Shuttling of Spin Polarized Electrons in Molecular Transistors

Shuttling of electrons in single-molecule transistors with magnetic leads in the presence of an external magnetic field is considered theoretically. For a current of partially spin-polarized electrons a shuttle instability is predicted to occur for a finite interval of external magnetic field strengths. The lower critical magnetic field is determined by the degree of spin polarization and it vanishes as the spin polarization approaches 100%. The feasibility of detecting magnetic shuttling in a $C_{60}$-based molecular transistor with magnetic (Ni) electrodes is discussed [A.~N.~Pasupathy et al., Science 306, 86 (2004)].Comment: Submitted to a special issue of "Synthetic Metals" to appear in March 201

Why ribonucleases cause death of cancer cells

Molecular properties and possible mechanisms of action of cytotoxic ribonucleases (RNases), potential antitumor therapeutics, are characterized. The analysis of recent publications and own experimental results have allowed the authors, on the one hand, to distinguish cellular components that are responsible for selective activity of exogenous RNases towards malignant cells, and on the other - to identify the contribution of definite molecular determinants to the enzyme cytotoxicity. The predominant effect of the RNase molecule charge on the cell death induction is shown. The RNase cytotoxic effects are caused by catalytic cleavage of available RNA, by products of its hydrolysis, as well as by non-catalytic electrostatic interaction of exogenous enzyme with cell components. Potential targets for RNase action in a cancer cell have been revealed. The role of modulation of the membrane calcium-dependent potassium channels and ras-oncogene functions in the RNase-induced cell damage is defined. The effect of cytotoxic RNases on gene expression via influencing the RNA interference is discussed

Genomic determinants of nitric oxide biosynthesis in Lactobacillus plantarum: Potential opportunities and reality

As the genomic determinants of nitric oxide (NO) biosynthesis were identified in mammals and microorganisms, it became possible to systematically analyze the genetic conditioning of the process in clinically significant lactobacilli. A computer screening of the genetic determinants of synthetic pathways leading to NO production was performed to verify the NO-synthase origin of NO in Lactobacillus plantarum. Experimental evidence for enzymatic NO generation from L-arginine, rather than nitrite, was obtained by EPR spectroscopy. It was shown with the example of L. plantarum NO synthase that the observed functional activity of proteins is due to a complex transformation of the genetic program into a real catalytic function under certain conditions. © 2007 Pleiades Publishing, Inc

Modulation of nitric oxide (NO) biosynthesis in lactobacilli

We characterized effects of nitric oxide synthase (NOS) substrate L-arginine and classical inhibitors of mammalian NOS on nitric oxide (NO) biosynthesis in probiotic bacteria Lactobacillus plantarum 8P-A3. NO-synthase origin of nitric oxide detected by fluorescent NO indicator 1,2-diaminoanthraquinone (DAA) was confirmed by induction of NO production by exogenous L-arginine. None of the used inhibitors of three isoforms of mammalian NOSs (L-NAME, L-NIL, nNOS inhibitor I) showed significant inhibitory effect of lactobacillar NO-synthase activity. © 2011 Allerton Press, Inc

Ribonucleases as antiviral agents

© 2014, Pleiades Publishing, Inc. Many ribonucleases (RNases) are able to inhibit the reproduction of viruses in infected cell cultures and laboratory animals, but the molecular mechanisms of their antiviral activity remain unclear. The review discusses the well-known RNases that possess established antiviral effects, including both intracellular RNases (RNase L, MCPIP1 protein, and eosinophil-associated RNases) and exogenous RNases (RNase A, BS-RNase, onconase, binase, and synthetic RNases). Attention is paid to two important, but not always obligatory, aspects of molecules of RNases that have antiviral properties, i.e., catalytic activity and ability to dimerize. The hypothetic scheme of virus elimination by exogenous RNases that reflects possible types of interaction of viruses and RNases with a cell is proposed. The evidence for RNases as classical components of immune defense and thus perspective agents for the development of new antiviral therapeutics is proposed

Mechanically Induced Thermal Breakdown in Magnetic Shuttle Structures

A theory of a thermally induced single-electron "shuttling" instability in a magnetic nanomechanical device subject to an external magnetic field is presented in the Coulomb blockade regime of electron transport. The model magnetic shuttle device considered comprises a movable metallic grain suspended between two magnetic leads, which are kept at different temperatures and assumed to be fully spin polarized with antiparallel magnetizations. For a given temperature difference shuttling is found to occur for a region of external magnetic fields between a lower and an upper critical field strength, which separate the shuttling regime from normal small-amplitude "vibronic" regimes. We find that (i) the upper critical magnetic field saturates to a constant value in the high temperature limit and that the shuttle instability domain expands with a decrease of the temperature, (ii) the lower critical magnetic field depends not only on the temperature independent phenomenological friction coefficient used in the model but also on intrinsic friction (which vanishes in the high temperature limit) caused by magnetic exchange forces and electron tunneling between the quantum dot and the leads. The feasibility of using thermally driven magnetic shuttle systems to harvest thermal breakdown phenomena is discussed.Comment: 9 pages, 2 figure

