A Comparative Study on Nickel Binding to Hpn-like Polypeptides from Two Helicobacter pylori Strains

Combined potentiometric titration and isothermal titration calorimetry (ITC) methods were used to study the interactions of nickel(II) ions with the N-terminal fragments and histidine-rich fragments of Hpn-like protein from two Helicobacter pylori strains (11637 and 26695). The ITC measurements were performed at various temperatures and buffers in order to extract proton-independent reaction enthalpies of nickel binding to each of the studied protein fragments. We bring up the problem of ITC results of nickel binding to the Hpn-like protein being not always compatible with those from potentiometry and MS regarding the stoichiometry and affinity. The roles of the ATCUN motif and multiple His and Gln residues in Ni(II) binding are discussed. The results provided the possibility to compare the Ni(II) binding properties between N-terminal and histidine-rich part of Hpn-like protein and between N-terminal parts of two Hpn-like strains, which differ mainly in the number of glutamine residues.     

Spherical Silica Functionalized by 2-Naphthalene Methanol Luminophores as a Phosphorescence Sensor

Photoluminescence is known to have huge potential for applications in studying biological systems. In that respect, phosphorescent dye molecules open the possibility to study the local slow solvent dynamics close to hard and soft surfaces and interfaces using the triplet state (TSD: triplet state solvation dynamics). However, for that purpose, probe molecules with efficient phosphorescence features are required with a fixed location on the surface. In this article, a potential TSD probe is presented in the form of a nanocomposite: we synthesize spherical silica particles with 2-naphthalene methanol molecules attached to the surface with a predefined surface density. The synthesis procedure is described in detail, and the obtained materials are characterized employing transmission electron microscopy imaging, Raman, and X-ray photoelectron spectroscopy. Finally, TSD experiments are carried out in order to confirm the phosphorescence properties of the obtained materials and the route to develop phosphorescent sensors at silica surfaces based on the presented results is discussed.     

Transcriptome Analysis of Cells Exposed to Actinomycin D and Nutlin-3a Reveals New Candidate p53-Target Genes and Indicates That CHIR-98014 Is an Important Inhibitor of p53 Activity

Co-treatment with actinomycin D and nutlin-3a (A + N) strongly activates p53. Previously we reported that CHIR-98014 (GSK-3 kinase inhibitor), acting in cells exposed to A + N, prevents activation of TREM2-an innate immunity and p53-regulated gene associated with Alzheimer’s disease. In order to find novel candidate p53-target genes and genes regulated by CHIR-98014, we performed RNA-Seq of control A549 cells and the cells exposed to A + N, A + N with CHIR-98014 or to CHIR-98014. We validated the data for selected genes using RT-PCR and/or Western blotting. Using CRISPR/Cas9 technology we generated p53-deficient cells. These tools enabled us to identify dozens of candidate p53-regulated genes. We confirmed that p53 participates in upregulation of BLNK, APOE and IRF1. BLNK assists in activation of immune cells, APOE codes for apolipoprotein associated with Alzheimer’s disease and IRF1 is activated by interferon gamma and regulates expression of antiviral genes. CHIR-98014 prevented or inhibited the upregulation of a fraction of genes stimulated by A + N. Downregulation of GSK-3 did not mimic the activity of CHIR-98014. Our data generate the hypothesis, that an unidentified kinase inhibited by CHIR-98014, participates in modification of p53 and enables it to activate a subset of its target genes, e.g., the ones associated with innate immunity.     

The Effect of the Osmotically Active Compound Concentration Difference on the Passive Water and Proton Fluxes across a Lipid Bilayer

The molecular details of the passive water flux across the hydrophobic membrane interior are still a matter of debate. One of the postulated mechanisms is the spontaneous, water-filled pore opening, which facilitates the hydrophilic connection between aqueous phases separated by the membrane. In the paper, we provide experimental evidence showing that the spontaneous lipid pore formation correlates with the membrane mechanics; hence, it depends on the composition of the lipid bilayer and the concentration of the osmotically active compound. Using liposomes as an experimental membrane model, osmotically induced water efflux was measured with the stopped-flow technique. Shapes of kinetic curves obtained at low osmotic pressure differences are interpreted in terms of two events: the lipid pore opening and water flow across the aqueous channel. The biological significance of the dependence of the lipid pore formation on the concentration difference of an osmotically active compound was illustrated by the demonstration that osmotically driven water flow can be accompanied by the dissipation of the pH gradient. The application of the Helfrich model to describe the probability of lipid pore opening was validated by demonstrating that the probability of pore opening correlates with the membrane bending rigidity. The correlation was determined by experimentally derived bending rigidity coefficients and probabilities of lipid pores opening.     

