Desmoglein 2 is less important than desmoglein 3 for keratinocyte cohesion.

Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non-epithelial tissues. Within the epidermis, the cadherin-type adhesion molecules desmoglein (Dsg) 1-4 and desmocollin (Dsc) 1-3 build the adhesive core of desmosomes. In keratinocytes, several isoforms of these proteins are co-expressed. However, the contribution of specific isoforms to overall cell cohesion is unclear. Therefore, in this study we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody-induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23, targeting the Dsg3 adhesive domain, led to profound loss of cell cohesion in human keratinocytes as revealed by the dispase-based dissociation assays. In contrast, an antibody against Dsg2 had no effect on cell cohesion although the Dsg2 antibody was demonstrated to interfere with Dsg2 transinteraction by single molecule atomic force microscopy and was effective to reduce cell cohesion in intestinal epithelial Caco-2 cells which express Dsg2 as the only Dsg isoform. To substantiate these findings, siRNA-mediated silencing of Dsg2 or Dsg3 was performed in keratinocytes. In contrast to Dsg3-depleted cells, Dsg2 knockdown reduced cell cohesion only under conditions of increased shear. These experiments indicate that specific desmosomal cadherins contribute differently to keratinocyte cohesion and that Dsg2 compared to Dsg3 is less important in this context

Diverging dc conductivity due to a flat band in disordered pseudospin-1 Dirac-Weyl fermions

Several lattices, such as the dice or the Lieb lattice, possess Dirac cones and a flat band crossing the Dirac point, whose effective model is the pseudospin-1 Dirac-Weyl equation. We investigate the fate of the flat band in the presence of disorder by focusing on the density of states (DOS) and dc conductivity. While the central hub-site does not reveal the presence of the flat band, the sublattice resolved DOS on the non-central sites exhibits a narrow peak with height 1/pg with g the dimensionless disorder variance. Although the group velocity is zero on the flat band, the dc conductivity diverges as ln(1/g) with decreasing disorder due to interband transitions around the band touching point between the propagating and the flat band. Generalizations to higher pseudospin are given

Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D

In recent years, several studies aimed to investigate the metabolic effects of non-functioning or absent cyclophilin D (CypD), a crucial regulatory component of mitochondrial permeability transition pores. It has been reported that the lack of CypD affects glucose and lipid metabolism. However, the findings are controversial regarding the metabolic pathways involved, and most reports describe the effect of a high-fat diet on metabolism. We performed a lipidomic analysis of plasma and liver samples of CypD-/- and wild-type (WT) mice to reveal the lipid-specific alterations resulting from the absence of CypD. In the CypD-/- mice compared to the WT animals, we found a significant change in 52% and 47% of the measured 225 and 201 lipid species in liver and plasma samples, respectively. The higher total lipid content detected in these tissues was not accompanied by abdominal fat accumulation assessed by nuclear magnetic resonance imaging. We also documented characteristic changes in the lipid composition of the liver and plasma as a result of CypD ablation with the relative increase in polyunsaturated membrane lipid species. In addition, we did not observe remarkable differences in the lipid distribution of hepatocytes using histochemistry, but we found characteristic changes in the hepatocyte ultrastructure in CypD-/- animals using electron microscopy. Our results highlight the possible long-term effects of CypD inhibition as a novel therapeutic consideration for various diseases

Relating the shape of protein binding sites to binding affinity profiles: is there an association?

<p>Abstract</p> <p>Background</p> <p>Various pattern-based methods exist that use <it>in vitro </it>or <it>in silico </it>affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between the protein affinity profiles and the structural characteristics of the binding sites is still unclear. Our aim was to investigate the association between virtual drug screening results (calculated binding free energy values) and the geometry of protein binding sites. Molecular Affinity Fingerprints (MAFs) were determined for 154 proteins based on their molecular docking energy results for 1,255 FDA-approved drugs. Protein binding site geometries were characterized by 420 PocketPicker descriptors. The basic underlying component structure of MAFs and binding site geometries, respectively, were examined by principal component analysis; association between principal components extracted from these two sets of variables was then investigated by canonical correlation and redundancy analyses.</p> <p>Results</p> <p>PCA analysis of the MAF variables provided 30 factors which explained 71.4% of the total variance of the energy values while 13 factors were obtained from the PocketPicker descriptors which cumulatively explained 94.1% of the total variance. Canonical correlation analysis resulted in 3 statistically significant canonical factor pairs with correlation values of 0.87, 0.84 and 0.77, respectively. Redundancy analysis indicated that PocketPicker descriptor factors explain 6.9% of the variance of the MAF factor set while MAF factors explain 15.9% of the total variance of PocketPicker descriptor factors. Based on the salient structures of the factor pairs, we identified a clear-cut association between the shape and bulkiness of the drug molecules and the protein binding site descriptors.</p> <p>Conclusions</p> <p>This is the first study to investigate complex multivariate associations between affinity profiles and the geometric properties of protein binding sites. We found that, except for few specific cases, the shapes of the binding pockets have relatively low weights in the determination of the affinity profiles of proteins. Since the MAF profile is closely related to the target specificity of ligand binding sites we can conclude that the shape of the binding site is not a pivotal factor in selecting drug targets. Nonetheless, based on strong specific associations between certain MAF profiles and specific geometric descriptors we identified, the shapes of the binding sites do have a crucial role in virtual drug design for certain drug categories, including morphine derivatives, benzodiazepines, barbiturates and antihistamines.</p

