Keratin Isotypes Control Desmosome Stability and Dynamics through PKCα

Expression and interaction of desmosomal components and keratins provide stable cell cohesion and protect the epidermis against various types of stress. The differentiation-specific isotype composition of the keratin cytoskeleton and desmosomes is regarded as a major determinant of adhesive strength. In support, wound healing is characterized by a transient decrease in desmosomal adhesion accompanied by increased expression of keratins K6/K16/K17 at the expense of K1/K10. The significance of altered keratin expression for desmosomal composition and adhesion remains incompletely understood at a mechanistic and functional level. Here, we investigated the respective contribution of K5/K14 or K6/K17 to desmosome adhesion, on their stable re-expression in keratinocytes lacking all keratins. This revealed that K5/K14 filaments support stable desmosomes, whereas “wound healing” keratins K6/K17 induce elevated protein kinase C alpha–mediated desmosome disassembly and subsequent destabilization of epithelial sheets. Moreover, our data suggest that K5/K14 sequester protein kinase C alpha in the cytoplasm, whereas K6/K17 or the absence of all keratins enables protein kinase C alpha translocation to the plasma membrane and induction of desmosome disassembly. Gain- and loss-of-function experiments support a major role of K5 in desmosome stability control via protein kinase C alpha. Our data show that keratin isotypes differently and specifically regulate wound healing and invasion by modulating intercellular adhesion

Electromagnetic Compression as Preforming Operation for Tubular Hydroforming Parts

With the aim to extent the forming limits of tube hydroforming a concept of using a previous electromagnetic compression operation will be introduced. One important limit for the possibilities of tube hydroforming is set by the initial circumference and the maximum tangential strain of the used material, whereby the initial circumference is typically determined by the smallest local circumference of the workpiece. The application of an appropriate contoured preform makes it possible to use tubes with a larger initial circumference. In the paper the investigation of the suitability of electromagnetic tube compression for the production of such a preform will be presented. The valuation is based on geometric criteria and material properties of the resulting preform which are strongly influenced by the process parameters. The discussed aspects are the roundness of the preform and the strain hardening of the material

Interpreting graph neural networks with Myerson values for cheminformatics approaches

Here we introduce a novel method to interpret the predictions of graph neural networks (GNNs) based on Myerson values from cooperative game theory. Myerson values are closely related to Shapley values and thus provide an interpretability approach similar to the SHAP values. We developed the technique for applications in drug discovery, but it can be used with any graph. Using the GNN as a coalition game and the interpreted graph as the cooperation structure, the Myerson values determine the worth of each node of the graph. The worth of all nodes of the graph adds up to the predicted value of the model, allowing for a simple and intuitive interpretation of the prediction. To interpret predictions on molecular graphs we show visual explanations on molecular structures using two molecular datasets

Food-derived serotonergic modulators: effects on mood and cognition

The most frequently described drugs in the treatment of mood disorders are selective serotonin reuptake and monoamine oxidase (MAO) inhibitors, enhancing serotonin levels in the brain. However, side-effects have been reported for these drugs. Because serotonin levels in the brain are dependent on the availability of the food-derived precursor tryptophan, foods such as chicken, soyabeans, cereals, tuna, nuts and bananas may serve as an alternative to improve mood and cognition. Here we discuss the effects of high- or low-tryptophan-containing food, as well as plant extracts with a modest monoamine reuptake and MAO-A inhibition functional profile, on mood and cognition in healthy and vulnerable human subjects and rodents. Together the studies suggest that there is an inverted U-shaped curve for plasma tryptophan levels, with low and too high tryptophan levels impairing cognition, and moderate to high tryptophan levels improving cognition. This relationship is found for both healthy and vulnerable subjects. Whereas this relationship may also exist for mood, the inverted U-shaped curve for plasma tryptophan levels and mood may be based on different tryptophan concentrations in healthy v. vulnerable individuals. Animal studies are emerging and allow further understanding of effects and the mode of action of food-derived serotonergic components on mood, cognition and mechanisms. Ultimately, insight into the concentrations of tryptophan and other serotonergic components in food having beneficial effects on mood and cognition in healthy, but particularly vulnerable, subjects may support well-being in our highly demanding societ

