Role of the Blood-Brain Barrier in the Formation of Brain Metastases

The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB). The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain. The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized. Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells. Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation.     

The Irritant Effects of Pharmaceutically Applied Surfactants

Dermal or transdermal medication may lead to irritant contact dermatitis. However, little information is available on the irritant effect of surfactants which are applied in topical formulations. Our aim was to examine the irritant effect of the most frequent compounds in topical products. A murine model was applied. The following compounds were examined: sodium lauryl sulphate (SLS), polyethoxylated (40EO) hydrogenated castor oil and sucrose laurate. SLS led to severe erythema, increase in transepidermal water loss (TEWL) and induced necrosis and accumulation of neutrophylic granulocytes and lymphocytes. Exposure to sucrose laurate resulted in an elevation of TEWL, but histology did not reveal impairment of the skin structure. Application of polyethoxylated (40EO) hydrogenated castor oil was not accompanied by tissue damage. Special attention should be paid to the irritant effect of SLS. Polyethoxylated (40EO) hydrogenated castor oil seems to be a non-irritant agent and sucrose laurate is also a promising candidate for application in topical preparations.     

Ultra-trace Analysis of Enantiomeric Impurities in Proteinogenic N-Fmoc-Amino-acid Samples on Cinchona Alkaloid-based Chiral Stationary Phases

The enantiomeric purity of N_α-Fmoc-protected amino acids is crucial from the viewpoint of peptide synthesis; therefore, a sensitive high-performance liquid chromatographic protocol was developed for the identification and quantification of enantiomeric impurities of commercially available N_α-Fmoc-protected amino acids on Cinchona alkaloid quinine- and quinidine-based weak anion exchanger-type chiral stationary phases. In the course of the evaluation of the chiral chromatographic method, the effect of the mobile phase composition, nature, and concentration of different additives were optimized. The specific phenomenon that quinine- and quinidine-based chiral stationary phases behave as pseudo-enantiomers permits that the sequence of elution of the enantiomers might be reversed by simple column switching. This is quite advantageous as regards the separation of the minor component in the presence of the major one. The method developed permits detection of less than 0.01 % enantiomeric impurity in the presence of the major enantiomer.     

Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and their Role in Disorders like Developmental Dyscalculia

The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing inter-group comparisons, a third group of subjects with dyslexia (DL) but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall fifty-eight subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, even though only numerical digits and no alphabetic characters were presented. Thus our results suggest that time-resolved multi-variate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders.     

General relativistic hypercomputing and foundation of mathematics

Looking at very recent developments in spacetime theory, we can wonder whether these results exhibit features of hypercomputation that traditionally seemed impossible or absurd. Namely, we describe a physical device in relativistic spacetime which can compute a non-Turing computable task, e.g. which can decide the halting problem of Turing machines or decide whether ZF set theory is consistent (more precisely, can decide the theorems of ZF). Starting from this, we will discuss the impact of recent breakthrough results of relativity theory, black hole physics and cosmology to well established foundational issues of computability theory as well as to logic. We find that the unexpected, revolutionary results in the mentioned branches of science force us to reconsider the status of the physical Church Thesis and to consider it as being seriously challenged. We will outline the consequences of all this for the foundation of mathematics (e.g. to Hilbert’s programme). Observational, empirical evidence will be quoted to show that the statements above do not require any assumption of some physical universe outside of our own one: in our specific physical universe there seem to exist regions of spacetime supporting potential non-Turing computations. Additionally, new “engineering” ideas will be outlined for solving the so-called blue-shift problem of GR-computing. Connections with related talks at the Physics and Computation meeting, e.g. those of Jerome Durand-Lose, Mark Hogarth and Martin Ziegler, will be indicated.     

Preparation and characterization of hydroxyapatite from eggshell

Hydroxyapatite (HAp) was successfully produced by using recycled eggshell. The observed phases of the synthesised materials were dependent on the mechanochemical activation method (ball milling and attrition milling). The structures of the HAp were characterized by X-ray diffraction, scanning electron microscopy and infrared spectroscopy. Attrition milling proved to be more efficient than ball milling, as resulted nanosize, homogenous HAp even after milling.     

Synthesis and Cell Growth Inhibitory Activity of Six Non-glycosaminoglycan-Type Heparin-Analogue Trisaccharides

The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Herein, we present the efficient synthesis of five Glc-GlcA-Glc-sequenced and one Glc-IdoA-Glc-sequenced non-glycosaminoglycan, heparin-related trisaccharides with various sulfation/sulfonylation and methylation patterns. The cell growth inhibitory effects of the compounds were tested against four cancerous human cell lines and two non-cancerous cell lines. Two d -glucuronate-containing tetra-O-sulfated, partially methylated trisaccharides displayed remarkable and selective inhibitory effects on the growth of ovary carcinoma (A2780) and melanoma (WM35) cells. Methyl substituents on the glucuronide unit proved to be detrimental, whereas acetyl substituents were beneficial to the cytostatic activity of the sulfated derivatives.     

First genetically verified occurrence of Ligula pavlovskii outside its native range and characteristics of its infection in Neogobius fluviatilis

In this study, we provide the first genetically verified distribution record beyond its native range of Ligula pavlovskii, a high-impact endoparasite of Ponto-Caspian gobies. According to parasitological surveys, ligulosis was detected for the first time in monkey goby individuals collected from Lake Balaton in 2004, 34 years after the first record of monkey goby in the lake. During a Lake Balaton survey in 2018, we detected tapeworms in 44.4% of the sampled monkey gobies. This prevalence is about two to ten times higher than it was reported from within the native range of the fish hosts. The same survey revealed an uneven spatial distribution of the ligulosis in the monkey gobies inhabiting different shoreline sections of the lake. We assume that the occurrence and recent distribution data of this high-impact endoparasite may provide useful information for potential biocontrol measures of invasive Ponto-Caspian gobies in the future.     

Postural instability-induced compensative movements in virtual reality

Virtual Reality - During virtual reality usage, two egocentric mental representations are constructed simultaneously. The first representation is rooted in the physical reality in which VR is set...     

The Effect of Electroporation of a Lyotroic Liquid Crystal Genistein-Based Formulation in the Recovery of Murine Melanoma Lesions

A lamellar lyotropic liquid crystal genistein-based formulation (LLC-Gen) was prepared in order to increase the aqueous solubility of the lipophilic phytocompound genistein. The formulation was applied locally, in a murine model of melanoma, with or without electroporation. The results demonstrated that, when the formulation was applied by electroporation, the tumors appeared later. During the 21 days of the experiment, the LLC-Gen formulation decreased the tumor volume, the amount of melanin and the degree of erythema, but when electroporation was applied, all these parameters indicated a better prognosis even (lower tumor volume, amount of melanin and degree of erythema). Although hematoxylin–eosin (HE) staining confirmed the above events, application of the LLC-Gen formulation by electroporation did not lead to a significant effect in terms of the serum concentrations of the protein S100B and serum neuron specific enolase (NSE), or the tissue expression of the platelet-derived growth factor receptor β (PDGFRβ) antibody.