Dynamical diseases of brain systems: different routes to epileptic seizures

In this overview, we consider epilepsies as dynamical diseases of brain systems since they are manifestations of the property of neuronal networks to display multistable dynamics. To illustrate this concept we may assume that at least two states of the epileptic brain are possible: the interictal state characterized by a normal, apparently random, steady-state electroencephalography (EEG) ongoing activity, and the ictal state, that is characterized by paroxysmal occurrence of synchronous oscillations and is generally called, in neurology, a seizure. The transition between these two states can either occur: 1) as a continuous sequence of phases, like in some cases of mesial temporal lobe epilepsy (MTLE); or 2) as a sudden leap, like in most cases of absence seizures. In the mathematical terminology of nonlinear systems, we can say that in the first case the system's attractor gradually deforms from an interictal to an ictal attractor. The causes for such a deformation can be either endogenous or external. In this type of ictal transition, the seizure possibly may be anticipated in its early, preclinical phases. In the second case, where a sharp critical transition takes place, we can assume that the system has at least two simultaneous interictal and ictal attractors all the time. To which attractor the trajectories converge, depends on the initial conditions and the system's parameters. An essential question in this scenario is how the transition between the normal ongoing and the seizure activity takes place. Such a transition can occur either due to the influence of external or endogenous factors or due to a random perturbation and, thus, it will be unpredictable. These dynamical changes may not be detectable from the analysis of the ongoing EEG, but they may be observable only by measuring the system's response to externally administered stimuli. In the special cases of reflex epilepsy, the leap between the normal ongoing attractor and the ictal attractor is caused by a well-defined external perturbation. Examples from these different scenarios are presented and discussed.     

爱立信IMS weShare分享每一天(系列之二)如何提供出色的用户体验?

爱立信IMS weShare业务有20%的开发与用户视觉体验相关(用户界面、图标、标签以及进度条),其它的80%则主要致力于设备间的系统.与此相对比,用户的体验则完全(100%)有赖于其可接触的事物.     

Effect of plasma treatment on the surface properties of polydimethylsiloxane

In this work, the analysis of the plasma modification of polydimethylsiloxane (PDMS) substrates was conducted. The influence of the modification onto the changes occurred within the geometrical structure and chemical composition of the surface was analyzed. Due to the study of the atomic force microscopy, it was possible to determine the relationships between the surface development and applied process parameters, defining the conditions facilitating to obtain isotropic or anisotropic orientations of wrinkles. A precise analysis of the chemical composition of the surface, executed before and after the modification processes, enabled to define the changes in their elementary composition. Moreover, the modification influence onto the changes of the contact angle and the surface free energy were also analyzed. So, based on the research it was stated that the increase of value of the surface free energy is proportional to the sp³ phase contents in the DLC coatings. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41635.     

Polymerization of β-butyrolactone initiated with Al(OiPr)3

Polymerization of β-butyrolactone has been studied in toluene with Al(OⁱPr)₃ as an initiator. The ring-opening polyaddition proceeds through a coordination–insertion mechanism at a very low rate. Well defined α-isopropylester, ω-hydroxy poly(β-butyrolactone)s (PBL) are formed with a narrow molecular weight distribution at low monomer-to-initiator molar ratios, When this ratio is higher (ca. 170), a competition occurs between propagation and side reactions, i.e. elimination, inter- and intra-molecular transesterifications and thermal degradation, which is responsible for a loss of control of the PBL molecular charcteristics. The addition of a Lewis base (1 equivalent of nicotine/Al) to the Al-alkoxide initiator has no significant effect on the polymerization rate, although the chain microstructure is deeply affected since predominantly syndiotactic PBL chains are formed (63% syndio-diads) in contrast to a completely atactic polymer in the absence of nicotine.     

Experimental verification of the kinetic model for the reaction yielding linear polyurethanes,claiming dependence of oligomer reactivities on molecular weights. III

Taking advantage of the algorithm developed earlier which makes it possible to calculate rate constants for the parallel-subsequent reactions of the kinetic model for the diisocyanate and diol polyaddition process, a mathematical model was developed for this process which then was subjected to mathematical decomposition. The procedure adopted allowed me to numerically resolve the obtained system of differential equations and to perform the numerical simulation of the polymerization process studied. For the reactions of 2,4-TDI and 1,4-butanediol, the results obtained were compared to experimental concentrations of urethane oligomer fractions found by means of GPC. It was found that the model suggested provides a better fit than does the model claiming dependence of chemical activity of oligomers solely on reactivity specifications for their functional groups. © 1996 John Wiley & Sons, Inc.     

