The Cardioprotective PKA-Mediated Hsp20 Phosphorylation Modulates Protein Associations Regulating Cytoskeletal Dynamics

The cytoskeleton has a primary role in cardiomyocyte function, including the response to mechanical stimuli and injury. The small heat shock protein 20 (Hsp20) conveys protective effects in cardiac muscle that are linked to serine-16 (Ser16) Hsp20 phosphorylation by stress-induced PKA, but the link between Hsp20 and the cytoskeleton remains poorly understood. Herein, we demonstrate a physical and functional interaction of Hsp20 with the cytoskeletal protein 14-3-3. We show that, upon phosphorylation at Ser16, Hsp20 translocates from the cytosol to the cytoskeleton where it binds to 14-3-3. This leads to dissociation of 14-3-3 from the F-actin depolymerization regulator cofilin-2 (CFL2) and enhanced F-actin depolymerization. Importantly, we demonstrate that the P20L Hsp20 mutation associated with dilated cardiomyopathy exhibits reduced physical interaction with 14-3-3 due to diminished Ser16 phosphorylation, with subsequent failure to translocate to the cytoskeleton and inability to disassemble the 14-3-3/CFL2 complex. The topological sequestration of Hsp20 P20L ultimately results in impaired regulation of F-actin dynamics, an effect implicated in loss of cytoskeletal integrity and amelioration of the cardioprotective functions of Hsp20. These findings underscore the significance of Hsp20 phosphorylation in the regulation of actin cytoskeleton dynamics, with important implications in cardiac muscle physiology and pathophysiology.     

Locating,characterizing and computing the stationary points of a function

A method for the localization, characterization and computation of the stationary points of a continuously differentiable real-valued function ofn variables is presented. It is based on the combinatorial topology concept of the degree of a mapping associated with an oriented polyhedron. The method consists of two principal steps: (i) localization (and computation if required) of a stationary point in ann-dimensional polyhedron; (ii) characterization of a stationary point as a minimum, maximum or saddle point. The method requires only the signs of gradient values to be correct and it can be successfully applied to problems with imprecise values.     

Improving the Price of Anarchy for Selfish Routing via Coordination Mechanisms

We reconsider the well-studied Selfish Routing game with affine latency functions. The Price of Anarchy for this class of games takes maximum value 4/3; this maximum is attained already for a simple network of two parallel links, known as Pigou’s network. We improve upon the value 4/3 by means of Coordination Mechanisms. We increase the latency functions of the edges in the network, i.e., if ? _e (x) is the latency function of an edge e, we replace it by $\hat{\ell}_{e}(x)$ with $\ell_{e}(x) \le \hat{\ell}_{e}(x)$ for all x. Then an adversary fixes a demand rate as input. The engineered Price of Anarchy of the mechanism is defined as the worst-case ratio of the Nash social cost in the modified network over the optimal social cost in the original network. Formally, if $\hat{C}_{N} (r)$ denotes the cost of the worst Nash flow in the modified network for rate r and C _opt (r) denotes the cost of the optimal flow in the original network for the same rate then $$\mathit{ePoA} = \max_{r \ge 0} \frac{\hat{C}_N(r)}{C_{\mathit{opt}}(r)}. $$ We first exhibit a simple coordination mechanism that achieves for any network of parallel links an engineered Price of Anarchy strictly less than 4/3. For the case of two parallel links our basic mechanism gives 5/4=1.25. Then, for the case of two parallel links, we describe an optimal mechanism; its engineered Price of Anarchy lies between 1.191 and 1.192.     

The “Panopticon” of search engines: the response of the European data protection framework

Nowadays, Internet users are depending on various search engines in order to be able to find requested information on the Web. Although most users feel that they are and remain anonymous when they place their search queries, reality proves otherwise. The increasing importance of search engines for the location of the desired information on the Internet usually leads to considerable inroads into the privacy of users. A heated debate is currently ongoing at European level regarding the question if search engine providers that are established outside the European Union are covered by the European data protection framework and the obligations it imposes on entities that process personal data. The scope of this paper is to examine the applicability of the European data protection legislation to non-EU-based search engine providers and to study the main privacy issues with regard to search engines, such as the character of search logs, their anonymisation and their retention period. Ixquick, a privacy-friendly meta-search engine, will be presented as an alternative to privacy intrusive existing practices of search engines.     

