Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity

The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. The identification of small natural ligands that could prevent the entry and/or replication of the coronavirus remains a pertinent approach to fight the coronavirus disease (COVID-19) pandemic. Previously, we showed that the phenolic compounds corilagin and 1,3,6-tri-O-galloyl-β-D-glucose (TGG) inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 target receptor on the cell membrane of the host organism. Building on these promising results, we now assess the effects of these phenolic ligands on two other crucial targets involved in SARS-CoV-2 cell entry and replication, respectively: transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin like protease (3CLpro) inhibitors. Since corilagin, TGG, and tannic acid (TA) share many physicochemical and structural properties, we investigate the binding of TA to these targets. In this work, a combination of experimental methods (biochemical inhibition assays, surface plasmon resonance, and quartz crystal microbalance with dissipation monitoring) confirms the potential role of TA in the prevention of SARS-CoV-2 infectivity through the inhibition of extracellular RBD/ACE2 interactions and TMPRSS2 and 3CLpro activity. Moreover, molecular docking prediction followed by dynamic simulation and molecular mechanics Poisson–Boltzmann surface area (MMPBSA) free energy calculation also shows that TA binds to RBD, TMPRSS2, and 3CLpro with higher affinities than TGG and corilagin. Overall, these results suggest that naturally occurring TA is a promising candidate to prevent and inhibit the infectivity of SARS-CoV-2.     

Genetic Deficiency and Pharmacological Stabilization of Mast Cells Ameliorate Pressure Overload-Induced Maladaptive Right Ventricular Remodeling in Mice

Although the response of the right ventricle (RV) to the increased afterload is an important determinant of the patient outcome, very little is known about the underlying mechanisms. Mast cells have been implicated in the pathogenesis of left ventricular maladaptive remodeling and failure. However, the role of mast cells in RV remodeling remains unexplored. We subjected mast cell-deficient WBB6F1-KitW/W-v (Kit^W/Kit^W-v) mice and their mast cell-sufficient littermate controls (MC^+/+) to pulmonary artery banding (PAB). PAB led to RV dilatation, extensive myocardial fibrosis, and RV dysfunction in MC^+/+ mice. In PAB Kit^W/Kit^W-v mice, RV remodeling was characterized by minimal RV chamber dilatation and preserved RV function. We further administered to C57Bl/6J mice either placebo or cromolyn treatment starting from day 1 or 7 days after PAB surgery to test whether mast cells stabilizing drugs can prevent or reverse maladaptive RV remodeling. Both preventive and therapeutic cromolyn applications significantly attenuated RV dilatation and improved RV function. Our study establishes a previously undescribed role of mast cells in pressure overload-induced adverse RV remodeling. Mast cells may thus represent an interesting target for the development of a new therapeutic approach directed specifically at the heart.     

Production of microparticles from milk fat products using the Supercritical Melt Micronization (ScMM) process

The ScMM (Supercritical Melt Micronization) process was applied for the production of microparticles from anhydrous milk fat (AMF) and a diacylglycerol-based modified milk fat (D-AMF). Both fats were able to dissolve ca. 30 wt% CO₂ in the studied pressure and temperature ranges, being the CO₂ amount slightly higher for AMF. A melting point depression was observed in both systems in the presence of CO₂. Two powder morphologies were obtained (spherical hollow particles and a mass sponge-like broken particles) depending on the ScMM process conditions. The concentration of CO₂ in the fat melt was the main process variable affecting the particle morphology, followed by the temperature of the melt. The small broken particles originated from the breakage of spherical fat particles that solidified before all CO₂ could escape from the atomized droplets. While the hollow spheres had a tendency to agglomerate, the broken microparticles constituted a free-flowing powder as long as they were stored at low temperatures (up to −18 °C). Both types of particles have a potential for being incorporated in refrigerated or frozen food products as a structuring agent.     

Phase Visualization Using a BaTiO3 Phase Conjugating Mirror

Abstract

A real-time phase visualization technique using a phase conjugating mirror is proposed, and experimental verification is presented.     

A comparison of three developmental stage scoring systems

In social psychological research the stage metaphor has fallen into disfavor due to concerns about bias, reliability, and validity. To address some of these issues, I employ a multidimensional partial credit analysis comparing moral judgment interviews scored with the Standard Issue Scoring System (SISS) (Colby and Kohlberg, 1987b), evaluative reasoning interviews scored with the Good Life Scoring System (GLSS) (Armon, 1984b), and Good Education interviews scored with the Hierarchical Complexity Scoring System (HCSS) (Commons, Danaher, Miller, and Dawson, 2000). A total of 209 participants between the ages of 5 and 86 were interviewed. The multidimensional model reveals that even though the scoring systems rely upon different criteria and the data were collected using different methods and scored by different teams of raters, the SISS, GLSS, and HCSS all appear to measure the same latent variable. The HCSS exhibits more internal consistency than the SISS and GLSS, and solves some methodological problems introduced by the content dependency of the SISS and GLSS. These results and their implications are elaborated.     

Pattern storage and processing in attractor networks with short-time synaptic dynamics

Neurophysiological experiments show that the strength of synaptic connections can undergo substantial changes on a short time scale. These changes depend on the history of the presynaptic input. Using mean-field techniques, we study how short-time dynamics of synaptic connections influence the performance of attractor neural networks in terms of their memory capacity and capability to process external signals. For binary discrete-time as well as for firing rate continuous-time neural networks, the fixed points of the network dynamics are shown to be unaffected by synaptic dynamics. However, the stability of patterns changes considerably. Synaptic depression turns out to reduce the storage capacity. On the other hand, synaptic depression is shown to be advantageous for processing of pattern sequences. The analytical results on stability, size of the basins of attraction and on the switching between patterns are complemented by numerical simulations.     

Bussy business: How urban bus drivers cope with time pressure, passengers, and traffic safety.

Adhering to the schedule, providing service to passengers, and driving safely are among the most important psychosocial demands of the bus driver's job. The ways bus drivers cope with these varying and conflicting demands are addressed in this article, which uses data from 4 interrelated studies. In a large-scale questionnaire study (Study 1), behavioral styles in coping with these psychosocial demands were identified. Next, in Studies 2 and 3, the relations of these styles with well-being and health status were examined. Study 4 addressed the coping process during work itself by examining the relations among objective workload indicators, perceived effort, and psychophysiological stress reactions during work. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unconstrained Inverse Electrocardiography: Epicardial Potentials

The inverse problem in electrocardiography is attacked via the development of a model appropriate for the computation of epicardial potentials from a knowledge of heart and torso geometry as well as surface potentials. The model takes the form of an integral equation of the first kind in which the kernel is interpreted as a Green's function. A theoretical investigation of system independence in the presence of error is developed, and two techniques for the theoretical consideration of system independence are examined. Application of these two techniques to concentric spherical systems indicates that spheres with ratios of inner-to-outer radii less than 0.5 contain less than twenty independent parameters in the presence of realistic noise levels. The number of independent parameters deteriorates rapidly as this ratio falls below 0.5. These results suggest that it is not feasible to determine epicardial potentials from torso potentials by using unconstrained solutions.