The Effect of Fullerenol C60(OH)36 on the Antioxidant Defense System in Erythrocytes

Background: Fullerenols (water-soluble derivatives of fullerenes), such as C₆₀(OH)₃₆, are biocompatible molecules with a high ability to scavenge reactive oxygen species (ROS), but the mechanism of their antioxidant action and cooperation with endogenous redox machinery remains unrecognized. Fullerenols rapidly distribute through blood cells; therefore, we investigated the effect of C₆₀(OH)₃₆ on the antioxidant defense system in erythrocytes during their prolonged incubation. Methods: Human erythrocytes were treated with fullerenol at concentrations of 50–150 µg/mL, incubated for 3 and 48 h at 37 °C, and then hemolyzed. The level of oxidative stress was determined by examining the level of thiol groups, the activity of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase), and by measuring erythrocyte microviscosity. Results: The level of thiol groups in stored erythrocytes decreased; however, in the presence of higher concentrations of C₆₀(OH)₃₆ (100 and 150 µg/mL), the level of -SH groups increased compared to the control. Extending the incubation to 48 h caused a decrease in antioxidant enzyme activity, but the addition of fullerenol, especially at higher concentrations (100–150 µg/mL), increased its activity. We observed that C₆₀(OH)₃₆ had no effect on the microviscosity of the interior of the erythrocytes. Conclusions: In conclusion, our results indicated that water-soluble C₆₀(OH)₃₆ has antioxidant potential and efficiently supports the enzymatic antioxidant system within the cell. These effects are probably related to the direct interaction of C₆₀(OH)₃₆ with the enzyme that causes its structural changes.     

Oncogenic Mutation BRAF V600E Changes Phenotypic Behavior of THLE-2 Liver Cells through Alteration of Gene Expression

The accumulation of mutations in cancer driver genes, such as tumor suppressors or proto-oncogenes, affects cellular homeostasis. Disturbances in the mechanism controlling proliferation cause significant augmentation of cell growth and division due to the loss of sensitivity to the regulatory signals. Nowadays, an increasing number of cases of liver cancer are observed worldwide. Data provided by the International Cancer Genome Consortium (ICGC) have indicated many alterations within gene sequences, whose roles in tumor development are not well understood. A comprehensive analysis of liver cancer (virus-associated hepatocellular carcinoma) samples has identified new and rare mutations in B-Raf proto-oncogene (BRAF) in Japanese HCC patients, as well as BRAF V600E mutations in French HCC patients. However, their function in liver cancer has never been investigated. Here, using functional analysis and next generation sequencing, we demonstrate the tumorigenic effect of BRAF V600E on hepatocytes (THLE-2 cell line). Moreover, we identified genes such as BMP6, CXCL11, IL1B, TBX21, RSAD2, MMP10, and SERPIND1, which are possibly regulated by the BRAF V600E-mediated, mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) signaling pathway. Through several functional assays, we demonstrate that BRAF L537M, D594A, and E648G mutations alone are not pathogenic in liver cancer. The investigation of genome mutations and the determination of their impact on cellular processes and functions is crucial to unraveling the molecular mechanisms of liver cancer development.     

Bifunctional Opioid/Melanocortin Peptidomimetics for Use in Neuropathic Pain: Variation in the Type and Length of the Linker Connecting the Two Pharmacophores

Based on the mechanism of neuropathic pain induction, a new type of bifunctional hybrid peptidomimetics was obtained for potential use in this type of pain. Hybrids consist of two types of pharmacophores that are connected by different types of linkers. The first pharmacophore is an opioid agonist, and the second pharmacophore is an antagonist of the pronociceptive system, i.e., an antagonist of the melanocortin-4 receptor. The results of tests in acute and neuropathic pain models of the obtained compounds have shown that the type of linker used to connect pharmacophores had an effect on antinociceptive activity. Peptidomimetics containing longer flexible linkers were very effective at low doses in the neuropathic pain model. To elucidate the effect of linker lengths, two hybrids showing very high activity and two hybrids with lower activity were further tested for affinity for opioid (mu, delta) and melanocortin-4 receptors. Their complexes with the target receptors were also studied by molecular modelling. Our results do not show a simple relationship between linker length and affinity for particular receptor types but suggest that activity in neuropathic pain is related to a proper balance of receptor affinity rather than maximum binding to any or all of the target receptors.     

Expression of Irisin/FNDC5 in Breast Cancer

Irisin is a myokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. FNDC5 and irisin levels have been poorly studied in the tumor tissues of breast cancer (BC). The aim of this study was to determine the levels of irisin expression in BC tissues and compare them to clinicopathological factors and Ki-67 and PGC-1α expression levels. Tissue microarrays (TMAs) with 541 BC tissues and 61 samples of non-malignant breast disease (NMBD; control) were used to perform immunohistochemical reactions. FNDC5 gene expression was measured in 40 BC tissue samples, 40 samples from the cancer margin, and 16 NMBD samples. RT-PCR was performed for the detection of FNDC5 gene expression. Higher irisin expression was found in BC patients compared to normal breast tissue. FNDC5/irisin expression was higher in patients without lymph node metastases. Longer overall survival was observed in patients with higher irisin expression levels. FNDC5/irisin expression was increased in BC tissues and its high level was a good prognostic factor for survival in BC patients.