The HaLoop approach to large-scale iterative data analysis

The growing demand for large-scale data mining and data analysis applications has led both industry and academia to design new types of highly scalable data-intensive computing platforms. MapReduce has enjoyed particular success. However, MapReduce lacks built-in support for iterative programs, which arise naturally in many applications including data mining, web ranking, graph analysis, and model fitting. This paper (This is an extended version of the VLDB 2010 paper “HaLoop: Efficient Iterative Data Processing on Large Clusters” PVLDB 3(1):285–296, 2010.) presents HaLoop, a modified version of the Hadoop MapReduce framework, that is designed to serve these applications. HaLoop allows iterative applications to be assembled from existing Hadoop programs without modification, and significantly improves their efficiency by providing inter-iteration caching mechanisms and a loop-aware scheduler to exploit these caches. HaLoop retains the fault-tolerance properties of MapReduce through automatic cache recovery and task re-execution. We evaluated HaLoop on a variety of real applications and real datasets. Compared with Hadoop, on average, HaLoop improved runtimes by a factor of 1.85 and shuffled only 4 % as much data between mappers and reducers in the applications that we tested.     

The Old-Age Healthy Dependency Ratio in Europe

The aim of this study is to answer the question of whether improvements in the health of the elderly in European countries could compensate for population ageing on the supply side of the labour market. We propose a state-of-health-specific (additive) decomposition of the old-age dependency ratio into an old-age healthy dependency ratio and an old-age unhealthy dependency ratio in order to participate in a discussion of the significance of changes in population health to compensate for the ageing of the labour force. Applying the proposed indicators to the Eurostat's population projection for the years 2010-2050, and assuming there will be equal improvements in life expectancy and healthy life expectancy at birth, we discuss various scenarios concerning future of the European labour force. While improvements in population health are anticipated during the years 2010-2050, the growth in the number of elderly people in Europe may be expected to lead to a rise in both healthy and unhealthy dependency ratios. The healthy dependency ratio is, however, projected to make up the greater part of the old-age dependency ratio. In the European countries in 2006, the value of the old-age dependency ratio was 25. But in the year 2050, with a positive migration balance over the years 2010-2050, there would be 18 elderly people in poor health plus 34 in good health per 100 people in the current working age range of 15-64. In the scenarios developed in this study, we demonstrate that improvements in health and progress in preventing disability will not, by themselves, compensate for the ageing of the workforce. However, coupled with a positive migration balance, at the level and with the age structure assumed in the Eurostat's population projections, these developments could ease the effect of population ageing on the supply side of the European labour market.     

Electrochemical studies of carbon-rich polymer-derived SiCN ceramics as anode materials for lithium-ion batteries

The electrochemical behavior of poly(phenylvinylsilylcarbodiimide)-derived SiCN ceramics as anode material for lithium-ion batteries is reported here for the first time. The novel carbon-rich silicon carbonitride (SiCN) ceramics have been synthesized by the thermal treatment of poly(phenylvinylsilylcarbodiimide) under argon atmosphere at five temperatures, namely 1100, 1300, 1500, 1700 and 2000 °C. The SiCN electrodes were prepared without any conducting additives and were tested in electrochemical two electrodes cell using cyclic voltammetry and galvanostatic techniques. The capacity of the carbon-rich SiCN samples was found to be stable upon galvanostatic cycling and reaches almost 300 mAh/g for the sample prepared at 1300 °C with oxygen as the impurity. The dependence of the microstructure, especially of the crystallinity of the segregated carbon phase and of the oxygen impurities on the electrochemical behavior of the SiCN material, was analysed. At all temperatures of thermolysis, the free carbon phase has been identified as “soft carbon”.