Membrane protein dynamics: limited lipid control

Correlation of lipid disorder with membrane protein dynamics has been studied with infrared spectroscopy, by combining data characterizing lipid phase, protein structure and, via hydrogen-deuterium (H/D) exchange, protein dynamics. The key element was a new measuring scheme, by which the combined effects of time and temperature on the H/D exchange could be separated. Cyanobacterial and plant thylakoid membranes, mammalian mitochondria membranes, and for comparison, lysozyme were investigated. In dissolved lysozyme, as a function of temperature, H/D exchange involved only reversible movements (the secondary structure did not change considerably); heat-denaturing was a separate event at much higher temperature. Around the low-temperature functioning limit of the biomembranes, lipids affected protein dynamics since changes in fatty acyl chain disorders and H/D exchange exhibited certain correlation. H/D exchange remained low in all membranes over physiological temperatures. Around the high-temperature functioning limit of the membranes, the exchange rates became higher. When temperature was further increased, H/D exchange rates went over a maximum and afterwards decreased (due to full H/D exchange and/or protein denaturing). Maximal H/D exchange rate temperatures correlated neither with the disorder nor with the unsaturation of lipids. In membrane proteins, in contrast to lysozyme, the onsets of sizable H/D exchange rates were the onsets of irreversible denaturing as well. Seemingly, at temperatures where protein self-dynamics allows large-scale H/D exchange, lipid-protein coupling is so weak that proteins prefer aggregating to limit the exposure of their hydrophobic surface regions to water. In all membranes studied, dynamics seemed to be governed by lipids around the low-temperature limit, and by proteins around the high-temperature limit of membrane functionality

A head-mounted display based augmented reality application for oral implantology

Die Dissertation beschäftigt sich mit der augmentierten Realität in der navigierten oralen Implantologie. Zur Visualisierung der Navigation wurde ein „head-mounted display“ und als Vergleichsgruppe ein Monitor verwendet. Acht Untersucher führten navigierte Bohrversuche durch. Hierbei wurde eine Implantatinsertion in Plastikmodellen von humanen Unterkiefern nachgeahmt. Abweichungen der realisierten Bohrkanäle zu der im Vorfeld geplanten Position wurden anhand von Computertomograhieaufnahmen vermessen. Die Untersucher zeigten große interindividuelle Unterschiede in den Abweichungen. Das System erwies sich als gleichwertig zur herkömmlichen Visualisierungsmethode mit einem Monitor.The present study deals with an augmented reality application for navigation in oral implantology. A head-mounted display was used as a means of visualization. Eight investigators performed navigated drillings in replica of human mandibles, imitating a step in implant insertion. Subsequently the deviations of the boreholes from the planned positions, as defined prior to the drillings, were measured using computertomography. The investigators showed remarkable interindividual differences in their deviations. The system is equal to conventional technologies using monitors as means of visualization

The use of a head-mounted display in oral implantology: a feasibility study.

To compare the accuracy of a navigation system for oral implantology using either a head-mounted display (HMD) or a monitor as a device for visualization.Drilling experiments in plastic mandibles were performed by seven investigators supported by a navigation system using an HMD. A set of drilling experiments was carried out using a traditional monitor setup as standard of reference. Prior to the experiments, CT scans of the mandibles were performed. Positions of the boreholes were determined with the planning software Mimics[Formula: see text]. In order to find the correct positions of the boreholes, individuals had to match two pairs of crosshairs. By an infrared tracking device, the navigation system was able to spot the artificial jaw and the angular piece of the drill allowing for the navigation. After the experiments, a second CT scan was acquired: (i) to identify the beginning and the end of the boreholes, (ii) to compare the positions of the planned implant and the boreholes and (iii) to calculate the deviations.Overall deviation of the starting point of the borehole was [Formula: see text] for the HMD and [Formula: see text] for the monitor, [Formula: see text] of the end point of the borehole for the HMD and [Formula: see text] for the monitor. The mean deviation of the axis was [Formula: see text] for the HMD and [Formula: see text] for the monitor.As overall accuracies do not differ significantly, the two methods seem to be equal. Personal skills seem to be crucial as the results show remarkable differences among the test persons. The results of our study demonstrate that the use of an HMD has no major drawbacks compared to the monitor setting. The striking advantage is that the surgeon is no longer obliged to turn his head away from the operation site during navigation, as all data relevant for the procedure are superimposed on the image of the real world in his field of view

Szigetüzemű napelemes rendszer szimulációja

Szigetüzemű napelemes rendszer szimulációjaBSc/BAVillamosmérnökg