High throughput cellular biosensor for the ultra-sensitive,ultra-rapid detection of aflatoxin M1

The aim of this study was the development of a rapid novel biosensor system based on the Bioelectric Recognition Assay (BERA) for the detection of aflatoxin M1 (AFM1). Membrane-engineering was achieved by electroinsertion of AFM1-homologous antibodies into the membrane of the cells. The sensor measured the electric response of cultured membrane-engineered fibroblast cells suspended in an alginate gel matrix due to the change of their membrane potential after the interaction of the analyte molecules with the antibodies. The BERA-based sensor was able to detect AFM1 rapidly (3min) at very low concentrations (5 pg/ml = 5 ppt), thus demonstrating a higher sensitivity than most currently available biosensor-based methods. In addition, the assay was quite selective against other aflatoxins, such as aflatoxin B1 and ochratoxin A. Furthermore, the assay system allowed for high throughput AFM1 analysis (160 individual tests/h), due to its multiple cell–electrode interface array. Although further research is required for the optimization of the assay, the elimination of possible matrix effects and its validation by assaying actual food samples, this novel biosensor offers new perspectives for ultra-rapid, ultra-sensitive and low-cost monitoring of mycotoxins in food commodities.     

Factorial design optimisation of grape (<Emphasis Type="Italic">Vitis vinifera</Emphasis>) seed polyphenol extraction

A 2³-full factorial design and response surface methodology were deployed to assess some basic factors (time, % ethanol and pH) affecting profoundly the extractability of polyphenolic phytochemicals from grape (V. vinifera) seeds. In an effort to obtain a thorough insight into the applicability of the models established, seed extracts from three different varieties were tested, by determining several indices of the polyphenolic composition, such as total polyphenol (TP), total flavanol (TFl) and proanthocyanidin (PC) concentrations. It has been shown that the models generated can adequately predict the recovery levels for each polyphenol group, but the optimal conditions predicted for TP, TFl and PC recovery varied significantly. Notable differences were also seen among the different varieties. Correlation of the polyphenol indices with the antiradical activity and reducing power of the extracts indicated that there is no consistent pattern to associate specific polyphenol classes with the antioxidant potential, which might be an evidence of antagonism. Examination of the optimally obtained extracts using liquid chromatography-mass spectrometry revealed that the most prominent compounds were catechin, some flavanol dimers and galloylated derivatives thereof.     

The promoting effect of Fe on Ni/GDC for the Solid Oxide H2O electrolysis

The study deals with the modification of commercial Ni/GDC powder with iron and its use as fuel functional electrode for Solid Oxide H₂O electrolysis. The Fe-NiO/GDC samples were prepared with the Deposition-Precipitation method and characterized, in their oxidized and reduced form, by using BET, HR-TEM, SAED, XRD, XPS and TG analysis in the presence of H₂O. The electrochemical investigation deals with the comparison of single SOECs at 900°C, under various pH₂O/pH₂ ratios. In the oxidized powders iron was detected, both in the bulk and on the surface, in the form of crystallized Fe₂O₃ species, which during H₂-reduction interacted with NiO towards the formation of a Ni-Fe alloy. The latter promoted the electrochemical performance of the Fe-Ni/GDC electrodes, where there are indications of strong dependence on the Fe wt% content. Specifically, the performance of the cell with 0.5 wt% Fe-Ni/GDC was threefold higher than that with Ni/GDC. On the other hand, the cell with 2 wt% Fe-Ni/GDC was worse, implying that the promoting effect of Fe lies on quite low wt% content. Finally, the examined Fe-doped electrodes exhibited increase of polarization in high pH₂O. This is primarily ascribed to the fact that Fe-Ni/GDC electrodes seem more susceptible to H₂O oxidation. Overall, Fe is considered as a promising Ni/GDC dopant, capable to substitute noble metals like Au, but further investigation is required for the elucidation of key preparation and performance parameters.     

Analysis of the Antenna＇s Setup Errors at the Global Navigation Satellite System Measurements

Today, the GNSS （global navigation satellite system） is used for more complicate and accurate applications such as monitoring or stake out works. The truth lies in the fact that in the most of the times not enough attention is paid to the antenna＇s setup. Usually, gross errors are found in the antenna＇s centering, leveling and in the measurement of its height, which are significant. In this paper, a thoroughly analysis of the above mentioned errors is carried out. The influence of these errors in the calculation of the X, Y, Z Cartesian geocentric coordinates and the ~, 2, h ellipsoid geodetic coordinates of a point P on the earth＇s surface, is analyzed and is presented in several diagrams. Also a new convenient method for the accurate measurement of the antenna＇s height is presented and it is strongly proposed. The conclusions outline the magnitude of these errors and prove the significance of the antenna＇s proper setup at the accurate GNSS applications.     

Chimeric Stimuli-Responsive Liposomes as Nanocarriers for the Delivery of the Anti-Glioma Agent TRAM-34

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.