Bacterial ribonuclease: Mutagenic effect in microbial test-systems

Pure enzyme samples of ribonuclease from Bacillus intermedius 7P (known commercially as 'binase') were investigated for genotoxicity in four microbial tests: the Ames plate incorporation method, Ara(R)-assay; the prophage induction test; and the DNA-repair test. The weak mutagenic effect of binase at high concentrations (0.1 mg/plate, 1 mg/plate) was established by induction of forward Ara(R)-mutations and histidine-reverse mutations (both frameshift mutations and base pair substitution). Metabolic activation with rat or chicken liver, human placenta or plant (from tulip bulbs) microsomal fractions in vitro was seen to abolish the binase mutagenicity. Bacillus intermedius 7P ribonuclease appears to possess DNA damaging activity in uvrA- and polA- mutants, but not in the recA-deficient Escherichia coil strain, and exhibits an induction of recA-dependent mutagenesis detected by the 8-fold increase of the prophage-induction level in lysogenic Bacillus subtilis culture and by the 5-fold increase of this level in the Streptomyces lavendulae 3 lysogenic strain. The importance of the roles of both of enzyme catalytic activity and native structure is emphasized. A proposed mechanism for exogenous ribonuclease action is discussed. Bacillus intermedius 7P ribonuclease probably does not act as a direct genotoxic agent interacting with DNA, but could provoke nucleotide imbalance through its catalytic action on membrane-associated RNAs, which results in alteration of DNA replication and, as a consequence, in recA-dependent mutagenesis

Antiviral activity of binase against the pandemic influenza A (H1N1) virus

The lack of effective antiviral drugs restricts the control of the dangerous RNA-containing influenza A (H1N1) virus. Extracellular ribonuclease of Bacilli (binase) was shown to manifest antiviral activity during single- and multi-cycle viral replication in the range of concentrations non-toxic to epithelial cells and 0.01-0.1 multiplicity of infection. During antiviral treatment for 15-30 min, the concentration of 1 μg/ml binase reduced the amount of focus-forming units of viruses by a factor of 3-10 and suppressed the virus-induced cytopathic effect in A549 human lung cells. The possible mechanisms of interaction between the virus and enzyme are discussed. Positive charges in both binase and viral hemagglutinin cause electrostatic interaction with negatively charged sialic acid on the host cell's surface followed by its penetration into the cell. Capsid elimination and release of viral RNA from endosome to the cytoplasm allows catalytic RNA cleavage by internalized binase. The data obtained confirm that binase is an effective antiviral agent against the pandemic influenza A (H1N1) virus. Certain progress in this field is associated with clarifying the detailed mechanism underlying the antiviral action of binase and development of the most effective way for its practical use. © 2013 Park-media, Ltd

Genotoxicity of helicobacter pylori δpai in DNA comet assay

Chronic infection with Helicobacter pylori is a factor inducing development of cancer diseases. The mechanism of its action on the «host» DNA is still not clear. In present study we investigate genotoxical potential of two strains of H. pylori: wild type H. pylori P12 and PAI-deficienl mutant H. pylori δPAI. DNA damage was detected by DNA comet assay in gastric adenocarcinoma (AGS) and epithelial adenocarcinoma (HeLa) cells under neutral conditions using Tail Moment as a quantitative parameter. It was shown, that infection of AGS and HeLa cells with both strains H. pylori at different multiplicity of infection (20-500) for 6 h and infection of AGS for 12 h did not induce DNA damage. Our results revealed a significant dose-dependent increasing of Tail Moment in the AGS cells after infection with mutant H. pylori δPAI for 24 h, while genotoxity of wild type H. pylori P12 under the same conditions was not observed

Proteomic analysis of 2,4,6-trinitrotoluene degrading yeast Yarrowia lipolytica

© 2017 Khilyas, Lochnit and Ilinskaya. 2,4,6-trinitrotoluene (TNT) is a common component of many explosives. The overproduction and extensive usage of TNT significantly contaminates the environment. TNT accumulates in soils and aquatic ecosystems and can primarily be destroyed by microorganisms. Current work is devoted to investigation of Yarrowia lipolytica proteins responsible for TNT transformation through the pathway leading to protonated Meisenheimer complexes and nitrite release. Here, we identified a unique set of upregulated membrane and cytosolic proteins of Y. lipolytica, which biosynthesis increased during TNT transformation through TNT-monohydride-Meisenheimer complexes in the first step of TNT degradation, through TNT-dihydride-Meisenheimer complexes in the second step, and the aromatic ring denitration and degradation in the last step. We established that the production of oxidoreductases, namely, NADH flavin oxidoreductases and NAD(P)+-dependent aldehyde dehydrogenases, as well as transferases was enhanced at all stages of the TNT transformation by Y. lipolytica. The up-regulation of several stress response proteins (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase) was also detected. The involvement of intracellular nitric oxide dioxygenase in NO formation during nitrite oxidation was shown. Our results present at the first time the full proteome analysis of Y. lipolytica yeast, destructor of TNT