participants, while other participants showed significant deviations between the two measurements. Thus, the test-retest reliability at the intra-individual level was rather low and challenges the value of the application for diagnostic purposes. However, across all participants the reliability and ecological validity of cEEGrid electrodes were satisfactory in the context of driving-related parameters

Kinetic evidence for a ligand-binding-induced conformational transition in the T cell receptor

Thermodynamics and kinetics of the interaction between T cell receptor specific for cytomegalovirus peptide (TCRCMV) and its specific ligand, pp65–HLA-A*0201 complex, were studied by surface plasmon resonance and stopped-flow methods. In the latter measurements, fluorescence resonance energy transfer (FRET) between fluorescently labeled reactants was used. Thermodynamic data derived from surface plasmon resonance measurements suggest that the complex formation is driven by both favorable enthalpy and entropy. Two reaction phases were resolved by the stopped-flow measurements. The rate constant of the first step was calculated to be close to the diffusion-controlled limit rate (3·105 to 106 M−1·s−1), whereas the second step's reaction rate was found to be concentration independent and relatively slow (2–4 s−1 at 25°C). These findings strongly suggest that the interactions between the TCR and its ligand, the peptide–MHC complex, proceed by a two-step mechanism, in which the second step is an induced-fit process, rate determining for antigen recognition by TCR