Investigation of the Process Chain Bending-Electromagnetic compression-Hydroforming on the Basis of an Industrial Demonstrator Part

The increasing significance of lightweight construction concepts requires innovative and adapted production technologies and process chains for the manufacturing of complex parts made of typical lightweight materials. The feasibility and potential of such a process chain consisting of the steps Bending - Electromagnetic compression (EMC) Hydroforming is shown in the present paper on the basis of a demonstrator part similar to a structural component from the automotive industry. Here, special focus is put on the requirements on the production steps and the workpiece properties. Furthermore, the development and testing of EMC-equipment that is optimally adapted to the special forming task is described

A Distinct Layer of the Medulla Integrates Sky Compass Signals in the Brain of an Insect

Mass migration of desert locusts is a common phenomenon in North Africa and the Middle East but how these insects navigate is still poorly understood. Laboratory studies suggest that locusts are able to exploit the sky polarization pattern as a navigational cue. Like other insects locusts detect polarized light through a specialized dorsal rim area (DRA) of the eye. Polarization signals are transmitted through the optic lobe to the anterior optic tubercle (AOTu) and, finally, to the central complex in the brain. Whereas neurons of the AOTu integrate sky polarization and chromatic cues in a daytime dependent manner, the central complex holds a topographic representation of azimuthal directions suggesting a role as an internal sky compass. To understand further the integration of sky compass cues we studied polarization-sensitive (POL) neurons in the medulla that may be intercalated between DRA photoreceptors and AOTu neurons. Five types of POL-neuron were characterized and four of these in multiple recordings. All neurons had wide arborizations in medulla layer 4 and most, additionally, in the dorsal rim area of the medulla and in the accessory medulla, the presumed circadian clock. The neurons showed type-specific orientational tuning to zenithal polarized light and azimuth tuning to unpolarized green and UV light spots. In contrast to neurons of the AOTu, we found no evidence for color opponency and daytime dependent adjustment of sky compass signals. Therefore, medulla layer 4 is a distinct stage in the integration of sky compass signals that precedes the time-compensated integration of celestial cues in the AOTu

Strength of Tubular Joints Made by Electromagnetic Compression at Quasistatic and Cyclic Loading

Electromagnetic compression of tubular profiles with high electrical conductivity is an innovative joining process for lightweight structures. The components are joined using pulsed magnetic fields which apply radial pressures of up to 200 MPa to tubular workpieces, causing a symmetric reduction of the diameter with typical strain rates of up to 10^4 sec^(-1). This process avoids any surface damage of the workpiece because there is no contact between component and forming tool. The strength of electromagnetically formed joints made of aluminum tubes under cyclic loads is essential to establish electromagnetic forming in automotive structures. In the present paper, the quasi-static performance of tubular joints made by electromagnetic compression produced of different mandrel materials will be analyzed as to the influence of process parameters. Therefore, experimental investigations on aluminum tubes (AA6060) joined on mandrels made of different aluminum, copper, and steel alloys were carried out. Furthermore, the behavior of joints with both mandrel and tube made of AA6060 at swelling cyclic loads (R = δ_ min / δ_ max =0) has been evaluated

Six state molecular revolver mounted on a rigid platform

The rotation of entire molecules or large moieties happens at 100 ps time scales and the transition process itself is experimentally inaccessible to scanning probe techniques. However, the reversible switching of a molecule between more than two metastable states allows to assign a rotational switching direction. Rotational switching is a phenomenon that is particularly interesting with regard to possible applications in molecular motors. In this work, single tetraphenylmethane molecules deposited on a Au(111) surface were studied in a low temperature scanning tunneling microscope (STM). These molecules comprise rotational axes mounted on a tripodal sulfur-anchored stand and with the STM tip, we were able to induce transitions between six rotational states of the molecular motif. We were able to identify critical parameters for the onset of rotational switching and to characterize the influence of the local environment. The subtle difference between fcc and hcp stacking and the rotational state of neighboring molecules clearly influence the population of the rotational states

Competition-based model of pheromone component ratio detection in the moth

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy